1.Application research of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early gastric cancer
Zhi ZHENG ; Zimeng WANG ; Rui XU ; Haiqiao ZHANG ; Zheng ZHANG ; Guotian RUAN ; Jie YIN ; Xiaoye LIU ; Jun CAI ; Guangyong CHEN ; Xiujing SUN ; Shengtao ZHU ; Peng LI ; Jun ZHANG ; Shutian ZHANG
Chinese Journal of Surgery 2025;63(7):587-596
Objective:To evaluate the short-term efficacy of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early-stage gastric cancer.Methods:This is a retrospective case series study. Data of 17 consecutive early gastric cancer patients from a prospective cohort at Beijing Friendship Hospital,Capital Medical University were analyzed between August 2023 and August 2024. Sixteen cases were from the department of general surgery and 1 from the department of gastroenterology. The cohort included 9 males and 8 females,with a mean age of 61.4 years (range: 46 to 79 years). Clinical data,including demographics,pathological features,surgical procedures,and follow-up outcomes,were collected through medical records and databases. All patients were followed for over 3 months,with follow-up ending on December 5,2024.Results:A total of 17 patients were involved. Among them, 5 patients underwent endoscopic submucosal dissection (ESD) combined with laparoscopic sentinel lymph node dissection (LSBD),and another 3 patients who underwent complete ESD resection received LSBD due to pathological stage meeting the expanded indications. 6 patients who underwent non-curative ESD resection received laparoscopic gastric regional resection (LRG) combined with LSBD,and another 3 patients directly received LRG combined with LSBD. The average number of sentinel lymph nodes dissected before surgery ( M(IQR)) was 8.9 (4.5) (range: 4 to 21),and the detection rate and accuracy rate were both 100%. Postoperative pathology confirmed that there was no metastasis in the sentinel lymph nodes of 5 patients who underwent ESD combined with LSBD and 3 patients who underwent LSBD after complete ESD resection. The vertical and horizontal margins of ESD were all negative. One patient was an absolute indication for ESD. For the 6 patients who underwent non-curative ESD resection combined with LRG and LSBD,the horizontal margins were all negative. Two patients showed 1 metastasis in each of the 21 and 9 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed during the operation. Postoperatively,73 and 39 lymph nodes were retrieved respectively. The former had 1 additional metastasis,while the latter had no metastasis. Among the 3 patients who underwent direct LRG combined with LSBD,the horizontal margins were negative. One patient was confirmed as an absolute indication for ESD by postoperative pathology,and one patient had 1 metastasis in 8 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed. Postoperatively,there was no metastasis in 54 lymph nodes. All patients had no complications such as infection,bleeding,perforation,or death after surgery. Among the 14 patients who did not receive additional radical surgery,they were able to pass gas and defecate within 3 days after surgery,with an average hospital stay of 6 days. The nutritional indicators and gastric radionuclide emptying imaging half-emptying time were similar to those before surgery at 3 months after surgery. Conclusions:Laparoscopic and endoscopic cooperative regional gastrectomy with sentinel lymph node basin dissection has the advantages of minimal invasiveness,preservation of gastric function,and precise treatment. It maybe suitable for patients with early-stage gastric cancer at high risk of lymph node metastasis and has good short-term efficacy.
