The therapeutic landscape of locally advanced or metastatic urothelial carcinoma (mUC) is rapidly evolving, and immune checkpoint inhibitors (ICI) have become an integral part of the standard therapy. However, the majority of patients do not benefit from this treatment. Hence, finding prognostic and predictive biomarkers may improve therapeutic decision-making. The aim of this study was to analyze the prognostic and predictive significance of liquid biomarkers (NLR, CRP, PLR, and LDH) in mUC patients treated with ICI.

We collected articles from PubMed, Cochrane, and Embase databases with primary outcomes of overall survival (OS), progression-free survival (PFS) and objective response rate (ORR).

We compiled data from a total of 6,673 ICI-treated patients with locally advanced or mUC from 31 articles. Pooled univariate analysis demonstrated that high pre-treatment NLR is significantly associated with worse OS (HR: 2.19; 95% CI: 1.80-2.68) and PFS (HR: 1.90; 95% CI: 1.57-2.31). Similarly, elevated CRP levels were associated with worse OS (HR: 1.75; 95% CI: 1.37-2.24) and PFS (HR: 1.58; 95% CI: 1.26-1.99).

Elevated pre-treatment NLR, CRP, PLR, and LDH are significantly associated with worse OS and PFS in ICI-treated urothelial carcinoma patients, suggesting that they have potential prognostic and predictive value in treatment decisions.

In this systematic review and meta-analysis we summarized the existing data on inflammatory laboratory biomarkers and their potential impact on immunotherapy outcomes in urothelial cancers.

https://www.crd.york.ac.uk/prospero/, identifier CRD42022291449.

Historically, lactate has been considered merely a metabolic byproduct. However, recent studies have revealed that lactate plays a much more dynamic role, acting as an immune signaling molecule that influences cellular communication, through the process of "lactate shuttling." Lactylation, a novel post-translational modification, is directly derived from lactate and represents an emerging mechanism through which lactate exerts its effects on cellular function. It has been shown to directly affect immune cells by modulating the activation of pro-inflammatory and anti-inflammatory pathways. This modification influences the expression of key immune-related genes, thereby impacting immune cell differentiation, cytokine production, and overall immune response. In this review, we focused on the role of lactate and lactylation in the dysregulation of immune responses in psoriasis and its relapse. Additionally, we discuss the potential applications of targeting lactate metabolism and lactylation modifications in the treatment of psoriasis, alongside the investigation of artificial intelligence applications in advancing lactate and lactylation-focused drug development, identifying therapeutic targets, and enabling personalized medical decision-making. The significance of this review lies in its comprehensive exploration of how lactate and lactylation contribute to immune dysregulation, offering a novel perspective for understanding the metabolic and epigenetic changes associated with psoriasis. By identifying the roles of these pathways in modulating immune responses, this review provides a foundation for the development of new therapeutic strategies that target these mechanisms.

Dyslipidemia has been linked to acute promyelocytic leukemia (APL), with abnormal lipid metabolism observed during treatment. However, its role in APL pathogenesis remains unclear. This study investigates the relationship between serum lipid levels and clinical features, risk stratification, bleeding tendency, and prognosis of newly diagnosed APL patients, focusing on the role of the PTK2 gene in regulating lipid metabolism and its potential as a therapeutic target.

We analyzed 90 newly diagnosed APL patients and 99 controls. Statistical analyses, including logistic regression, survival analysis, and protein-protein interaction (PPI) network, were used to assess lipid correlations with APL. Subgroup analyses explored specific clinical impacts, and functional experiments validated PTK2's role in lipid metabolism.

Elevated triglycerides (TG) were positively associated with high-risk APL, while reduced high-density lipoprotein cholesterol (HDL-C) levels correlated with lower risk. Low-density lipoprotein cholesterol (LDL-C) was an independent prognostic marker, with lower levels linked to poorer outcomes. PTK2 expression significantly promoted APL cell proliferation, migration, and lipid metabolism, highlighting its role in APL pathogenesis. PTK2 regulates lipid metabolism-related factors, such as LDL and fibrinogen, through molecular pathways.

Dyslipidemia is closely related to APL, with TG and LDL-C levels being key prognostic indicators. PTK2 plays a crucial role in lipid metabolism regulation and APL progression, providing a new molecular basis for risk assessment and targeted therapy. These findings offer potential biomarkers for early diagnosis and personalized treatment strategies.

This study aimed to investigate the prognostic value of pretreatment lactate dehydrogenase to albumin ratio (LAR) in advanced non-small cell lung cancer (NSCLC) patients treated with first-line programmed cell death protein 1 (PD-1) checkpoint inhibitors and chemotherapy.

A retrospective cohort study was conducted on advanced NSCLC patients treated with first-line PD-1 checkpoint inhibitors plus chemotherapy at Guangxi Medical University Cancer Hospital. The receiver operating characteristic (ROC) analysis determined the optimal LAR cutoff values for prediction. Univariate and multivariate analyses identified independent prognostic factors, and survival curves were estimated using the Kaplan-Meier method. Subgroup analysis evaluated the association between high LAR and disease progression and death risk.

A total of 210 patients were enrolled, with a mean age of 58.56 ± 10.61 years and a male proportion of approximately 79.05%. ROC analysis found the optimal LAR cutoff value was 5.0, resulting in a sensitivity of 78.87% and a specificity of 44.6% (area under the ROC curve 0.622; P = 0.001). Multivariate analysis revealed a significant positive association between LAR and overall survival (OS) after adjusting for confounders (HR = 2.22, 95% CI = 1.25-3.96, P = 0.007). Subgroup analysis confirmed the relationship between high LAR and the risk of disease progression and death across all patient subgroups.

