1.Study on the protective mechanism of midazolam on cardiac func-tion and angiogenesis in myocardial infarction rats by regulating the JNK/STAT3 pathway
Aifang LI ; Dong LIANG ; Yuanhui DAI ; Siyu CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1342-1350
AIM:To investigate the protective ef-fect of midazolam(MID)on cardiac function and angiogenesis in myocardial infarction(MI)rats and its effect on c-Jun N-terminal kinase-signal trans-ducer and activator of transcription 3(JNK/STAT3)pathway.METHODS:MI rat model was established by left anterior descending coronary artery ligation method.A total of 68 rats were modeled.After ex-cluding the rats that died(n=3,mortality rate≈4.4%)or failed modeling(n=5),the 60 MI rats in-cluded in this experiment were randomly divided in-to the model group(Model group),MID low,medi-um and high dose group(1 mg/kg MID-L group,3 mg/kg MID-M group,6 mg/kg MID-H group),MID high dose+JNK activator Anisomycin group(6 mg/kg MID-H+Anisomycin group),12 rats in each group.Another 12 rats undergoing sham surgery were selected as the control group.All rats were echocardiographic and evaluated for cardiac func-tion.The myocardial tissue pathological morpholo-gy and the myocardial fibrosis degree were ob-served by hematoxylin-eosin(HE)staining and Mas-son staining.The serum myocardial injury markers[creatine kinase isoenzyme(CK-MB)and brain na-triuretic peptide(BNP)]and inflammatory factors[tumor necrosis fa ctor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)],myocardial tis-sue oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)]levels were detected by enzyme-linked immunosorbent assay(ELISA).The vascular endothelial growth factor(VEGF),vascular endothe-lial growth factor receptor 2(VEGFR2),p-JNK,JNK,p-STAT3 and STAT3 proteins expression levels were detected by Protein blot method(Western blot).RE-SULTS:Compared with Control group,the myocar-dial tissue damage degree in Model group was more severe,the myocardial interstitial fibrosis de-gree was greatly deepened,the collagen volume fraction was significantly increased,the left ventric-ular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly in-creased,the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),GSH and SOD levels were significantly de-creased,and the VEGF,VEGFR2 proteins expression levels were significantly decreased,the p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P<0.05).Compared with Model group,with the MID dose increase,the myocardial tissue damage de-gree in MID-L,MID-M and MID-H groups was signif-icantly reduced,the myocardial interstitial fibrosis degree was reduced,the collagen volume fraction was decreased,the LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly decreased,the LVEF,LVFS,GSH and SOD levels were significantly increased,and the VEGF,VEGF2R protein expression levels were significantly in-creased,p-JNK/JNK and p-STAT3/STAT3 were signifi-cantly decreased(P<0.05).Compared with MID-H group,the myocardial tissue damage degree in MID-H+Anisomycin group was more severe,the myocardial interstitial fibrosis degree was greatly deepened,the collagen volume fraction was signifi-cantly increased,the cardiac function was weak-ened,the oxidative stress and inflammation were aggravated,LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were increased,the LVEF,LVFS,GSH,SOD,VEGF and VEGFR2 proteins expres-sion levels were significantly decreased,p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P<0.05).CONCLUSION:MID may improve myocardial tissue damage in MI rats by regulating JNK/STAT3 pathway,reduce oxidative stress and inflammatory response,promote angiogenesis,so as to play a role in cardiac protection.
2.Construction and validation of a risk prediction model for hyperuricemia in perimenopausal and postmenopausal women
Mei ZHANG ; Yi DIAO ; Bo WANG ; Mengqi LI ; Guitao LI ; Chuanwanyun DUAN ; Hui TAO ; Luming FAN ; Aifang YE ; Yong MAO
Chongqing Medicine 2025;54(8):1804-1810
Objective To develop and compare prediction models for hyperuricemia(HUA)in perim-enopausal and postmenopausal women using Lasso regression,random forest,and multivariate logistic regres-sion.Methods A multi-stage,stratified cluster sampling method was used to select 12 790 subjects from An-ning City,Yunnan Province.Prediction models for HUA were constructed using Lasso regression,random for-est,and multivariate logistic regression.The efficacy of the model was evaluated by accuracy,sensitivity,speci-ficity,F1 score,and area under the curve(AUC).Results LASSO regression analysis screened 19 variables for inclusion in the model,such as age,waist circumference,diastolic blood pressure,BMI,HDL-C,fasting blood glucose(FBG),etc.The accuracy rate was 0.701,the sensitivity was 0.703,the specificity was 0.680,and the F1 score was 0.806.The AUC(95%CI)was 0.770(0.748-0.792).The results of the random forest model show that variables such as creatinine,triglyceride-glucose index(TyG),TG,BMI,TC,Urea nitrogen(Urea),and ALT were relatively important,with an accuracy rate of 0.663,a sensitivity of 0.653,a specificity of 0.738,and an F1 score of 0.774.The AUC(95%CI)was 0.763(0.741-0.785).Multivariate logistic re-gression results showed that 11 variables including creatinine(Cr),TyG,BMI,Urea,and ALT were included in the model,with an accuracy rate of 0.705,a sensitivity of 0.707,a specificity of 0.686,an F1 score of 0.809,and an AUC(95%CI)of 0.771(0.749-0.793).Conclusion The overall performance of LASSO re-gression and multivariate logistic regression models is better.The random forest model has a strong variable screening ability and high specificity,and can be used as a supplement to provide more accurate predictions.
