1.Association between liver fibrosis staging and colorectal space-occupying lesions in metabolic associated fatty liver disease
Jing QI ; Ziheng ZHAO ; Shanshan GAO ; Kun LI
Journal of Clinical Hepatology 2026;42(6):1301-1309
ObjectiveTo investigate whether there exists an independent association beyond shared risk factors between colorectal space-occupying lesions and metabolic associated fatty liver disease (MAFLD), and to provide new ideas for early identification of colorectal space-occupying lesions in the MAFLD population. MethodsA retrospective analysis was performed for 12 252 patients who were hospitalized in The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) and underwent both colonoscopy and abdominal imaging (abdominal ultrasound, magnetic resonance imaging, or computed tomography) from September 1, 2018 to August 31, 2023. According to colonoscopy findings, the patients were divided into colorectal space-occupying lesion group with 6 545 patients and non-colorectal space-occupying lesion group with 5 707 patients. Baseline data were compared between the two groups. The univariate and multivariate Logistic regression analyses were used to identify influencing factors for colorectal space-occupying lesions, and further analysis was performed to investigate the association of MAFLD and liver fibrosis (assessed by fibrosis-4 [FIB-4], nonalcoholic fatty liver disease fibrosis score [NFS], and aspartate aminotransferase-to-platelet ratio index) with colorectal space-occupying lesions. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThe univariate analysis showed that compared with the non-colorectal space-occupying lesion group, the colorectal space-occupying lesion group had significantly higher age (Z=-95.628, P<0.001), proportion of male patients (χ2=406.910, P<0.001), body weight (Z=-24.928, P<0.001), body mass index (BMI) (Z=-21.367, P<0.001), diastolic blood pressure (Z=-15.527, P<0.001), systolic blood pressure (Z=-16.965, P<0.001), proportion of patients with history of coronary heart disease (χ2=28.112, P<0.001)/hypertension (χ2=152.993, P<0.001)/diabetes (χ2=52.175, P<0.001)/cerebral infarction (χ2=14.097, P<0.001), white blood cell count (WBC) (Z=-12.801, P<0.001), hemoglobin (HGB) (Z=-19.258, P<0.001), aspartate aminotransferase (Z=-6.673, P=0.001), alanine aminotransferase (Z=-10.375, P<0.001), alkaline phosphatase (Z=-10.496, P<0.001), gamma-glutamyl transpeptidase (GGT) (Z=-18.893, P<0.001), blood urea nitrogen (Z=-13.291, P<0.001), creatinine (Z=-16.798, P<0.001), uric acid (Z=-16.822, P<0.001), triglyceride (Z=-10.186, P<0.001), and fasting blood glucose (Z=-15.761, P<0.001). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=1.052, 95% confidence interval [CI]: 1.045 — 1.057, P<0.001), sex (OR=0.523, 95%CI: 0.466 — 0.587, P<0.001), BMI (OR=1.031, 95%CI: 1.018 — 1.046, P<0.001), history of hypertension (OR=1.140, 95%CI: 1.019 — 1.276, P=0.022), WBC (OR=1.057, 95%CI: 1.028 — 1.087, P<0.001), GGT (OR=1.001, 95%CI: 1.000 — 1.002, P=0.021), Alb (OR=0.982, 95%CI: 0.969 — 0.995, P=0.008), and HGB (OR=1.004, 95%CI: 1.001 — 1.008, P=0.019) were independent influencing factors for colorectal space-occupying lesions. In the MAFLD population, after adjustment for age, sex, BMI, history of hypertension, WBC, HGB, GGT, and Alb, intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 and NFS was still an influencing factor for colorectal space-occupying lesions (FIB-4: OR=1.457, 95%CI: 1.176 — 1.810, P<0.05; NFS: OR=1.499, 95%CI: 1.244 — 1.809, P<0.05). Liver fibrosis degree based on FIB-4 was not significantly associated with the pathological type, location, size, or number of colorectal space-occupying lesions (all P>0.05). While intermediate-to-high risk of advanced liver fibrosis based on NFS was not associated with pathological type, location, or size, it might be associated with the number of lesions (χ2=9.770, P<0.05). ConclusionAge, sex, BMI, history of hypertension, WBC, HGB, GGT, and Alb are independent influencing factors for colorectal space-occupying lesions. Intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 or NFS is independently associated with colorectal space-occupying lesions, and liver fibrosis assessed by NFS might be associated with the increase in the number of lesions.
