Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To investigate the mechanism of natural antigen B(nAgB)to protect Immune thrombocytopenia(ITP)mouse model by influencing autophagy.Methods:Twenty-eight female BALB/c mice aged 8-10 weeks were randomly divided into four groups.7 mice of each group were immunized intraperitoneally,the control group was treated with PBS as the control group;ITP group was treated with anti-CD41 monoclonal antibody(anti-CD41Ab)only;nAgB group was treated with nAgB intraperitoneal injection for 5d;nAgB+ITP group was treated with nAgB intraperitoneal injection for 5d,then treated with anti-CD41 Ab.The peripheral blood platelet count in each group was tested;and the spleen and liver should be isolated and weighed,the organ index was calculated;qRT-PCR was used to detect spleen microtubule-associated protein 1 light chain 3(LC3),p62,Beclin-1 mRNA expression levels.Western blot was used to detect the protein expression level of spleen LC3 Ⅱ/LC3 Ⅰ,p62,Beclin-1.Results:Compared with the control group,mice in the ITP group showed a significant decrease in blood PLT count[(102.1±17.9)× 109/L vs(485.4±185.2)×109/L,P＜0.01],a significant increase in spleen index(P＜0.01),mice in the nAgB group showed a significant increase in blood PLT count,rising to(1051±127.6)× 109/L on the 3 day after modeling.Compared with the ITP group,mice in the nAgB+ITP group showed a significant increase in PLT count on the 1 day of anti-CD41 Ab administration[(428.6±131.6)× 109/L vs(102.1±17.9)×109/L,P＜0.05],however,the spleen index was significantly decreased(P＜0.05).qRT-PCR and Western blot results showed that compared with the control group,the mRNA and protein expression levels of spleen LC3,p62 and Beclin-1 were increased in the ITP group of mice(P＜0.05,P＜0.01).Compared with the ITP group,the nAgB+ITP group could significantly decrease mRNA levels of spleen LC3,p62 and Beclin-1(P＜0.05,P＜0.01),and also significantly decrease the protein expression levels of LC3 Ⅱ/LC3 Ⅰ,p62 and Beclin-1(P＜0.05,P＜0.01).Conclusion:nAgB inhibits the transcription and expression levels of autophagy-related genes and regulates immune intolerance,thereby protecting ITP mouse models.

The goal of medical talent training under the new medical science concept is to comprehensively enhance the quality of medical education and cultivate high-quality medical talents with interdisciplinary integration, innovation spirit, and an international perspective to meet the demands of the new era. To achieve this goal, the joint education program between Chongqing Medical University and the University of Leicester integrates comprehensive quality development into the undergraduate medical education system, introducing the cutting-edge international course "Respiratory and Cancer Precision Medicine". This course centers on precision medicine, spanning respiratory diseases and oncology, and uses a clinical-basic cyclical integrated course design with a highly-informationized blended teaching model. Students have gained a close integration of clinical practice and research capabilities, significantly enhancing their inquiry spirit, critical thinking, independent learning, and higher-order cognitive skills. They also engage in innovative thinking and interdisciplinary collaboration within an international context to better address complex medical issues. This paper provides a detailed analysis of the practice and research of the introduced course, offering valuable insights for cultivating high-quality medical talents.

Objective To analyze the risk factors for delayed hemorrhage in patients with early gastric carcinoma(EGC)after endoscopic submucosal dissection(ESD),as well as to explore the predictive value of predictive models.Methods The clinical data of 386 EGC treated with ESD patients from July 2019 to March 2024 were retrospectively analyzed.They were followed up for a short period of time(24 h～30 d postoperatively)after ESD,and were divided into the group of occurrence(50 cases)and the group of non-occurrence(336 cases)according to the occurrence or non-occurrence of delayed hemorrhage.To understand the clinical data of the patients,multivariate Logistic regression was used to analyze the risk factors for delayed hemorrhage in patients with EGC after ESD,and plot receiver operating characteristic curve(ROC curve)to analyze the predicted value.Results The proportions of cardia gastric fundus,lesion diameter ≥ 3 cm,submucosa with fibrosis,coarse blood vessels,and having ulcer or scar in the occurrence group were significantly higher than those in the non-occurrence group,the differences were statistically significant(P＜0.05).The results of multivariate Logistic regression analysis(with an introduction level of 0.05)showed that the lesion location was cardia-gastric fundus(OR=1.088,95％CI:1.040～1.138),the diameter of the lesion was ≥3 cm(OR=1.095,95％CI:1.057～1.135),and fibrosis under the mucosa(OR=1.130,95％CI:1.061～1.203),thick blood vessels under the mucosa(OR=1.177,95％CI:1.116～1.241),and the presence of ulcer or scar(OR=1.082,95％CI:1.057～1.108)were the risk factors for the occurrence of delayed hemorrhage in patients with EGC after ESD(P＜0.05).A prediction model was established:Logit(P)=-9.238+Location of lesion as cardia-gastric fundus × 0.084+Diameter of lesion ≥ 3 cm× 0.091+Submucosal with fibrosis × 0.122+Submucosal with thick blood vessels × 0.163+Ulcer or scar×0.079(P＜0.05),the likelihood ratio test yielded x2=131.09,DF=8,P＜0.05,which indicated that the constructed prediction model was valid.Hosmer-Lemeshow goodness-of-fit test showed a good model fit(P＞0.05).The ROC curve showed an area under the curve(AUC)value of 0.929 at a cutoff value of 12.00,with a sensitivity of 88.00％(95％CI:0.757～0.955)and a specificity of 83.04％(95％CI:0.780～0.869).Conclusion Postoperative delayed hemorrhage in patients with EGC treated with ESD is associated with cardia-gastric fundus,lesion diameter ≥3 cm,submucosal fibrosis,thick blood vessels,and the presence of ulcer or scar,and the prediction value of the prediction model constructed accordingly is good.