Pretreatment LAR may be a potential independent prognostic marker for advanced NSCLC patients receiving PD-1 checkpoint inhibitors plus chemotherapy. A large-scale, prospective study is necessary to confirm these findings.

The expression level of programmed death ligand 1 (PD-L1) is the only approved biomarker for predicting response to immunotherapy, yet its efficacy is not always consistent. Lactate dehydrogenase (LDH) has been associated with tumor aggressiveness and poorer prognosis across various cancer types and may serve as a useful biomarker for monitoring treatment response. The objective of this study is to analyze the relationship between LDH levels prior to the start of treatment with immune checkpoint inhibitors (ICIs) and clinical outcomes in patients with non-small cell lung cancer (NSCLC).

A retrospective study was conducted including patients diagnosed with NSCLC who were treated with at least 3 cycles of immunotherapy. Data on demographics, clinical and pathological characteristics, treatment received, pretreatment LDH levels, and clinical outcomes such as treatment response and overall survival (OS) were analyzed.

A total of 181 patients diagnosed with NSCLC were included. Elevated pretreatment LDH levels (>244 U/L) were associated with significantly reduced OS. The median survival was 548 days in patients with LDH ≤ 244 U/L, compared to 332 days in those with LDH > 244 U/L (P = .037). Among men, OS was greater in the LDH ≤ 244 U/L group (623 days) versus 332 days in the LDH > 244 U/L group (P = 0.043). In patients with metastatic disease, OS was higher in those with LDH ≤ 244 U/L (474 days) compared to 249 days in those with LDH > 244 U/L (P = .023). In patients receiving both immunotherapy and chemotherapy, OS was greater in those with LDH ≤ 244 U/L (623 days) compared to 281 days in the LDH > 244 U/L group (P = .042).

High levels of LDH prior to the start of treatment with ICIs are associated with lower treatment efficacy and a worse prognosis of the disease, especially in male, metastatic patients with a PD-L1 expression level <1%.

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis to oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also contribute to immune evasion through mechanisms such as reactive oxygen species (ROS) generation and the upregulation of immune checkpoint molecules like PD-L1. This review explores the potential of targeting metabolic weaknesses in drug-resistant cancers to enhance therapeutic efficacy. Key metabolic pathways involved in resistance, including glycolysis, glutamine metabolism, and the kynurenine pathway, are discussed. The combination of metabolic inhibitors with immune checkpoint inhibitors (ICIs), particularly anti-PD-1/PD-L1 therapies, represents a promising approach to overcoming both metabolic and immune evasion mechanisms. Clinical trials combining metabolic and immune therapies have shown early promise, but further research is needed to optimize treatment combinations and identify biomarkers for patient selection. In conclusion, targeting cancer metabolism in combination with immune checkpoint blockade offers a novel approach to overcoming drug resistance, providing a potential pathway to improved outcomes in cancer therapy. Future directions include personalized treatments based on tumor metabolic profiles and expanding research to other tumor types.

Due to its rarity, it is challenging to predict the survival of patients with synchronous multiple primary esophageal squamous carcinomas (SMPESCs). We aimed to construct nomograms to predict survival outcomes and help to make therapeutic strategy for patients with SMPESCs.

The clinical and survival data of 135 patients with SMPESCs were analyzed retrospectively. Univariate and multivariate Cox analyses were used to identify independent prognostic factors. Nomograms were constructed to predict 1-year, 3-year and 5-year disease-free survival (DFS) and overall survival (OS). In addition, we further evaluated the effect of postoperative adjuvant therapy on SMPESCs patients with lymph node metastasis.

In univariate and multivariate analyses of DFS and OS, age, site of the main lesion, lymph node metastasis, total number of lymph nodes dissected, lactate dehydrogenase level and lymphocyte-to-monocyte ratio were identified as independent prognostic factors. These characteristics were further included to establish nomograms. For the internal validation of the nomogram predictions of survival outcomes, the concordance indices were 0.752 and 0.756, respectively. Decision curve analysis also proved the efficacy of the nomograms. Furthermore, adjuvant therapy had a statistically significant benefit for OS but not DFS in patients with lymph node metastasis.

These nomograms could effectively predict the 1-year, 3-year and 5-year survival outcomes of patients with SMPESCs. Furthermore, adjuvant therapy has the potential to improve OS in patients with lymph node metastasis.

To investigate the prognostic value of lactate dehydrogenase (LDH), serum albumin (ALB) and the lactate dehydrogenase/albumin ratio (LAR) in diffuse large B-cell lymphoma (DLBCL) before primary treatment.

The clinical data of 212 primary adult DLBCL patients admitted to the First People's Hospital of Lianyungang from January 2017 to December 2022 were analyzed retrospectively. The optimal cutoff values of LDH, ALB, and LAR were determined using ROC curves. Survival curves of LDH, ALB, and LAR were plotted and analyzed using the Cox regression model and Kaplan-Meier method with the log-rank test.

Among the 212 patients admitted, the study derived the optimal cutoff values for ALB, LDH, and LAR as 38, 301, and 6, respectively. The Kaplan-Meier method and log-rank test analysis indicated a significant association between lower ALB levels, elevated LDH levels, elevated LAR levels, and shorter overall survival (OS) and progression-free survival (PFS) (P < 0.05). Additionally, the critical values of ALB and LDH were grouped into three categories. The differences in OS and PFS among these three groups were statistically significant (P < 0.05). Cox multifactorial analysis revealed that the LAR was an independent factor influencing the prognosis of OS and PFS, with a higher prognostic value than LDH and ALB alone.

