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.

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.

BACKGROUND:Hydrogen,as an antioxidant,can reduce oxidative stress induced by strenuous exercise and achieve the effect of improving fatigue.Several studies have been reported on the potential effects of hydrogen-rich water or hydrogen-rich gas on improving exercise fatigue and athletic performance. OBJECTIVE:To investigate the effects of hydrogen-rich gas inhalation prior to high-intensity exercise on proprioception and muscular endurance performance after exercise fatigue. METHODS:Through a randomized,double-blind,crossover,and repeated measurement experimental design,24 healthy men were randomly divided into group A and group B,with 12 in each group.In the first phase of the crossover experiment,group A inhaled hydrogen-rich gas(hydrogen group)for 20 minutes and group B inhaled placebo gas(air;placebo group)for 20 minutes.Then,cycle ergometers were used to establish the fatigue model.Visual analog fatigue scale,heart rate variability,knee joint proprioception(passive position perception,joint motion perception,and muscle force perception)and isometric knee extension muscle endurance were tested before and after intervention.After a 7-day washout period,two groups exchanged intervention methods and the above tests were performed again in the second phase of the experiment.Differences between the results of groups A and B in the two phases were compared,and finally the results of the two phases were integrated to compare the overall differences between hydrogen intervention and placebo intervention. RESULTS AND CONCLUSION:In the first phase of the crossover experiment,the visual analog fatigue scale score of the hydrogen group after intervention was significantly lower than that of the placebo group(P<0.01).The root mean square of the difference between the adjacent R-R,mean low-frequency output power,mean high-frequency output power,and isometric muscle endurance after intervention in the hydrogen group were significantly higher than those in the placebo group(P<0.05).Passive position perception and joint motion perception after intervention in the hydrogen group were significantly better than those in the placebo group(P<0.05).There was no significant difference in muscle force perception between the two groups(P>0.05),but muscle force perception in the placebo group after intervention was significantly worse than that before intervention(P<0.01).The difference trend of all test results after intervention in the two groups in the first phase of the experiment showed the same results in the second phase of the experiment.The integrated results also showed that the hydrogen group had better test values for the above indicators than the placebo group(P<0.05).Linear regression analysis showed a positive correlation between post-intervention visual analog fatigue scale scores and passive position perception results(r=0.327,P=0.023),i.e.,the higher subjective fatigue level after high-intensity exercise indicated the worse passive position perception results.To conclude,inhaling hydrogen-rich gas before high-intensity exercise can reduce the degree of fatigue after exercise,thereby improving proprioception and muscle endurance performance,which may be a new strategy to reduce the occurrence of injury.And its effectiveness can be achieved repeatedly.

Under the theory of preventive treatment of disease,Traditional Chinese medicine(TCM)has accumulated wealth experience in cancer prevention such as recurrence and metastasis,and cancer treatment,that plays a unique advantage on several stages of cancer.As an important treatment method of traditional Chinese medicine to prevent disease,Gao Fang has the function of correcting deviation and removing disease,and has four functions including regulating,supplementing,preventing and treating,which plays a pivotal role in the prevention and treatment of malignant tumor.Gao Fang is an effective means to treat tumor.Therefore,this article intends to discuss the effect of Gao Fang on tumor under the perspective of preventive treatment of the disease.

Spontaneous intracerebral hemorrhage (ICH) is a neurological disease with high mortality and morbidity rates, and early neurological deterioration (END) is one of the key factors in evaluating outcome of patients. Early identification and effective intervention of END in patients with ICH is of great significance for their treatment and prognosis. This article reviews the predictive factors for END in patients with ICH from the perspectives of blood markers, hematoma characteristics, blood pressure variability, and imaging signs.

Objective:To investigate the correlation between overweight or obesity defined by body mass index (BMI) and functional outcome in patients with hypertensive intracerebral hemorrhage (HICH).Methods:Patients with HICH admitted to the Department of Neurosurgery, the First People's Hospital of Lianyungang from October 2020 to February 2022 were included retrospectively. According to BMI, they were divided into underweight or normal group (<24 kg/m 2) and overweight or obese group (≥24 kg/m 2). At one year after onset, the functional outcome were evaluated using the modified Rankin Scale. 0-2 was defined as good outcome, while >2 were defined as poor outcome. Cox proportional hazards regression model was used to analyze the correlation between BMI and the outcome of patients. Results:A total of 394 patients with HICH were enrolled, including 263 males (66.8%), aged 60.2±12.0 years. At one year after onset, 145 patients (36.8%) had poor outcome and 54 (13.7%) died. Compared with the underweight or normal group, the overweight or obese group had a higher proportion of previous type 2 diabetes history, as well as higher baseline diastolic blood pressure, low-density lipoprotein cholesterol and liver enzyme levels, better early outcome after discharge, and lower mortality at 1 year (all P<0.05). Multivariate analysis showed that the overweight or obese group had significantly better functional outcome compared to the underweight or normal group (hazard ratio 0.598, 95% confidence interval 0.419-0.854; P=0.005), but there was no statistically significant difference in all-cause mortality risk (hazard ratio 1.201, 95% confidence interval, 0.462-3.126; P=0.707). Conclusion:The overweight or obese patients with HICH have significantly better functional outcome at one year after onset, indicating that the obesity paradox also exists in patients with HICH.

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 compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks.Methods:The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children′s Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria.Results:The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.02, P=0.984). Conclusion:The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.