This study aimed to evaluate the long-term trends in lung cancer (LC) and chronic obstructive pulmonary disease (COPD) mortality attributable to particulate matter (PM2.5) in China and to identify the contributions of population aging and other risk factors to changes in mortality rates.

Using data from 1991 to 2021, we assessed trends in LC and COPD deaths attributable to PM2.5 through linear regression. Decomposition analysis was conducted to determine the extent to which changes in mortality rates were driven by demographic and non-demographic factors.

The crude mortality rates attributable to PM2.5 increased significantly for LC (500.40%) and COPD (85.26%). From 1990 to 2021, LC mortality attributable to PM2.5 increased annually by 4.11% (95% CI: 3.64%, 4.59%), while COPD mortality decreased annually by 1.23% (95% CI: -0.82%, -1.65%). Decomposition analysis revealed that 43.0% of the increase in LC mortality was due to population aging, and 57.0% was attributed to changes in other risk factors. For COPD, population aging contributed to an 18.547/100,000 increase, whereas other risk factors reduced mortality by 10.628/100,000.

The findings highlight the critical roles of population aging and risk factor modification in LC and COPD mortality trends. Interventions to address aging-related vulnerabilities and air pollution control are essential to mitigate future health burdens.

Ferroptosis, an iron-dependent form of cell death mediated by lipid peroxidation, plays a critical role in tumor progression. The natural small molecule compound dracorhodin perchlorate (DP) exhibits antitumor activity, but its effects on colorectal cancer (CRC) and the underlying mechanisms remain unclear.

This study aimed to elucidate the role and mechanism of DP in CRC development and ferroptosis promotion.

Using RNA-Seq, molecular docking and molecular dynamics simulation, we observed ferroptosis levels and expression of HMOX1, SLC7A11, and GPX4 in CRC cells treated with DP. We also examined the impact of modulating HMOX1, SLC7A11, and GPX4 on DP-induced ferroptosis and antitumor effects.

DP inhibited various malignant behaviors of CRC cells and induced ferroptosis. Mechanistically, RNA-Seq, molecular dynamics simulations, and molecular docking studies have collectively confirmed that DP directly binds to the HO-1 molecule, thereby upregulating HO-1 expression and inducing iron overload. Additionally, DP downregulates the expression of SLC7A11 and GPX4, collectively promoting the occurrence of ferroptosis in CRC cells. The HO-1 inhibitor ZnPP and SLC7A11 overexpression significantly inhibited the antitumor activity and ferroptosis induced by DP. Hemin and ferroptosis inducers enhanced its therapeutic effectiveness. DP safely suppressed subcutaneous tumor growth and exhibited synergistic effects with cisplatin both in vitro and in vivo. HMOX1 knockdown weakened the ferroptosis induced by DP in CRC.

The findings strongly support the activation of HMOX1 by DP, downregulation of the SLC7A11/GSH/GPX4 axis, and induction of ferroptosis in CRC cells. DP inhibited CRC progression and acted synergistically when combined with cisplatin. Our research provides a scientific basis for the use of DP in the treatment of CRC and offers new insights into the application of traditional Chinese medicine in the fight against CRC.

Animal-derived traditional Chinese medicines have a long-standing history in Chinese medicine, which exhibit unique efficacy due to similar structure and function with human tissue. As the major types of constituents that accounted for a relatively high proportion of animal-derived TCMs, peptides with molecular weight between 100 Da and hundreds of thousands of kDa have caught wide attention due to their outstanding bioavailability and excellent specificity.

This review aims to comprehensively delve into the up-to-date research progress in their pharmacology, mechanism, sequence composition, and therapeutic application, laying a solid foundation for future clinical treatment and scientific research.

Relevant information on the peptides from animal-derived TCMs was collected from scientific literature databases including PubMed, CNKI, literature sources (Ph.D. and M.Sc. dissertations), and Web of Science by using the keywords "Peptides", "Animal", and "TCMs" for gradual screening in the past 30 years.

To date, the peptides from 27 kinds of animal-derived TCMs have been systematically combed. Their pharmacological activity and underlying mechanisms on multiple systems (nervous, circulatory, skeletal, and immune), as well as anti-tumor, antioxidative, and antimicrobial effects, have been sorted out. Besides, the potential safety issues and deficiencies (low bioavailability, imperfect quality management, and toxicity of raw materials) have also been pointed out.

Comprehensive analysis showed that low development and resource waste accompanied by the inadequate report about the pharmacological activity of most peptides from animal-derived TCMs make it have good research prospects. Although a breakthrough in the field of healthcare products has been made, the development potential for clinical products that bring surprising turnaround will be obtained if the above-mentioned confusions and current needs (improve identification technology and design reasonable dosage forms) are implemented.

The development of precise molecular biomarkers for breast cancer prognosis holds immense potential to improve treatment outcomes. This study aimed to investigate the role of amino acid metabolism genes as predictive markers for breast cancer prognosis and their association with the immune-tumour microenvironment. By employing advanced machine learning algorithms and bioinformatics analysis techniques, the impact of amino acid metabolism-related genes (AAMRGs) on the immune status and overall survival of patients with breast cancer was examined. An AAMRG-based risk model was established to assess the prognostic significance. Validated risk models (AIMP2, IYD, and QARS1) accurately predicted patient outcomes [1 y: 0.87 (0.96-0.78); 3 y: 0.82 (0.87-0.76); 5 y: 0.80 (0.86-0.75)]. Furthermore, this study revealed evidence suggesting that QARS1 may influence breast cancer cell proliferation through methionine metabolism. This analysis provides valuable insights into the mechanisms of breast cancer, emphasizing the significance of AAMRGs as prognostic biomarkers and potential therapeutic targets for optimizing personalized treatment strategies.

To investigate the prognostic value of serum testosterone combining with body mass index (BMI) on the prostate cancer (PCa) after androgen deprivation therapy (ADT).

In this study, we included the patients from June, 2017 to June, 2022 who were diagnosed with PCa and received ADT. The data of these patients were reviewed and analyzed. The ratio of serum testosterone to BMI (T/BMI) was calculated and the patients were divided into high T/BMI and low T/BMI group based on the optimal T/BMI cutoff value.

