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.

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::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Objective:To observe the effects of warming needle therapy combined with the modified Hua Tan Tong Luo Tang(decoction for dissipating phlegm and unblocking collaterals)on post-stroke cognitive impairment due to obstruction of wind-phlegm. Methods:A total of 78 patients who met the inclusion criteria were randomly assigned to an observation group and a control group,with 39 patients in each group.Both groups received conventional treatment.The control group was additionally treated with the modified Hua Tan Tong Luo Tang,while the observation group received warming needle therapy in addition to the treatment given to the control group.Scores on the mini-mental state examination(MMSE),Montreal cognitive assessment(MoCA),and activities of daily living(ADL)were assessed before and after treatment.Adverse reactions and clinical efficacy were analyzed and compared between the two groups after treatment. Results:The total effective rate was 82.1%in the observation group and 61.5%in the control group,showing statistical significance between the two groups(P<0.05).After treatment,the MMSE,MoCA,and ADL scores of both groups were significantly higher than those before treatment within each group(P<0.05).Notably,the scores in the observation group were higher than those in the control group(P<0.05).No adverse reactions occurred in either group during the treatment period. Conclusion:Based on the conventional treatment,compared to modified Hua Tan Tong Luo Tang alone,warming needle therapy combined with the modified Hua Tan Tong Luo Tang showed superior clinical efficacy in treating post-stroke cognitive impairment due to obstruction of wind-phlegm,and this combined therapy also showed high safety.

Objective:To investigate the expression of miRNA-144 in the peripheral blood of patients with type 2 diabetes foot ulcer (DFU) and its correlation with the pathogenesis of the disease.Methods:A total of 106 patients with DFU admitted to the General Hospital of the Western Theater Command of the Chinese People′s Liberation Army from March 2020 to June 2022 were retrospectively selected as the observation group, and 106 patients with type 2 diabetes mellitus (T2DM) who did not have DFU admitted to our hospital during the same period were selected as the control group. According to the median expression level of miRNA-144 in peripheral blood of DFU patients as the segmentation point, 106 patients in the observation group were divided into low expression group and high expression group. We compared the clinical data of the observation group and the control group, and analyzed the relationship between different levels of miRNA-144 expression and clinical characteristics of DFU patients; A multivariate analysis was conducted on the factors related to the occurrence and development of the disease course in DFU patients, and a column chart model was constructed for model validation.Results:The course of diabetes, fasting blood glucose (FPG), erythrocyte sedimentation rate (ESR), glycosylated hemoglobin (HbA 1c), white blood cell count (WBC), C-reactive protein (CRP), corticotropin releasing hormone (CRH), interleukin-6 (IL-6), adrenaline (E), norepinephrine (NE), cortisol (Cor) and miRNA-144 expression levels in the observation group were significantly higher than those in the control group, while transcutaneous partial pressure of oxygen (TcPO 2), ankle brachial index (ABI), triglyceride (TG) and hemoglobin (Hb) were significantly lower than those in the control group, the difference was statistically significant (all P<0.05). There were statistically significant differences in foot ulcer healing rate, Wagner grading, and ulcer course between the high expression group of miRNA-144 and the low expression group of DFU patients after 8 weeks (all P<0.05). Multivariate regression analysis showed that the duration of diabetes>5 years, HbA 1c>8.5%, TcPO 2<60 mmHg, CRP>10 mg/L, Cor>190 μg/L, and miRNA-144 expression level>35 were independent risk factors for the occurrence of DFU in T2DM patients. The total score of 315 points after constructing the nomogram prediction model for the above factors, and the corresponding probability of occurrence and development of DFU was 72.56%. Conclusions:The expression level of miRNA-144 in the peripheral blood of DFU patients is significantly related to the occurrence and development of the disease course, and the course of diabetes and the changes of HbA 1c, TcPO 2, CRP, Cor levels are independent risk factors for the occurrence and development of DFU, which should be focused on clinically.

Objective:To evaluate the association between N-acylsphingosine amide hydrolase 1 (ASAH1) and pyroptosis during acute lung injury (ALI) in septic mice.Methods:Forty SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-23 g, were divided into 4 groups ( n=10 each) by a random number table method: sham operation group (Sham group), ALI group, HCFU solvent+ ALI group (HA group) and ASAH1 inhibitor HCFU+ ALI group (AA group). The abdominal cavity was only opened in Sham group, and cecal ligation puncture was performed in ALI, HA and AA groups. HCFU solvent 0.2 ml was intraperitoneally injected at 2 h before operation in HA group, and HCFU 10 mg/kg was intraperitoneally injected at 2 h before operation in AA group. The mice were sacrificed at 24 h under deep anesthesia, the eyeballs were removed to collect the blood, the bronchoalveolar lavage fluid (BALF) was collected, and lung tissues and blood samples were collected for microscopic examination of the pathological changes (using HE staining) which were scored and for determination of concentrations of protein in BALF (by BCA method), concentrations of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in BALF (by enzyme-linked immunosorbent assay), and expression of NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) in lung tissues (by Western blot), gasdermin D protein (GSDMD), ASAH1 and cysteine protease-1 (caspase-1) (by Western blot). The wet/dry lung weight (W/D) ratio was calculated. Results:Compared with Sham group, the lung injury score, W/D ratio and concentrations of protein in BALF, IL-1β, IL-6 and TNF-α in serum were significantly increased, and the expression of NLRP3, GSDMD and caspase-1 in lung tissues was up-regulated in ALI, HA and AA groups, and the expression of ASAH1 was significantly up-regulated in ALI and HA groups ( P<0.05). Compared with ALI and HA groups, the lung injury score, W/D ratio, and concentrations of protein in BALF, IL-1β, IL-6 and TNF-α in serum were significantly increased, the expression of NLRP3, GSDMD and caspase-1 in lung tissues was up-regulated, and the expression of ASAH1 was down-regulated in AA group ( P<0.05 or 0.01). Conclusions:ASAH1 is involved in the endogenous protective mechanism underlying ALI in septic mice, which may be related to the inhibition of cell pyroptosis.

The tumor microenvironment,particularly the hypoxic property and glutathione(GSH)overexpression,substantially inhibits the efficacy of cancer therapy.In this article,we present the design of a magnetic nanoplatform(MNPT)comprised of a photosensitizer(Ce6)and an iron oxide(Fe3O4)/manganese oxide(MnO2)composite nanozyme.Reactive oxygen species(ROS),such as singlet oxygen(1O2)radicals produced by light irradiation and hydroxyl radicals(·OH)produced by catalysis,are therapeutic species.These therapeutic substances stimulate cell apoptosis by increasing oxidative stress.This apoptosis then triggers the immunological response,which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer.Furthermore,MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

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.

Traditional drugs for the treatment of abdominal tumors often do not have the ability to target tumors and destroy normal cells while killing tumor cells. Therefore, new therapies are urgently needed to accurately target and kill tumor cells. As a drug carrier, extracellular vesicles have the advantages of naturalness, biotaxis, and low side effects, so they have attracted much attention in the research on the treatment of abdominal tumors. In this paper, the research progress in mechanism of action of extracellular vesicle drug delivery system in the treatment of abdominal tumors such as gastric, liver, pancreatic, bile duct, colorectal, and ovarian cancers with an extracellular vesicle drug delivery system was reviewed, including inhibiting the growth of abdominal tumor cells, reversing the drug resistance of the tumor stem cells, inhibiting the exocytosis of chemotherapeutic drugs from the tumor cells, and remodeling the tumor immune microenvironment.