Objective:To systematically investigate the association and regulatory mechanism between genetic variants in the binding region of pancreatic and duodenal homeobox 1 (PDX1) and pancreatic cancer susceptibility in the Chinese population.Methods:Chromatin immunoprecipitation sequencing (ChIP-seq) was performed using the human pancreatic cancer cell line BxPC-3 to identify and annotate genetic variants within the PDX1 binding region. A two-center case-control study was conducted, and logistic regression models were employed to analyze the association between PDX1-related variants and pancreatic cancer susceptibility. Functional experiments were performed to elucidate the molecular mechanisms of these genetic variants.Results:ChIP-seq analysis identified 1 608 PDX1 binding regions. SNPs within these regions were significantly enriched in susceptible areas of pancreatic cancer ( P<0.001). The common variant rs154659, located within the most significant PDX1 binding peak, was further investigated. The multivariate logistic regression model showed that compared with individuals with TT genotype, individuals with CC genotype had a reduced risk of pancreatic cancer by 29.2% ( OR=0.708, 95% CI: 0.589-0.850). Functional studies demonstrated that the rs154659[C] allele displayed higher relative luciferase activity than the rs154659[T] allele. Knockdown of PDX1 significantly attenuated the relative luciferase differences between the two alleles. Conclusion:Genetic variants in the PDX1 binding region are associated with pancreatic cancer risk. The rs154659 modulates pancreatic cancer susceptibility by specifically altering PDX1 binding activity.

A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades; the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized. However, little research has focused on viruses-entities characterized by smaller dimensions, simpler structures, greater diversity, and more intricate interactions with their surrounding milieu compared to bacteria. To date, alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders, including schizophrenia, major depressive disorder, autism spectrum disorder, and Alzheimer's disease, accompanied by metabolic disruptions that may directly or indirectly impact brain function. In addition, eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses. Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented. However, limitations due to the lack of large-scale cohort studies, reliability, clinical applicability, and the unclear role of viruses in microbiota interactions pose a challenge for future studies. Nevertheless, it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.
Humans ; Mental Disorders/virology* ; Animals ; Brain/virology* ; Gastrointestinal Microbiome/physiology* ; Viruses ; Virus Diseases/complications*

Objective To evaluate the application of evidence-based perioperative patient-controlled analgesia(PCA)management in patients with liver cancer receiving transcatheter arterial chemoembolization(TACE)treatment.Methods By using the application model of clinical evidence-based practice,the review indicators were formulated based on the best evidence.The baseline assessment was conducted,the barrier factors were analyzed,the best clinical decision was made,the implementation steps of PCA management,including training,monitoring,education,etc.were refined,and two rounds of clinical review were carried out.The knowledge-belief-practice level and the implementation of review indicators in 50 medical and nursing staff engaged in PCA management,as well as the changes in pain scores,the incidence of adverse reactions due to PCA management,and the patient's satisfaction in 159 patients after the application of evidence were compared with their corresponding values determined before the application of evidence.Results After implementing the evidence-based practice plan and applying the evidence,at multiple time points the pain scores and the incidences of adverse reactions were decreased significantly(P＜0.05),the patient's satisfaction increased remarkably(P＜0.01),the execution rate of medical and nursing staff for the review indicators were strikingly increased(P＜0.01),and the knowledge-belief-practice level concerning PCA management was prominently improved(P＜0.01).Conclusion The implementation of perioperative PCA management in patients with liver cancer receiving TACE treatment can help to reduce the perioperative pain level,improve the patient discomfort,increase the patient's satisfaction degree,and improve the ability of medical staff in performing PCA management and evidence-based practices.