2.Jianpi Yiqi Prescription Inhibits Proliferation and Invasion of Hepatic Carcinoma Cells by Targeting PTPN1
Shanshan SUN ; Jing HONG ; Shufan SONG ; Zongxi SUN ; Chao WANG ; Shaoyuan ZHUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):80-88
ObjectiveTo investigate the key targets of Jianpi Yiqi prescription (JYP) in the treatment of hepatocellular carcinoma (HCC) based on network pharmacology and explore the effect of JYP on the invasion and proliferation of hepatocellular carcinoma cells via protein tyrosine phosphatase, non-receptor type 1 (PTPN1) by bioinformatics analysis and CRISPR/Cas9. MethodsThe potential targets of JYP in the treatment of HCC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissTargetPrediction, GeneCards, NCBI, and CTD. Additionally, the active components of JYP that could interact with PTPN1 were screened out, and then molecular docking between the targets and active components was performed in Autodock 4.0. UALCAN, HPA, and LinkedOmics were used to analyze the expression of PTPN1 in the HCC tissue, and the relationship of PTPN1 expression with the overall survival (OS) of HCC patients was discussed. CRISPR/Cas9 was used to knock down the expression of PTPN1 in HepG2 and SK-hep-1 cells, and the knockdown effect was examined by sequencing, Real-time PCR, and Western blot. HepG2 cells were classified into blank control, low-, medium-, and high-dose JYP (5.25, 10.5, 21 g·kg-1), and PTPN1 knockout groups. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of PTPN1 in HepG2 cells of each group. The effects of JYP and PTPN1 knockdown on the proliferation, invasion, and apoptosis of HepG2 cells were detected by Cell Counting Kit-8 (CCK-8), Transwell, and Annexin V-FITC/PI methods, respectively. ResultsJYP had the most active components targeting PTPN1, and 31 of the active components had the binding energy less than -5.0 kcal·mol-1 in molecular docking. The mRNA and protein levels of PTPN1 in the HCC tissue were higher than those in the normal tissue (P<0.01). Compared with that in the normal tissue, the mRNA level of PTPN1 in the HCC tissue was up-regulated at the pathological stages Ⅰ-Ⅲ and grades G1-G3 (P<0.01), and it was not significantly up-regulated at the stage Ⅳ or grade G4. The mRNA level of PTPN1 in the TP53-mutated HCC tissue was higher than that in the TP53-unmutated HCC tissue (P<0.01). The high mRNA level of PTPN1 was associated with the OS reduction (P<0.01). After treatment with the JYP-containing serum or knockdown of PTPN1, HepG2 cells demonstrated decreased proliferation and invasion and increased apoptosis (P<0.01). ConclusionPTPN1 may be one of the core targets of JYP in the treatment of HCC. It is highly expressed in the HCC tissue and cells, which is associated with the poor prognosis of patients. The expression level of PTPN1 is significantly up-regulated in the HCC tissue of the patients with TP53 mutation. However, TP53 mutation or deletion does not affect the expression of PTPN1 in HCC cells. JYP can significantly down-regulate the expression of PTPN1 to inhibit the proliferation and invasion and promote the apoptosis of HCC cells.
3.Epidemiological characteristics of human metapulmonaryvirus in hospitalized children with respiratory infections in Hebei Province
Hongfei DU ; Mengchuan ZHAO ; Xiaoshuang ZHANG ; Shanshan ZHOU ; Jing HUANG ; Xinguang LIU
Chinese Journal of Microbiology and Immunology 2025;45(2):93-98
Objective:To explore the epidemiological characteristics of human metapneumovirus (hMPV) in children hospitalized for acute respiratory tract infections in Hebei, and provide a theoretical basis for the clinical diagnosis and treatment of acute respiratory tract infections in children in Hebei.Methods:Retrospectively, 41 499 children hospitalized in Hebei Children′s Hospital for acute respiratory tract infections from January 2017 to December 2021 were included to analyze the morbidity of children of different genders and ages, and in different seasons, and to statistically analyze the epidemiological data such as the positive detection rate of hMPV, the detection rates of mixed infections with other pathogens, and the clinical diagnosis.Results:The overall positive detection rate of hMPV in hospitalized children with acute respiratory infections from 2017 to 2021 was 5.94%(2 464/41 499), with the highest positive detection rate of hMPV in the age group of 3 to 4 years (7.66%, 520/6 789) and the lowest in the age group of ≥5 years (2.89%, 180/6 225), with a statistically significant difference ( P<0.001); the positive detection rates in male and female children were respectively 5.97%(1 496/25 056) and 5.94%(968/16 443), and the difference was not statistically significant ( P>0.05). The positive detection rates of hMPV from 2017 to 2021 were 5.10%(408/7 998), 9.64%(915/9 491), 4.27%(426/9 969), 5.91%(368/6 226), and 4.44%(347/7 815), respectively, and the positive detection rate of hMPV in 2018 was significantly higher than that in the other years ( P<0.001). hMPV circulated throughout the year, with obvious seasonality, with the highest positive detection rate in spring and winter.The mixed detection rate of hMPV with other respiratory pathogens was 42.74% (1 053/2 464), of which mixed detection with rhinovirus was the most common, with a mixed detection rate of 48.24%(508/1 053).Clinical diagnosis of hPMV-positive children was mostly bronchopneumonia. Conclusions:hMPV is one of the important pathogens in hospitalized children with acute respiratory infections in Hebei, which is common in children under 5 years of age and can occur throughout the year, with peak epidemics in winter and spring. Mixed infections of hMPV with other respiratory pathogens are common and can increase the risk of worsening clinical symptoms in children.