Decreased ALB levels and elevated LDH and LAR levels at the time of initial diagnosis are indicative of a poor prognosis in DLBCL patients. Furthermore, the study highlighted that the LAR has a higher prognostic value than LDH and ALB alone.

The aim of this retrospective study was to analyze the efficacy and risk factors of immune checkpoint inhibitors (ICIs) in lung cancer patients.

One hundred lung cancer patients who were treated in our hospital from May 2021 to May 2023 were selected as the study subjects and divided into chemotherapy group (n = 50) and ICIs group (n = 50), in which the chemotherapy group was given the combined treatment of vincristine and cisplatin (NP), while the ICIs group was given ICIs for treatment. The therapeutic effect and adverse reactions (hypertriglyceridemia, anemia, hypertension and hypoproteinemia) of the two groups were compared, and fasting venous blood was collected. The levels of carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199) were compared between the two groups before and after treatment. According to the therapeutic effect, 100 patients with lung cancer were divided into complete remission (CR) + partial remission (PR) group (n = 52) and stable (SD) + progressive (PD) group (n = 48). The clinical data and pathologic data of the two groups were compared.

The rates of objective effective rate (ORR) in chemotherapy group and ICIs group were 36.00% and 68.00% respectively, and the level of ORR in ICIs group was significantly higher than that in chemotherapy group, with statistical significance (P < 0.05). There was no significant difference in serum CEA and CA199 levels between the two groups before operation (P > 0.05). Three months after operation, the serum CEA and CA199 levels in ICIs group were significantly lower than those in chemotherapy group, and the difference was statistically significant (P < 0.05). The adverse reactions of hypertriglyceridemia, anemia, hypertension and hypoproteinemia in chemotherapy group and ICIs group during treatment were all grade 1-2, and the incidence of adverse reactions was similar between the two groups (P > 0.05). There was no significant difference in sex, age, anatomic position, pathologic type, smoking history and differentiation between the two groups (P > 0.05). In SD + PD group, the preoperative maximum tumor diameter > 4 cm, tumor node metastasis (TNM) stage IV, lactate dehydrogenase (LDH) ≥ 183 U/L, and tumor volume ≥ 120m3 were significantly higher than those in CR + PR group, and the prognostic nutritional index (PNI) ≥ 41.8 and the proportion of ICIs were significantly lower than those in CR + PR group, with statistical significance (P < 0.05). Multifactorial logistic regression analysis showed that preoperative maximum tumor diameter > 4 cm and LDH ≥ 183 U/L were risk factors for poor lung cancer outcome, and PNI ≥ 41.8 and ICIs treatment were protective factors for poor lung cancer outcome (P < 0.05).

ICIs is effective in the treatment of lung cancer, which can obviously reduce the tumor load and has high safety. In addition, the maximum tumor diameter and LDH are risk factors that affect the poor curative effect of lung cancer. High PNI level and ICIs treatment are helpful to improve the effect of lung cancer, and early monitoring is helpful to guide the treatment plan and evaluate the treatment effect.

Background and Objectives: Neoadjuvant chemotherapy (NAC) improves survival by increasing pathologic complete response (pCR). Blood-based indexes have been studied in breast cancer for predicting pCR and prognosis, but the results are conflicting. We aimed to assess the impact of inflammatory and nutritional indexes on pCR and survival. Materials and Methods: We retrospectively analyzed 304 patients. Pre-NAC laboratory data were used to calculate their neutrophil-to-lymphocyte ratios (NLR), pan-immune inflammation values (PIV), lactate dehydrogenase-albumin ratios (LAR), and prognostic nutritional indexes. The optimal cut-off values were determined through an analysis of the receiver operating characteristic curve. Survival analyses were performed using the Kaplan-Meier method. Multivariate regression analyses were performed to reveal the factors predicting pCR. Univariate and multivariate survival analyses were conducted to identify prognostic factors predicting survival. Results: The median follow-up was 38.5 months. pCR was achieved in 41.4% of the patients. In the univariate analyses, the NLR (p = 0.032) and PIV (p = 0.002) were indexes associated with pCR. In the multivariate analysis, the PIV (p = 0.008) was the only index significantly correlated with pCR. According to the multivariate Cox regression analyses, clinical stage 3 (p = 0.032), a pathologic response other than pCR (p = 0.021), and a high LAR (≥4.72) (p = 0.002) were correlated with increased recurrence risk. The univariate Cox regression analyses revealed that failure to achieve pCR (p = 0.037) and the presence of a high LAR (p = 0.044) were significant predictors of overall survival. However, the multivariate analyses failed to identify any significant predictors of death. Conclusions: We found that the PIV was more effective than the other indexes in predicting pCR. To our knowledge, this study is the first to determine an association between the LAR and disease-free survival in patients with breast cancer receiving NAC. We concluded that a high LAR was a poor prognostic factor, especially in patients without a pCR. Therefore, close postoperative monitoring and the intensification of adjuvant treatment should be considered for these patients. However, further studies are needed to confirm our findings.

The expression level of programmed death ligand 1 (PD-L1) is the only approved biomarker for predicting response to immunotherapy, yet its efficacy is not always consistent. Lactate dehydrogenase (LDH) has been associated with tumor aggressiveness and poorer prognosis across various cancer types and may serve as a useful biomarker for monitoring treatment response. The objective of this study is to analyze the relationship between LDH levels prior to the start of treatment with immune checkpoint inhibitors (ICIs) and clinical outcomes in patients with non-small cell lung cancer (NSCLC).

