Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Objective By simulating the etiology of abnormal uterine bleeding-ovulatory dysfunction(AUB-O)and establishing a rat model of abnormal uterine bleeding(AUB),this study aims to provide an experimental platform for investigating pathological mechanisms and developing therapeutic drugs for AUB.Methods After acclimation,24 adult(10-week-old)female SD rats were randomly divided into a normal control group(6 rats)and a model group(18 rats).The normal control group was housed in a barrier environment,while the model group underwent bilateral ovariectomy via dorsal approach in the same environment and rested for one week before starting to receive modeling drugs.In the model group,from Days 1 to 3 of modeling,each rat received a daily subcutaneous injection of 0.5 mg estradiol into the dorsal region.From Days 4 to 7,a daily subcutaneous injection of 5.0 mg progesterone was administered.On Day 6,rats received bilateral injections of 0.5 mL soybean oil per uterine cavity(total 1.0 mL)via the same dorsal surgical incision.On Day 8,mifepristone(10 mg/kg)was administered via oral gavage.The estrous cycle stage and its dynamic changes were continuously monitored during modeling.Uterine bleeding was recorded during the 48-hour observation period post-modeling.Serum and uterine tissue samples were collected from the model group at 0,12,24,36,and 48 h after mifepristone administration,while the normal control group was sampled at 36 h.The samples were subjected to HE staining,serum sex hormone ELISA,immunohistochemistry,TUNEL apoptosis staining,Western blotting,transcriptome sequencing,and bioinformatics analysis for comprehensive evaluation of the AUB rat model.Results The AUB rats exhibited uterine bleeding,endometrial detachment and injury,incomplete uterine restoration,inflammatory cell infiltration in the endometrium,enhanced tissue apoptosis,and structural damage of the stroma,glands,and vasculature.Compared with the normal control group,the levels of serum follicle-stimulating hormone(FSH),estradiol,and luteinizing hormone(LH)were significantly increased in the AUB rats(P＜0.05).The vascular density of the endometrium was significantly reduced(P＜0.05).The expression of vascular endothelial growth factor(VEGF)was qualitatively observed to be markedly enhanced at the site of endometrial detachment but significantly decreased around the stromal blood vessels(P＜0.01).Matrix metalloproteinase-9(MMP-9)expression was qualitatively observed to be strongly upregulated at the site of endometrial injury but significantly reduced in the non-detached stroma and glands(P＜0.01).Endometrial stromal cell apoptosis was significantly enhanced(P＜0.01).The expression levels of fibroblast growth factor 2(FGF2)and endothelin-1(ET-1)in uterine tissues were significantly decreased(P＜0.05).After comparing the transcriptome sequencing results of uterine tissues between AUB and normal rats,a total of 4 723 differentially expressed genes were identified,including 2 191 up-regulated genes and 2 532 down-regulated genes.KEGG enrichment analysis revealed that these differentially expressed genes were significantly enriched in pathways related to inflammation,immune apoptosis,cell signal transduction,proliferation and differentiation,and muscle contraction,among others.Conclusion An AUB rat model can be successfully established using a sequential administration protocol of estrogen,progesterone,and mifepristone to simulate the etiology of AUB-O.In this model,endometrial injury is associated with inflammation and apoptosis,with pathological manifestations influenced by abnormal vasoconstriction and impaired endometrial regeneration.This rat model closely recapitulates pathological characteristics of non-structural AUB observed in clinical practice,making it a validated experimental platform for exploring the pathological mechanisms and therapeutic interventions of non-structural AUB.

Objective:To evaluate the diagnostic performance of artificial intelligence-assisted diagnostic systems in cervical cytopathological examination.Methods:Cervical cytology slide data were retrospectively collected from four hospitals for the external validation of the developed artificial intelligence-assisted diagnostic system. Subsequently, prospective data collection was conducted for human-machine assisted studies.Results:In the retrospective study, a total of 3 162 valid samples were collected as external validation data. The system showed an area under the curve (AUC) of 0.890 (95% CI: 0.878-0.902), accuracy of 0.885 (95% CI: 0.873-0.896), sensitivity of 0.928 (95% CI: 0.914-0.941), and specificity of 0.852 (95% CI: 0.834-0.867). In the prospective study, 212 valid samples were collected, and five junior cytologists participated in the human-machine assisted study. Without artificial intelligence assistance, the average AUC for the five cytologists was 0.686 (95% CI: 0.650-0.722), the accuracy was 0.699 (95% CI: 0.671-0.727), the sensitivity was 0.653 (95% CI: 0.599-0.703), the specificity was 0.719 (95% CI: 0.685-0.750), the Fleiss κ value was 0.510, and the reading time was 223 seconds. With artificial intelligence assistance, the AUC, accuracy, sensitivity, and specificity increased by 0.166, 0.143, 0.225, and 0.107, respectively. Additionally, Fleiss κ was 0.730 and the reading time decreased by 188 seconds. All differences were statistically significant (all P<0.001). Conclusions:Artificial intelligence-assisted diagnosis system shows excellent performance and good generalizability, significantly improving the diagnostic accuracy, consistency, and efficiency of junior cytologists. It can be an effective auxiliary tool for junior cytologists in clinical practice.

