BACKGROUND:Magnetic nanomaterials,as a hot topic in the biomedical field in recent years,are often used to enhance the targeted delivery of drugs to the affected area.OBJECTIVE:To investigate the effects of magnetic nano drug carriers on skeletal muscle injury markers and inflammatory responses in rats with sports injuries.METHODS:Magnetic nanoparticles were prepared.A total of 88 male SD rats were randomly divided into a blank group(n=8),an injury control group(n=32),a Yunnan Baiyao group(n=24),and a magnetic nano-drug carrier group(n=24)by using a random number table method.The latter three groups were modeled with exercise-induced muscle injury(treadmill slope of-16°,running speed of 16 m/min,and training time of 120 min).Immediately after exercise,after verifying the success of the model,Yunnan Baiyao patch was applied to the gastrocnemius muscle of the rats in the Yunnan Baiyao group.Yunnan Baiyao patch loaded with magnetic nanoparticles was applied to the gastrocnemius muscle of the rats in the magnetic nano-drug carrier group.At 24,48,and 120 hours after exercise,blood was drawn from the abdominal aorta of rats to detect the activities of creatine kinase and lactate dehydrogenase,as well as the levels of myoglobin,interleukin-6,and tumor necrosis factor-α.Hematoxylin-eosin staining was used to observe the infiltration of inflammatory cells in the gastrocnemius muscle.RESULTS AND CONCLUSION:(1)Compared with the blank group,the levels of myoglobin,creatine kinase,lactate dehydrogenase and tumor necrosis factorα in the injury control group at 24,48 and 120 hours after exercise were increased(P＜0.05),and the level of interleukin 6 at 24 and 120 hours after exercise was increased(P＜0.05).Compared with the injury control group,the level of myoglobin in the Yunnan Baiyao group at 24 and 48 hours after exercise was decreased(P＜0.05),the activities of creatine kinase and lactate dehydrogenase at 24,48 and 120 hours were decreased(P＜0.05),and the levels of interleukin 6 and tumor necrosis factor α at 120 hours after exercise were decreased(P＜0.05).Compared with the Yunnan Baiyao group,the level of myoglobin in the magnetic nano-drug carrier group at 24 and 48 hours after exercise was decreased(P＜0.05),the activities of creatine kinase and tumor necrosis factor α at 48 and 120 hours after exercise were decreased(P＜0.05),and the lactate dehydrogenase activity was reduced(P＜0.05).(2)Hematoxylin-eosin staining showed that a large number of inflammatory cells infiltrated in the muscle fibers of the injury control group 24 hours after exercise,and then the inflammatory cell infiltration gradually decreased,and the local damaged muscle fibers began to regenerate 120 hours after exercise.A large number of inflammatory cells infiltrated in the muscle fibers of the Yunnan Baiyao group and the magnetic nano-drug carrier group 24 hours after exercise,and then the inflammatory cell infiltration gradually decreased,and the damaged muscle fibers were regenerating 120 hours after exercise,and there was no significant difference from the blank group.(3)The results show that Yunnan Baiyao patch combined with magnetic nanoparticles can accelerate the recovery of exercise-induced muscle injury in rats,and the effect is better than that of Yunnan Baiyao alone.

BACKGROUND:Magnetic nanomaterials,as a hot topic in the biomedical field in recent years,are often used to enhance the targeted delivery of drugs to the affected area.OBJECTIVE:To investigate the effects of magnetic nano drug carriers on skeletal muscle injury markers and inflammatory responses in rats with sports injuries.METHODS:Magnetic nanoparticles were prepared.A total of 88 male SD rats were randomly divided into a blank group(n=8),an injury control group(n=32),a Yunnan Baiyao group(n=24),and a magnetic nano-drug carrier group(n=24)by using a random number table method.The latter three groups were modeled with exercise-induced muscle injury(treadmill slope of-16°,running speed of 16 m/min,and training time of 120 min).Immediately after exercise,after verifying the success of the model,Yunnan Baiyao patch was applied to the gastrocnemius muscle of the rats in the Yunnan Baiyao group.Yunnan Baiyao patch loaded with magnetic nanoparticles was applied to the gastrocnemius muscle of the rats in the magnetic nano-drug carrier group.At 24,48,and 120 hours after exercise,blood was drawn from the abdominal aorta of rats to detect the activities of creatine kinase and lactate dehydrogenase,as well as the levels of myoglobin,interleukin-6,and tumor necrosis factor-α.Hematoxylin-eosin staining was used to observe the infiltration of inflammatory cells in the gastrocnemius muscle.RESULTS AND CONCLUSION:(1)Compared with the blank group,the levels of myoglobin,creatine kinase,lactate dehydrogenase and tumor necrosis factorα in the injury control group at 24,48 and 120 hours after exercise were increased(P＜0.05),and the level of interleukin 6 at 24 and 120 hours after exercise was increased(P＜0.05).Compared with the injury control group,the level of myoglobin in the Yunnan Baiyao group at 24 and 48 hours after exercise was decreased(P＜0.05),the activities of creatine kinase and lactate dehydrogenase at 24,48 and 120 hours were decreased(P＜0.05),and the levels of interleukin 6 and tumor necrosis factor α at 120 hours after exercise were decreased(P＜0.05).Compared with the Yunnan Baiyao group,the level of myoglobin in the magnetic nano-drug carrier group at 24 and 48 hours after exercise was decreased(P＜0.05),the activities of creatine kinase and tumor necrosis factor α at 48 and 120 hours after exercise were decreased(P＜0.05),and the lactate dehydrogenase activity was reduced(P＜0.05).