3.Study on the protective mechanism of midazolam on cardiac func-tion and angiogenesis in myocardial infarction rats by regulating the JNK/STAT3 pathway
Aifang LI ; Dong LIANG ; Yuanhui DAI ; Siyu CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1342-1350
AIM:To investigate the protective ef-fect of midazolam(MID)on cardiac function and angiogenesis in myocardial infarction(MI)rats and its effect on c-Jun N-terminal kinase-signal trans-ducer and activator of transcription 3(JNK/STAT3)pathway.METHODS:MI rat model was established by left anterior descending coronary artery ligation method.A total of 68 rats were modeled.After ex-cluding the rats that died(n=3,mortality rate≈4.4%)or failed modeling(n=5),the 60 MI rats in-cluded in this experiment were randomly divided in-to the model group(Model group),MID low,medi-um and high dose group(1 mg/kg MID-L group,3 mg/kg MID-M group,6 mg/kg MID-H group),MID high dose+JNK activator Anisomycin group(6 mg/kg MID-H+Anisomycin group),12 rats in each group.Another 12 rats undergoing sham surgery were selected as the control group.All rats were echocardiographic and evaluated for cardiac func-tion.The myocardial tissue pathological morpholo-gy and the myocardial fibrosis degree were ob-served by hematoxylin-eosin(HE)staining and Mas-son staining.The serum myocardial injury markers[creatine kinase isoenzyme(CK-MB)and brain na-triuretic peptide(BNP)]and inflammatory factors[tumor necrosis fa ctor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)],myocardial tis-sue oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)]levels were detected by enzyme-linked immunosorbent assay(ELISA).The vascular endothelial growth factor(VEGF),vascular endothe-lial growth factor receptor 2(VEGFR2),p-JNK,JNK,p-STAT3 and STAT3 proteins expression levels were detected by Protein blot method(Western blot).RE-SULTS:Compared with Control group,the myocar-dial tissue damage degree in Model group was more severe,the myocardial interstitial fibrosis de-gree was greatly deepened,the collagen volume fraction was significantly increased,the left ventric-ular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly in-creased,the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),GSH and SOD levels were significantly de-creased,and the VEGF,VEGFR2 proteins expression levels were significantly decreased,the p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P<0.05).Compared with Model group,with the MID dose increase,the myocardial tissue damage de-gree in MID-L,MID-M and MID-H groups was signif-icantly reduced,the myocardial interstitial fibrosis degree was reduced,the collagen volume fraction was decreased,the LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly decreased,the LVEF,LVFS,GSH and SOD levels were significantly increased,and the VEGF,VEGF2R protein expression levels were significantly in-creased,p-JNK/JNK and p-STAT3/STAT3 were signifi-cantly decreased(P<0.05).Compared with MID-H group,the myocardial tissue damage degree in MID-H+Anisomycin group was more severe,the myocardial interstitial fibrosis degree was greatly deepened,the collagen volume fraction was signifi-cantly increased,the cardiac function was weak-ened,the oxidative stress and inflammation were aggravated,LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were increased,the LVEF,LVFS,GSH,SOD,VEGF and VEGFR2 proteins expres-sion levels were significantly decreased,p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P<0.05).CONCLUSION:MID may improve myocardial tissue damage in MI rats by regulating JNK/STAT3 pathway,reduce oxidative stress and inflammatory response,promote angiogenesis,so as to play a role in cardiac protection.