A total of 84 patients were screened and divided into high T/BMI group (> 0.244) (n = 35) and low T/BMI group (≤ 0.244) (n = 49). Higher possibility of metastasis occurred in low T/BMI than high T/BMI group (P < 0.001) and the PFS in low T/BMI group was significantly lower (P < 0.001) compared to high T/BMI group. Serum testosterone in the high BMI group was significantly lower than that in the non-high BMI group. Testosterone, BMI, and T/BMI were significantly different in the tumor progression group than that in non-tumor progression group (P < 0.05). The result from univariate Cox regression analysis demonstrated that BMI (HR = 1.247, P = 0.001), testosterone (HR = 0.936, P = 0.009), T/BMI(HR = 1.036, P = 0.017), and the metastasis (HR = 1.593, P = 0.025) were significantly correlated with PFS. The result from multivariate Cox regression analysis demonstrated that T/BMI (HR = 1.037, P = 0.015) was significantly correlated with PFS.

T/BMI has a certain predicting value for the prognosis and correlated with PFS of the PCa patients. Higher level of BMI and lower level of testosterone are more associated with poor outcomes than those with low BMI and high testosterone.

Optimal timing for surgery after neoadjuvant chemoradiotherapy (NCRT) remains controversial, necessitating reliable preoperative indicators. This study examines how sarcopenia and surgical timing affect prognosis in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).

This retrospective study analyzed patients with LA-ESCC who underwent NCRT and surgery at three institutions in China from 2014 to 2023. The skeletal muscle area at the third lumbar vertebra was measured to calculate the skeletal muscle index (SMI). Prognostic analysis was performed using Cox proportional hazards models and propensity score matching (PSM), with survival curves generated using the Kaplan-Meier method and statistical significance set at p<0.05.

A total of 415 patients were analyzed, with a median follow-up of 39.1 months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 59.3% and 53.1%, respectively. Malnutrition and time to surgery (TTS) were independent prognostic factors for both OS and PFS (p < 0.05). Patients with long TTS showed better OS [hazard ratio (HR) = 0.62, p = 0.01] and PFS (HR = 0.68, p = 0.02) compared with those with short TTS. Among patients with sarcopenia, long TTS significantly improved OS (HR = 0.56; p = 0.01) and PFS (HR = 0.62; p = 0.02), while no survival benefit was observed for TTS in patients who were nonsarcopenic (p > 0.05).

Sarcopenia does not independently impact OS or PFS. Patients with sarcopenia benefit from a longer surgical time interval after NCRT. In addition, preoperative evaluation of muscle quality may aid in optimizing surgical timing to improve outcomes.

Metabolic heterogeneity resulting from the intra-tumoral heterogeneity mediates massive adverse outcomes of tumor therapy, including chemotherapeutic resistance, but the mechanisms inside remain largely unknown. Here, we find that the de novo pyrimidine synthesis pathway determines the chemosensitivity. Chemotherapeutic drugs promote the degradation of cytosolic Carbamoyl-phosphate synthetase II, Aspartate transcarbamylase, and Dihydroorotase (CAD), an enzyme that is rate-limiting for pyrimidine synthesis, leading to apoptosis. We also find that CAD needs to be cleaved by caspase-3 on its Asp1371 residue, before its degradation. Overexpressing CAD or mutating Asp1371 to block caspase-3 cleavage confers chemoresistance in xenograft and Cldn18-ATK gastric cancer models. Importantly, mutations related to Asp1371 of CAD are found in tumor samples that failed neoadjuvant chemotherapy and pharmacological targeting of CAD-Asp1371 mutations using RMY-186 ameliorates chemotherapy efficacy. Our work reveals the vulnerability of de novo pyrimidine synthesis during chemotherapy, highlighting CAD as a promising therapeutic target and biomarker.

Homologous recombination deficiency (HRD) is associated with sensitivity to platinum-based chemotherapy and PARP inhibitors in BRCA-associated cancers, including ovarian, breast, prostate, and pancreatic cancers. This study explores HRD and homologous recombination repair (HRR) gene alterations in a pan-cancer cohort to guide precision oncology.

Clinical and genomic data from 9,262 patients with 17 solid tumor types were analyzed using the OncoScreenTM Plus kit. HRD scores, biallelic HRR and tumor suppressor gene alterations, and their clinical correlations were evaluated.

HRD scores varied across cancer types, all showing a long tail in distribution. The prevalence of pathogenic alterations in pan-cancer HRR was 21.3%, with 13.7% of the cases having an HRD score ≥42. HRD-related events (LOH, LST, and TAI) exhibited similarities and cancer-specific patterns at the chromosomal arm level. Biallelic loss of HRR genes, especially BRCA1, BRCA2, RAD51D, RAD51 C, and PPP2R2 A was linked to higher HRD scores in BRCA-associated cancers, while BARD1, RAD51D, RAD54L, BRCA1, and MRE11 were associated with elevated HRD scores in in other cancer types (non-BRCA cancers). TP53 biallelic alterations, with or without HRR alterations, were linked to increased HRD scores. Higher HRD scores were associated with late-stage, older, metastatic, PD-L1 positive, non-MSI-H/non-POLE samples were correlated with genomic instability indexes, such as structural chromosomal instability (SCIN), weighted genome instability index (WGII), and whole-genome doubling (WGD).

This is the largest pan-cancer HRD study in an Asian population, providing insights for future HRD testing and targeted therapy.

Metabolic reprogramming occurs alongside tumor development. As cancers advance from precancerous lesions to locally invasive tumors and then to metastatic tumors, metabolic patterns exhibit distinct changes, including mutations in metabolic enzymes and modifications in the activity of metabolic regulatory proteins. Alterations in metabolic patterns can influence tumor evolution, either establishing or alleviating metabolic burdens and facilitating cancer growth. To fully understand how metabolic reprogramming helps tumors grow and find the metabolic activities that are most useful for treating tumors, we need to have a deeper understanding of how metabolic patterns are controlled as tumors grow. Post-translational modifications (PTMs), a critical mechanism in the regulation of protein function, can influence protein activity, stability, and interactions in several ways. In tumor cells, PTMs-mediated metabolic reprogramming is a crucial mechanism for adapting to the challenging microenvironment and sustaining fast growth. This article will deeply explore the intricate regulatory mechanism of PTMs on metabolic reprogramming and its role in tumor progression, with the expectation of providing new theoretical basis and potential targets for tumor treatment.

This study aims to explore the value of Nuclear Transcription Factor Erythroid 2-Related Factor 2 (Nrf2) and the selective autophagy adapter protein p62/Sequestosome 1 (SQSTM1) in diagnosing cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SIL).

