Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Mechanosignaling activation of TGFβmaintains intervertebral disc homeostasis

Intervertebral disc （IVD） degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal （NC） cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta （TGFβ）, decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease （DDD）. Knockout of TGFβ type II receptor （TβRII） or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.

Bladder cancer epidemiology and genetic susceptibility

Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women （approximately 4：1）. Here, we summarize the bladder cancer-related risk factors, in- cluding environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk fac- tors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study （GWAS） has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction stud- ies need to be conducted to provide more information for the etiology of bladder cancer.

Genetic variants in the Hedgehog signaling pathway genes are associated with gastric cancer risk in a Chinese Han population

The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.

P53 codon 72 polymorphism and ovarian cancer risk:a meta-analysis

Objective： p53 is a tumor suppressor gene and is involved in the etiology of ovarian cancer. Studies investigating the associations between the p53 codon 72 polymorphism and ovarian cancer risk showed conflicting results. We performed this meta-analysis from eligible studies to evaluate this purported relationship. Methods： This meta-analysis was performed from 9 case-control studies, including 825 ovarian cases and 1073 controls. The fixed and random effect models were used to estimate the odds ratios（ORs） for various contrasts of this polymorphism. Results： The combined results based on all studies showed that a significantly decreased risk was associated with the variant Pro/Pro genotype, compared with Arg/Pro＋Arg/Arg genotypes（OR, 0.70; 95%CI, 0.51-0.95）. When stratifying the studies by ethnicity, we found that individuals with the variant genotype Pro/pro had a significantly decreased risk of ovarian cancer compared with Arg/Arg genotype（OR, 0.43; 95%CI, 0.20-0.89） and Arg/Pro＋Arg/Arg genotypes（OR, 0.61; 95%CI, 0.37-0.99） among Africans. Conclusion： This meta-analysis suggests that the p53 codon 72 polymorphism may contribute to genetic susceptibility to ovarian cancer. More studies based on larger sample size should be performed to confirm the findings.

全基因组关联研究发现中国人群前列腺癌两个新易感位点9q31.2和19q13.4

0前言在全球范围内，前列腺癌的发病率和病死率存在着巨大差异。该病在西方发达国家发病率最高，在非裔美国人群病死率最高，而在亚洲人群中发病率及病死率均为全球最低，提示不同人种在前列腺癌的遗传方面存在异质性。在欧美和日本人群中，全基因组关联研究（GWAS）技术已经被用于检测前列腺癌的遗传易感性位点，但至今尚无关于GWAS检测中国人群前列腺癌易感位点的报道。

Alternative polyadenylation-related genetic variants contribute to bladder cancer risk

Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.

Biological functions and potential implications of circular RNAs

Circular RNAs(circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges,interacting with proteins, modulating the expression of related genes and translating into peptides or proteins.CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice.This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment.

Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

Although tobacco and alcohol consumption are two common risk factors of head and neck cancer （HNC）, other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Hu- man DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic vari- ants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms （SNPs） in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly in- creased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus in- teractions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway- based analyses of DNA repair genes derived from genome-wide association studies （GWASs） in HNC are needed.

CASP8 promoter polymorphism,mRNA expression and risk of prostate cancer among Chinese men

Caspase-8 （CASPS） plays a key role in apoptosis. We examined by genotyping whether the -652 six-nucleotide insertion-deletion （6N ins/del） polymorphism in the CASP8 promoter region was associated with prostate cancer risk in a hospital-based case-control study of 406 Chinese prostate cancer patients and 408 age-matched cancerfree controls. Additionally, 23 prostate cancer tissues were analyzed for CASP8 mRNA expression. We found a significantly decreased prostate cancer risk for the 6N ins/del genotype [adjusted odds ratio （OR）=0.68; 95% confidence interval （C/）=0.51-0.92] and del/del genotype （OR=0.34; 95% CI=0.19-0.63） compared with the ins/ins genotype. The 6N del allele was associated dose-dependently with decreased prostate cancer risk （Ptrend = 0.001）. RT-PCR showed that individuals with the 6N del allele had lower CASP8 mRNA levels than those with the ins/ ins genotype （P = 0.024）. These findings suggested that the CASPS-652 6N ins/del polymorphism may affect the susceptibility to prostate cancer and reduce prostate cancer risk among Chinese men.

