1.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
ObjectiveTo explore the feasibility, evaluation methods and metabolic differences of high-fat diet(HFD) combined with myocardial ischemia-reperfusion injury(MIRI) to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome(PBSBCS). MethodsThirty-two SD rats were randomly divided into the sham operation, HFD, MIRI, and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet(regular chow), while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery, while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography, including left ventricular ejection fraction(EF), left ventricular fractional shortening(FS), cardiac output(CO), and stroke volume(SV). Serum levels of creatine kinase(CK), CK-MB, triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), lactate dehydrogenase(LDH), endothelin-1(ET-1), endothelial nitric oxide synthase(eNOS), tumor necrosis factor-α(TNF-α), interleukin-18(IL-18), oxidized LDL(ox-LDL), and cardiac troponin T(cTnT) were measured by biochemical assays and enzyme-linked immunosorbent assay(ELISA). Myocardial histopathology was evaluated via hematoxylin-eosin(HE) staining, while myocardial infarction and no-reflow area were assessed using 2,3,5-triphenyltetrazolium chloride(TTC), Evans blue, and thioflavin staining. Changes in syndrome characteristics[body weight, tongue surface red-green-blue [RGB] values, and pulse amplitude] of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). ResultsCompared with the sham operation group, the HFD and MIRI+HFD groups showed significant increases in body weight(P<0.01), RGB values and pulse amplitude decreased in the HFD, MIRI and MIRI+HFD groups, TC, TG, LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups, while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased, serum eNOS level decreased, and CK-MB, LDH, and cTnT activities increased in the HFD, MIRI and MIRI+HFD groups(P<0.05, P<0.01). Whole blood viscosity was increased in the HFD group at medium shear rate, and in the MIRI and MIRI+HFD groups at low, medium and high shear rates(P<0.05, P<0.01). Platelet aggregation rate increased in the MIRI and MIRI+HFD groups, accompanied by elevated ET-1, TNF-α, and IL-18 levels, reduced cardiac function indices, expanded myocardial no-reflow and infarction areas, and increased serum CK, CK-MB, LDH, and cTnT activities(P<0.05, P<0.01). Compared with the MIRI group, the HFD and MIRI+HFD groups showed significant increase in body weight, TC, TG, LDL-C and ox-LDL levels, and significant decrease in HDL-C content(P<0.01). The MIRI+HFD group showed decrease in RGB values and pulse amplitude, and an increase in whole blood viscosity, platelet aggregation, blood perfusion peak time, myocardial no-reflow and infarction areas, elevated ET-1, TNF-α and IL-18 levels, decreased eNOS content, EF and SV, increased serum CK, CK-MB and cTnT activities, and worsened myocardial pathology(P<0.05). Compared with the HFD group, the MIRI+HFD group showed similar aggravated trends(P<0.05, P<0.01). Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury, and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices, effectively simulating clinical features of coronary heart disease(CHD), which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.
2.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
ObjectiveTo explore the feasibility, evaluation methods and metabolic differences of high-fat diet(HFD) combined with myocardial ischemia-reperfusion injury(MIRI) to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome(PBSBCS). MethodsThirty-two SD rats were randomly divided into the sham operation, HFD, MIRI, and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet(regular chow), while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery, while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography, including left ventricular ejection fraction(EF), left ventricular fractional shortening(FS), cardiac output(CO), and stroke volume(SV). Serum levels of creatine kinase(CK), CK-MB, triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), lactate dehydrogenase(LDH), endothelin-1(ET-1), endothelial nitric oxide synthase(eNOS), tumor necrosis factor-α(TNF-α), interleukin-18(IL-18), oxidized LDL(ox-LDL), and cardiac troponin T(cTnT) were measured by biochemical assays and enzyme-linked immunosorbent assay(ELISA). Myocardial histopathology was evaluated via hematoxylin-eosin(HE) staining, while myocardial infarction and no-reflow area were assessed using 2,3,5-triphenyltetrazolium chloride(TTC), Evans blue, and thioflavin staining. Changes in syndrome characteristics[body weight, tongue surface red-green-blue [RGB] values, and pulse amplitude] of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). ResultsCompared with the sham operation group, the HFD and MIRI+HFD groups showed significant increases in body weight(P<0.01), RGB values and pulse amplitude decreased in the HFD, MIRI and MIRI+HFD groups, TC, TG, LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups, while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased, serum