A retrospective study was conducted including patients diagnosed with NSCLC who were treated with at least three cycles of immunotherapy. Data on demographics, clinical and pathological characteristics, treatment received, pre-treatment LDH levels, and clinical outcomes such as treatment response and overall survival (OS) were analyzed.

A total of 181 patients diagnosed with NSCLC were included. Elevated pre-treatment LDH levels (more than 244 U/l) were associated with significantly reduced OS. The median survival was 548 days in patients with LDH less than 244 U/l, compared to 332 days in those with LDH more than 244 U/l (p = 0.037). Among men, OS was greater in the LDH less than 244 U/l group (623 days) versus 332 days in the LDH more than 244 U/l group (p = 0.043). In patients with metastatic disease, OS was higher in those with LDH less than 244 U/l (474 days) compared to 249 days in those with LDH more than 244 U/l (p = 0.023). In patients receiving both immunotherapy and chemotherapy, OS was greater in those with LDH less than 244 U/l (623 days) compared to 281 days in the LDH more than 244 U/l group (p = 0.042).

High levels of LDH prior to the start of treatment with ICIs are associated with lower treatment efficacy and a worse prognosis of the disease, especially in male, metastatic patients with a PD-L1 expression level less than 1%.

The lung immune prognostic index (LIPI) is a biomarker that combines the lactate dehydrogenase (LDH) value and the derived neutrophil/lymphocyte ratio (dNLR). Its prognostic ability has been reported in non-small cell lung cancer (NSCLC) with immunotherapy. In the context of extensive-stage small cell lung cancer (ES-SCLC) with chemoimmunotherapy, its role remains to be determined.

A retrospective, multicenter study of patients with ES-SCLC who received atezolizumab plus chemotherapy as first-line treatment was conducted. 101 patients were divided into three groups: LIPI good (n = 33), LIPI intermediate (n = 41), and LIPI poor (n = 27). The Kaplan-Meier method was used for analysis of overall survival (OS) and progression-free survival (PFS), using the log-rank test for comparisons. Univariate and multivariate Cox models were developed to assess the LIPI as an independent predictor of survival.

The good LIPI group had a significantly longer median PFS than the intermediate and poor LIPI groups: 9.6 vs 5.4 vs 5.2 months, respectively (p < 0.001). Significant differences in OS between good, intermediate, and poor LIPI were also observed, with median OS of 23.4 vs 9.8 vs 6.0 months, respectively (p < 0.001). Multivariate Cox regression analysis for PFS identified liver metastases and intermediate and poor LIPI as worse prognostic factors (p < 0.050). For OS, a worse prognosis was confirmed in both the intermediate LIPI group (HR: 2.18, 95% CI: 1.07-4.41, p = 0.031) and the poor LIPI group (HR: 5.40, 95% CI: 2.64-11.07, p < 0.001).

In patients with ES-SCLC treated with chemoimmunotherapy, an intermediate and poor pretreatment LIPI score was associated with worse PFS and OS prognosis.

Thrombophilia combined with pregnancy poses significant risks for adverse pregnancy outcomes. Unfortunately, there are no indicators at high risk for predicting adverse pregnancy outcomes. This study investigates the predictive efficiency of serum immune-inflammatory markers on adverse pregnancy outcomes.

This retrospective cohort study includes 223 pregnant women diagnosed with thrombophilia who delivered at the Fujian Provincial Hospital South Branch from January 2022 to April 2024. Clinical information and pregnancy outcomes were collected. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship and predictive accuracy between immune-inflammatory markers and adverse pregnancy outcomes were analyzed.

In this study, 50 (22.4%) patients had adverse pregnancy outcomes. Significant differences were observed in neutrophils counts, monocytes counts, LDH, SII, and SIRI levels between the adverse pregnancy outcome groups (APOs) and the control groups (P<0.05). The area under the receiver operating characteristic (ROC) curve analysis revealed that SII (AUC=0.762), SIRI (AUC=0.764), and LDH (AUC=0.732) had high predictive values for adverse pregnancy outcomes. Notably, the combined model had the highest AUC of 0.805. Multivariate logistic regression identified SII had the highest odd ratio (OR) (OR=8.512; 95% CI(3.068-23.614)), followed by LDH (OR=4.905; 95% CI (1.167-11.101)), SIRI (OR=3.549; 95% CI(0.847-8.669)), and neutrophils count (OR=1.726; 95% CI (0.563-2.938)) as independent risk factors for adverse outcomes.

Elevated levels of immune-inflammatory markers such as SII, SIRI, and LDH level are strong predictors of adverse pregnancy outcomes in thrombophilia-complicated pregnancies. These markers are significantly associated with maternal-neonatal outcomes. Our findings underscore the importance of monitoring immune-inflammatory markers in pregnant women with thrombophilia to improve maternal and neonatal outcomes.

Osteoarthritis (OA) is the most common joint disease. The occurrence and progression of OA are regulated by epigenetics. A large number of studies have shown the important regulatory role of noncoding RNAs in joint diseases. As the largest class of noncoding small RNAs, the importance of piRNAs in many diseases, especially cancer, has been increasingly recognized. However, few studies have explored the role of piRNAs in OA. Our study showed that hsa_piR_019914 decreased significantly in OA. This study aimed to demonstrate the role of hsa_piR_019914 as a potential biological target of OA in chondrocytes.