Paraffin specimens from 125 cervical SCC patients, 102 low-grade SIL (LSIL) patients, 101 high-grade SIL (HSIL) patients, and 49 patients with benign/reactive cervical squamous epithelium were collected at Yichang Central People's Hospital from 2010 to 2023. Immunohistochemistry was used to detect Nrf2 and p62 expression. Positive expression was defined by visible light yellow, brownish-yellow, or brown cytoplasmic particles. The correlation between the two proteins and their diagnostic value were analyzed.

Both Nrf2 and p62 were predominantly localized to the cytoplasm in various cervical lesions. The expression levels of Nrf2 and p62 were significantly higher in LSIL, HSIL, and SCC than in benign/reactive epithelium (all P<0.001), and lower in LSIL than in HSIL and SCC (all P<0.001). A positive correlation was found between Nrf2 and p62 in all lesion types (all P<0.05). ROC analysis indicated that the diagnostic accuracy was enhanced when Nrf2 and p62 were used in combination, as opposed to using either marker individually.

Nrf2 and p62 are either not expressed or expressed at low levels in benign/reactive squamous epithelium, with expression increasing in LSIL, and being highest in HSIL and SCC. Both markers show a positive correlation across different cervical lesions, and either Nrf2 or p62 alone can effectively diagnose various cervical lesions, with even better diagnostic outcomes when used in combination.

According to the International Agency for Research on Cancer, China had the highest mortality burden of esophageal cancer (EC) globally in 2022.

This study aims to analyze the national and provincial trends, patterns, and risk factors of EC deaths in China.

Data from the National Mortality Surveillance System were used to estimate national and provincial deaths, age-standardized mortality rates (ASMRs), and years of life lost (YLL). An age-period-cohort-based Nordpred model was used to predict trends until 2030. Multilevel Poisson and logistic regression were conductedto assess factors influencing EC mortality and the place of death.

From 2008 to 2021, EC deaths and YLLs decreased from 227,677 to 167,529 and from 5.32 million to 3.50 million, respectively. Meanwhile, the ASMR and age-standardized YLL rate decreased from 24.34 to 11.01 per 100,000 and from 535.91 to 231.08 per 100,000, respectively. By 2030, EC deaths and ASMR are predicted to decline to 150,768 and 7.85 per 100,000, respectively. Nationwide, the average age at death increased from 68.46 to 72.45 years, with an increasing proportion of YLLs in the 65-69 age group. Overall premature mortality was observed to decrease, except for an increase in YLLs among urban populations aged ≥60 years. Higher burdens were observed in rural areas compared to urban areas and among males compared to females. Nationwide, individuals with agriculture-related occupations and lower educational levels exhibited significantly higher risks of EC death. Regions with higher prevalences of smoking and harmful drinking, and lower educational, economic, and medical levels were significantly associated with high mortality. Home was the leading place of EC deaths (80.02 %).

The EC mortality burden in China is decreasing but remains a significant threat to public health. Promoting education, occupational prevention, healthy lifestyles, and medical treatment for targeted populations and regions is essential.

High body mass index (BMI), defined as a BMI greater than or equal to 20-25 kg/m2, is considered a rapid-increased risk factor for cancer. Based on comparative risk assessment framework, we elaborate the mortality burden of cancers attributable to high BMI in China. In 2018, we estimated that there were 85.19 thousand cancer-related deaths and 2,220.01 thousand cancer-related years of life lost (YLLs) attributable to high BMI in China. Of these, 62.14 thousand deaths and 1,698.81 thousand YLLs were from males. With higher socioeconomic levels, the burden generally increases initially and then decreases. By 2030, the projected age-standardized mortality rate attributable to high BMI in China will be 6.67 per 100,000 people, increased by 3.25% from that in 2005. In summary, the swift increase and substantial disparities in the cancer burden attributable to high BMI underscore the urgent need for evidence-based policies and interventions in China.

We aimed to evaluate the association between BMI and OS in patients with cancer by a combination of available evidence.

Articles published from January 1st 2019 to June 1st 2024 were identified from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan Fang Library. Cohort studies including adult patients (≥ 18 years), who were confirmed with cancer and followed for 12 months or more, and whose BMI measurements and OS were available, were included. We used both fixed and random-effects models to estimate overall hazard ratios (HRs) for OS. The primary outcome was OS. The exposure was BMI, which was further classified into four groups based on both WHO and Chinese criteria.

The current meta-analysis included 36 studies, involving 123,913 cancer patients (56,951 men and 66,962 women, medium follow-up 41.3 months). Compared with cancer patients with normal weight, the estimated HRs of OS for underweight was 1.43 (95% CI: 1.30, 1.56; I2 = 60; p < 0.001), while it was 0.95 (95%CI 0.90, 1.01; I2 = 81; p = 0.11) for those with overweight and obesity where overweight and obesity were combined together. Cancer patients with overweight (HRs = 0.92; 95%CI 0.86, 0.99; I2 = 75; p = 0.02), but not with obesity, were associated with a better OS.

Underweight was significantly associated with worse OS in cancer patients. If analyzed separately, only overweight but not obesity had a moderately favorable effect on cancer survival.

Exogenous microRNA-144 (miR-144) is considered as a potential biological drug for gastric cancer because of its biological activity to inhibit the epithelial-mesenchymal transition (EMT). However, the specific molecular mechanisms have not been fully revealed. In addition, their vulnerability to degradation by RNA enzymes in the blood limits their bioavailability. In this paper, a polyamidoamine (PAMAM)-wrapped miR-144 (PAMAM/miR-144) is prepared as a nanocarrier system to protect miR-144 from nuclease degradation. The PAMAM/miR-144 nanocarrier system achieves the optimal antitumor activity against gastric cancer migration and reduce mTOR protein expression by transferring miR-144 into human gastric cancer HGC-27 cells. At the same time, the PAMAM/miR-144 nanocarrier system significantly decreases the EMT via targeting mTOR signal pathway in HGC-27 cells and noticeably inhibited the growth of subcutaneous gastric cancer xenografts in nude mice. PAMAM/miR-144 nanocarrier system has effectively improved the bioavailability of miR-144, thus providing a promising combination modality for anticancer therapy.