4.National Metabolic Management Center(MMC) comprehensive management standards for patients with diabetes, hypertension, and hyperlipidemia
Weiqing WANG ; Yufan WANG ; Guixia WANG ; Aifang WANG ; Chunfang WEN ; Fanrong TIAN ; Guang NING ; Ping FENG ; Dalong ZHU ; Libin LIU ; Bangqun JI ; Heng SU ; Jianling DU ; Shu LI ; Yunsong LI ; Liu YANG ; Li LI ; Shengli WU ; Jinsong KUANG ; Yubo SHA ; Ping ZHANG ; Yawei ZHANG ; Yifei ZHANG ; Qidong ZHENG ; Zhongyan SHAN ; Dong ZHAO ; Zhigang ZHAO ; Tingyu KE ; Yu SHI ; Xuejiang GU ; Ning XU ; Fengmei XU ; Zuhua GAO ; Rong TANG ; Qijuan DONG ; Songbo FU ; Yi SHU ; Weici XIE ; Yuancheng DAI
Chinese Journal of Endocrinology and Metabolism 2024;40(12):1007-1023
Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.
5.Research Progress on the Mechanism of Baicalin Against Colorectal Cancer
Baiyan WANG ; Yihao ZHANG ; Dandan GUO ; Aifang LI ; Sugai YIN ; Shuying FENG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(10):2732-2738
Colorectal cancer(CRC)is the third leading cause of cancer death in the world,and the incidence of colorectal cancer is also increasing year by year,and the treatment options such as radiotherapy,chemotherapy and surgical removal of cancerous sites are not ideal,so there is an urgent need to find a new treatment strategy and solution.The adjuvant treatment of colorectal cancer with traditional Chinese medicine has the characteristics of multi-target,multi-level,multi-link and overall regulation,which plays an increasingly important role in tumor treatment and has become a hot field for anti-tumor drug screening.Skullcap has been widely studied as one of the main drugs adjuvant to treat colorectal cancer by traditional Chinese medicine.This paper reviews the anti-colorectal cancer effect of skullcap and its active ingredients and the current research progress,aiming to provide the background information and the reference for the treatment of colorectal cancer.
6.Application value of nucleic acid mass spectrometry in detecting drug-resistance genes in Mycobacterium tuberculosis
LI Aifang ; CAO Junjie ; LEI Jing
China Tropical Medicine 2024;24(12):1529-
Objective To investigate the application value of nucleic acid mass spectrometry (MassARRAY) in the detection of drug resistance genes of Mycobacterium tuberculosis (MTB). Methods Pulmonary samples (sputum, bronchoalveolar lavage fluid) from suspected pulmonary tuberculosis patients and tissue and pus samples from suspected extrapulmonary tuberculosis patients were collected from Xi'an Chest Hospital from September 2022 to May 2023. Two samples from the same patient were subjected to both the melt curve method and the MassARRAY method to detect common drug resistance genes in patient samples, alongside mycobacterial culture and microplate drug susceptibility test. The efficacy of the Melt curve method and MassARRAY method for the detection of various drugs was evaluated using the microporous plate method as the standard. Results A total of 72 pulmonary specimens (40 sputa, 32 bronchoalveolar lavage fluids) and 36 extrapulmonary (18 tissues and 18 pus) were collected. The positive rate of mycobacterial culture was 32.4% (35/108). The detection rate of drug resistance genes by nucleic acid mass spectrometry was 52.8% (57/108). The resistance detection rates for rifampicin by nucleic acid mass spectrometry, melting curve, and microplate method were 14.0% (8/57), 13.0% (6/46), and 20.0% (7/35) respectively, with no significant difference among the three methods (F=0.851, P>0.05). There was no significant difference in the detection rates of isoniazid, ethambutol, streptomycin, and fluoroquinolones among the three methods. Using phenotypic drug susceptibility results of culture-positive samples as the reference standard, the Kappa values of rifampicin, isoniazid, ethambutol, and streptomycin detected by nucleic acid mass spectrometry were 1.000, 1.000, 0.635, and 0.821, respectively. Conclusions Nucleic acid mass spectrometry is a highly sensitive and specific method for detecting drug-resistance genes in Mycobacterium tuberculosis samples. It is a rapid, sensitive, accurate, and flexible molecular detection method with a promising application prospect in diagnosing drug-resistant tuberculosis.
7.National Metabolic Management Center(MMC) comprehensive management standards for patients with diabetes, hypertension, and hyperlipidemia
Weiqing WANG ; Yufan WANG ; Guixia WANG ; Aifang WANG ; Chunfang WEN ; Fanrong TIAN ; Guang NING ; Ping FENG ; Dalong ZHU ; Libin LIU ; Bangqun JI ; Heng SU ; Jianling DU ; Shu LI ; Yunsong LI ; Liu YANG ; Li LI ; Shengli WU ; Jinsong KUANG ; Yubo SHA ; Ping ZHANG ; Yawei ZHANG ; Yifei ZHANG ; Qidong ZHENG ; Zhongyan SHAN ; Dong ZHAO ; Zhigang ZHAO ; Tingyu KE ; Yu SHI ; Xuejiang GU ; Ning XU ; Fengmei XU ; Zuhua GAO ; Rong TANG ; Qijuan DONG ; Songbo FU ; Yi SHU ; Weici XIE ; Yuancheng DAI
Chinese Journal of Endocrinology and Metabolism 2024;40(12):1007-1023
Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.