4.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
5.Analysis on psychosocial factors for early puberty in children
Ying LI ; Shanshan WANG ; Yue YU ; Min ZUO ; Jing LI ; Xuebing LING ; Fangbiao TAO ; Deyun LIU ; Ying SUN
Chinese Journal of Epidemiology 2025;46(3):469-475
Objective:To investigate the effects of psychosocial factors on early puberty and its sex specific differences.Methods:Bengbu Yuhui Longitudinal Study of Children Development Cohort, consisting of 1 162 students in grades 1-3 (524 girls) and their parents, was established in April 2021 in Bengbu, Anhui Province. The parents were surveyed by questionnaire to collect the information about their children's 56 items of psychosocial factor exposures, including 5 dimensions: major life events, early life adversity, interpersonal/relational conflict, family economic status and daily life troubles. Pubertal growth and physical examinations were conducted by trained professionals at baseline, the 1 st (May 2022), 2 nd (October 2022), 3 rd (May 2023), and 4 th (October 2023) follow-up surveys. In this study, the pubertal development status data were from the 4 th follow-up examination. Fianally, the valid data on pubertal development of 1 105 children were obtained, including the data from 510 girls (46.15%). Multinomial logistic regression model was used to analyze the association between psychosocial factors and early puberty, and the final predictors of early puberty were explored by using four models [least absolute shrinkage and selection operator (LASSO), multiple logistic regression, ridge regression, and Bayesian]. Results:The detection rates of early puberty in boys and girls were 13.60% and 16.30%, respectively. The median of intra-group absolute correlation of psychosocial factor exposure (0.042-0.066) was generally higher than that of inter-group among girls (0.031-0.059), while no similar diference was found among boys. LASSO model showed that moving house, being raised by someone other than parents, sexual abuse, peer conflict, high monthly household income, and high exposure to electronics on school days were predictors of early puberty in girls, while moving house and high monthly household income were the predictors of early puberty in girls in all four models (LASSO, multiple logistic regression, ridge regression, and Bayesian). Among boys, only a transient loss from family was a predictor of early puberty.Conclusion:Early puberty in children can be predicted by psychosocial factors, and there are gender-specific differences.
6.Application of tabletop deduction and simulation drills in the training of infection prevention and control for acute respiratory infectious diseases on hospital ships
Anhua QIAO ; Zhengmei XU ; Li GUI ; Fei PENG ; Jing CHEN ; Zhihao YUE ; Yi CHEN ; Shanshan YANG
Journal of Navy Medicine 2025;46(7):662-666
Objective To carry out a joint simulation exercise of tabletop deduction for the staff performing overseas medical services on hospital ships,so as to improve the infection prevention and control.Methods Sixty mission members were selected by convenience sampling to carry out joint simulation drills for tabletop deduction.The effects of the drills were assessed by the survey on the satisfaction and participation of mission members,before-and-after control study,and mission execution.Results Overseas medical service tasks were successfully completed through the desktop-propelled joint simulation drills.The total score of response for infectious emergencies,prevention score,preparedness score,and rescue score after training were higher than those before training(P<0.05).There were high degrees of participation and satisfaction in the drills(≥4.5 points).Conclusion The tabletop deduction and simulation exercise achieve good results in the infection prevention and control of hospital ships.The scheme of tabletop deduction combined with simulation drills will be optimized to continuously improve the infection prevention and control of hospital ships.