Objective:To evaluate the diagnostic performance of artificial intelligence-assisted diagnostic systems in cervical cytopathological examination.Methods:Cervical cytology slide data were retrospectively collected from four hospitals for the external validation of the developed artificial intelligence-assisted diagnostic system. Subsequently, prospective data collection was conducted for human-machine assisted studies.Results:In the retrospective study, a total of 3 162 valid samples were collected as external validation data. The system showed an area under the curve (AUC) of 0.890 (95% CI: 0.878-0.902), accuracy of 0.885 (95% CI: 0.873-0.896), sensitivity of 0.928 (95% CI: 0.914-0.941), and specificity of 0.852 (95% CI: 0.834-0.867). In the prospective study, 212 valid samples were collected, and five junior cytologists participated in the human-machine assisted study. Without artificial intelligence assistance, the average AUC for the five cytologists was 0.686 (95% CI: 0.650-0.722), the accuracy was 0.699 (95% CI: 0.671-0.727), the sensitivity was 0.653 (95% CI: 0.599-0.703), the specificity was 0.719 (95% CI: 0.685-0.750), the Fleiss κ value was 0.510, and the reading time was 223 seconds. With artificial intelligence assistance, the AUC, accuracy, sensitivity, and specificity increased by 0.166, 0.143, 0.225, and 0.107, respectively. Additionally, Fleiss κ was 0.730 and the reading time decreased by 188 seconds. All differences were statistically significant (all P<0.001). Conclusions:Artificial intelligence-assisted diagnosis system shows excellent performance and good generalizability, significantly improving the diagnostic accuracy, consistency, and efficiency of junior cytologists. It can be an effective auxiliary tool for junior cytologists in clinical practice.

Objective By simulating the etiology of abnormal uterine bleeding-ovulatory dysfunction(AUB-O)and establishing a rat model of abnormal uterine bleeding(AUB),this study aims to provide an experimental platform for investigating pathological mechanisms and developing therapeutic drugs for AUB.Methods After acclimation,24 adult(10-week-old)female SD rats were randomly divided into a normal control group(6 rats)and a model group(18 rats).The normal control group was housed in a barrier environment,while the model group underwent bilateral ovariectomy via dorsal approach in the same environment and rested for one week before starting to receive modeling drugs.In the model group,from Days 1 to 3 of modeling,each rat received a daily subcutaneous injection of 0.5 mg estradiol into the dorsal region.From Days 4 to 7,a daily subcutaneous injection of 5.0 mg progesterone was administered.On Day 6,rats received bilateral injections of 0.5 mL soybean oil per uterine cavity(total 1.0 mL)via the same dorsal surgical incision.On Day 8,mifepristone(10 mg/kg)was administered via oral gavage.The estrous cycle stage and its dynamic changes were continuously monitored during modeling.Uterine bleeding was recorded during the 48-hour observation period post-modeling.Serum and uterine tissue samples were collected from the model group at 0,12,24,36,and 48 h after mifepristone administration,while the normal control group was sampled at 36 h.The samples were subjected to HE staining,serum sex hormone ELISA,immunohistochemistry,TUNEL apoptosis staining,Western blotting,transcriptome sequencing,and bioinformatics analysis for comprehensive evaluation of the AUB rat model.Results The AUB rats exhibited uterine bleeding,endometrial detachment and injury,incomplete uterine restoration,inflammatory cell infiltration in the endometrium,enhanced tissue apoptosis,and structural damage of the stroma,glands,and vasculature.Compared with the normal control group,the levels of serum follicle-stimulating hormone(FSH),estradiol,and luteinizing hormone(LH)were significantly increased in the AUB rats(P＜0.05).The vascular density of the endometrium was significantly reduced(P＜0.05).The expression of vascular endothelial growth factor(VEGF)was qualitatively observed to be markedly enhanced at the site of endometrial detachment but significantly decreased around the stromal blood vessels(P＜0.01).Matrix metalloproteinase-9(MMP-9)expression was qualitatively observed to be strongly upregulated at the site of endometrial injury but significantly reduced in the non-detached stroma and glands(P＜0.01).Endometrial stromal cell apoptosis was significantly enhanced(P＜0.01).The expression levels of fibroblast growth factor 2(FGF2)and endothelin-1(ET-1)in uterine tissues were significantly decreased(P＜0.05).After comparing the transcriptome sequencing results of uterine tissues between AUB and normal rats,a total of 4 723 differentially expressed genes were identified,including 2 191 up-regulated genes and 2 532 down-regulated genes.KEGG enrichment analysis revealed that these differentially expressed genes were significantly enriched in pathways related to inflammation,immune apoptosis,cell signal transduction,proliferation and differentiation,and muscle contraction,among others.Conclusion An AUB rat model can be successfully established using a sequential administration protocol of estrogen,progesterone,and mifepristone to simulate the etiology of AUB-O.In this model,endometrial injury is associated with inflammation and apoptosis,with pathological manifestations influenced by abnormal vasoconstriction and impaired endometrial regeneration.This rat model closely recapitulates pathological characteristics of non-structural AUB observed in clinical practice,making it a validated experimental platform for exploring the pathological mechanisms and therapeutic interventions of non-structural AUB.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.