1.Qishao Capsules Improve Diabetic Renal Injury in db/db Mice by Inhibiting Podocyte Apoptosis via Regulating Caspase-8 and Caspase-3
Jingwei LIU ; Zhenhua WU ; Bing YANG ; Fengwen YANG ; Miao TAN ; Tingting LI ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):126-135
ObjectiveTo observe the effect of Qishao capsules on renal injury in db/db mice with diabetic kidney disease (DKD),and explore its mechanism of protecting the kidney by inhibiting podocyte apoptosis. Methodsdb/m mice (7 mice) were used as the normal group,and db/db mice (35 mice) were randomly divided into a model group,a dapagliflozin group (0.001 g·kg-1·d-1),and low-,medium-,and high-dose groups of Qishao capsules (0.341 3,0.682 5,and 1.365 g·kg-1·d-1,respectively). Drug intervention lasted for 8 consecutive weeks. After sampling,the serum renal function indicators [creatinine(SCr),and urea nitrogen(BUN)],fasting blood glucose (FBG),24 h urinary protein quantification (24 h-UTP), and other indicators of the mice were measured. The pathological tissue morphology of the kidney was observed by periodic acid-silver methenamine (PASM) and Masson's trichrome (Masson) staining. Immunohistochemical detection of cysteine-dependent aspartate-specific protease (Caspase)-3 and B-cell lymphoma 2 (Bcl-2) was performed. Western blot was used to detect the protein expression of Caspase-8,Caspase-7,Caspase-3, and other molecules. Terminal deoxynucleotidyl transferase dUTP nick End labeling (TUNEL) staining was used to observe apoptosis in renal tissue. Immunofluorescence staining of Wilms tumor suppressor gene-1
2.A machine learning-based model for predicting the risk of diabetic kidney disease in type 2 diabetes mellitus
Tingting LI ; Peng SU ; Jinbo CHEN ; Xiaoyan HE ; Yi CAO ; Xin ZHANG ; Qingling TANG ; Xubin MIAO ; Xiaohua LIANG ; Dong MA
Chinese Journal of Diabetes 2025;33(4):241-247
Objective To compare and find an optimal model for predicting the risk of DKD occurrence in patients with type 2 diabetes mellitus(T2DM).Methods A total of 2005 patients with T2DM were enrolled in this study from The Second Hospital of Shijiazhuang City during December 2017 to December 2022.All the subjects were divided into a training set(n=1403)and a validation set(n=602)according to the ratio of 3∶1 by simple random sampling.With the occurrence of DKD as the outcome variablein the training set,important feature variables were screened by LASSO regression.Six different machine learning models were established according to the feature variables,thenthe optimal model was determined by comparison,and anonlinerisk predictor for DKD occurrence was constructed in patients with T2DM.Results Taking the occurrence of DKD as the outcome variable in the training set,the results of LASSO regression analysis showed that the optimal value of the model was 10-fold cross validation lambda.1se=0.01662473,and 15 characteristic variables with nonzero coefficient were screened out to be related to the occurrence of DKD.The data included sex,age,family history of DM,DM duration,LDL-C,HbA1c,WBC,PDW,Scr,urine α1-microglobulin,urine β2-microglobulin,urine microalbumin,hypertension,hypokalemia,and DR.In the training set and validation set,the prediction performance of XGBoost model was better than that of other models(AUC=0.872,0.893,95%CI 0.853~0.891,0.865~0.921),the sensitivity was 0.779,0.863,and the specificity was 0.721,0.758,respectively.The F1 scores were 0.774 and 0.787.DCA analysis showed that the XGBoost model had a greater net benefit and threshold probability.According to the XGBoost model,the online predictor of DKD risk in T2DM patients was laid out,and two patients were selected for application,the results showed that the predictive value of the model was 0.185 in non-DKD patients,and the predictive value was 0.510 in DKD patients.Conclusions The XGBoost model is the best model for predicting the occurrence of DKD in T2DM patients,and an online predictor was successfully built.