The combination of immune checkpoint inhibitors (ICIs) and radiotherapy (RT) has shown promise in improving the outcomes in non-small cell lung cancer (NSCLC) patients; however, the potential benefits and predictors remain unclear. This meta-analysis evaluated the efficacy and safety of ICI + RT compared to RT or ICI monotherapy and explored the potential factors influencing the treatment efficacy of this combination therapy. The efficacy was assessed using hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS). Multivariable data were pooled, and subgroup analyses were performed to identify the influencing factors. The safety was evaluated using odds ratios (OR) of any grade and grade ≥3 treatment-related adverse events (TRAEs). ICI + RT significantly improved the OS of patients with brain metastases compared to RT alone (HR = 0.42; P = 0.004). The combination therapy showed improved OS (HR = 0.71; P < 0.001) and PFS (HR = 0.69; P < 0.001) compared to ICI monotherapy. Subgroup analysis revealed significant survival benefits in metastatic and oligometastatic NSCLC patients receiving sequential ICI after RT and those undergoing intracranial or extracranial RT. ICI + RT increased the incidence of any grade TRAEs (OR = 1.3; P = 0.007) compared to ICI alone; no significant difference was observed in grade ≥3 TRAEs. ICI + RT provides significant survival benefits over monotherapy in advanced NSCLC, with a manageable toxicity profile. Prospective trials are needed to validate these findings and refine patient selection for combination therapy.

This study tested the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in restaging locally advanced gastric cancer after neoadjuvant therapy (NAT) using pathologic T stage (ypT) and pathologic N stage (ypN) as the reference standard.

Between August 2022 and September 2023, the study enrolled a prospective cohort of 70 gastric cancer patients who underwent NAT and subsequent surgical resection. MRI procedures, including DLSB T2-weighted imaging (T2WI), ZOOMit diffusion-weighted imaging (DWI), and XD-VIBE dynamic contrast-enhanced imaging (DCE), were performed after NAT and before surgery. Four abdominal radiologists independently assigned radiologic T stage (yrT) and radiologic N stage (yrN) based on individual and combined sequences. Inter-reader agreement was quantified using Kendall's coefficient. Diagnostic accuracy was determined by comparing MRI assessments and pathologic outcomes, with pairwise comparisons analyzed via the McNemar test. Subgroup analysis evaluated the performance in identifying good responders to NAT.

Inter-reader agreement was almost perfect for T restaging and substantial for N restaging. Diagnostic accuracy for T restaging was 0.432 using DLSB-T2WI, 0.586 using ZOOMit DWI, 0.557 using XD-VIBE DCE, and 0.586 using mpMRI. The accuracy demonstrated by DWI, DCE and mpMRI was superior to that of T2WI (all P < 0.05). For N restaging, the accuracy of the mpMRI protocol was 0.443. Notably, mpMRI achieved an AUC of 0.879 (95% confidence interval 0.835-0.915) for differentiating ypT0-1 tumors.

Advanced mpMRI strategies can serve as a valuable tool for restaging gastric cancer after NAT. Accurately differentiating good responders to neoadjuvant therapy through mpMRI holds significant clinical implications for personalized treatment strategies and improved patient outcomes.

Hepatocellular carcinoma (HCC) was associated with high morbidity and mortality, representing a significant health challenge. Chondroitin sulfate (CS), a glycosaminoglycan composed of glucuronic acid and N-acetylgalactosamine, is implicated in HCC progression through its role in cancer cell migration and proliferation as well as interactions with cell surface receptors integrin β-1 and CD44. Chondroitin polymerization factor 2 (CHPF2), the key to CS synthesis, has an undefined role in HCC. Our study aims to demonstrate that decreasing CHPF2 enzyme activity can inhibit the migration and proliferation of HCC cells. Bioinformatics analysis and in vitro experiments on clinical HCC samples confirmed the knockdown of CHPF2 inhibited HCC cell proliferation and migration. We further explored Rabdosia rubescens, a plant used in cancer therapy, for its potential to modulate CHPF2. Structural biology and ligand fishing identified ponicidin, a compound that significantly suppresses HCC cell growth and migration in both in vitro and in vivo models. These findings propose CHPF2 as a novel biomarker and ponicidin as a potential therapeutic agent for HCC management.

The role of intraoperative radiotherapy (IORT) for adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Therefore, a prospective phase 1 trial was conducted to assess the safety and feasibility of IORT for locally advanced AEG.

The study enrolled patients with AEG at stages II-IVA from January 2019 to September 2019. Eligible patients received esophagectomy and a single fraction of electron beam radiotherapy. The primary endpoint of the study was a safety profile for IORT. Additionally, survival outcomes and the locoregional recurrence rate (LRR) were compared between the non-IORT and IORT cohorts using propensity score-matching.

For 15 (93.8 %) of the 16 patients in the study, R0 resection was successfully achieved, with only one patient undergoing R1 resection. A total postoperative complication morbidity rate of 43.8 % (7/16) was observed, with major complications (Clavien-Dindo classification ≥3) in 12.5 % of the cases (2/16). Total treatment-related adverse events were reported for seven patients (43.8 %, 7/16). After matching, a lower LRR was observed in the IORT group than in the non-IORT group (0 % [0/12] vs 33.3 % [4/12]; p = 0.028). However, the two groups did not differ significantly in 3-year progression-free survival (PFS: IORT [50.9 %] vs non-IORT [53.4 %]; p = 0.93) or 3-year overall survival (OS: IORT [58.3 %] vs IORT [72.9 %]; p = 0.23).

The current study demonstrated favorable feasibility and safety of IORT for locally advanced AEG. Although IORT is beneficial for improving local control, it may not prolong PFS or OS for patients with locally advanced AEG. A phase 2 trial is warranted for further validation of these outcomes.

Cancer places a significant burden on patients and healthcare systems. Dexmedetomidine, an α2 adrenergic agonist commonly used in anaesthesia, has potential effects on cancer biology. We systematically reviewed and analysed the impact of intraoperative dexmedetomidine on postoperative survival and tumour recurrence in patients with cancer.

We conducted a comprehensive search of PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure up to April 2024. Two researchers extracted data including authors, year, country, study design, follow-up, patient characteristics, and hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival and recurrence-free survival. Quality assessment was conducted using the Cochrane tool for randomised controlled trials (RCTs) and the Newcastle-Ottawa Scale for retrospective studies.

The review identified 12 studies: six RCTs and six retrospective studies. In the RCTs, intraoperative dexmedetomidine showed no significant effect on overall survival (odds ratio [OR] 0.87, 95% CI 0.67-1.13, P=0.29) but improved recurrence-free survival (OR 0.65, 95% CI 0.47-0.91, P=0.01). Retrospective studies indicated that dexmedetomidine was associated with decreased overall survival (post-matching HR 1.52, 95% CI 1.15-2.00, P=0.003), and had no significant effect on recurrence-free survival (post-matching HR 1.29, 95% CI 0.96-1.72, P=0.09).