Objective:To systematically investigate the association and regulatory mechanism between genetic variants in the binding region of pancreatic and duodenal homeobox 1 (PDX1) and pancreatic cancer susceptibility in the Chinese population.Methods:Chromatin immunoprecipitation sequencing (ChIP-seq) was performed using the human pancreatic cancer cell line BxPC-3 to identify and annotate genetic variants within the PDX1 binding region. A two-center case-control study was conducted, and logistic regression models were employed to analyze the association between PDX1-related variants and pancreatic cancer susceptibility. Functional experiments were performed to elucidate the molecular mechanisms of these genetic variants.Results:ChIP-seq analysis identified 1 608 PDX1 binding regions. SNPs within these regions were significantly enriched in susceptible areas of pancreatic cancer ( P<0.001). The common variant rs154659, located within the most significant PDX1 binding peak, was further investigated. The multivariate logistic regression model showed that compared with individuals with TT genotype, individuals with CC genotype had a reduced risk of pancreatic cancer by 29.2% ( OR=0.708, 95% CI: 0.589-0.850). Functional studies demonstrated that the rs154659[C] allele displayed higher relative luciferase activity than the rs154659[T] allele. Knockdown of PDX1 significantly attenuated the relative luciferase differences between the two alleles. Conclusion:Genetic variants in the PDX1 binding region are associated with pancreatic cancer risk. The rs154659 modulates pancreatic cancer susceptibility by specifically altering PDX1 binding activity.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective To optimize the conditions and improve the efficiency for the differentiation of pluripotent stem cells(PSCs)into cerebral organoids.Methods Based on the induction differentiation system for inducing hu-man embryonic stem cells(hESCs)H9 towards cerebral organoids,a combination of small molecule compounds was added to the developmental stage of neural progenitor cells in the early stage of cerebral organoid differentia-tion,and the efficiency of neural progenitor cell formation,apoptosis and differentiation into neurons in cerebral or-ganoids in the differentiation stage were observed through morphology,the expression of marker genes was detected by RT-qPCR and the effect of small molecule compound combination on cerebral organoids was comprehensively evaluated.Results At the critical stage of neural progenitor cell development(1 d-14 d)of cerebral organoids,dorsomorphine,A83-01,GSK-3β inhibitor CHIR99021 and SMAD inhibitor SB-431542 were successively added to the medium.It could significantly increase the expression of marker genes in the neural progenitor cell stage,promote the formation of specific neural tube-like structures and reduce apoptosis in the central region of cerebral organoids.Conclusions By using the combination of four small molecule compounds,the formation efficiency in early cerebral organoids can be significantly improved,apoptosis in cerebral organoids can be reduced,neuronal formation can be promoted,and tissue structure heterogeneity in the culture process can be reduced.

Objective To retrospectively analyze the research on the integrated medical and elderly care in China in re-cent ten years,and explore the research hotspots and future research trend of the integrated medical and elderly care.Methods Using the method of literature research,the journal articles with the theme of combination of medical care and nursing,integration of medical care and nursing or medical care and nursing service from 2013 to 2023 were searched in CNKI.The sources were lim-ited to Peking University Core,CSSCI,CSCD and AMI,and the selected articles were analyzed by CiteSpace.Results This ar-ticle takes 896 literatures as research objects,we found that the number of articles reached a peak in 2018,the higher number of articles issued by the institutions are medicine-related institutions.The high-frequency keywords are the integrated medical and elderly care,elderly services,senior citizens,elderly care institutions and elderly care model.The strongest emergent word de-tected is health care integration.Conclusion In the past ten years,domestic research on the integration of medical care and eld-erly care has shown diversification and innovation.Policy tools,pension insurance,community and rural pension,quality evalua-tion index system,influencing factors were the research focus of scholars.Future research needs to focus on the application of quantitative methods,empirical and practical analysis.

Objective:To explore the application effect of the teaching method combining process-oriented-guided inquiry learning (POGIL) theory and micro-class in orthopedic clinical internship.Methods:The 118 interns who completed internship from January 2022 to December 2022 were randomly divided into a control group (58) and an experimental group (60). The control group received traditional teaching, while the experimental group received a teaching method combining POGIL theory and micro-class. After the internship, the two groups were compared for assessment scores (basic theoretical knowledge and professional theoretical knowledge), learning status (classroom performance and self-learning ability), clinical practice ability (Leicester Assessment Scale), and teaching satisfaction. The t-test and chi-square test were performed using SPSS 21.0. Results:After the internship, the assessment scores, classroom performance, self-directed learning ability scores, clinical skills, case writing scores, and teaching satisfaction of the experimental group were all higher than those of the control group ( t/ χ2=5.01, 3.72, 2.20, 6.57, 3.56, 4.52, P<0.05). Conclusions:The teaching method combining POGIL theory and micro-class can enhance the master of theoretical knowledge by orthopedic interns, optimize classroom performance, cultivate self-learning ability, and improve clinical practice ability and teaching satisfaction.

Objective:To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5.Methods:It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas.Results:A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95% CI 1.77-3.56, P<0.001), hypertension ( OR=5.88, 95% CI 1.57-22.10, P=0.009), and diabetes ( OR=4.66, 95% CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95% CI 3.64-11.36, P<0.001) and hypertension ( OR=6.09, 95% CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female ( OR=0.23, 95% CI 0.07-0.72, P=0.011), age (every 10 years increase, OR=3.90, 95% CI 2.42-6.29, P<0.001), diabetes ( OR=5.37, 95% CI 2.19-13.19, P<0.001) and serum magnesium ( OR=0.01,95% CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions:The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.