(2)Hematoxylin-eosin staining showed that a large number of inflammatory cells infiltrated in the muscle fibers of the injury control group 24 hours after exercise,and then the inflammatory cell infiltration gradually decreased,and the local damaged muscle fibers began to regenerate 120 hours after exercise.A large number of inflammatory cells infiltrated in the muscle fibers of the Yunnan Baiyao group and the magnetic nano-drug carrier group 24 hours after exercise,and then the inflammatory cell infiltration gradually decreased,and the damaged muscle fibers were regenerating 120 hours after exercise,and there was no significant difference from the blank group.(3)The results show that Yunnan Baiyao patch combined with magnetic nanoparticles can accelerate the recovery of exercise-induced muscle injury in rats,and the effect is better than that of Yunnan Baiyao alone.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveTo construct and evaluate various machine learning models for predicting the risk of chronic obstructive pulmonary disease （COPD） in individuals， thereby providing data support for early screening and intervention. MethodsA total of 823 subjects were selected for this study， comprising 142 individuals in the high-risk group for COPD and 681 individuals in the low-risk group. Data collected included demographic characteristics， smoking history， symptoms （such as cough and shortness of breath）， and scores from the Chronic obstructive pulmonary disease screening questionnaire. Four machine learning algorithms—Logistic regression， random forest， support vector machine， and XGBoost—were utilized to construct risk prediction models. The performance of these models was assessed using 5-fold cross-validation， with evaluation metrics including accuracy， precision， recall， F1-score， area under the receiver operating characteristic curve （AUC）， and average precision （AP）. Furthermore， a feature importance analysis was performed. ResultsThe Logistic Regression model exhibited superior performance， achieving an AUC of 0.982 and an AP of 0.939. This was closely followed by the Random Forest model， which recorded an AUC of 0.975 and an AP of 0.890. Feature importance analysis revealed that smoking history， symptoms of shortness of breath， and body weight were significant predictors. All models demonstrated robust performance in identifying low-risk populations； however， variations were observed in their efficacy in identifying high-risk populations. ConclusionMachine learning models have proven effective in identifying individuals at high risk for COPD. Among these， the Logistic regression model exhibits the best overall performance， efficiently identifying high-risk populations and serving as a valuable clinical auxiliary screening tool. Various models， each with distinct performance characteristics， are suited to different clinical screening scenarios， thereby offering targeted decision-making support for the establishment of a hierarchical and intelligent COPD screening pathway.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Objective:To investigate the influence of diabetes mellitus (DM) and high-sen-sitivity C-reactive protein (Hs-CRP) on the risk of digestive system malignancy.Methods:The pro-spective cohort study was conducted. The clinical data of 93 928 participants who participated health examination in 9 hospitals at Tangshan, including Kailuan General Hospital Affiliated to North China University of Science and Technology et al, in 2006 were selected. According to the presence or absence of DM and the level of Hs-CRP, all participants were divided into 4 groups, including the DM(-)CRP(-) group defined as absence of DM and Hs-CRP ≤3 mg/L, the DM(-)CRP(+) group defined as absence of DM and Hs-CRP>3 mg/L, the DM(+)CRP(-) group defined as presence of DM and Hs-CRP ≤3 mg/L, and the DM(+)CRP(+) group defined as presence of DM and Hs-CRP >3 mg/L. The data of participants were collected by a fixed team of physicians. The first physical examination in 2006 was taken as the starting point for follow-up. The end event of follow-up was defined as the occurrence of digestive system malignancy or death, and the follow-up was up to December 31, 2021. Observation indicators: (1) comparison of clinical data among the 4 groups of participants; (2) the incidence and cumulative incidence rate of digestive system malignancy in participants; (3) influence of DM and Hs-CRP level on the risk of digestive system malignancy; (4) the combined influence of DM and Hs-CRP level on the risk of digestive system malignancy; (5) sensitivity analysis. Comparison of measurement data with normal distribution among multiple groups was conducted using the one-way analysis of variance. For pairwise comparison, least significant difference test was used for homogeneity of variance, and Dunnett′s T3 test was used for heterogeneity of variance. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis rank sum test, and Dunn-Bonferroni test was used for pairwise comparison. Comparison of count data among multiple groups was conducted using the chi-square test, and Bonferroni test was used among multiple comparisons. The Kaplan-Meier method was used to plot cumulative incidence curve, and Log-rank test was used for cumulative incidence rate analysis. The Cox proportional risk model was used for multivariate analysis. All models were adjusted for relevant confounders. Results:(1) Comparison of clinical data among the 4 groups of participants. Of the 93 928 participants, there were 70 743 cases in the DM(-)CRP(-) group, 14 644 cases in the DM(-)CRP(+) group, 6 425 cases in the DM(+)CRP(-) group, and 2 116 cases in the DM(+)CRP(+) group. There were significant differences in gender, age, fasting blood glucose, Hs-CRP, triglyceride, alanine aminotransferase, body mass index, marrital status, smoking, drinking, high school degree or above, physical exercise, high salt diet, high fat diet, positive hepatitis B virus surface antigen, fatty liver, liver cirrhosis, gallstone, taking hypoglycemic drugs, taking lipid-lowering drugs among the 4 groups of participants ( P<0.05). (2) The incidence and cumulative incidence rate of digestive system malignancy in participants. At the end-up of follow-up, 2 008 cases developed digestive system malignancy in the 93 928 participants, including 717 cases of colorectal cancer, 456 cases of liver cancer, 396 cases of gastric cancer, 195 cases of esophageal cancer, 144 cases of pancreatic cancer, 65 cases of gallbladder cancer or extrahepatic cholangiocarcinoma, 35 cases of small bowel cancer. The cumulative incidence rates of digestive system malignancy were 2.19%, 2.42%, 2.86%, 3.59% in participants of the DM(-)CRP(-) group, DM(-)CRP(+) group, DM(+)CRP(-) group, DM(+)CRP(+) group, respectively, showing a significant difference among the 4 groups ( χ2=31.72, P<0.05). (3) Influence of DM and Hs-CRP level on the risk of digestive system malignancy. After adjusting for the confounding factors of the participants, results of multivariate analysis showed that DM and Hs-CRP >3 mg/L were independent influencing factors for the incidence of digestive system malignancy ( hazard ratio=1.32, 1.19, 95% confidence interval as 1.13-1.56, 1.06-1.33, P<0.05). Futher analysis showed that there was a significant difference in interaction between DM and Hs-CRP >3 mg/L ( P<0.05). (4) The combined influence of DM and Hs-CRP level on the risk of digestive system malign-ancy. After adjusting for confounding factors, results of multivariate analysis showed that using the DM(-)CRP(-) group as the control group, the risk of incidence of digestive system malignancy increased in the DM(-)CRP(+) group, DM(+)CRP(-) group, and DM(+)CRP(+) group, respectively ( hazard ratio=1.14, 1.23, 1.79, 95% confidence interval as 1.01-1.29, 1.02-1.48, 1.38-2.31, P<0.05). In the site-specific analysis of digestive system malignancy, using the DM(-)CRP(-) group as the control group, the risk of incidence of liver cancer increased in the DM(-)CRP(+) group ( hazard ratio=1.37, 95% confidence interval as 1.07-1.75, P<0.05), the risk of incidence of liver cancer and pancrea-tic cancer increased in the DM(+)CRP(-) group ( hazard ratio=1.60, 1.74, 95% confidence interval as 1.16-2.21, 1.00-3.02, P<0.05), the risk of incidence of small bowel cancer, pancreatic cancer and colorectal cancer increased in the DM(+)CRP(+) group ( hazard ratio=5.05, 2.31, 2.23, 95% confidence interval as 1.57-16.21, 1.00-5.31, 1.54-3.24, P<0.05). (5) Sensitivity analysis. After adjusting for confounding factors of excluding 3 types of participants (103 cases of digestive system malignancy within 1 year of follow-up, 2 370 cases of taking glucose-lowering drugs, and 915 cases of taking lipid-lowering drugs), results of multivariate analysis showed that using the DM(-)CRP(-) group as the control group, the risk of incidence of digestive system malignancy increased in the DM(+)CRP(-) group, and DM(+)CRP(+) group, respectively ( hazard ratioexcluding cases of digestive system malignancy within 1 year of follow-up=1.26, 1.66, 95% confidence interval as 1.04-1.52, 1.26-2.18, P<0.05; hazard ratioexcluding cases taking glucose-lowering drugs=1.23, 1.75, 95% confidence interval as 1.02-1.49, 1.31-2.33, P<0.05; hazard ratioexcluding cases taking lipid-lowering drugs=1.24, 1.80, 95% confidence interval as 1.03-1.49, 1.39-2.34, P<0.05). Conclusions:DM and Hs-CRP >3 mg/L are independent influencing factors for the incidence of digestive system malignancy. There is an interation and synergistic effect between DM and Hs-CRP to promote the incidence of digestive system malignancy.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.