Meta-analysis reveals inconsistent evidence regarding impact of intraoperative dexmedetomidine on cancer outcomes after surgery. RCTs suggest improved recurrence-free survival, whereas retrospective studies suggest potential reductions in overall survival. The limited and contradictory data highlight the necessity for more high-quality RCTs to clarify the effects of dexmedetomidine on survival and prognosis in this population.

The triglyceride-glucose (TyG) index, derived from the calculation of two biomarkers, fasting plasma glucose and triglyceride levels, is a reliable indicator of insulin resistance and has been demonstrated to be associated with the adverse clinical outcomes of patients in the intensive care unit (ICU). This study aims to investigate the relationship between the TyG index and the 28-day all-cause mortality of these patients during their ICU stay.

This study employed a multicenter retrospective cohort design, analyzing data from 18,883 ICU patients in the eICU database. We calculated the TyG index for each patient and assessed its association with 28-day all-cause mortality. The Cox proportional hazards model was utilized for analysis, adjusting for various clinical and laboratory variables to control for confounding factors. We performed sensitivity analyses, subgroup analyses, and interaction analyses to evaluate the robustness of the results.

The study identified a significant positive correlation between the TyG index and 28-day all-cause mortality. Specifically, each one-unit increase in the TyG index corresponded to a 58% increase in mortality risk (HR=1.58, 95% CI: 1.25-2.00, P=0.0001). Additionally, the analysis revealed a non-linear threshold effect of the TyG index on mortality, with a cutoff point at 8.82; mortality was lower below this value and significantly increased above it. Sensitivity and subgroup analyses indicated robust findings, while E-value analysis suggested resilience against unmeasured confounding.

This study establishes the TyG index as an independent predictor of 28-day all-cause mortality in critically ill patients, highlighting its potential value in clinical management and risk assessment. By recognizing the non-linear effect of the TyG index, clinicians can more effectively adjust treatment strategies to reduce mortality among high-risk patients.

Ovarian cancer (OC) is among the most lethal gynecologic malignancies, characterized by poor prognosis. While aging is a well-established risk factor, the underlying mechanisms distinguishing early- and late-onset ovarian cancer remain poorly understood.

This study analyzed the global burden and age-related trends of ovarian cancer using the GBD database. A cut-off age of 55 years was used to differentiate between early and late onset ovarian cancer, and a Mendelian randomization method was also used to investigate the causal relationship between aging and ovarian cancer. Machine learning was applied to identify tumor-specific age-associated genes, followed by bioinformatics analyses and single-cell sequencing to explore the roles of these genes and immune profile alterations in ovarian cancer. Additionally, models were constructed, and drug sensitivity analyses performed to evaluate their potential as diagnostic markers or therapeutic targets.

Ovarian cancer incidence and mortality exhibit age-related trends, with telomere length positively associated with increased risk (OR = 1.27, 95% CI: 1.01-1.60, P = 3.90 × 10⁻2). Older patients with OC have a worse prognosis. PRKCD and UCP2 were significantly upregulated in ovarian cancer. PRKCD facilitates epithelial-mesenchymal transition (EMT), contributing to ovarian cancer progression, while UCP2 modulates ROS dynamics, influencing chemoresistance. Immune microenvironment analysis revealed differences between high- and low-expression groups, particularly in T cells, macrophages, and other immune cells. Both genes are sensitive to a varity of drugs, including dasatinib, fluvastatin, highlighting their potential as therapeutic targets.

Aging is a significant risk factor for ovarian cancer, with PRKCD and UCP2 closely linked to its onset and progression. These genes show promise as novel biomarkers and therapeutic targets for ovarian cancer.

Exosomes play important role in biological functions, including both normal and disease process. Multiple cell types can secret exosomes, which act as message carriers. Increased evidences reveal that exosomes are promising diagnosis biomarkers in malignant tumors.

In this study, we enrolled 78 participants, including 20 lung adenocarcinoma (LUAD), 18 lung squamous carcinoma (LUSC), 20 lung benign diseases (LUBN) and 20 healthy controls (NL) and we performed parallel reaction-monitoring (PRM)-mass spectrometry to screening the proteomic variation by label free analysis in exosomes from all groups, which has been widely used to quantify and detect target proteins.

Total 14 protein were identified as candidate biomarkers, complement components C9, apolipoprotein B (APOB), filamin A (FLNA), guanine nucleotide binding protein G subunit 2 (GNB2), fermitin family homolog 3 (FERMT3) showed significantly differentiation in total lung cancer (LUAD and LUSC together), we then obtained combination analysis of 5 proteins and the area under the curve (AUC), sensitivity (SN) and specificity (SP) were 63.0%, 65.0%, and 75.0%, respectively, in comparison to NL group. And the LUAD combination panel, peroxiredoxin 6 (PRDX6), integrin alpha-IIb (ITGA2B) and hemoglobin subunit delta (HBD) revealed AUC was 95.0%, SN was 90.0% and SP was 95.0% in comparison to NL controls. In LUSC analysis, combination analysis of fibronectin 1 (FN1), pregnancy zone protein (PZP) and complement C1q tumor necrosis factor related protein 3 (C1QTNF3) showed that AUC was 88.1%, SN was 75.0%, SP was 100% in paralleled with NL group. Finally C9, FLNA, PZP were overexpressed in lung cancer H1299 and A549 cell lines and the results indicated that C9 acted as oncogenic role by increasing proliferation, migration and invasion of lung cancer cells, while FLNA and PZP played tumor-suppression by inhibition biological functions of lung cancer cells.

Taken together, our study revealed multiple exosomal proteins which could be applied as candidate biomarkers in diagnosis of lung cancer.