eNOS level decreased, and CK-MB, LDH, and cTnT activities increased in the HFD, MIRI and MIRI+HFD groups(P<0.05, P<0.01). Whole blood viscosity was increased in the HFD group at medium shear rate, and in the MIRI and MIRI+HFD groups at low, medium and high shear rates(P<0.05, P<0.01). Platelet aggregation rate increased in the MIRI and MIRI+HFD groups, accompanied by elevated ET-1, TNF-α, and IL-18 levels, reduced cardiac function indices, expanded myocardial no-reflow and infarction areas, and increased serum CK, CK-MB, LDH, and cTnT activities(P<0.05, P<0.01). Compared with the MIRI group, the HFD and MIRI+HFD groups showed significant increase in body weight, TC, TG, LDL-C and ox-LDL levels, and significant decrease in HDL-C content(P<0.01). The MIRI+HFD group showed decrease in RGB values and pulse amplitude, and an increase in whole blood viscosity, platelet aggregation, blood perfusion peak time, myocardial no-reflow and infarction areas, elevated ET-1, TNF-α and IL-18 levels, decreased eNOS content, EF and SV, increased serum CK, CK-MB and cTnT activities, and worsened myocardial pathology(P<0.05). Compared with the HFD group, the MIRI+HFD group showed similar aggravated trends(P<0.05, P<0.01). Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury, and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices, effectively simulating clinical features of coronary heart disease(CHD), which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.
3.Research Progress on the Epidemiology, Clinical Characteristics, and Resistance Mechanisms of Burkholderia Cepacia Complex
Wenjie CUI ; Rongqi LU ; Yali LIU
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1148-1156
The
4.Mechanism of action of energy metabolism in hepatic ischemia-reperfusion injury and related targeted therapies
Tiantian YANG ; Lu HUANG ; Xiao ZHANG ; Yali REN ; Weitian XU ; Song ZHANG
Journal of Clinical Hepatology 2025;41(9):1956-1960
Hepatic ischemia-reperfusion injury (HIRI) is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy, and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies, in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.
5.Issues in primary care of anaphylaxis in children
Lei XI ; Yali YANG ; Qiuyu YAO ; Xu LU
Chinese Pediatric Emergency Medicine 2024;31(7):497-500
In recent years, there has been an increasing trend regarding the incidence of anaphylaxis among children in China. Despite the existence of relevant diagnosis and treatment guidelines for regulation, due to reasons such as uneven allocation of medical resources, there are still many problems in the specific implementation process of primary health care institutions, and these problems may lead to untimely and irregular handling of allergic reactions, thereby increasing the risk for pediatric patients. This review discussed the related issues existing about the diagnosis and treatment of anaphylaxis in children in primary health care institutions.
6.Effect of EPDR1 on hepatocyte lipid deposition
Guifang WANG ; Xuebing CHANG ; Laying HU ; Lu LIU ; Yali HUANG ; Lingyu SONG ; Yuxia ZHOU ; Bing GUO
Chinese Journal of Pathophysiology 2024;40(7):1205-1212
AIM:This study aims to examine the ependymin-related protein 1(EPDR1)expression in various tissues from wild-type C57BL/6 mice and type 2 diabetes(db/db)mice.The impact of EPDR1 on lipid accumulation in al-pha mouse liver 12(AML12)hepatocytes was also investigated.METHODS:Western blot was used to detect EPDR1 protein expression in the heart,liver,spleen,lung,kidney,gastrocnemius,brown adipose and brain tissues of C57BL/6 mice.Western blot and immunohistochemical(IHC)staining were also used to compare EPDR1 protein expression in the liver,gastrocnemius muscle,heart and kidney tissues of db/db and C57BL/6 mice.To develop an AML12 cell lipid deposi-tion model,palmitic acid(PA)+oleic acid(OA)was used,and the cells were transfected with adenovirus overexpressing EPDR1 or treated with exogenous recombinant EPDR1 protein(rEPDR1).ELISA was conducted to determine intracellu-lar triglyceride(TG)content,and oil red O staining was employed to assess the effect of EPDR1 on lipid accumulation in AML12 cells.RESULTS:Western blot and IHC staining results revealed that EPDR1 was widely expressed in various tis-sues of wild-type mice,with the liver exhibiting the highest protein expression level.However,EPDR1 expression was down-regulated in the liver,gastrocnemius muscle,heart and kidney tissues in diabetic db/db mice compared with wild-type mice.Oil red O staining revealed that overexpression of EPDR1 in AML12 liver cells or rEPDR1 treatment led to re-duced lipid accumulation.Furthermore,the TG content significantly decreased compared with the model group(P<0.05).CONCLUSION:EPDR1 is expressed in various tissues of wild-type mice,but showed diminished expression in the liver tissues of diabetic mice.Nevertheless,enhancing the expression of EPDR1 can aid in reducing lipid accumula-tion in hepatocytes.These findings provide an experimental foundation for further exploration of the role of EPDR1 in the development of fatty liver in diabetic liver tissue.
