In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective To analyze the characteristics of postoperative hospital-acquired infections and drug sensitivity in lung transplant recipients over the past 5 years in a single center. Methods A total of 724 lung transplant recipients at Wuxi People's Hospital from January 2019 to December 2023 were selected. Based on the principles of hospital-acquired infection diagnosis, a retrospective analysis was conducted on the hospital infection situation and infection sites of lung transplant recipients, and an analysis of the distribution of hospital-acquired infection pathogens and their antimicrobial susceptibility test status was performed. Results Among the 724 lung transplant recipients, 275 cases of hospital-acquired infection occurred, with an infection rate of 38.0%. The case-time infection rate decreased from 54.2% in 2019 to 22.8% in 2023, showing a downward trend year by year (Z=30.98, P<0.001). The main infection site was the lower respiratory tract, accounting for 73.6%. The pathogens were mainly Gram-negative bacteria, with the top four being Acinetobacter baumannii (37.1%), Pseudomonas aeruginosa (17.3%), Klebsiella pneumoniae (13.7%), and Stenotrophomonas maltophilia (13.4%), with imipenem resistance rates of 89%, 53%, 58% and 100%, respectively. Gram-positive bacteria were mainly Staphylococcus aureus (3.6%), with a methicillin resistance rate of 67%. Conclusions Over the past 5 years, the hospital-acquired infections in lung transplant recipients have shown a downward trend, mainly involving lower respiratory tract infections, with the main pathogens being Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, all of which have high resistance rates to imipenem.

[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective To investigate the role of solute carrier family 7 member 11(SLC7A11)in the pathogenesis and progression of clear cell renal cell carcinoma(ccRCC)and its prognostic significance.Methods Mendelian randomization analysis was employed to identify genes causally associated with the risk of ccRCC.The expression patterns and prognostic relevance of SLC7A11 were assessed using RNA sequencing data and clinical information obtained from the UCSC Xcna pan-cancer cohort.Gene set enrichment analysis(GSEA)was conducted using data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset(training set).A prognostic model based on SLC7A11 was then developed using stepwise Cox regression and validated externally in the E-MTAB-1980 cohort(validation set).Results Elevated level of SLC7A11 was associated with an increased risk of ccRCC(HR=1.27,95％CI:1.15-1.40,P＜0.001).SLC7A11 was overexpressed in various tumors and correlated with higher T stage and poorer survival(P＜0.05).GSEA demonstrated that SLC7A11 was enriched in pathways related to proliferation and metastasis,including E2F and epithelial-to-mesenchymal transition signaling pathways.Moreover,the SLC7A11 prognostic model exhibited robust predictive performance in both the training set(1-,3-,and 5-year AUC=0.78,0.73,0.71,respectively)and the external validation set(1-,3-,and 5-year AUC=0.70,0.71,0.72,respectively).Conclusion SLC7A11 can be a potential biomarker and therapeutic target for ccRCC,offering novel perspectives for precision medicine.

Objective To assess the clinical significance of extra-adipose capsule route and intra-adipose capsule route for the resection of benign adrenal tumors with retroperitoneal laparoscopic adrenalectomy(RLA),and to explore the selection of route based on the mayo adhesive probability(MAP)scoring system.Methods Clinical data of 102 patients who received RLA and pathologically diagnosed as benign adrenal tumors during Feb.2015 and Dec.2020 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively reviewed,and MAP scores were assessed with the preoperative tomography images.The gross and MAP score stratified perioperative outcomes between extra-adipose capsule route(classical group,n=56)and intra-adipose capsule route(modified group,n=46)were compared respectively.Results All procedures were successfully completed with no conversion to open surgery and with no need for transfusion.There were no significant differences in operation time[(102.1±26.3)min vs.(110.2±32.1)min,P=0.17]and intraoperative blood loss[(53.5±34.0)mL vs.(61.1±48.4)mL,P=0.35]between the two groups.Subgroup analysis based on MAP score showed that for low risk patients(MAP score 0-2),operative results were comparable between the two groups,but for high risk patients(MAP score 3-5),the operation time was significantly shorter[(114.7±20.7)min vs.(137.2±23.0)min,P＜0.01],and blood loss was significantly less[(52.7±33.1)mL vs.(92.8±49.7)mL,P=0.01]in the classical group than in the modified group.Conclusion RLA could be performed with either surgical routes safely and effectively.MAP scoring system could be an effective tool for preoperative surgical route planning.Compared with the modified route,classical route is more suitable for patients with high MAP score to achieve better operative outcomes.

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

Objective To investigate the impact of type 2 inflammation markers blood eosinophils(EOS)and fractional exhaled nitric oxide(FeNO)on bronchodilator responsiveness(BDR)in patients with chronic obstructive pulmonary disease(COPD).Methods This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October,2019 to October,2023,who all underwent bronchial dilation test(BDT)of the large and small airways.Based on smoking history,blood EOS,and FeNO,these patients were divided group A(blood EOS<300/μL+FeNO<35 ppb+smoking history<20 pack-years),group B(blood EOS<300/μL+FeNO<35 ppb+smoking history≥20 pack-years),group C(blood EOS≥300/μL or FeNO≥35 ppb+smoking history≥20 pack-years),and group D(blood EOS≥300/μL or FeNO≥35 ppb+smoking history<20 pack-years)for analyzing the relationship between clinical indexes and BDR.Results BDR evaluation based on forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and maximum mid-expiratory flow(MMEF)yielded consistent results,all showing a younger mean age,higher FeNO levels,and higher blood EOS counts and percentages in patients positive for BDT(P<0.05).The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D.The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D.In the overall patients,age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF(P<0.05).Conclusion Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients,and their clinical significance needs further investigation.