Hepatocellular carcinoma (HCC) is known for its high invasiveness, high fatality rate. Both hypoxia and senescence play crucial roles in the initiation and progression of cancer, yet their prognostic implications in HCC are yet to be fully understood. The hypoxia-senescence co-related genes (HSCRGs) were screened from public databases. Transcriptome data and clinical information were obtained from patients with HCC using the Cancer Genome Atlas, GSE76427, and International Cancer Genome Consortium (ICGC). The random forest tree algorithm was used to identify the characteristic genes of the disease, and the genes were verified by related experiments. SVM algorithm was used to classify HCC patients based on HSCRGs. The prediction model based on HSCRGs was established by LASSO, univariate and multivariate COX regression analysis. We used the ICGC for outside validation. The risk score model was analyzed from subgroup analysis, immune infiltration, and functional strength. The expression patterns of key prognostic genes in tumor microenvironment were decoded by single cell analysis. A total of 184 HSCRGs were identified. The expression pattern and functional characteristics of MLH1 gene in HCC were verified. Two HCC subtypes were identified based on HSCRGs. Then, a prediction model based on HSCRGs was established, and risk score was identified as an independent prognostic indicator of HCC. A new nomogram is constructed and shows good prediction ability. We further determined that the level of infiltration of immune cells and the expression of immune checkpoints are significantly affected by the risk score. The immune microenvironment was different between the two risk groups. The high-risk group was dominated by immunosuppressed cells, and the prognosis was poor. Single-cell analysis revealed the expression of seven key prognostic genes in the tumor microenvironment. Finally, qPCR results further verified the expression levels of seven prognostic genes. HSCRGs are of great significance in the prognosis prediction, risk stratification and targeted therapy of patients with HCC.

Emerging evidence indicates the importance of tertiary lymphoid structures (TLSs) in predicting the outcomes of nonsmall cell lung cancer (NSCLC) patients; however, their prognostic value and correlations with peripheral inflammatory prognostic indices in stage I patients have been less well studied.

Stage I NSCLC patients were recruited retrospectively; the presence and location of TLSs (peritumoral [pTLSs] and intratumoral [iTLSs]) were determined via hematoxylin and eosin (H&E)-stained slides. Peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index (ALI), were obtained and compared among these subgroups. Disease-free survival (DFS) and overall survival (OS) were tested via Kaplan-Meier analysis, and risk factors for survival were determined via a Cox proportional hazards model.

A total of 24.73% and 92.73% of patients were positive for pTLSs and iTLSs, respectively. The absolute number of iTLSs was significantly greater than that of pTLSs (P < .001). Low preoperative LMR and ALI were detected only in patients with pTLSs but not in those without. Only pTLS was found to be a risk factor for both DFS and OS, and it was independently associated with OS (HR = 3.93, 95% confidence interval [CI] = 1.16-13.37; P = .028). Accordingly, patients with pTLSs had relatively poor DFS (log rank = 5.46, P = .019) and OS (log rank = 10.48, P = .001) rates.

Among the heterogeneous results concerning the prognostic value of pTLSs and iTLSs in stage I NSCLC, our results for the first time indicated that the presence of pTLSs may predict poor outcomes in these patients and no correlation of iTLSs with the outcomes was validated; however, additional studies with large sample size are needed in future.

Complete hearing loss, especially the age-related type, poses a significant public health challenge globally. This study aims to assess the global burden on the prevalence of complete hearing loss from 1992 to 2021 and forecast trends up to 2036.

Using data from the Global Burden of Disease (GBD) Study 2021, we assessed the global burden of complete hearing loss across 204 countries and territories. We analyzed temporal trends in ASPR using Joinpoint regression, evaluated the contributions of age, period, and cohort effects through Age-Period-Cohort modeling, and performed decomposition analysis to determine the impact of demographic and epidemiological changes on prevalence trends. Predictions of future ASPR trends were made using Bayesian Age-Period-Cohort (BAPC) and Autoregressive Integrated Moving Average (ARIMA) models.

By 2021, the global prevalence of complete hearing loss had reached 9.9 million cases, with the ASPR declining from 134.35 to 117.79 per 100,000. The overall Estimated Annual Percentage Change (EAPC) was-0.45. The most significant reductions were observed in low-SDI regions, particularly Sub-Saharan Africa (EAPC: -0.74). In contrast, high-SDI regions, including North America and Western Europe, showed more modest declines (EAPC: -0.18). Notably, East Asia exhibited a 62.3% increase in prevalence, with high-income Asia Pacific showing the highest relative rise at 83.97%. Age-related hearing loss remained the dominant cause, especially among individuals aged 60 and above. Males were more affected than females. Population aging and growth were the major drivers of the increased prevalence in high-SDI regions, while population growth was the primary factor in low-SDI areas.

The burden of complete hearing loss remains high in prevalence, particularly in aging populations within high-SDI regions, despite overall reductions in ASPR. Significant regional disparities remain, highlighting the need for targeted interventions to improve access to hearing care and affordable technologies in low-SDI regions.

With advances in sequencing techniques, microbiota dysbiosis and pathogenic microbes that accelerate colorectal cancer progression have been identified and widely reported. However, few studies have focused on the microbiota taxa of rectal mucus in rectal cancer (RC) patients. Here, we analyzed the composition and characteristics of the rectal mucosa microbiota of RC patients from Wenzhou city, China, and compared the results with those of healthy controls.

To explore the changes in the characteristics of the rectal mucosal flora associated with RC, and identify biomarkers of microbe taxa for RC.

Rectal mucosa samples from a Chinese cohort of 72 recently diagnosed RC patients and 71 healthy controls were obtained. A validation cohort, which included 22 RC patients and 60 healthy controls, was also established. Changes in the rectal mucosal flora were observed by cultivation, 16S ribosomal DNA gene sequencing analysis and quantitative polymerase chain reaction analysis.

The 16S ribosomal DNA results demonstrated that RC patients presented increased bacterial community richness and alpha diversity as well as an altered rectal mucosal microbiota, with depletion of Proteobacteria and Thermi and enrichment of Bacteroidetes and Fusobacteria in cancerous mucosal tissues (CM) and enrichment of Firmicutes and Cyanobacteria in adjacent noncancerous mucosal tissues (AM). The culture results showed that the mean loads of Escherichia coli, Bifidobacterium, Enterococcus, and Lactobacillus were significantly reduced in RC patients. The ratios of Prevotella to Ruminococcus [areas under the receiver operating curve: 0.795 in AM vs normal control mucosa (NM), 0.77 in CM vs NM] and of Prevotella stercorea to Propionibacterium acnes (areas under the receiver operating curve: 0.808 in AM vs NM, 0.843 in CM vs NM) exhibited excellent abilities to differentiate between healthy controls and RC patients.

RC patients have an altered rectal mucosal microbiota, and the ratio of Prevotella to Ruminococcus or the ratio of Prevotella stercorea to Propionibacterium acnes may serve as a marker for RC diagnosis.