The GEO database and bioinformatics analysis were used for a series of screenings, and the OA model using human articular chondrocytes (C28/I2 cells), SW1353 cells under inflammatory factor stimulation was used to determine that hsa_piR_019914 was significantly downregulated in OA. Overexpression or inhibition of hsa_piR_019914 in C28/I2 cells was achieved by transfecting mimics or inhibitors. The effect of hsa_piR_019914 on the biological function of chondrocytes was verified by qPCR, flow cytometry, and colony formation assays in vitro. The target gene of hsa_piR_019914, lactate dehydrogenase A (LDHA), was screened by small RNA sequencing and quantitative polymerase chain reaction (qPCR), LDHA was knocked out in C28/I2 cells by the transfection of siRNA LDHA, and the relationship between hsa_piR_019914, LDHA, and reactive oxygen species (ROS) production was verified by flow cytometry.

The piRNA hsa-piR-019914 was significantly downregulated in osteoarthritis (OA). Hsa-piR-019914 reduced inflammation-mediated chondrocyte apoptosis and maintained cell proliferation and clone formation in vitro. Hsa-piR-019914 reduced the production of LDHA-dependent ROS through targeted regulation of LDHA expression, maintained chondrocyte-specific gene expression of ACAN and COL2, and inhibited the gene expression of MMP3 and MMP13.

Collectively, this study showed that hsa_piR_019914 was negatively correlated with the expression of LDHA, which mediates ROS production. Under the stimulation of inflammatory factors, overexpression of hsa_piR_019914 had a protective effect on chondrocytes in vitro, and the absence of hsa_piR_019914 exacerbated the negative effect of inflammation on chondrocytes. Studies on piRNAs provide new therapeutic interventions for OA.

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism.

ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins.

After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells.

PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.

Current guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM.

18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance.

Pre-treatment Epstein-Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels.

The PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations.

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16 years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5 years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5 years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non-small-cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes: terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI), and squamous cell carcinoma (LUSQ) into four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated the immune landscape of NSCLC tissues in molecular subtypes using a multi-omics dataset, including tumor-infiltrating leukocytes (TILs) analyzed using flow cytometry, RNA sequences, whole exome sequences, metabolomic analysis, and clinicopathologic findings. In the PI subtype, the number of TILs increased and the immune response in the tumor microenvironment (TME) was activated, as indicated by high levels of tertiary lymphoid structures, and high cytotoxic marker levels. Patient prognosis was worse in the PP subtype than in other adenocarcinoma subtypes. Glucose transporter 1 (GLUT1) expression levels were upregulated and lactate accumulated in the TME of the PP subtype. This could lead to the formation of an immunosuppressive TME, including the inactivation of antigen-presenting cells. The TRU subtype had low biological malignancy and "cold" tumor-immune phenotypes. Squamous cell carcinoma (LUSQ) did not show distinct immunological characteristics in its respective subtypes. Elucidation of the immune characteristics of molecular subtypes could lead to the development of personalized immune therapy for lung cancer. Immune checkpoint inhibitors could be an effective treatment for the PI subtype. Glycolysis is a potential target for converting an immunosuppressive TME into an antitumorigenic TME in the PP subtype.

Numerous inflammatory indicators have been demonstrated to be strongly correlated with tumor prognosis. However, the association between inflammatory indicators and the prognosis of patients with nasopharyngeal carcinoma (NPC) receiving treatment with programmed death receptor-1 (PD-1) immunosuppressant monoclonal antibodies remains uncertain. Inflammatory indicators in peripheral blood were collected from 161 NPC patients at 3 weeks after initial PD-1 treatment. Through univariate and multivariate analyses, as well as nomogram and survival analyses, we aimed to identify independent prognostic factors related to 1-year progression-free survival (PFS). Subsequently, a prognostic nomogram was devised, and its predictive and discriminating abilities were assessed utilizing calibration curves and the concordance index. Our univariate and multivariate analyses indicated that age (P = .012), M stage (P < .001), and systemic immune-inflammation index (SII) during the third week following initial PD-1 treatment (SII3, P = .005) were independently correlated with the 1-year PFS of NPC patients after PD-1 treatment. Notably, we constructed a novel nomogram based on the SII3, age, and M stage. Importantly, utilizing the derived cutoff point from the nomogram, the high-risk group exhibited significantly shorter PFS than did the low-risk group (P < .001). Furthermore, the nomogram demonstrated a greater concordance index for PFS than did the tumor node metastasis stage within the entire cohort. We successfully developed a nomogram that integrates the SII3 and clinical markers to accurately predict the 1-year PFS of NPC patients receiving PD-1 inhibitor treatment.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. There is an urgent need to find more effective drugs that inhibit NSCLC. Fargesin (FGS) has demonstrated anti-tumor effects; however, its efficacy and the molecular mechanism of inhibiting NSCLC are unclear. Herein, we investigated FGS' inhibitory effects on NSCLC by CCK8 and EdU assays and cell cycle analysis of A549 cells in vitro and in a nude mouse tumor transplantation model in vivo. FGS (10-50 μM) significantly inhibited cell proliferation and down-regulated expression levels of CDK1 and CCND1. Transcriptomic analysis showed that FGS regulated the cell metabolic process pathway. Differential metabolites with FGS treatment were enriched in glycolysis and pyruvate pathways. Cell metabolism assay were used to evaluate the oxygen consumption rate (OCR), Extracellular acidification rate (ECAR) in A549 cells. FGS also inhibited the production of cellular lactate and the expression of LDHA, LDHB, PKM2, and SLC2A1. These genes were identified as important oncogenes in lung cancer, and their binding to FGS was confirmed by molecular docking simulation. Notably, the over-expression and gene silencing experiments signified PKM2 as the molecular target of FGS for anti-tumorigenesis. Moreover, the H3 histone lactylation, were correlated with tumorigenesis, were inhibited with FGS treatment. Conclusively, FGS inhibited the aerobic glycolytic and H3 histone lactylation signaling pathways in A549 NSCLC cells by targeting PKM2. These findings provide evidence of the therapeutic potential of FGS in NSCLC.

