Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein-protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C-C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis.

Colitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p, and let-7f-5p were dysregulated during the development of intestinal dysplasia. Subsequently, we first identified the role of these three miRNAs in CAC. Adenomatous polyposis coli (APC) was revealed as a new target of miR-223-3p, and solute carrier family 9- subfamily A-member 9 (SLC9A9) and APC membrane recruitment protein 3 (AMER3) were suggested as two new targets for let-7f-5p. For miR-31-5p, we proved that it can target LATS2 mRNA so as to modulate Hippo pathway in Caco2 cells. Second, to examine if targeting these three miRNAs would lead to CAC prevention, pedunculoside, a natural triterpene glycoside capable of rescuing the down-regulation of LATS2 and APC caused by either miR-31-5p or miR-223-3p overexpression, respectively, was used in the in vivo AOM/DSS-induced CAC model. The results showed that pedunculoside (25 mg/kg) substantially mitigated the damage to mice intestine caused by DSS/AOM. These results suggested that miRNAs-elicited post-transcriptional regulation is involved in the pathogenesis of CAC, and CAC can be prevented through targeting key miRNAs that are ectopically expressed in CAC.

Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72-1.62, P < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83-0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein-protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.

Recent progress in high throughput sequencing technologies has provided an opportunity to probe T cell receptor (TCR) repertoire, bringing about an explosion of TCR sequencing data and analysis tools. For easier and more heuristic analysis TCR sequencing data, we developed a client-based HTML program (VisTCR). It has a data storage module and a data analysis module that integrate multiple cutting-edge analysis algorithms in a hierarchical fashion. Researchers can group and re-group samples for different analysis purposes by customized "Experiment Design File." Moreover, the VisTCR provides a user-friendly interactive interface, by all the TCR analysis methods and visualization results can be accessed and saved as tables or graphs in the process of analysis. The source code is freely available at https://github.com/qingshanni/VisTCR.

Glioma is a relatively low aggressive brain tumor. Although the median survival time of patients for lower-grade glioma (LGG) was longer than that of patients for glioblastoma, the overall survival was still short. Therefore, it is urgent to find out more effective molecular prognostic markers. The role of the Fam20 kinase family in different tumors was an emerging research field. However, the biological function of Fam20C and its prognostic value in brain tumors have rarely been reported. This study aimed to evaluate the value of Fam20C as a potential prognostic marker for LGG. A total of 761 LGG samples (our cohort, TCGA and CGGA) were included to investigate the expression and role of Fam20C in LGG. We found that Fam20C was drastically overexpressed in LGG and was positively associated with its clinical progression. Kaplan-Meier analysis and a Cox regression model were employed to evaluate its prognostic value, and Fam20C was found as an independent risk factor in LGG patients. Gene set enrichment analysis also revealed the potential signaling pathways associated with Fam20C gene expression in LGG; these pathways were mainly enriched in extracellular matrix receptor interactions, cell adhesion, cell apoptosis, NOTCH signaling, cell cycle, etc. In summary, our findings provide insights for understanding the potential role of Fam20C and its application as a new prognostic biomarker for LGG.

Background: Alcohol use has been linked to a number of physical conditions, but the relationship between alcohol drinking and depression, one of the most common mental disorders that is a significant contributor to the global burden of disease, is still under debate. We aim to help fill the literature gap on the causal effect of alcohol use on depression by using genetic instruments of ALDH2 rs671 and ADH1B rs1229984 in the Mendelian randomization (MR) framework. Materials and Methods: We collected a sample of 476 middle-aged and older adults from mainland China. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to measure the status of depression. The frequency and intensity of alcohol consumption were measured by (1) a binary indicator of drinking or not, (2) the total number of drinking occasions during the past 30 days, and (3) the weekly ethanol consumption in grams. Results: MR estimates indicated that alcohol use was causally associated with a lower risk of depression. Parameter estimates of drinking or not (b = -0.127, p = 0.048), number of drinking occasions (b = -0.012, p = 0.040), and weekly ethanol consumption (b = -0.001, p = 0.039) were all negative and statistically significant. The results were robust after adjustments for potential confounders (e.g., income, smoking, and parental drinking behaviors), and the exclusion of heavy or former drinkers. Conclusions: This is one of the first study to investigate the causal relationship between alcohol use and mental health using an MR design in East Asian populations. Further studies are needed to clarify the mechanisms of this causal link.

