This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

Objective To investigate the diagnostic value of superb microvascular imaging(SMI)grading,CT angiography(CTA),and serum small and dense low-density lipoprotein cholesterol(sdLDL-C)in elderly hypertension patients with acute cerebral infarction(ACI).Methods A ret-rospective study was conducted on 180 elderly hypertension patients admitted to our hospital from June 2021 to June 2023,and those admitted due to ACI were assigned into ACI group(95 cases)and those without into non-ACI group(85 cases).The SMI grade,CTA,and serum sdLDL-C level were compared between the two groups.ROC curve was plotted to analyze the diagnostic value of SMI grading and CTA combined with serum sdLDL-C for ACI in patients with hyperten-sion.Multivariate logistic regression analysis was employed to analyze the factors affecting the oc-currence of ACI in the patients.Results The ACI group had significantly larger proportion of hy-perlipidemia,and higher DBP,SBP,and HDL-C,and LDL-C than the non-ACI group(P＜0.05).The proportion of SMI grade 2 and grade 3 and serum sdLDL-C level were also greatly higher[35.79％vs 10.59％,43.16％vs 8.24％,(1.62±0.25)mmol/L vs(1.35±0.19)mmol/L,P＜0.01],and the proportion of SMI grade 0 and grade 1 was lower(11.58％vs 51.76％,9.47％vs 29.41％,P＜0.01)in the ACI group than the non-ACI group.ROC curve analysis showed that the AUC value of SMI grade and CTA combined with serum sdLDL-C in diagnosing ACI in patients with hypertension was 0.934(95％CI:0.897-0.972).Multivariate logistic regression analysis in-dicated that SMI grade,CTA,and sdLDL-C were risk factors for ACI in hypertensive patients(P＜0.01).Conclusion Combination of carotid artery plaque SMI grading,CTA,and serum sdLDL-C has high auxiliary diagnostic value for elderly hypertension patients with ACI.

Objective To construct an evidence-based practice model for nurses in preventing deep vein thrombosis(DVT)and provide a scientific and targeted theoretical basis for nurses to carry out evidence-based nursing practice in DVT prevention.Methods Based on the previous evidence-based nursing practice project on DVT prevention after hip and knee arthroplasty,the research team used theoretical analysis and brainstorming to develop a draft of the work model.Expert meetings were organized to validate the content of the draft using the Delphi method,leading to the finalization of the evidence-based practice model for nurses in preventing DVT.Results The Knowledge-to-Action(KTA)framework was selected as the basic framework for constructing the evidence-based nursing practice model for preventing DVT.Theoretical Domain Framework,Theory of Planned Behavior,and Social Cognitive Theory were chosen to explore the influencing factors of nurses'behavior change in preventing DVT through evidence-based practice.The authority coefficient of the participating experts was 0.904,indicating high reliability.The final model consisted of 6 key components:knowledge generation,problem identification,localization and adaptation,knowledge application,sustained knowledge use,and conceptual framework for behavior change through evidence-based practice.Conclusion Based on theoretical analysis and clinical practice,this study developed an evidence-based practice model for nurses in preventing DVT using the expert meeting.The research methodology was scientific,and the content was reliable,providing a theoretical basis for nurses to engage in evidence-based nursing practice for DVT prevention.