2.Transcriptomics of the Lieber-DeCarli mouse model of alcoholic liver injury
Tianyin RUAN ; Siyuan WANG ; Xutao LI ; Hao ZHANG ; Yuan PENG ; Chenghai LIU ; Yanyan TAO
Acta Laboratorium Animalis Scientia Sinica 2025;33(2):204-215
Objective To investigate the characteristics of liver injury in the Lieber-DeCarli alcoholic liver disease(ALD)mouse model and to analyze its transcriptomic profile.Methods Eighteen male C57BL/6J mice were randomly divided into an alcohol-fed group(n = 10)and a control group(n = 8).The alcohol-fed group received a Lieber-DeCarli ethanol diet,starting with an adaptive one-week phase using incremental concentrations of ethanol(10~57.3 mL/L),followed by 2 weeks of a 57.3 mL/L concentration of 95%ethanol,for a total of 3 weeks.The control group was provided with an isocaloric control diet for 3 weeks.At the end of the study,mice were sacrificed,and serum and liver tissue samples were collected.Serum liver function markers(ALT,AST),hepatic lipids(TC,TG),reduced glutathione(GSH),total superoxide dismutase(T-SOD),and malondialdehyde(MDA)were measured using biochemical assays.The levels of inflammatory cytokines(IL-6,IL-10,TNF-α,TGF-β1)in liver tissue were assessed by ELISA.Histopathological changes in liver tissue were examined using hematoxylin-eosin(HE)and Oil Red O staining.Immunohistochemical staining using the F4/80 antibody was employed to assess changes in macrophage expression.RNA-seq analysis was conducted to identify differentially expressed genes between the two groups of liver tissues,followed by GO and KEGG pathway enrichment analysis.qRT-PCR was used to validate the expression of these differentially expressed genes.Results Compared with the control group,the alcohol-fed mice exhibited a significant decrease in body weight(P<0.01).Serum ALT and AST levels were significantly elevated(P<0.01),while liver tissue levels of TC,TG,and MDA were significantly increased(P<0.05).Conversely,GSH and T-SOD levels were significantly reduced(P<0.05).The levels of inflammatory factors IL-6,TNF-α,and TGF-β1 were increased,which was consistent with the qRT-PCR validation results(P<0.05).Histological examination revealed disrupted hepatic lobular structure,with macrovesicular steatosis,microvesicular steatosis,and ballooning degeneration.Additionally,fat droplets in liver tissue were significantly increased,and macrophage expression was upregulated.Differential gene expression analysis,using a threshold of|log2 FC|>1 and q<0.05,identified 2063 differentially expressed genes,of which 1236 were upregulated and 827 downregulated.Enriched pathways included xenobiotic metabolism via cytochrome P450,cytokine-cytokine receptor interaction,chemokine signaling,steroid hormone biosynthesis,glutathione metabolism,and retinol metabolism.(P<0.05).qRT-PCR validation confirmed the significant upregulation(e.g.,Mmp12,Gstm3,Cyp2a22)and downregulation(e.g.,Serpina1e,Acmsd,Mup3d)of 10 genes from each category,consistent with the transcriptome sequencing results.Conclusions The primary pathological mechanisms underlying alcoholic liver injury involve pathways related to xenobiotic metabolism and act via cytochrome P450,cytokine-cytokine receptor interaction,chemokine signaling,glutathione metabolism,and retinol metabolism.
3.Preliminary efficacy and safety analysis of modified SIOPEL-4 protocol for newly diagnosed pediatric hepatoblastoma with lung metastases
Jiaxin PENG ; Can HUANG ; An'an ZHANG ; Yali HAN ; Haishan RUAN ; Xiaoxia WANG ; Min XU ; Yuan XIN ; Liting YU ; Zhibao LYU ; Mingxuan FENG ; Shayi JIANG ; Yijin GAO
Chinese Journal of Pediatrics 2025;63(12):1343-1348
Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.
4.Research on the feasibility of dynamic contrast-enhanced magnetic resonance imaging in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns
Peng RUAN ; Siqin SUN ; Yinghong GE ; Yunfei ZHA
Chinese Journal of Burns 2025;41(2):163-170
Objective:To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.Methods:This study was an experimental study. Thirty-two male big ear white rabbits aged 6-8 months were assigned into electric burn group of 20 rabbits with high-voltage electric burns in the right lower limb and control group of 12 rabbits with sham injury in the right lower limb using the random number table method. At 0.5, 24.0, 48.0, and 72.0 h post injury, the lower limbs of rabbits in the two groups underwent axial fast spin echo T1-weighted imaging, fast spin echo T2-weighted imaging, and DCE-MRI examination. A reference region-based hemodynamic model was applied to obtain the blood perfusion parameters of skeletal muscle in the injured limbs, including the volume transfer constant K trans value and rate constant K ep value. The skeletal muscle tissue from the electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury and the control group of rabbits at 0.5 h post injury was harvested for immunohistochemical staining to observe the microvascular changes and calculate the microvascular density (MVD). The correlation between the K trans and K ep values and the MVD of skeletal muscle tissue in electric burn group of rabbits at 0.5-72.0 h post injury was analyzed. The number of samples was 5 in the electric burn group, and the number of samples was 3 in the control burn group. Results:From 0.5-72.0 h post injury, the K trans and K ep values in skeletal muscle tissue of electric burn group of rabbits exhibited the trends of increase first and decrease then, both of which reached peak values at 24.0 h post injury. The K trans values at 0.5, 