The ancestral origin and genomic history of Chinese Hui people remain to be explored due to the paucity of genome-wide data. Some evidence argues that an eastward migration of Central Asians gave rise to modern Hui people, which is referred to as the demic diffusion hypothesis; other evidence favors the cultural diffusion hypothesis, which posits that East Asians adopted Muslim culture to form the modern culturally distinct populations. However, the extent to which the observed genetic structure of the Huis was mediated by the movement of people or the assimilation of Muslim culture also remains highly contentious. Analyses of over 700 K SNPs in 109 western Chinese individuals (49 Sichuan Huis and 60 geographically close Nanchong Hans) together with the available ancient and modern Eurasian sequences allowed us to fully explore the genomic makeup and origin of Hui and neighboring Han populations. The results from PCA, ADMIXTURE, and allele-sharing-based f-statistics revealed a strong genomic affinity between Sichuan Huis and Neolithic-to-modern Northern East Asians, which suggested a massive gene influx from East Asians into the Sichuan Hui people. Three-way admixture models in the qpWave/qpAdm analyses further revealed a small stream of gene influx from western Eurasians into the Sichuan Hui people, which was further directly confirmed via the admixture event from the temporally distinct Western sources to Sichuan Hui people in the qpGraph-based phylogenetic model, suggesting the key role of the cultural diffusion model in the genetic formation of the Sichuan Huis. ALDER-based admixture date estimation showed that this observed western Eurasian admixture signal was introduced into the Sichuan Huis during the historic periods, which was concordant with the extensive western-eastern communication along the Silk Road and historically documented Huis' migration history. In summary, although significant cultural differentiation exists between Hui people and their neighbors, our genomic analysis showed their strong genetic affinity with modern and ancient Northern East Asians. Our results support the hypothesis that the Sichuan Huis arose from a mixture of minor western Eurasian ancestry and predominant East Asian ancestry.

Background: Prenatal diagnosis and genetic counseling play an important role in preventing and controlling birth defects. No reports were found of prenatal diagnosis of couples carrying both the thalassemia and deafness genes. In this study, we presented the prenatal screening and diagnosis of a couple with both thalassemia and deafness genes, contributing to better genetic counseling. Case Report: A couple visited our hospital for a routine prenatal examination. As required by the policy in our region, they underwent screening and genetic diagnosis for thalassemia. Meanwhile, they did not accept the recommendation to test for spinal muscular atrophy and deafness genes. The female was confirmed to be a Hb Quong Sze (Hb QS) carrier (αQSα/αα, βN/βN), and the male had Hb H disease combined with β-thalassemia (--SEA/αCSα, βCDs41-42 (-TTCT)/βN). A prenatal diagnosis of the fetus revealed a Hb CS heterozygote. Subsequent complementary testing showed that the male was a double heterozygote of the GJB2 gene c.299_300delAT combined with c.109G>A, and Sanger sequencing confirmed that the female was a carrier of c.508_511dup in the GJB2. Fortunately, the chorionic villi results indicated that the fetus was only a carrier of deafness. Conclusion: Since both partners carried thalassemia and deafness genes, the couple required prenatal diagnosis for the respective mutations. Expanded carrier screening (ECS) is a more advanced technology that can detect multiple disease genes simultaneously.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide with a poor prognosis. Alcoholic liver disease accounts for approximately one-third of all HCC cases. Current evidence proved that aberrant over-expression of TNFRSF12A correlates with the severity of disease, making it a likely indicator of disease a more aggressive and worse prognosis outcome. Emerging studies have confirmed that epigenetic changes are critical events in the development and progression of liver cancer. The study to investigate the mechanisms by which alcohol abuse mediated changes in the methylation level of TNFRSF12A affect the occurrence, development and prognosis of HCC were under warranted. Thus, in this study we mined two publicly available datasets to detect the association between DNA methylation level of CpG sites in gene TNFRSF12A and the development of HCC in those with alcohol abuse history. Finally, we discovered that the hypomethylation of two methylation sites-cg00510447 and cg26808293-could identify HCC from other non-HCC liver diseases. Also, hypomethylation of these two sites could identify alcoholic cirrhosis from other non-hepatocellular carcinoma liver diseases. Most important, the prognostic analysis revealed that the hypomethylation of cg00510447 and cg26808293 in HCC patients with alcohol abuse history could predict poor prognosis. Further stratified analyses by gender discovered that in male HCC patients with alcohol abuse history, hypomethylation of cg26808293 signified poor prognosis. The further mechanism analysis revealed that the DNA methyltransferases DNMT3L might regulate TNFRSF12A methylation and affect the occurrence, development and prognosis of HCC, especially in patients with a history of alcohol abuse. These findings provide new insights into the role of epigenetic mechanisms in the transformation of alcoholic liver disease into HCC.