3.A machine learning-based model for predicting the risk of diabetic kidney disease in type 2 diabetes mellitus
Tingting LI ; Peng SU ; Jinbo CHEN ; Xiaoyan HE ; Yi CAO ; Xin ZHANG ; Qingling TANG ; Xubin MIAO ; Xiaohua LIANG ; Dong MA
Chinese Journal of Diabetes 2025;33(4):241-247
Objective To compare and find an optimal model for predicting the risk of DKD occurrence in patients with type 2 diabetes mellitus(T2DM).Methods A total of 2005 patients with T2DM were enrolled in this study from The Second Hospital of Shijiazhuang City during December 2017 to December 2022.All the subjects were divided into a training set(n=1403)and a validation set(n=602)according to the ratio of 3∶1 by simple random sampling.With the occurrence of DKD as the outcome variablein the training set,important feature variables were screened by LASSO regression.Six different machine learning models were established according to the feature variables,thenthe optimal model was determined by comparison,and anonlinerisk predictor for DKD occurrence was constructed in patients with T2DM.Results Taking the occurrence of DKD as the outcome variable in the training set,the results of LASSO regression analysis showed that the optimal value of the model was 10-fold cross validation lambda.1se=0.01662473,and 15 characteristic variables with nonzero coefficient were screened out to be related to the occurrence of DKD.The data included sex,age,family history of DM,DM duration,LDL-C,HbA1c,WBC,PDW,Scr,urine α1-microglobulin,urine β2-microglobulin,urine microalbumin,hypertension,hypokalemia,and DR.In the training set and validation set,the prediction performance of XGBoost model was better than that of other models(AUC=0.872,0.893,95%CI 0.853~0.891,0.865~0.921),the sensitivity was 0.779,0.863,and the specificity was 0.721,0.758,respectively.The F1 scores were 0.774 and 0.787.DCA analysis showed that the XGBoost model had a greater net benefit and threshold probability.According to the XGBoost model,the online predictor of DKD risk in T2DM patients was laid out,and two patients were selected for application,the results showed that the predictive value of the model was 0.185 in non-DKD patients,and the predictive value was 0.510 in DKD patients.Conclusions The XGBoost model is the best model for predicting the occurrence of DKD in T2DM patients,and an online predictor was successfully built.
4.Involvement of asprosin in regulation of liver lipid synthesis in mice un-der obesity and exercise weight loss through NRF2
Zeyu ZHANG ; Miao LIU ; Yi HAN ; Tingting YAO ; Tao LI ; Rendong LI ; Xuehie YI ; Tie MA
Chinese Journal of Pathophysiology 2025;41(4):732-742
AIM:This study aims to explore the role of asprosin(ASP)in regulating hepatic lipid anabolic metabolism,as well as the effects of ASP and its downstream pathways on hepatic lipid anabolic metabolism under obesity and exercise intervention.METHODS:To explore the effect of ASP on liver lipid synthesis under physiological condi-tion,5-week-old male C57BL/6J were randomly divided into 4 groups:wild-type(WT)group,WT+ASP group,knockout(KO)group,and KO+ASP group.The mice in KO and KO+ASP groups were ASP gene heterozygous KO mice,and the re-combinant ASP protein was intraperitoneally injected into the mice in WT+ASP and KO+ASP groups for one month before sampling.To explore the role of ASP on liver lipid synthesis under obesity and exercise intervention,5-week-old male C57BL/6J mice were randomly divided into 3 groups:normal control(NC)group,high-fat diet(HFD)group,and HFD+exercise group.After 10 weeks of HFD feeding,the mice in HFD group received no intervention,while those in HFD+ex-ercise group underwent 8 weeks of treadmill exercise intervention.The mice in both groups were fed with HFD during the intervention period.After the interventions,liver tissues were collected from the mice.Western blot and RT-qPCR meth-ods were used to detect the expression levels of ASP,fibroblast growth factor 21(FGF21),nuclear factor E2-related factor 2(NRF2),stearoyl-coenzyme A desaturase 1(SCD1)and fatty acid synthase(FASN)in the mouse liver.ELISA was used to detect the triglycerol(TG)and cyclic adenosine monophosphate(cAMP)levels in the