Objective To systematically evaluate the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.Methods Databases such as PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,CBM,and VIP were searched for randomized controlled trials(RCTs)related to the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.The search covered all publications up to June 2023.Statistical analysis was performed using RevMan 5.4 software and Stata 15.0.Results Twelve RCTs were included,involving 2 192 patients,of which 1 154 were in the ciprofol group and 1 038 in the propofol group.Compared with the propofol group,the anesthesia induction time(MD=0.28 min,95％CI 0.08-0.47 min,P=0.006)and recovery time(MD=1.16 min,95％CI 0.44-1.87 min,P=0.001)were significantly longer in the ciprofol group,and the inci-dences of injection pain(OR=0.04,95％CI 0.02-0.06,P＜0.001),hypotension(OR=0.64,95％CI 0.49-0.83,P=0.0008),hypoxemia(OR=0.44,95％CI 0.21-0.91,P=0.03),and respirato-ry depression(OR=0.19,95％CI 0.11-0.32,P＜0.001)were significantly lower.There were no sta-tistically significant differences between the two groups in terms of sedation success rate,physician satisfac-tion,the difference in heart rate before and after anesthesia induction,incidence of body movement,brady-cardia,nausea and vomiting,and dizziness.Conclusion The anesthetic effect of cyclopofol and propofol is similar when used for anesthesia outside the operating room.Compared to propofol,ciprofol offers comparable anesthetic effects for sedation and anesthesia outside the operating room,with a lesser impact on respiratory function and more stable hemodynamics.Ciprofol also significantly lowers the incidence of adverse reactions such as injection pain,hypotension,hypoxemia,and respiratory depression.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective:To evaluate the safety and efficacy of ciprofol and propofol for gynecological surgeries with general anesthesia through a meta-analysis.Methods:Electronic databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database were searched for randomized controlled trials comparing the safety and efficacy of ciprofol and propofol in gynecological surgeries with general anesthesia from inception to May 2023. Meta-analysis was performed using Revman 5.4 software.Results:Six randomized controlled trials were included, involving 741 patients, of which 371 received ciprofol and 370 received propofol. Compared with propofol group, the emergence time was significantly prolonged, the difference in mean arterial blood pressure, systolic blood pressure and diastolic blood pressure before and after anesthesia induction was decreased, and the incidence of injection pain, respiratory depression, body movement and hypotension was decreased in ciprofol group ( P<0.05). There were no significant differences between the two groups in terms of time of successful anesthesia induction, difference in BIS values and heart rate before and after anesthesia induction, and incidence of tachycardia, bradycardia and hypertension ( P>0.05). Conclusions:Ciprofol is comparable to propofol in terms of efficacy and has better safety than propofol when used in gynecologic surgeries with general anesthesia.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Objective: To investigate the associations of deficits in prepotent response inhibition with attention deficit and impulsive behavior in children with attention deficit hyperactivity disorder (ADHD), so as to provide insights into response inhibition training in ADHD to relieve clinical symptoms. Methods: From March to December 2022, 57 children with ADHD were selected from the clinical psychology department of a tertiary hospital in Hangzhou City as the ADHD group, and 55 normal children matched by age and gender were selected from a primary school as the control group. Prepotent response inhibition, attention deficit and impulsive behavior were assessed by inhibition conflict task, visual continuous performance test (CPT) and matching familiar figures test (MFFT), respectively. The associations of deficits in prepotent response inhibition with attention deficit and impulsive behavior were analyzed using multiple linear regression model, and the predictive value of deficits in prepotent response inhibition on ADHD was evaluated using receiver operating characteristic (ROC) curve. Results: The children included in the ADHD group had a mean age of (8.77±1.60) years and 44 males (77.19%), and the children included in the control group had a mean age of (9.20±1.77) years and 42 males (76.36%). The error rate of inhibition conflict task, missing report rate of visual CPT and the number of MFFT errors were higher in the ADHD group than in the control group [22.50% (12.50%) vs. 8.75% (7.00%), 24.00% (30.00%) vs. 7.50% (7.00%), 8.67±3.32 vs. 4.47±3.16; all P<0.05]. Multiple linear regression model showed that the error rate of inhibition conflict task was positively associated with the missing report rate of visual CPT (R2=0.135, β=0.091, P<0.001) and the number of MFFT errors (R2=0.092, β=0.009, P<0.001). The area under the ROC curve was 0.891, the sensitivity was 93.00%, the specificity was 80.00%, and the cut-off was 13.13%. Conclusions The deficits in prepotent response inhibition are positively associated with attention deficit and impulsive behavior.