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.

Non-small cell lung cancer (NSCLC) is a common malignancy and is associated with poor survival outcomes. Biomarkers of systemic inflammation derived from blood tests collected as part of routine clinical care offer prognostic information for patients with NSCLC that may assist clinical decision making. They are an attractive tool, as they are inexpensive, easily measured, and reproducible in a variety of healthcare settings. Despite the wealth of evidence available to support them, these inflammatory biomarkers are not yet routinely used in clinical practice. In this narrative review, the key inflammatory indices reported in the literature and their prognostic significance in NSCLC are described. Key challenges limiting their clinical application are highlighted, including the need to define the optimal biomarker of systemic inflammation, a lack of understanding of the systemic inflammatory landscape of NSCLC as a heterogenous disease, and the lack of clinical relevance in reported outcomes. These challenges may be overcome with standardised recording and reporting of inflammatory biomarkers, clinicopathological factors, and survival outcomes. This will require a collaborative approach, to which this field of research lends itself. This work may be aided by the rise of data-driven research, including the potential to utilise modern electronic patient records and advanced data-analysis techniques.

Chimeric antigen receptor (CAR) T cell therapy holds enormous potential for the treatment of hematologic malignancies. Despite its benefits, it is still used as a second line of therapy, mainly because of its severe side effects and patient unresponsiveness. Numerous researchers worldwide have attempted to identify effective predictive biomarkers for early prediction of treatment outcomes and adverse effects in CAR T cell therapy, albeit so far only with limited success. This review provides a comprehensive overview of the current state of predictive biomarkers. Although existing predictive metrics correlate to some extent with treatment outcomes, they fail to encapsulate the complexity of the immune system dynamics. The aim of this review is to identify six major groups of predictive biomarkers and propose their use in developing improved and efficient prediction models. These groups include changes in mitochondrial dynamics, endothelial activation, central nervous system impairment, immune system markers, extracellular vesicles, and the inhibitory tumor microenvironment. A comprehensive understanding of the multiple factors that influence therapeutic efficacy has the potential to significantly improve the course of CAR T cell therapy and patient care, thereby making this advanced immunotherapy more appealing and the course of therapy more convenient and favorable for patients.

Ovarian cancer (OC) has the highest mortality rate among female reproductive system tumours, with limited efficacy of traditional treatments and 5-year survival rates that rarely exceed 40%. Circular RNA (circRNA) is a stable endogenous circular RNA that typically regulates protein expression by binding to downstream miRNA. It has been demonstrated that circRNAs play an important role in the proliferation, migration, and glucose metabolism (such as the Warburg effect) of OC and can regulate the expression of glucose metabolism-related proteins such as GLUT1 and HK2, promoting anaerobic glycolysis of cancer cells, increasing glucose uptake and ATP production, and affecting energy supply and biosynthetic substances to support tumour growth and invasion. This review summarises the formation and characteristics of circRNAs and focuses on their role in regulating glucose metabolism in OC cells and their potential therapeutic value, providing insights for identifying new therapeutic targets.

Fast progression (FP) represents a desperate situation for advanced non-small cell lung cancer (NSCLC) patients undergoing immune checkpoint inhibitor therapy. We aimed to develop a predictive framework based on machine learning (ML) methods to identify FP in advanced NSCLC patients using blood test biomarkers.

We extracted data of 1546 atezolizumab-treated patients from four multicentre clinical trials. In this study, patients from the OAK trial were taken for model training, whereas patients from the other trials were used for independent validations. The FP prediction model was developed using 21 pretreatment blood test variables in seven ML approaches. Prediction performance was evaluated by the receiver operating characteristic (ROC) curve.

The prevalence of FP was 7.6% (118 of 1546) in all atezolizumab-treated patients. The most important variables for the prediction model were: C reactive protein, neutrophil count, lactate dehydrogenase and alanine transaminase. The Support Vector Machine (SVM) algorithm applied to these four blood test parameters demonstrated good performance: the area under the ROC curve obtained from the training cohort (OAK), validation cohort 1 (BIRCH) and cohort 2 (merged POPLAR and FIR) were 0.908, 0.666 and 0.776, respectively. In addition, the absolute difference in median survival between the SVM-predicted FP and non-FP groups was significant in both progression-free survival and overall survival (p<0.001).

SVM trained using a 4-biomarker panel has good performance in predicting the occurrence of FP regardless of programmed cell death ligand 1 expression, hence providing evidence for decision-making in single-agent atezolizumab immunotherapy for patients with advanced NSCLC.

Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer.

We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model.

A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493-9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding.

Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.

