Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn's disease (CD) remains limited.

To systematically review the global variation in the rates of surgery in CD.

A comprehensive search analysis was performed using multiple electronic databases from inception through July 1, 2020, to identify all full text, randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD. Outcomes included continent based demographic data, CD surgery rates over time, as well as the geoepidemiologic variation in CD surgery rates. Statistical analyses were conducted using R.

Twenty-three studies spanning four continents were included. The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America, Europe, Asia, and Oceania were 30% (range: 1.7%-62.0%), 40% (range: 0.6%-74.0%), 17% (range: 16.0%-43.0%), and 38% respectively. No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America (R 2 = 0.035) and Europe (R 2 = 0.100). A moderate, negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time (R 2 = 0.520) in Asia.

There appears to be significant inter-continental variation regarding surgery rates in CD. Homogenous evidence-based guidelines accounting for the geographic differences in managing patients with CD is prudent. Moreover, as a paucity of data on surgery rates in CD exists outside the North American and European continents, future studies, particularly in less studied locales, are warranted.

The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial-mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets.Our data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute to pathology in modern day humans.

It is well known that psoriasis is closely related to smoking, and the cholinergic receptor nicotinic subunit alpha-5 (Chrna5) plays an important role in smoking-related diseases. However, studies on the relationship between Chrna5 and psoriasis are limited. This study aimed to examine the role of Chrna5 in psoriasis development and pathogenesis. Analysis in psoriatic tissues and imiquimod (IMQ)-induced mouse models showed that Chrna5 was highly expressed in psoriatic lesional skin. To further verify the function of Chrna5, we constructed Chrna5-knockout mice and induced the psoriasis model. We found that Chrna5 knockout significantly reduced the severity of psoriasis and could regulate inflammation via the mitogen-activated protein kinase kinase kinase 1 (MEKK1)/c-Jun NH(2)-terminal kinase (JNK)-MAPK/NF-κB pathway. The single-cell sequencing results revealed that after Chrna5 knockout, the keratinocyte subpopulation was significantly reduced and the related Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway was downregulated, further indicating the importance of Chrna5 in psoriasis. Human keratinocytes were analyzed, and silencing Chrna5 inhibited keratinocyte proliferation and migration. In summary, Chrna5 played important roles in the development and pathogenesis of psoriasis, and targeting Chrna5 may be an effective strategy for the treatment of psoriasis.