Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Accumulating evidence indicated that microRNAs (miRNA) play an important role in tumor invasion and metastasis by regulating their target genes.However, whether the miRNA-216b-5p(miR-216b-5p ) and their target genes butyrophilin subfamily 3 member A2(BTN3A2) promote glioma invasion and metastasis is unclear.This study aims to study whether miR-216b-5p promoted migration and invasion in glioma cells by negatively regulating BTN3A2.The differential expression analysis of GSE15824 and GSE4290 was analyzed by GEO2R.We found that only BTN3A2 is up-regulated in both GSE15824 and GSE4290 (P<0.05).The gene set enrichment analysis (GSEA) analysis indicated BTN3A2 was related to many cancer-related pathways (P<0.05).The results of survival curves showed that the overall survival of patients with high expression of BTN3A2 decreased significantly (P <0.001).The expression of BTN3A2 was increased with the increase of WHO grade (P<0.05), while the expression of BTN3A2 was increased in 1p/19q uncombined deletion and IDH mutant patients (P<0.001).Western blotting results showed that BTN3A2 was up-regulated in seven glioma tissues and glioma cell lines U87, U251 and LN-229 and downregulated in the miR-216b-5p mimics group; Transwell results showed that transfection with BTN3A2 silencing plasmids(si-BTN3A2) or miR-216b-5p mimics plasmids could inhibit the ability of migration and invasion in LN-229 cells in vitro (P<0.05).The online websites predicted miR-216b-5p as a potential target gene of BTN3A2.The survival curve results show that compared with patients with low expression of miR-216b-5p , the survival rate of patients with high expression was significantly increased (P=0.025).The relative expression of miR-216b-5p was decreased in U87, U251 and LN229 cells was detected by real time quantitative PCR (P<0.05).The results of dual luciferase assay showed that BTN3A2 could bind to miR-216b-5p (P<0.05).Transwell experiment results showed that overexpression of miR-216b-5p can inhibit the migration and invasion ability of LN229 cells (P<0.05).In summary, miR-216b-5p promotes the migration and invasion by targeting BTN3A2 of LN-229 glioma cells.

Objective: To study the main factors that influencing Pneumoconiosis patients' healthcare seeking behaviors. Methods: Conducting a descriptive analysis to analyze the relationship between the annual hospitalization rate and social security status (medical insurance, location of medical insurance, proportion of insurance used for reimbursement of pneumoconiosis, whether there is employment injury insurance at work, whether to apply for compensation after diagnosing pneumoconiosis, whether they receive social assistance and a minimum allowance) , social relationship status of patients (whether there is pneumoconiosis in the family or relatives, whether there is a pneumoconiosis in a friend or a colleague, and whether or not he/she has received financial assistance) , life quality of patients (subjective feelings) and living standard of patients (dietary level) based on data acquired from 120 pneumoconiosis patients. Results: The results of single factor analysis reveal that the location of medical insurance, the proportion of insurance for reimbursement of pneumoconiosis, whether there is employment injury insurance at work, whether to apply for compensation after diagnosing pneumoconiosis are statistically significant in pneumoconiosis patients' hospital utilization ratio (P<0.05) . The place where medical insurance is located is the current place of residence, the reimbursement ratio of medical insurance for pneumoconiosis is listed as 50%-70%, the work unit has medical insurance, those who have not applied for compensation for pneumoconiosis have a higher utilization rate of hospitalization services. The annual hospitalization rate was 73.3%, 80.0%, 60.6%, 63.0%, respectively. Conclusion The location of patient medical insurance, the proportion of insurance used for reimbursement of pneumoconiosis, whether there is employment injury insurance at work, and whether to apply for compensation after pneumoconiosis are the influencing factors of the patients' annual hospitalization rate.