Areca nut (AN) was classified as a carcinogen by the International Agency for Research on Cancer (IARC) of the WHO in 2003. AN has the same carcinogenic components as cigarettes, such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), but its effects on interactions with genetic factors related to lung cancer have rarely been investigated.  METHODS: Here, a propensity score-matched case‒control study was conducted in Hainan, which included 445 patients with lung cancer and 445 cancer-free controls. Then, the associations between single-nucleotide polymorphisms (SNPs) in the CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction effects with AN chewing and smoking on lung cancer were analyzed. In addition, we explored the associations among AN, cigarettes, and genes related to lung cancer using the Comparative Toxicogenomics Database (CTD).

The results indicate that the CHRNA3 rs938682 (A > G) GG genotype (OR = 0.669, 95% CI = 0.454 ~ 0.984, P = 0.042) can decrease the risk of lung cancer. The CHRNB4 rs7178270 (C > G) GG genotype (OR = 1.729, 95% CI = 1.168 ~ 2.571, P = 0.006) can increase the risk of lung cancer. The CHRNA5 rs17486278 CC genotype was associated with a high risk in males, smokers, and drinkers. The CHRNA3 rs938682 GG genotype was associated with a low risk in AN chewers. The CHRNB4 rs7178270 GG genotype was associated with high risk in drinkers and AN chewers. CHRNB4 rs7178270 and AN chewing have an interaction effect on lung cancer in Hainan.

This study is the first to elucidate the hidden impacts of AN on lung cancer and provides a key evidence regarding the interactive effects of AN and cigarettes with SNPs in nAChRs genes on lung cancer.

This retrospective study aims to evaluate the impact of antibiotics (ATBs) use on the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC), providing insights into the prudent use of ATBs in patients undergoing immunotherapy.

We retrospectively collected data from patients with advanced HCC treated with immune checkpoint inhibitors (ICIs) at our institution between January 1, 2021, and December 30, 2023. Patients were divided into two groups based on ATBs use: an ATB group and a non-ATB group. Clinical baseline characteristics were analyzed, and survival curves were plotted using the Kaplan-Meier model. A Cox proportional hazards model was employed to analyze influencing factors.

Among the 102 advanced HCC patients receiving ICIs treatment, 29 were in the ATB group, and 73 were in the non-ATB group. The progression-free survival (PFS) (P = 0.034) and overall survival (OS) (P = 0.021) were significantly shorter in the ATB group compared to the non-ATB group. The difference in PFS between the two groups was associated with ATBs use and patients' AFP levels, while ATBs use was identified as an independent risk factor for the difference in OS between the groups.

ATB use in the context of immunotherapy for advanced HCC is associated with reduced PFS and OS. Caution is warranted in the administration of ATBs to patients undergoing immunotherapy.

To understand the current status and changing trends in the lifetime risk of residents in Henan Province, China to develop and die from cancer.

Lifetime risk was estimated using the Adjusted for Multiple Primaries (AMP) method, incorporating cancer incidence, mortality, and all-cause mortality data from 55 cancer registries in Henan Province, China. Estimates were calculated overall and stratified by gender and area. The annual percent change (APC) in lifetime risk from 2010 to 2020, stratified by gender and cancer site, was estimated using a log-linear model.

In 2020, the lifetime risk of developing and dying from cancer was 30.19 % (95 % CI: 29.63 %-30.76 %) and 23.62 % (95 % CI: 23.28 %-23.95 %), respectively. These estimates were higher in men, with values of 31.22 % (95 % CI: 30.59 %-31.85 %) for developing cancer and 26.73 % (95 % CI: 26.29 %-27.16 %) for dying from cancer, compared with women, who had values of 29.02 % (95 % CI: 28.12 %-29.91 %) and 20.08 % (95 % CI: 19.51 %-20.64 %), respectively. There were also geographical differences, with higher estimates in urban areas compared with rural areas. Residents had the highest lifetime risk of developing lung cancer, with a rate of 6.94 %, followed by breast cancer (4.14 %), stomach cancer (3.95 %), esophageal cancer (3.75 %), and liver cancer (2.86 %). Similarly, the highest lifetime risk of dying from cancer was observed for the following sites: lung (5.99 %), stomach (3.60 %), esophagus (3.39 %), liver (2.78 %), and colorectum (1.55 %). Overall, the lifetime risk of developing cancer increased, with an APC of 0.75 % (P < 0.05). Varying trends were observed across different cancer sites. There were gradual decreases in nasopharynx, esophagus, stomach, and liver cancers. Conversely, increasing trends were noted for most other sites, with the highest APCs observed in thyroid, prostate, lymphoma, kidney, and gallbladder cancers.

The lifetime risks of developing and dying from cancer were 30.19 % and 23.62 %, respectively. Variations in cancer risk across different regions, genders, specific cancer sites, and over calendar years provide important information for cancer prevention and policy making in the population.

T cells are crucial regulators in cancer treatment due to their cytotoxic ability. Recently, immunotherapies based on bispecific antibodies (Bi-Ab) have achieved remarkable effects in cancer treatment, attributed to their capability of recruiting and activating T cells to kill tumors. In the present study, we investigated whether CD155 is an effective target for T-cell-mediated immunotherapy against human gynecological malignancies. We demonstrated that CD155 is expressed on common gynecological tumor cells, including cervical, uterine, and ovarian cancers. Next, we evaluated the specific cytotoxic activity of T cells armed with CD155Bi-Ab (CD155Bi-T cells) against tumor cells. Compared with control T cells treated with separate anti-CD155 and anti-CD3 mAbs, CD155Bi-T cells exhibited significant cytotoxicity against CD155-positive gynecological tumor cells. Specifically, in the luciferase assay, the cytotoxicity of CD155Bi-T cells was 2.67-fold higher than that of control T cells at an effector/target ratio of 5:1, indicating a significant enhancement in tumor-killing activity. This enhanced cytotoxic activity was further supported by increased expression of activation markers (CD69 and 4 - 1BB), higher production of T-cell-derived cytokines (IL- 2, IFN-γ, and TNF-α), and elevated levels of the cell-killing mediators (perforin and granzyme B). Taken together, our findings demonstrate that CD155 is a promising target for gynecological tumors, and CD155Bi-T cells hold significant potential for immunotherapy against CD155+ gynecological malignancies.