24.0, 48.0, and 72.0 h post injury (with t values of -15.77, -14.91, -40.35, and -40.25, respectively, P<0.05) and the K ep values at 0.5, 24.0, and 48.0 h post injury (with t values of -5.39, -6.82, and -6.83, respectively, P<0.05) in skeletal muscle tissue in electric burn group of rabbits were significantly higher than those in control group. The MVD in skeletal muscle tissue in control group of rabbits at 0.5 h post injury and in electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury was (24.7±3.5), (21.8±2.2), (40.8±9.1), (16.4±2.4), and (9.8±0.8) per mm2, respectively. The MVD in skeletal muscle tissue in electric burn group of rabbits at 24.0 h post injury was significantly higher than that in control group at 0.5 h post injury ( t=2.89, P<0.05), and the MVD in skeletal muscle tissue at 48.0 and 72.0 h post injury was significantly lower than that in control group at 0.5 h post injury (with t values of 4.01 and 9.52, respectively, P<0.05). The K trans and K ep values of skeletal muscle tissue in rabbits in electric burn group were significantly positively correlated with microvascular density at 0.5 to 72.0 h post injury (with both r values of 0.95, P<0.05). Conclusions:The quantitative perfusion parameters K trans and K ep values of DCE-MRI can effectively reflect the microcirculatory perfusion changes of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.
5.Research Progress of Dihydromyricetin in Pharmacological Effects and Its Preparation
Peng ZHANG ; Kaitong LI ; Honglan WANG ; Yuanle SHEN ; Huini RUAN ; Zihong LI ; Jianfang FENG ; Liuping WANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(12):192-196,后插1
Dihydromyricetin is a flavonoid mainly found in Ampelopsis grossedentata,which has attracted extensive attention due to its diverse pharmacological activities in recent years.However,its low oral bioavailability limits its clinical application.In this article,the pharmacological effects of dihydromyricetin on antibacterial,antiviral,antitumor,inhibition of neuroinflammation,antioxidant,and hepatorenal protection were reviewed.By summarizing,it can be seen that the pharmacological effects of dihydromyricetin are related to the traditional efficacy of Ampelopsis grossedentata.Scholars have used new preparation technologie to design dosage forms and new drug delivery systems such as liposomes,nanoparticles,microemulsions and nanoemulsions,microcapsules and nanocapsules,which can improve the bioavailability and efficacy of dihydromyricetin.Which can provide reference for the development of new drugs.
6.Distribution characteristics of sports facilities in China and their association with residents′ mortality risk: an ArcGIS analysis
Xinxin YE ; Citian PENG ; Liang XUE ; Yingyan RUAN ; Xu WEN ; Cong HUANG
Chinese Journal of Health Management 2025;19(10):770-780
Objective:To analyze the distribution characteristics of sports facilities in China using geographic information system (ArcGIS) and to investigate their association with mortality risk among residents.Methods:This prospective cohort study included 97 912 community residents from the Chinese Family Database (CFD) between 2013 and 2017. After excluding participants lost to follow-up and those with incomplete data, 53 937 individuals were retained for the analysis. The distribution characteristics of sports facilities in China was mapped using ArcGIS, and the death events were recorded via structured interviews and questionnaires. The Poisson regression was used to assess the association between the distribution characteristics of sports facilities near participants′ residences and their mortality risk.Results:In 2013, a total of 79 714 sports facilities were identified across 262 districts (counties) in China, with large-scale sports facilities accounting for the highest proportion (87.09%). The median number of sports facilities within the residential buffer zone was 17 (4, 30), and the median distance from the residence to the nearest sports facility was 453.2 (341.5, 1 863.5) m. Among the 53 937 community residents analyzed in this study, there were 27 761 males and 26 176 females, 1 326 deaths (2.5%) occurred during the follow-up. Poisson regression revealed that a higher number of sports facilities in the buffer zone (≥21 vs 0-2) was associated with lower mortality risk ( RR=0.74, 95% CI: 0.64-0.85; P0.05). Subgroup analyses showed that being≥60 years old ( RR=0.82, 95% CI: 0.70-0.95), males ( RR=0.78, 95% CI: 0.64-0.95), females ( RR=0.79, 95% CI: 0.64-0.97), having a junior high school education or less ( RR=0.84, 95% CI: 0.71-0.99), and having a urban residence ( RR=0.77, 95% CI: 0.66-0.90) were all negatively associated with residents′ mortality risk (all P0.05). After adjusting for age, greater distance to the nearest sports facility ( RR=1.41, 95% CI: 1.08-1.83) and failing to meet the"10-minute fitness circle"criterion ( RR=1.25, 95% CI: 1.02-1.53) were associated with higher mortality risk among males (both P0.05). After adjusting for age and gender, urban residents with a greater distance to the nearest sports facility ( RR=1.29, 95% CI: 1.04-1.60) or not meeting the 10-minute fitness circle ( RR=1.18, 95% CI: 1.00-1.38) showed a significantly higher mortality risk (both P0.05). Conclusions:The ArcGIS analysis revealed that the distribution of sports facilities in China is characterized by a high proportion of large-scale facilities. Lower facility density within residential buffer zone and greater distance to the nearest facility increase mortality risk among adults.