mouse liver,and HE stain-ing and oil red O staining were performed to observe the morphological changes of mouse liver tissues.RESULTS:(1)Compared with WT mice,KO mice exhibited significantly reduced body weight and liver weight,while liver index and he-patic TG levels were significantly increased.The mRNA and protein levels of cAMP,ASP,FGF21 and NRF2 in the liver were significantly decreased,whereas the mRNA and protein levels of SCD1 and FASN were significantly increased.In the WT+ASP group,liver index and hepatic TG levels were significantly reduced,but there were no statistical differences in body weight and liver weight.The mRNA and protein levels of SCD1 and FASN in the liver were significantly de-creased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level decreased,but the protein level increased.(2)Compared with KO mice,KO+ASP mice had significantly reduced hepatic TG level,with a certain degree of reduction in liver weight and liver index,but without statistical significance.The cAMP level and the mRNA and protein levels of ASP,FGF21 and NRF2 in the liver were significantly increased,while the mRNA and protein levels of SCD1 and FASN were significantly decreased.(3)Compared with NC mice,HFD mice showed increased body weight,liver weight,and hepatic TG level.The cAMP level and the mRNA and protein levels of NRF2 in the liver were significantly decreased,while the mRNA and protein levels of SCD1 and FASN were significant-ly increased.The FGF21 mRNA level increased,but its protein level decreased.The ASP mRNA level decreased,but its protein level increased.(4)Compared with HFD mice,HFD+exercise mice had significantly reduced body weight,liver weight,and hepatic TG level.The mRNA and protein levels of SCD1 and FASN in the liver were significantly decreased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level de-creased,but its protein level increased.The ASP mRNA level increased,but its protein level decreased.CONCLU-SION:(1)The ASP exerts an inhibitory effect on hepatic lipogenesis through the cAMP/FGF21/NRF2 pathway.(2)Un-der HFD feeding condition,the protein expression of FGF21 decreases,leading to our speculation that ASP may develop resistance.Aerobic exercise intervention can attenuate ASP resistance under high-fat condition and alleviate hepatic lipid accumulation caused by HFD.
5.The correlation between TNF- α 308 gene loci polymorphism and febrile seizures in children
Renjian WANG ; Yujuan HUANG ; Miao XU ; Jian LIU ; Tingting CHEN ; Xiuhe XU ; Lei SHEN
International Journal of Pediatrics 2025;52(4):274-278
Objective:To analyze the distribution of tumor necrosis factor-alpha(TNF-α)308 gene loci polymorphism in children with febrile seizures(FS)and to explore the correlation between TNF-α 308 gene polymorphisms and FS in children.Methods:A total of 320 children diagnosed with FS in the Department of Emergency,Shanghai Children's Hospital from September 1st,2020 to June 30th,2021 were enrolled as the study subjects,which were divided into simple febrile seizures(SFS)group(232 cases)and complex febrile seizures(CFS)group(88 cases)based on their clinical characteristics,and the clinical characteristics and laboratory indexes of the two groups were compared. Children with no history of convulsions were selected as the control group(160 cases). The high-resolution melting and gene sequencing technology were used to analyze the polymorphism of TNF-α 308 gene in each group and the distribution of different gene types and allele frequencies among the groups was compared. A multivariate Logistic regression model was constructed to analyze the relationship between TNF-α 308 gene polymorphism and FS.Results:The age,mean corpuscular volume,mean corpuscular hemoglobin and platelet distribution width of the CFS group were significantly higher than those in the SFS group,and the difference was statistically significant(all P<0.05).There was no significant difference in gender distribution,family history of FS,history of FS,body temperature at time of convulsions,WBC,Hb,CRP and PLT between the two groups(all P>0.05).The genotype frequency distribution of TNF-α 308 polymorphism in the three groups was in line with the