Background: There is a continued debate and inconsistent findings in previous literature about the relationship of catechol-O-methyltransferase (COMT) and Parkinson's disease (PD) susceptibility as well as cognitive dysfunction. To substantiate this existing gap, we comprehensively examine COMT genotype effects on the development of PD and test the hypothesis that the Met158 allele of the COMT gene is associated with cognitive dysfunction by conducting a meta-analysis review. Methods: PubMed/MEDLINE, Embase, Cochrane databases search (18/30/08) yielded 49 included studies. Data were extracted by two reviewers and included COMT genotype, publication year, diagnostic status, ancestry, the proportion of male participants, and whether genotype frequencies were consistent with Hardy-Weinberg equilibrium. Unadjusted odds ratios (ORs) were used to derive pooled estimates of PD risk overall and in subgroups defined by ethnicity, gender, and onset of disease. Moreover, the association of certain cognitive domains in PD and COMT gene type was explored. Meta-analyses were performed using random-effect models and p value-based methods. All statistical tests were two-sided. The present study was registered with PROSPERO (CRD42018087323). Results: In the current studies, we found no association between COMT Val158/108Met polymorphism and PD susceptibility. However, the gender-stratified analyses revealed marginally significant effects in heterozygote model analyses in women (P = 0.053). In addition, stratification according to onset of PD also shows significant effects of COMT Val158/108Met polymorphism on late-onset population both in recessive (P = 0.017) and allelic (P = 0.017) genetic models. For the intelligence quotient (IQ) score and Unified Parkinson Disease Rating Scale III (UPDRS III), there was no evidence for genetic association, except in subgroup analyses in Asian populations (IQ score, P = 0.016; UPDRS III, P < 0.001). Conclusion: The COMT Val158/108Met polymorphism is associated with the risk for PD in female or late-onset PD. Methionine/methionine carriers of Asian population performed significantly worse than the valine allele carriers in IQ score and UPDRS III.

Modern East Asians derived from the admixture of aborigines and incoming farmers expanding from Yellow and Yangtze River Basins. Distinct genetic differentiation and subsequent admixture between Northeast Asians and Southeast Asians subsequently evidenced by the mitochondrial DNA, Y-chromosomal variations, and autosomal SNPs. Recently, population geneticists have paid more attention to the genetic polymorphisms and background of southern-Han Chinese and southern native populations. The genetic legacy of northern-Han remains uncharacterized. Thus, we performed this comprehensive population genetic analyses of modern and ancient genetic variations aiming to yield new insight into the formation of modern Han, and the genetic ancestry and phylogenetic relationship of the northern-Han Chinese population. We first genotyped 25 forensic associated markers in 3,089 northern-Han Chinese individuals using the new-generation of the Huaxia Platinum System. And then we performed the first meta-analysis focused on the genetic affinity between Asian Neolithic∼Iron Age ancients and modern northern-Han Chinese by combining mitochondrial variations in 417 ancient individuals from 13 different archeological sites and 812 modern individuals, as well as Y-chromosomal variations in 114 ancient individuals from 12 Neolithic∼Iron Age sites and 2,810 modern subjects. We finally genotyped 643,897 genome-wide nucleotide polymorphisms (SNPs) in 20 Shanxi Han individuals and combined with 1,927 modern humans and 40 Eurasian ancient genomes to explore the genetic structure and admixture of northern-Han Chinese. We addressed genetic legacy, population structure and phylogenetic relationship of northern-Han Chinese via various analyses. Our population genetic results from five different reference datasets indicated that Shanxi Han shares a closer phylogenetic relationship with northern-neighbors and southern ethnically close groups than with Uyghur and Tibetan. Genome-wide variations revealed that modern northern-Han derived their ancestry from Yakut-related population (25.2%) and She-related population (74.8%). Summarily, the genetic mixing that led to the emergence of a Han Chinese ethnicity occurred at a very early period, probably in Neolithic times, and this mixing involved an ancient Tibeto-Burman population and a local pre-Sinitic population, which may have been linguistically Altaic.

The origin and diversification of Muslim Hui people in China via demic or simple cultural diffusion is a long-going debate. We here generated genome-wide data at nearly 700,000 single nucleotide polymorphisms (SNPs) from 45 Hui and 14 Han Chinese individuals collected from Guizhou province in southwest China. We applied principal component analysis (PCA), ADMIXTURE, f-statistics, qpWave, and qpAdm analysis to infer the population genetic structure and admixture history. Our results revealed the Guizhou Hui people have a limited amount of West Eurasian related ancestry at a proportion of 6%, but show massive genetic assimilation with indigenous southern Han Chinese and Tibetan or Tungusic/Mongolic related northern East Asians. We also detected a high frequency of North Asia or Central Asia related paternal Y-chromosome but not maternal mtDNA lineages in Guizhou Hui. Our observation supports the cultural diffusion has played a vital role in the formation of Hui people and the migration of Hui people to southwest China was probably a sex-biased male-driven process.