Objective This study aimed to examine whether body mass index(BMI)was causally associated with blood transfusion reactions.Methods A two-sample Mendelian randomization(MR)analysis using the inverse variance weighted(IVW),MR-Egger regression,weighted median method(WME),weighted model method(WM),simple model method(SM)and simple median method(SM)was performed.Public genome-wide association study(GWAS)analysis was used as the data source,with summary statistical data sets of BMI(n=126 003;GWAS ID:ebi-a-GCST90095042)as the exposure variable and summary statistical data sets of transfusion reactions(n=199 451;GWAS ID:finn-b-ST19)as the outcome variable.The causal association between BMI and transfusion reactions was analyzed.Results 42 single nucleotide polymorphisms associated with transfusion reactions were identified by MR analysis.The IVW showed evidence to support the causal relationship between BMI and transfusion reactions(OR=0.29,95%CI=0.10～0.85).Nonetheless,the effect value β of the MR-Egger regression approach contrasts with that of IVW.The outcomes of the heterogeneity analysis,pleiotropy analysis,and sensitivity analysis indicated that P>0.05.Conclusion The results of MR analysis supported the possibility of a causal relationship between BMI and blood transfusion reactions,that is,the reduction of BMI will increase the risk of blood transfusion reactions.

Objective:To evaluate the application effectiveness of a training program for a nutritional support training base from the perspective of clinical nurses, and to provide a reference for optimizing and improving the training program.Methods:In October 2022, a clinical training program for nutritional support nurses was established based on the core competencies. The clinical training program was carried out from July to September 2023. The trainees who completed the training course were invited to participate in qualitative interviews to evaluate the course. The interview content was recorded, transcribed, and encoded using NVivo 11.0 software. The data were sorted and analyzed using thematic framework analysis.Results:Semi-structured qualitative interviews were conducted with 10 clinical nurses until data saturation was achieved. Three general themes and 10 sub-themes were extracted, including overall evaluation of the training course (rich, comprehensive, and reasonable training content; professional and skilled teaching team), changes brought by the course (improvement of clinical work confidence, strengthening of peer learning, enhancement of the initiative of independent learning, and identification of the factors that hinder the development of specialty), and recommendations for the course (the diversity of teaching forms, reasonable arrangement of practical training departments, increase in operational practice opportunities, establishment of online courses).Conclusions:The students had high overall evaluation on the training course of the nutritional support base. Based on their suggestions, the course can be optimized in the future by diversifying the teaching forms, rationally arranging the practical training departments, strengthening operational practices, and constructing online courses.

Objective:To design a vest-type breast dressing bra and explore its application effect in the external application of traditional Chinese medicine therapy for patients with granulomatous lobular mastitis(GLM).Methods:A randomized controlled study was conducted, utilizing convenience sampling to select female patients with 122 GLM who underwent their first topical medication treatment in the Breast Department of Guangdong Provincial Hospital of Traditional Chinese Medicine between January and May 2023. The patients were divided into a control group and an observation group, with 61 patients in each, using a random number table. Following medication application, patients in the control group used a regular sports bra to secure the medication, while patients in the observation group used a custom-designed vest-style breast medication bra for the same purpose. Three hours after the intervention, comparisons were made between the two groups in terms of the incidence of medication detachment, medication displacement, clothing contamination, patient satisfaction, and safety.Results:Both groups of patients completed the study. The age of the observation group was (32.18 ± 5.50) years old, while the age of the control group was (33.66 ± 5.20) years old. Three hours after the intervention, the incidence of medication detachment, medication displacement, clothing contamination in the observation group were 3.28% (2/61), 6.56% (4/61), and 8.20% (5/61), which were lower than those in the control group with 18.03% (11/61), 26.23% (16/61), and 67.21% (41/61), respectively. The differences were statistically significant ( χ2=6.97, 8.61, 45.23; all P<0.05). The satisfaction level of patients towards the bra in the observation group was (4.43 ± 0.85) points, higher than that of the control group (3.85 ± 1.08) points, with a statistically significant difference ( t=3.30, P<0.05). The incidence rates of skin allergic reactions were 3.28%(2/61) and 4.92%(3/61) in the observation group and the control group, respectively, with no statistically significant difference ( P>0.05). Conclusions:The vest-type breast dressing bra designed in this study can properly secure the medicinal paste, reduce the rate of medication detachment, medication displacement, clothing contamination, and enhance patient satisfaction. It facilitates the external application of traditional Chinese medicine for patients with GLM and is worthy of clinical promotion.