7.Effects of behavior change intervention based on multiple-theory model in patients with dyslipidemic ischemic stroke
Jing WANG ; Yitong CHEN ; Meiru WU ; Meixia YANG ; Shanshan PEI ; Yongmei DENG
Journal of Clinical Medicine in Practice 2025;29(16):46-50
Objective To explore the effects of behavior change intervention based on the multi-ple-theory model on patients with dyslipidemic ischemic stroke.Methods A total of 93 patients with dyslipidemic ischemic stroke who were hospitalized in the vascular neurology ward of Beijing Tiantan Hospital,Capital Medical University from January to August 2024 were selected as the study subjects using the convenience sampling method.They were randomly divided into control group(n=49)and intervention group(n=44)using the envelope-drawing method.Patients in the control group re-ceived routine stroke health education,while those in the intervention group underwent a 3-month be-havior change program guided by the multiple-theory model.The levels of healthy behaviors,body mass index(BMI),total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL-C),and low-density lipoprotein(LDL-C)were compared between the two groups.Results There were no statistically significant differences in general information and disease-related data between the two groups(P>0.05).At 1-,3-,and 6-month after the intervention,the level of healthy behaviors in the intervention group was higher than that in the control group,with statistically significant differ-ences(P<0.05).There was a statistically significant difference in BMI between the two groups at 6 months after the intervention(P<0.05).The TC levels in the intervention group at 3 and 6 months after the intervention were lower than those in the control group,with statistically significant differences(P<0.05).The HDL-C level in the intervention group at 6 months after the intervention was high-er than that in the control group,with a statistically significant difference(P<0.05).The LDL-C levels in the intervention group at 1-,3-,and 6-month after the intervention were lower than those in the control group,with statistically significant differences(P<0.05).There were no statistically significant differences in TG levels between the intervention group and the control group at different time points after the intervention(P>0.05).Conclusion The behavior change intervention pro-gram based on the multiple-theory model can effectively improve and maintain healthy behaviors and improve blood lipid levels in patients with dyslipidemic ischemic stroke.
8.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
9.Analysis on psychosocial factors for early puberty in children
Ying LI ; Shanshan WANG ; Yue YU ; Min ZUO ; Jing LI ; Xuebing LING ; Fangbiao TAO ; Deyun LIU ; Ying SUN
Chinese Journal of Epidemiology 2025;46(3):469-475
Objective:To investigate the effects of psychosocial factors on early puberty and its sex specific differences.Methods:Bengbu Yuhui Longitudinal Study of Children Development Cohort, consisting of 1 162 students in grades 1-3 (524 girls) and their parents, was established in April 2021 in Bengbu, Anhui Province. The parents were surveyed by questionnaire to collect the information about their children's 56 items of psychosocial factor exposures, including 5 dimensions: major life events, early life adversity, interpersonal/relational conflict, family economic status and daily life troubles. Pubertal growth and physical examinations were conducted by trained professionals at baseline, the 1 st (May 2022), 2 nd (October 2022), 3 rd (May 2023), and 4 th (October 2023) follow-up surveys. In this study, the pubertal development status data were from the 4 th follow-up examination. Fianally, the valid data on pubertal development of 1 105 children were obtained, including the data from 510 girls (46.15%). Multinomial logistic regression model was used to analyze the association between psychosocial factors and early puberty, and the final predictors of early puberty were explored by using four models [least absolute shrinkage and selection operator (LASSO), multiple logistic regression, ridge regression, and Bayesian]. Results:The detection rates of early puberty in boys and girls were 13.60% and 16.30%, respectively. The median of intra-group absolute correlation of psychosocial factor exposure (0.042-0.066) was generally higher than that of inter-group among girls (0.031-0.059), while no similar diference was found among boys. LASSO model showed that moving house, being raised by someone other than parents, sexual abuse, peer conflict, high monthly household income, and high exposure to electronics on school days were predictors of early puberty in girls, while moving house and high monthly household income were the predictors of early puberty in girls in all four models (LASSO, multiple logistic regression, ridge regression, and Bayesian). Among boys, only a transient loss from family was a predictor of early puberty.Conclusion:Early puberty in children can be predicted by psychosocial factors, and there are gender-specific differences.
10.Pachymic acid attenuates lipopolysaccharides-induced acute kidney inju-ry by inhibiting inflammation and renal tubular epithelial cell apoptosis
Xun MO ; Shanshan YU ; Jing JIA ; Yuting CHEN ; Yulin PENG ; Fang-fang WANG ; Xiong YU ; Rongyu CHEN ; Wanlin TAN ; Xiaoxiao XU ; Luqun LIANG ; Yuanyuan RUAN ; Mingjun SHI ; Yuanyuan WANG ; Bing GUO
Chinese Journal of Pathophysiology 2025;41(5):995-1005
AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Result Analysis
Print
Save
E-mail