Investigating potential novel therapeutic targets and biomarkers for ankylosing spondylitis using plasma protein screening.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and sacroiliac joints. Recent genetic studies suggest certain plasma proteins may play a causal role in AS development. This study aims to identify and characterize these proteins using Mendelian randomization (MR) and colocalization analyses. Methods: Plasma protein data were obtained from recent publications in Nature Genetics, integrating data from five previous GWAS datasets, including 738 cis-pQTLs for 734 plasma proteins. GWAS summary data for AS were sourced from IGAS and other European cohorts. MR analyses were conducted using "TwoSampleMR" to assess causal links between plasma protein levels and AS. Colocalization analysis was performed with the coloc R package to identify shared genetic variants. Sensitivity analyses and protein-protein interaction (PPI) network analyses were conducted to validate findings and explore therapeutic targets. We performed Phenome-wide association study (PheWAS) to examine the potential side effects of drug protein on AS treatment. Results: After FDR correction, eight significant proteins were identified: IL7R, TYMP, IL12B, CCL8, TNFAIP6, IL18R1, IL23R, and ERAP1. Elevated levels of IL7R, IL12B, CCL8, IL18R1, IL23R, and ERAP1 increased AS risk, whereas elevated TYMP and TNFAIP6 levels decreased AS risk. Colocalization analysis indicated that IL23R, IL7R, and TYMP likely share causal variants with AS. PPI network analysis identified IL23R and IL7R as potential new therapeutic targets. Conclusions: This study identified eight plasma proteins with significant associations with AS risk, suggesting IL23R, IL7R, and TYMP as promising therapeutic targets. Further research is needed to explore underlying mechanisms and potential for drug repurposing.

Clinical experience in laparoscopic treatment of gallbladder perforation.

Aim: We herein present our clinical experience in laparoscopic surgery for gallbladder perforation (GBP). Materials and Methods: Retrospective analysis was performed on the clinical data of 44 patients who diagnosed with GBP from January 2015 to November 2020. Results: The mean age of the 44 patients was 64.0 years and the female-to-male ratio was 20:24. The most common type of GBP was Type II, followed by Type I and Type III (31:9:4). 72.7% of the patients were diagnosed with GBP at the time of surgery. Laparoscopic surgery was performed for 38 (86.4%) patients, with a conversion rate of 13.2%. The mean length of hospital stays was 7.8 days. The mortality and morbidity rates were 2.3% and 11.4%, respectively. Conclusions: Pre-operative diagnosis of GBP is difficult. Laparoscopic surgery is safe, feasible and effective for patients with GBP.

An Indo-Pacific Humpback Dolphin Genome Reveals Insights into Chromosome Evolution and the Demography of a Vulnerable Species.

The Indo-Pacific humpback dolphin (Sousa chinensis) is a small inshore species of odontocete cetacean listed as Vulnerable on the IUCN Red List. Here, we report on the evolution of S. chinensis chromosomes from its cetruminant ancestor and elucidate the evolutionary history and population genetics of two neighboring S. chinensis populations. We found that breakpoints in ancestral chromosomes leading to S. chinensis could have affected the function of genes related to kidney filtration, body development, and immunity. Resequencing of individuals from two neighboring populations in the northwestern South China Sea, Leizhou Bay and Sanniang Bay, revealed genetic differentiation, low diversity, and small contemporary effective population sizes. Demographic analyses showed a marked decrease in the population size of the two investigated populations over the last ~4,000 years, possibly related to climatic oscillations. This study implies a high risk of extinction and strong conservation requirement for the Indo-Pacific humpback dolphin.

lncRNA differentiation antagonizing nonprotein coding RNA overexpression accelerates progression and indicates poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: lncRNA differentiation antagonizing nonprotein coding RNA (lncRNA DANCR) has been suggested to play an oncogenic role in multiple cancers. However, to the best of our knowledge, the clinical significance and role of DANCR in pancreatic ductal adenocarcinoma (PDAC) has not been illuminated till now. The present study aims to identify the functional role of DANCR in PDAC. METHODS: The expression of DANCR was detected in PDAC cells and tissues. The correlation of DANCR expression and PDAC clinicopahological features was analysed. Kaplan-Meier method was used to depict the overall survival (OS) rate and shorter progression-free survival (PFS) of PDAC patients, and Log-rank test was performed to analyse the difference. Univariate and multivariate COX regression model were utilized to analyse the risk factors for prognosis. Transwell assay and Matrigel assay were conducted to detect the effect of DANCR on the migration and invasion of PDAC cells, respectively. Colony formation assay and Cell Counting Kit-8 (CCK-8) assay were performed to evaluate the function of DANCR on proliferation. The mechanisms of DANCR exerting its function were also explored. RESULTS: DANCR was revealed to promote PDAC progression, with relatively higher expression levels in PDAC cell lines and tissues. Correlation analysis of the clinicopathological features and DANCR expression found that high DANCR expression was statistically correlated with vascular invasion (P=0.013), advanced T stage (P=0.005), lymph node metastasis (P<0.001) and advanced TNM stage (P<0.001). Notably, survival analysis discovered that high DANCR expression predicted lower OS rate and shorter PFS period. In addition, high DANCR expression was identified as an independent risk factor for poor OS (HR=1.199, 95% CI=1.113-1.290, P<0.001) and PFS (HR=1.199, 95% CI=1.114-1.290, P<0.001) of PDAC. Moreover, in vitro assays detected that the migration and invasion of Panc1 cells with DANCR deficiency were significantly suppressed in the Transwell assay and the Matrigel assay. However, the motility of BxPC3 cells with DANCR overexpression was obviously increased. In addition, the loss of DANCR suppressed the proliferation of Panc1 cells in the CCK-8 assay and the colony formation assay, while ectopic expression of DANCR in BxPC3 cells promoted the proliferation. Besides, microRNA-33a-5p/AXL signaling pathway may be involved in mediating the function of DANCR. CONCLUSION: Overexpression of lncRNA DANCR in PDAC is associated with cancer progression and predicts poor OS and PFS. DANCR could promote the proliferation and metastasis of PDAC cells. DANCR may serve as a potential prognostic marker and therapeutic target in PDAC.