Gastric cancer (GC) remains a significant global health challenge, particularly due to the resistance of gastric cancer stem cells (GCSCs) to chemotherapy. This study investigates the role of heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), a member of the heterogeneous nuclear ribonucleoproteins (hnRNPs), in modulating mitochondrial metabolic reprogramming and contributing to chemoresistance in GCSCs. Through extensive analysis of tumor cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets, HNRNPA2B1 was identified as a key regulator in GCSCs, correlating with poor prognosis and enhanced resistance to chemoresistance. CRISPR-Cas9 mediated knockout of HNRNPA2B1 in GCSCs led to a significant decrease in mitochondrial function, reduced migration, invasion, and sphere formation abilities, and markedly increased apoptosis. These changes were accompanied by a shift in metabolic activity, evidenced by decreased oxygen consumption and increased extracellular acidification. Our results highlight HNRNPA2B1 as a pivotal factor in sustaining the malignant phenotype of GCSCs and present it as a potential therapeutic target to improve chemotherapy efficacy in GC.

Methyltransferase-like 3/14/16 (METTL3/14/16) presents the regulating valve in N6-methyladenosine (m6A) modification, involved in carcinogenesis. We addressed elucidating the relationship between single-nucleotide polymorphisms (SNPs) of the METTL3/14/16 gene and breast cancer (BC) susceptibility.

A case-control study included 680 BC patients and 680 healthy controls, individually matched for age (±2 years).

7 SNPs were screened by bioinformatics tools. Conditional Logistic analysis was used to explore the association between SNPs and BC susceptibility. SNPs-reproductive factors interaction was assessed. qRT-PCR was conducted to detect the METTL3/14/16 expression of different SNPs. The potential biomechanism was explored using bioinformatics tools.

Among the 7 analyzed SNPs, METTL3 rs1061026 T>G exhibited a significant association with reduced susceptibility to BC. The TC+CC genotype of METTL14 rs428409 elevated BC risk, while the AG+GG genotype of METTL14 rs3087958 restrained BC risk. The stratified analysis further identified the protective effect of rs1061026 T>G and rs3087958 T>G, and the detrimental effect of rs428409 T>G in specific subgroups. Haplotype analysis revealed that haplotypes Grs1061026Crs1061027 and Grs368669Trs428409Grs3087958 were protective for BC. BC patients who carried the C allele in METTL14 rs428409 were more likely to be HER-2 positive. Individuals with age at menarche ≥14, number of pregnancies >1, and G allele in rs1061026 had a 47.7% decreased risk of BC. There were considerable multiplicative interactions between SNPs and reproductive factors. The relative expression of METTL3/14 was altered due to rs1061026 T>G, rs428409 T>C, and rs3087958 A>G. These three SNPs might interfere with the m6A modification and the expression level of BC-related genes.

Our findings suggested that rs1061026 T>G, rs428409 T>C, and rs3087958 A>G might be associated with the risk of BC.

BackgroundA non-invasive and reliable method is essential for diagnosing sub-1 cm thyroid lesions.ObjectiveWe have developed a nomogram that integrates ultrasound features and clinical risk factors to effectively diagnosed sub-1 cm thyroid lesions.MethodsOur study included 406 patients with sub-1 cm thyroid lesions. We collected their demographic data and ultrasound characteristics of the thyroid, followed by conducting univariate and multivariate analyses to identify the risk factors. Subsequently, we developed a nomogram for predicting sub-1 cm thyroid lesions, comparing its diagnostic performance with that of American College of Radiology TIRADS (ACR TI-RADS) and Chinese Thyroid Imaging Reporting and Data Systems (C TI-RADS).ResultsSix variables, including female gender, capsular invasion, solid composition, aspect ratio >1, irregular margin and microcalcification, were identified as potential predictors and used to develop a predictive nomogram. Receiver operating characteristic curves were constructed and compared with ACR TI-RADS and C TI-RADS classifications. The area under the curve of the nomogram was found to be at 0.85, while the AUC of ACR TI-RADS classification and C TI-RADS classification were at 0.771 and 0 .736 respectively.ConclusionsBy utilizing this user-friendly nomogram, the likelihood of sub-1 cm malignancy in thyroid lesions can be objectively quantified.

Circulating tumor cells (CTCs) are cardinal intermediaries in the metastatic cascade, particularly in triple-negative breast cancer (TNBC), owing to their high-affinity interactions that bolster survival and dissemination. Addressing this pivotal mechanism, we have developed APEVs@DOX, a pioneering biomimetic delivery system. Utilizing activated platelet membranes as a scaffold, APEVs@DOX recapitulates the natural affinity between platelets and CTCs, enabling targeted delivery of doxorubicin. Our results, substantiated by meticulous in vitro and in vivo experimentation, revealed 78 % reduction in lung metastasis nodules in murine models relative to controls, affirming APEVs@DOX's proficiency in CTCs capture and eradication. This study not only illuminates the potential of CTCs-targeted therapies in the precision medicine armamentarium for TNBC but also contributes empirical data to guide the strategic design of anti-metastatic interventions. The therapeutic impact of APEVs@DOX in curtailing metastatic spread offers a beacon of hope for advancing TNBC treatment paradigms.

Since China's regulatory reforms were initiated in 2015, the development of new indications for novel drugs has become an important trend. Between 2018 and 2024, China's National Medical Products Administration (NMPA) approved 313 new indications for 151 novel drugs. This cross-sectional study comprehensively depicts the landscape of China's new indications for novel drugs, including the characteristics of approvals, quality, and quantity of clinical trial evidence. The quality characteristics of the efficacy evidence for new indications were affected by the treatment areas and conditional approval programs. The efficacy of a novel drug for a new indication can be demonstrated by one pivotal trial or one pivotal trial plus supportive evidence in most cases.

Cervical cancer (CC) is a major health threat to women, with immunotherapies targeting the programmed death receptor 1/programmed death ligand 1(PD-1/PD-L1) axis showing promise but encountering resistance in a significant patient population. This resistance has driven a critical quest to uncover the underlying mechanisms. This study uncovers a novel metabolic axis involving the nicotinamide adenine dinucleotide (NAD+) salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) and the deacetylase Sirtuin 1 (SIRT1), which regulates PD-L1 expression and nuclear localization in CC. This axis may be a key factor contributing to the resistance observed in immunotherapy. This study reveals that PD-L1 overexpression in cancers is regulated by both transcriptional and post-transcriptional processes. Acetyl-proteomic analysis pinpoints SIRT1 as a central regulator in the deacetylation of histone H3 at lysines 27, which may influence PD-L1 subcellular distribution. This finding reveals the epigenetic control of immune checkpoint proteins by metabolic pathways, offering a new perspective on the regulation of PD-L1. The identification of the NAMPT/SIRT1 metabolic axis as a critical factor suggests that targeting this axis may enhance therapeutic responses.