Hardy-Weinberg equilibrium( P>0.05).The AA genotype of TNF-α 308 locus was not detected in the study.Compared with the control group[17 cases(10.6%)],the distribution proportion of GA genotype in the CFS group[22cases(25.0%)]and the SFS group[52cases(22.4%)]was increased,and the difference was statistically significant( χ2=11.126, P=0.004);Compared with the control group[17 frequencies(5.3%)],the frequency distribution proportion of allele A in the CFS group[22 frequencies(12.5%)]and SFS group[52 frequencies(11.2%)]was also increased,and the difference was statistically significant( χ2=9.960, P=0.007). Adding control factors such as gender,age,family history of FS,body temperature at time of convulsions and blood routine markers,the multivariate Logistic regression model was constructed to show that there was no statistically significant association between TNF-α 308 genotype and CFS in children( OR=1.805,95% CI:0.926~3.519, P=0.083). Conclusion:In this study,there was no significant correlation between TNF-α 308 gene loci polymorphism and CFS in children.
6.Involvement of asprosin in regulation of liver lipid synthesis in mice un-der obesity and exercise weight loss through NRF2
Zeyu ZHANG ; Miao LIU ; Yi HAN ; Tingting YAO ; Tao LI ; Rendong LI ; Xuehie YI ; Tie MA
Chinese Journal of Pathophysiology 2025;41(4):732-742
AIM:This study aims to explore the role of asprosin(ASP)in regulating hepatic lipid anabolic metabolism,as well as the effects of ASP and its downstream pathways on hepatic lipid anabolic metabolism under obesity and exercise intervention.METHODS:To explore the effect of ASP on liver lipid synthesis under physiological condi-tion,5-week-old male C57BL/6J were randomly divided into 4 groups:wild-type(WT)group,WT+ASP group,knockout(KO)group,and KO+ASP group.The mice in KO and KO+ASP groups were ASP gene heterozygous KO mice,and the re-combinant ASP protein was intraperitoneally injected into the mice in WT+ASP and KO+ASP groups for one month before sampling.To explore the role of ASP on liver lipid synthesis under obesity and exercise intervention,5-week-old male C57BL/6J mice were randomly divided into 3 groups:normal control(NC)group,high-fat diet(HFD)group,and HFD+exercise group.After 10 weeks of HFD feeding,the mice in HFD group received no intervention,while those in HFD+ex-ercise group underwent 8 weeks of treadmill exercise intervention.The mice in both groups were fed with HFD during the intervention period.After the interventions,liver tissues were collected from the mice.Western blot and RT-qPCR meth-ods were used to detect the expression levels of ASP,fibroblast growth factor 21(FGF21),nuclear factor E2-related factor 2(NRF2),stearoyl-coenzyme A desaturase 1(SCD1)and fatty acid synthase(FASN)in the mouse liver.ELISA was used to detect the triglycerol(TG)and cyclic adenosine monophosphate(cAMP)levels in the mouse liver,and HE stain-ing and oil red O staining were performed to observe the morphological changes of mouse liver tissues.RESULTS:(1)Compared with WT mice,KO mice exhibited significantly reduced body weight and liver weight,while liver index and he-patic TG levels were significantly increased.The mRNA and protein levels of cAMP,ASP,FGF21 and NRF2 in the liver were significantly decreased,whereas the mRNA and protein levels of SCD1 and FASN were significantly increased.In the WT+ASP group,liver index and hepatic TG levels were significantly reduced,but there were no statistical differences in body weight and liver weight.The mRNA and protein levels of SCD1 and FASN in the liver were significantly de-creased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level decreased,but the protein level increased.(2)Compared with KO mice,KO+ASP mice had significantly reduced hepatic TG level,with a certain degree of reduction in liver weight and liver index,but without statistical significance.The cAMP level and the mRNA and protein levels of ASP,FGF21 and NRF2 in the liver were significantly increased,while the mRNA and protein levels of SCD1 and FASN were significantly decreased.