Genome Sequence of the Freshwater Yangtze Finless Porpoise.

The Yangtze finless porpoise (Neophocaena asiaeorientalis ssp. asiaeorientalis) is a subspecies of the narrow-ridged finless porpoise (N. asiaeorientalis). In total, 714.28 gigabases (Gb) of raw reads were generated by whole-genome sequencing of the Yangtze finless porpoise, using an Illumina HiSeq 2000 platform. After filtering the low-quality and duplicated reads, we assembled a draft genome of 2.22 Gb, with contig N50 and scaffold N50 values of 46.69 kilobases (kb) and 1.71 megabases (Mb), respectively. We identified 887.63 Mb of repetitive sequences and predicted 18,479 protein-coding genes in the assembled genome. The phylogenetic tree showed a relationship between the Yangtze finless porpoise and the Yangtze River dolphin, which diverged approximately 20.84 million years ago. In comparisons with the genomes of 10 other mammals, we detected 44 species-specific gene families, 164 expanded gene families, and 313 positively selected genes in the Yangtze finless porpoise genome. The assembled genome sequence and underlying sequence data are available at the National Center for Biotechnology Information under BioProject accession number PRJNA433603.

[Experimental study on the improving effect of motor nerve babysitting on delayed nerve anastomosis].

OBJECTIVE: To observe whether the motor nerve babysitter could improve the delayed nerve anastomosis and promote the functional recovery. METHODS: Sixteen SD rats weighing 200-250 g were randomly divided into 2 groups. In group A, the left musculocutaneous nerve was transected to make the model of biceps brachii denervation and anastomosed to its proximal end 6 weeks later; In group B, the musculocutaneous nerve was transected and the distal end was coapted to the purely motor medial pectoral nerve immediately (nerve babysitter) and the musculocutaneous nerve was separated from the medial pectoral nerve, and reanastomosed to its proximal end 6 weeks later. In the animal model, the left limbs served as experimental sides, the right limbs as control sides. After 6 and 12 weeks of the second surgery, behavioral test (grooming test) was performed and the degree of the biceps brachii atrophy was observed, the latent period and the amplitude of the maximum action potentials of the biceps brachii were detected, the wet muscle weight, muscle fiber cross-section area and the activity of Na+-K+-ATPase of the biceps brachii were measured. RESULTS: After 4 weeks of the second surgery, grooming behavior was found in group B, while few grooming behavior was seen in group A till 6 weeks after the secondary surgery. After 6 weeks of the second surgery, the recovery rate of the latent period and the amplitude, the wet muscle weight, muscle fiber cross-section area and the enzymatic activity of Na+-K+-ATPase of the biceps brachii in group A was 187.25% +/- 1.97%, 46.25% +/- 4.63%, 55.14% +/- 1.99%, 49.97% +/- 1.71%, and 65.81% +/- 2.24%, respectively, which was significantly different from that in group B (155.96% +/- 3.02%, 51.21% +/- 2.13%, 74.18% +/- 1.82%, 55.05% +/- 1.64% and 71.08% +/- 1.53%, respectively, P < 0.05). After 12 weeks of the second surgery, the recovery rate of the latent period and amplitude, the wet muscle weight, muscle fiber cross-section area and the enzymatic activity of Na+-K+-ATPase of the biceps brachii in group A was 145.36% +/- 3.27%, 51.84% +/- 5.02%, 77.92% +/- 1.73%, 61.04% +/- 2.68% and 71.94% +/- 1.65%, respectively, which was significantly different from that in group B (129.83% +/- 8.36%, 75.22% +/- 2.78%, 84.51% +/- 1.34%, 78.75% +/- 3.69% and 84.86% +/- 1.81%, respectively, P < 0.05). CONCLUSION: Motor nerve babysitting could reduce muscular damage after denervation, improve the effect of delayed nerve repair and promote the functional recovery of musculocutaneous nerve.