Pancreatic cancer is among the most lethal malignant neoplasms, and few patients with pancreatic cancer benefit from immunotherapy. We retrospectively analyzed advanced pancreatic cancer patients who received PD-1 inhibitor-based combination therapies during 2019-2021 in our institution. The clinical characteristics and peripheral blood inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and lactate dehydrogenase [LDH]) were collected at baseline. Chi-squared and Fisher's exact tests were used to evaluate relationships between the above parameters and tumor response. Cox regression analyses were employed to assess the effects of baseline factors on patients' survival and immune-related adverse events (irAEs). Overall, 67 patients who received at least two cycles of PD-1 inhibitor were considered evaluable. A lower NLR was independent predictor for objective response rate (38.1% vs. 15.2%, P = .037) and disease control rate (81.0% vs. 52.2%, P = .032). In our study population, patients with lower LDH had superior progression-free survival (PFS) and overall survival(OS) (mPFS, 5.4 vs. 2.8 months, P < .001; mOS, 13.3 vs. 3.6 months, P < .001). Liver metastasis was verified to be a negative prognostic factor for PFS (2.4 vs. 7.8 months, P < .001) and OS (5.7 vs. 18.0 months, P < .001). The most common irAEs were hypothyroidism (13.4%) and rash (10.5%). Our study demonstrated that the pretreatment inflammatory markers were independent predictors for tumor response, and the baseline LDH level and liver metastasis were potential prognostic markers of survival in patients with pancreatic cancer treated with PD-1 inhibitors.

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive type of extranodal non-Hodgkin lymphoma (NHL), and the prognosis is poor. Currently, the most used prognostic models are the Memorial Sloan-Kettering Cancer Center (MSKCC) and International Extranodal Lymphoma Study Group (IELSG) scores; however, their predictive effects are changing with increasing incidence and changing treatment regimens. A growing body of evidence has demonstrated that inflammatory and nutritional markers are factors that can determine tumor prognosis. Therefore, the aim of this study was to identify and validate novel prognostic factors for PCNSL. Clinical information was collected from 223 patients with PCNSL. Patients younger than 18 years of age were excluded. Progression-free survival (PFS) and overall survival (OS) were used as endpoints, and receiver operating characteristic (ROC) curve analyses were conducted to determine the cutoff values for the inflammatory indicators. Correlations between variables and PFS or OS were assessed using univariate and multivariate analyses, and positive indicators were selected for survival analysis. A prognostic nutritional index (PNI) < 49.38 was associated with worse PFS (p = 0.003), and outcomes significantly differed between patients with a PNI ≥ 49.38 and < 49.38 (p < 0.001). Age < 60 years (p < 0.001) and C-reactive protein (CRP) levels < 3.14 (p = 0.001) were associated with better OS. In elderly patients (≥ 60 years), a lactate dehydrogenase-to-lymphocyte ratio (LLR) < 95.69 (p = 0.021) was associated with better OS, and the outcome significantly differed between patients with an LLR ≥ 95.69 and LLR < 95.69 (p = 0.015). The PNI and CRP levels are prognostic factors for PCNSL, and CRP was the first time shown to be a prognosis factor of PCNSL. In elderly patients with PCNSL, the LLR can predict prognosis.

This research aimed to evaluate the prognostic significance of baseline prognostic nutritional index (PNI) and lactate dehydrogenase (LDH) for the outcome of individuals diagnosed with non-metastatic nasopharyngeal carcinoma (NPC).

A retrospective analysis was conducted on data from 810 patients with non-metastatic NPC who underwent intensity-modulated radiation therapy (IMRT) with or without chemotherapy. The best cut-offs for PNI and LDH were identified by X-tile software to be 48.5 and 150, respectively. To find the independent prognostic factors for survival outcomes, univariate and multivariate regression analyses were conducted, and AUCs were used to compare their prognostic values.

Multivariate analysis revealed that patients with PNI > 48.5 had better overall survival (OS) (HR: 0.502, P < 0.001), progression-free survival (PFS) (HR: 0.618, P < 0.001), and distant metastasis-free survival (DMFS) (HR: 0.637, P = 0.005). Higher LDH was associated with poorer OS (HR: 1.798, P < 0.001), PFS (HR: 1.671, P < 0.001), and DMFS (HR: 1.756, P < 0.001). The combination of low PNI and high LDH in non-metastatic NPC patients was correlated with poor OS (P < 0.001), PFS (P < 0.001), and DMFS (P < 0.001). The combination of PNI and LDH had the highest AUCs for predicting OS, PFS, and DMFS.

PNI and LDH might become valuable predictors of the prognosis of non-metastatic NPC patients undergoing IMRT with or without chemotherapy. Prognostic accuracy can be enhanced by combining PNI and LDH.

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with 3 CD19 targeting products now FDA-approved for this indication. However, up to 60% of patients ultimately progress or relapse following CAR-T cell therapy. Mechanisms of resistance to CAR-T cell therapy in patients with DLBCL are likely multifactorial and have yet to be fully elucidated. Determining patient, tumor and therapy-related factors that may predict an individual's response to CAR-T cell therapy requires ongoing analysis of data from clinical trials and real-world experience in this population. In this review we will discuss the factors identified to-date that may contribute to failure of CAR-T cell therapy in achieving durable remissions in patients with DLBCL.

Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2-like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.

We employed single-cell RNA sequencing to construct a single-cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.

Six subgroups of TAMs were annotated and M2-like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up-regulation of several cancer pathways and intercellular interaction-related genes are associated with the recurrence of malignant glioma. Moreover, the M2-like TAMs can activate the PI3K/Akt/HIF-1α/CA9 pathway in the malignant glioma cells via SPP1-CD44-mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.

Our study uncovers the distinction of M2-like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.