Evolution and major changes of the diagnosis and treatment protocol for COVID‐19 patients in China 2020–2023

Since the identification of the first case of pneumonia of unknown cause in 2019,the COVID‐19 pandemic has spread the globe for over 3 years.As the most populous country in the world,China's disease prevention policies and response plans concern the health of the country's 1.4 billion people and beyond.During the course of the pandemic,scientific research has been accumulated and given evidence‐based support to the official guidance of COVID‐19 management.The National Health Commission of China have compiled,published,and updated a total of 10 versions of the“Diagnosis and Treatment Protocol for COVID‐19 Patients”to better inform clinical practitioners and staff to effectively screen,diagnose,manage,treat,and care for cases of severe acute respiratory syndrome coronavirus 2 infection.This paper compares and summarizes each version of the protocol in terms of etiology and epidemiology,clinical manifestation and diagnosis,treatment and nursing,disease control and management,presenting detailed changes,additions,deletions,and refinement of the protocols.

Diagnosis,Treatment,and Associated Factors Among Patients with HCV Infection—Jiangsu Province,China,2004–2020

What is already known on this topic?The global efforts to address the hepatitis C virus(HCV)are progressing,but there are still significant gaps in the diagnosis and treatment of HCV,leading to an increasing number of deaths related to HCV.What is added by this report?An extensive investigation was conducted to assess HCV RNA diagnosis,treatment uptake,and associated factors among individuals infected with HCV within Jiangsu Province.The study encompassed a large geographical area and utilized a substantial sample size.What are the implications for public health practice?Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems,deaths,and healthcare expenses.This is essential for achieving the global target of eliminating hepatitis C.

Prevalence and molecular characteristics of Listeria monocytogenes in cooked products and its comparison with isolates from listeriosis cases

This study aimed to investigate the prevalence and molecular characteristics ofListeria monocytogenes in cooked products in Zigong City, China. The overall occurrence of the L. monocytogenes in the ready-to-eat （RTE） shops and mutton restaurants surveyed was 16.2% （141/873）. An occurrence of 13.5% was observed in RTE pork, 6.5% in RTE vegetables, and more than 24.0% in either cooked mutton or cooked haggis. Serotype 1/2b （45.4%）, 1/2a （33.3%）, and 1/2c （14.2%） were the predominant types. By comparing the clonal complexes （CCs） based on multilocus sequence typing （MLST） of the L. monocytogenes from cooked foods in Zigong City and 33 listeriosis cases from different districts of China, CC87, CC9, CC8, and CC3 were showed to be prevalent in cooked products and CC87 and CC3 were the first two frequent types in the 33 clinic-source strains. All CC87 stains harbored the newly reported Listeria pathogenicity island 4 （LIPI-4） gene fragment ptsA, and all CC3 strains possessed the Listeria pathogenicity island 3 （LIPI-3） gene fragment llsX. These may increase the occurrence of the strains belonging to CC87 and CC3 in listeriosis cases in China and also underline the risk of infection owing to the consumption of the cooked products from Zigong. ST619 （serotype 1/2b） harbored both llsX and ptsA, indicating a potential hypervirulent sequence type in Zigong.

Texture Repairing by Unified Low Rank Optimization

In this paper, we show how to harness both low-rank and sparse structures in regular or near-regular textures for image completion. Our method is based on a unified formulation for both random and contiguous corruption. In addition to the low rank property of texture, the algorithm also uses the sparse assumption of the natural image： because the natural image is pieeewise smooth, it is sparse in certain transformed domain （such as Fourier or wavelet transform）. We combine low-rank and sparsity properties of the texture image together in the proposed algorithm. Our algorithm based on convex optimization can automatically and correctly repair the global structure of a corrupted texture, even without precise information about the regions to be completed. This algorithm integrates texture rectification and repairing into one optimization problem. Through extensive simulations, we show our method can complete and repair textures corrupted by errors with both random and contiguous supports better than existing low-rank matrix recovery methods. Our method demonstrates significant advantage over local patch based texture synthesis techniques in dealing with large corruption, non-uniform texture, and large perspective deformation.