8.Research Progress on the Mechanism of Baicalin Against Colorectal Cancer
Baiyan WANG ; Yihao ZHANG ; Dandan GUO ; Aifang LI ; Sugai YIN ; Shuying FENG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(10):2732-2738
Colorectal cancer(CRC)is the third leading cause of cancer death in the world,and the incidence of colorectal cancer is also increasing year by year,and the treatment options such as radiotherapy,chemotherapy and surgical removal of cancerous sites are not ideal,so there is an urgent need to find a new treatment strategy and solution.The adjuvant treatment of colorectal cancer with traditional Chinese medicine has the characteristics of multi-target,multi-level,multi-link and overall regulation,which plays an increasingly important role in tumor treatment and has become a hot field for anti-tumor drug screening.Skullcap has been widely studied as one of the main drugs adjuvant to treat colorectal cancer by traditional Chinese medicine.This paper reviews the anti-colorectal cancer effect of skullcap and its active ingredients and the current research progress,aiming to provide the background information and the reference for the treatment of colorectal cancer.
9.The application value of GeneXpert MTB/RIF Ultra in the detection of special specimens of tuberculosis
WU Xia ; YANG Yuanli ; LI Aifang ; ZHENG Huiqiang ; TAN Xiaowen ; GUI Xiaoli ; KANG Lei ; ZHOU Yong ; YANG Han ; LEI Jing
China Tropical Medicine 2023;23(8):846-
Abstract: Objective To compare the diagnostic efficacy of the upgraded version of the GeneXpert automated fluorescent quantitative PCR system (GeneXpert MTB/RIF Ultra, GeneXpert Ultra) and the original version of the GeneXpert system (GeneXpert MTB/RIF, Xpert), real-time fluorescent quantitative nucleic acid detection (FQ-PCR), real-time fluorescent thermostatic amplification of Mycobacterium tuberculosis RNA (SAT-RNA), real-time fluorescent thermostatic amplification detection of DNA (thermostatic amplification method) and traditional BACTEC MGIT 960 liquid culture (culture method) for special specimens of tuberculosis, in order to analyze its application value in clinical detection. Methods Using prospective research methods, a total of 170 special specimens (including 47 pleural and ascites effusion samples, and 34 24-hour urinary sediment specimens, 49 tissue specimens and 40 fester specimens) were collected i'an Chest Hospital from January to September 2021. GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were used for detection. Clinical diagnosis was used as the standard, and sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate, and Kappa value were compared among the methods. Results The sensitivities of GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were 65.18% (73/112), 49.11% (55/112), 37.50% (42/112), 19.64% (22/112), 8.04% (9/112), and 22.32% (25/112), respectively. The sensitivity of GeneXpert Ultra was higher than that of the other five methods, and the differences were statistically significant (χ2=66.25, 42.10, 28.89, 13.09, 4.92, 15.18, all P<0.05). GeneXpert Ultra result analysis showed that: 5.48%(4/73) cases had trace, that is, trace Mycobacterium tuberculosis load, 79.45% (58/73) cases were extremely low, 10.96% (8/73) cases were low, 2.74% (2/73) were medium, , and 1.36% (1/73) were high load. In 4 trace samples, the Xpert detection was negative for all. Of the 73 GeneXpert Ultra positive reports, 63 were rifampicin-sensitive, 6 were rifampicin-resistant, and 4 were rifampicin-resistant but of unclear resistance. Of the 55 Xpert positive reports, 45 were rifampicin-sensitive, 2 were rifampicin-resistant, and 8 were rifampicinresistant but of unclear resistance.. Conclusions The new generation of GeneXpert MTB/RIF Ultra has high sensitivity, specificity and drug resistance detection rate, and its advantage is even more apparent in the pathogenic diagnosis of special
specimens of tuberculosis. It can be used as one of the preferred methods in samples with low bacterial load.
10.Meta-analysis of the association between brain-derived neurotrophic factor in peripheral blood and Alzheimer's disease
Zemei LI ; Junping GUO ; Xiaolan ZHANG ; Aifang ZHONG ; Xiahui FANG ; Zaohuo CHENG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(1):87-94
Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.

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