The objective of this study was to explore the value of serum lactic dehydrogenase (LDH) in the early diagnosis and prognostic evaluation of pneumonia associated with the novel coronavirus infection.

A total of 101 patients with coronavirus disease 2019 (COVID-19) pneumonia were included in the study. According to the severity of the initial chest computed tomography (CT), the patients were divided into the ordinary pneumonia group and the severe pneumonia group and then divided into the remission group and the nonremission group according to the changes of the chest CT after medication treatment. The differences in general characteristics, underlying diseases, clinical symptoms, laboratory findings, and imaging examination outcomes between groups were observed retrospectively. To analyze the diagnostic performance of LDH, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated.

Compared with ordinary pneumonia patients, patients in the severe group presented with significantly higher LDH, neutrophil count, high-sensitivity troponin T (HS-TnT), C-reactive protein (CRP), human serum amyloid A (SAA), N-terminal pro-brain natriuretic peptide (NTproBNP), and D-dimer. Compared with remission patients, non-remission patients presented with significantly higher LDH, neutrophil count, HS-TnT, CRP, SAA, procalcitonin (PCT), creatine kinase-MB mass (CKMB_M), NTproBNP, and D-dimer. In multivariate logistic regression analysis, we found that LDH [odds ratio (OR), 1.015; 95% confidence interval (CI), 1.006-1024; p = 0.001] and neutrophil count (OR, 1.352; 95% CI, 1.008-1.811; p = 0.044) were independently associated with exacerbation in COVID-19 patients. For ROC analysis, the AUC was 0.833 (95% CI, 0.729-0.936; p < 0.001) when we use the LDH value of 256.69 U/L to discriminate the ordinary pneumonia and severe pneumonia patients. The AUC was 0.759 (95% CI, 0.603-0.914; p = 0.008) and the sensitivity is 92.3% when we combined the LDH (cutoff value 258.46 U/L) and the neutrophil count (cutoff value 6.76 × 109/L) to discriminate remission and non-remission patients.

The level of LDH is associated with the severity of COVID-19 pneumonia and can be used as important indicators to evaluate the prognosis of patients.

To identify risk factors for infection complications in patients with gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) and nodal DLBCL (N-DLBCL) during treatment, respectively.

Total 51 GI-DLBCL patients and 80 N-DLBCL patients were included after retrieving clinical data from a single medical center in the past ten years. Logistic regression analysis was utilized to analyze patients' data, including baseline demographics, treatments and laboratory values, to determine independent risk factors of infection in these patients.

Total 28 of 51 patients (54.9%) in the GI-DLBCL group and 52 of 80 patients (65%) in the N-DLBCL group were observed infection events during treatment. A multivariate logistic regression model revealed that Ann-arbor stage IV (P = 0.034; odds ratio [OR]: 10.635; 95% confidence interval [CI]: 1.152-142.712), extra-nodal lesions ≥ 2 (P = 0.041; OR: 23.116; 95%CI: 1.144-466.949) and high serum lactate dehydrogenase (LDH) at the time of diagnosis (LDH > 252U/L; P = 0.033; OR: 6.058; 95%CI: 1.159-31.659) were independent risk factors for the development of infection in patients with GI-DLBCL after systemic treatment. In the N-DLBCL group, high serum C-reactive protein (CRP) (P = 0.027; OR: 1.104; 95%CI: 1.011-1.204) and a low platelet count (P = 0.041; OR: 0.991; 95%CI: 0.982-1.000) at routine blood tests just before infection occurred were identified as significant risk factors related to infection events during treatment.

Discordant independent risk factors induced infection may be present during the treatment in patients with GI-DLBCL and N-DLBCL. Close monitoring these risk factors is likely an effective strategy to prevent microbial infections in these patients.

The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients.

Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis.

Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73-2.48; p < 0.0001; I2 = 62%) and progression-free survival (HR = 1.42; 95%CI: 1.22-1.66; p < 0.0001; I2 = 36%). The prognostic values of GRIm on overall survival and progression-free survival were observed across various tumour types and tumour stages. Sensitivity analysis supported the stability and reliability of the above results.

Our evidence suggested that the GRIm score could be a valuable prognostic marker in cancer patients, which can be used by clinicians to stratify patients and formulate individualized treatment plans.

Lactate dehydrogenase (LDH) is an enzyme that catalyzes the reversible conversion of lactate to pyruvate while reducing NAD+ to NADH (or oxidizing NADH to NAD+). Due to its central role in the Warburg effect, LDH-A isoform has been considered a promising target for treating several types of cancer. However, research on inhibitors targeting LDH-B isoform is still limited, despite the enzyme's implication in the development of specific cancer types such as breast and lung cancer. This study aimed to identify small-molecule compounds that specifically inhibit LDH-B. Our in silico analysis identified eight commercially available compounds that may affect LDH-B activity. The best five candidates, namely tucatinib, capmatinib, moxidectin, rifampicin, and acetyldigoxin, were evaluated further in vitro. Our results revealed that two compounds, viz., tucatinib and capmatinib, currently used for treating breast and lung cancer, respectively, could also act as inhibitors of LDH-B. Both compounds inhibited LDH-B activity through an uncompetitive mechanism, as observed in in vitro experiments. Molecular dynamics studies further support these findings. Together, our results suggest that two known drugs currently being used to treat specific cancer types may have a dual effect and target more than one enzyme that facilitates the development of these types of cancers. Furthermore, the results of this study could be used as a new starting point for identifying more potent and specific LDH-B inhibitors.