7.A longitudinal study on the relationship between pre-pregnancy urolithiasis and pre-eclampsia: the mediating effect of hyperuricemia in early pregnancy
Ye CHEN ; Mengting SUN ; Ziye LI ; Qi ZOU ; Yuan PENG ; Xiaorui RUAN ; Manjun LUO ; Tingting WANG ; Jiabi QIN
Chinese Journal of Epidemiology 2025;46(1):140-146
Objective:To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia.Methods:Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc. Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results:A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR=2.65, 95% CI: 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P<0.05). Conclusions:Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.
8.Diagnostic performance evaluation of artificial intelligence-assisted diagnostic systems in cervical cytopathological examination
Zichen YE ; Yihui YANG ; Lian XU ; Ronggan WEI ; Xiling RUAN ; Peng XUE ; Yu JIANG ; Youlin QIAO
Chinese Journal of Epidemiology 2025;46(3):499-505
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.
9.Effects of Jianpi Huatan Prescription on Cholesterol Synthesis in Liver of Subclinical Hypothyroidism Mice Based on cAMP/CREB/HMGCR Signaling Pathway
Peng LUO ; Hang XU ; Lin RUAN ; Dongyu MIN ; Tianshu GAO ; Lianqun JIA ; Yuehua WU ; Wei CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(1):85-90
Objective To observe the effects of Jianpi Huatan Prescription on hepatic cholesterol synthesis in subclinical hypothyroidism(SCH)mice;To discuss its mechanism based on cAMP/CREB/HMGCR signaling pathway.Methods Totally 80 C57BL/6 male mice were randomly divided into control group(10 mice)and modeling group(70 mice),and the modeling group was given methimazole 0.08 mg/(kg·d)in drinking water for 16 weeks to establish a SCH mdoel.The model mice were randomly divided into model group,euthyrox group and Jianpi Huatan Prescription high-,medium-and low-dosage groups,with 10 mice in each group,and were given corresponding drugs for gavage for 6 weeks.HE staining and Oil red O staining were used to observe the morphology and lipid deposition of liver tissue,ELISA was used to detect serum contents of thyroid stimulating hormone(TSH),triiodothyronine(T3),thyroid hormone(T4),total cholesterol(TC),triglycerides(TG),and TC,cyclic adenosine monophosphate(cAMP)in liver tissue,Western blot was used to detect the expressions of protein kinase A(PKA),cyclic adenosine response element binding protein(CREB),p-CREB and 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)in liver tissue.Results Compared with the control group,the liver tissue of mice in the model group showed fat vacuoles of different sizes and obvious lipid deposition;the contents of TSH,TC,TG in serum and TC,cAMP in liver tissue significantly increased(P<0.05,P<0.01);the protein expressions of PKA,p-CREB and HMGCR significantly increased(P<0.01).Compared with the model group,lipid deposition in liver tissue and structure of liver cells was improved to varying degrees in euthyrox group and Jianpi Huatan Prescription high-and medium-dosage groups,and the contents of serum TSH,TC,TG,and liver tissue TC,cAMP decreased(P<0.05,P<0.01);the expressions of PKA,p-CREB and HMGCR protein in liver tissue increased significantly(P<0.01).Conclusion Jianpi Huatan Prescription can significantly inhibit hepatic cholesterol synthesis in SCH mice,and improve hepatic fat vacuoles and lipid deposition,and its mechanism may be to reduce TSH levels in SCH mice by regulating the cAMP/CREB/HMGCR signaling pathway.
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.

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