(3)Compared with NC mice,HFD mice showed increased body weight,liver weight,and hepatic TG level.The cAMP level and the mRNA and protein levels of NRF2 in the liver were significantly decreased,while the mRNA and protein levels of SCD1 and FASN were significant-ly increased.The FGF21 mRNA level increased,but its protein level decreased.The ASP mRNA level decreased,but its protein level increased.(4)Compared with HFD mice,HFD+exercise mice had significantly reduced body weight,liver weight,and hepatic TG level.The mRNA and protein levels of SCD1 and FASN in the liver were significantly decreased,while the cAMP level and the mRNA and protein levels of NRF2 were significantly increased.The FGF21 mRNA level de-creased,but its protein level increased.The ASP mRNA level increased,but its protein level decreased.CONCLU-SION:(1)The ASP exerts an inhibitory effect on hepatic lipogenesis through the cAMP/FGF21/NRF2 pathway.(2)Un-der HFD feeding condition,the protein expression of FGF21 decreases,leading to our speculation that ASP may develop resistance.Aerobic exercise intervention can attenuate ASP resistance under high-fat condition and alleviate hepatic lipid accumulation caused by HFD.
7.Study on the construction of competency of middle-level cadre in functional department of research institute
Lianying MIAO ; Tingting JI ; Li LU ; Yongsi HAO ; Panhe LIU ; Peng ZHENG ; Yongjun CHEN
China Medical Equipment 2024;21(2):162-165
Objective:To analyze the current situation of middle-level cadres in functional departments of scientific research institutes and to construct a job competency model for middle-level cadre.Methods:A cluster random sampling method was used to conduct a questionnaire survey in March 2022 on the satisfaction level of middle-level cadres in the functional departments of the Institute of Blood Transfusion of the Chinese Academy of Medical Sciences,a mid-level cadre competency questionnaire survey was conducted to collect data among functional department personnel of scientific research institutes affiliated to the Chinese Academy of Medical Sciences and Peking Union Medical College.The principal component analysis method was used to extract factors,and the maximum variance rotation method was used to conduct exploratory factor analysis to construct a competency model.Results:The Middle-level cadres in scientific research institutes had problems such as old age,traditional management style,etc.The competency model of middle-level cadres in functional departments of scientific research institutes included 3 main competencies:responsibility taking ability,communication ability and learning execution ability,and 34 competency factors.Conclusion:The competency model of middle-level cadres in functional departments of scientific research institutes can provide basis and reference for the selection and appointment,education and training,performance management and career planning of middle-level cadres in scientific research institutes.
8.Construction and immunogenicity study of 293T cell line stably expressing rabies virus glycoprotein
Yu WANG ; Shoufeng ZHANG ; Tingting YU ; Lijuan MI ; Naiquan YAO ; Faming MIAO ; Rongliang HU
Chinese Journal of Veterinary Science 2024;44(11):2393-2399
In order to obtain a cell line which high expressed of rabies virus glycoprotein the produc-tion of rabies subunit vaccine,the RABV glycoprotein gene sequence was amplified by RT-PCR and cloned into the lentiviral expression vector.The recombinant plasmid pLV-RVG,envelope plasmid pMD2.0G and packaging plasmid psPAX2 were co-transfected into HEK-293T cells to harvest lentivirus and infect new HEK-293T cells.The 293T-RVG cell line was obtained by puro-mycin pressure screening.Indirect immunofluorescence assay(IFA)and Western blot showed that the 67 kD RABV-G protein was highly expressed in the cells.The neutralizing antibody titer reached 2.19 IU/mL within 14 days after immunization,which was higher than the internationally recognized protection threshold(0.5 IU/mL).This study showed that the cell line 293T-RVG with stable and high expression of rabies virus glycoprotein was successfully constructed.The cell line could protect mice against rabies virus challenge and could be used as a subunit vaccine with poten-tial for large-scale production and application.
9.Feasibility of radiomics combined with machine learning in predicting lymphovascular and perineural invasion of gastric cancer
Shuangquan AI ; Miao YANG ; Zilong YUAN ; Yaoyao HE ; Tingting NIE ; Yulin LIU
Journal of Practical Radiology 2024;40(5):746-751
Objective To explore the feasibility of radiomics features combined with different machine learning methods based on CT scans to predict lymphovascular and perineural invasion in patient with gastric cancer.Methods A total of 142 patients with gas-tric cancer lymphovascular confirmed by operative pathological examination were retrospectively selected.Among all patients,there were 96 positive cases and 46 negative cases.Among 137 patients with perineural invasion,there were 76 positive cases and 61 nega-tive cases.The 3D-Slicer package was used for delineation,and the Pyradiomics package was used to extract radiomics features.All data were randomly divided into training set and test set in an 8∶2 ratio.Intraclass correlation coefficient(ICC),Pearson correla-tion analysis,least absolute shrinkage and selection operator(LASSO)algorithm were used for feature selection.Support vector machine(SVM),K-nearest neighbor(KNN),decision tree(DT),random forest(RF),extreme tree(ET),extreme gradient boosting(XGBoost),and LightGBM were used to compare the models of lymphovascular and perineural invasion,respectively.Receiver operating characteris-tic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive performance of these models.Results The lymphovascular group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.926,0.753,1.000,0.999,1.000,1.000,and 0.917,and the AUC in the test set were 0.894,0.692,0.456,0.678,0.753,0.650,and 0.650,respectively.The perineural invasion group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.864,0.794,1.000,1.000,1.000,1.000,and 0.866,and the AUC in the test set were 0.861,0.706,0.700,0.672,0.731,0.667,and 0.678,respectively.Conclusion Based on venous phase CT radiomics features combined with machine learning methods,it is feasible to predict lymphovascu-lar and perineural invasion of gastric cancer preoperatively.Among the variousmachine learning methods,SVM shows the best predictive performance for lymphovascular and perineural invasion in patient with gastric cancer.
10.Effect of structured therapy and education based on personal strength on ischemic stroke:a randomized con-trolled trial
Tingting YU ; Fuliang CAI ; Guihua MIAO ; Chen GU ; Yuan PENG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(8):965-971
Objective To evaluate the effect of structured therapy and education based on personal strength on ischemic stroke. Methods From March,2021 to September,2023,a total of 114 patients with ischemic stroke from the First People's Hos-pital of Kunshan were randomly divided into control group(n=57)and experimental group(n=57).The control group received routine medicine,rehabilitation training and standard health education,while the experimental group received routine medicine,rehabilitation training and structured therapy and education based on personal strength,for six weeks.They were compared with the scores of modified Rankin Scale(mRS),motor-evoked po-tential(MEP)latency and amplitude,modified Barthel Index and Self-Recovery Efficacy Scale score and recur-rence within three months after the start of the study.The scores of Morisky Medication Adherence Scale(MMAS)and Five Facet Mindfulness Questionaire(FFMQ)were also compared. Results After treatment,the score of mRS(t=5.002),MEP latency period(t=9.739)and amplitude(t=4.394),modi-fied Barthel Index(t=11.261),the score of Self-Recovery Efficacy Scale(Z=-2.638),and the scores of MMAS(t=19.521)and FFMQ(t=15.381)were better in the experimental group than in the control group(P<0.05). Conclusion Structured therapy and education based on personal strength could faciliate to improve the recovery and self-management of ischemic stroke patients.

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