7.Modified Xiaoyao powder for postpartum depression: A systematic review and meta-analysis
Mengyuan Hu ; Xiaowen Zhang ; Xuya Zhang ; Dan Cheng ; Yali Zhang ; Xinyu Zhang ; Lingling Li ; Xinjie Li ; Xue Li ; Yi Lu
Journal of Traditional Chinese Medical Sciences 2024;11(1):120-130
Objective:
To evaluate the effectiveness and safety of modified Xiaoyao powder for postpartum depression (PPD) by conducting a systematic review of randomized controlled trials (RCTs).
Methods:
The Chinese National Knowledge Infrastructure Databases (CNKI), the Chinese Scientific Journals Database (VIP), Wanfang, Google Scholar, the SinoMed, Embase, Cochrane Library, and PubMed databases were searched from their inception to April 25, 2023. The Cochrane Risk of Bias tool was used to assess the quality of the trials. We applied the risk ratio to present dichotomous data and the mean difference to present continuous data. Data with similar characteristics were pooled for meta-analysis and heterogeneity was assessed using I2.
Results:
This review included 35 trials involving 2848 participants. The quality of the included studies was low (unclear randomization processes and insufficient reporting of blinding). Participants treated with modified Xiaoyao powder plus Western medicine showed lower Hamilton Depression Scale (HAMD) depression score than those who used Western medicine alone (mean difference = −2.15; 95% confidence interval:−2.52 to 1.78; P < .00001), and higher effective rate (relative risk = 1.19; 95% confidence interval: 1.15 to 1.24; P < .00001), When comparing modified Xiaoyao alone with Western medicine, the HAMD depression score remained low, however, the efficacy rate was higher in the modified Xiaoyao group. Regarding adverse events, the modified Xiaoyao group reported weight gain, nausea, and diarrhea, but no severe adverse events were reported.
Conclusion
Modified Xiaoyao may help relieve depression in PPD when used alone or in combination with Western medicine, with minor side effects. Therefore, future high-quality, large-sample size RCTs are warranted.
8.Treatment failure and drug resistance among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022
Yan LI ; Xuanhe WU ; Lu SHI ; Guixia LI ; Shanling WANG ; Yating WANG ; Tailin CHEN ; Tingting WANG ; Yali XIE ; Weiwei SHEN ; Haijiang LIN ; Xiaoxiao CHEN ; Na HE
Shanghai Journal of Preventive Medicine 2024;36(11):1031-1038
ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age (P25,P75) was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.
9.Combined CT-based extracellular volume with pathologic indicators predicts early postoperative recurrence of gastric mesenchymal tumors
Hong LU ; Haitao LI ; Ping CAI ; Xinyue DU ; Xiaoqin YIN ; Guishen JIANG ; Huafeng CHAI ; Xue WEI ; Yali DENG ; Guolan DENG
Journal of Army Medical University 2024;46(23):2661-2669
Objective To investigate the clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95%CI 0.758~0.918),0.774(95%CI 0.656~0.892),and 0.700(95%CI 0.589~0.810),respectively,and the value of their combined model was 0.899(95%CI 0.811~0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71%and 86.52%,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P<0.001,95%CI 0.140~0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.
10.HUVEC-Based OGD/R Injury Model to Study the Effect of Danggui-Chuanxiong Herb Pair Medicine on the Main Pharmacological Components on VEGF-PI3K-AKT/NF-κB Signaling Pathway
Qiuru JI ; Wenjuan NI ; Xiaoyan WANG ; Shuqi ZHANG ; Yali WU ; Lu NIU ; Kun LI ; Weixia LI ; Jinfa TANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(3):691-703
Objective To study the effects of Danggui-Chuanxiong herb pair medicine on vasoactive substances,adhesion factors,inflammatory factors,and VEGF-PI3K-AKT/NF-κB signaling pathways,in order to elucidate the mechanism of Danggui-Chuanxiong herb pair on the treatment of ischemic stroke(IS).Methods The oxygen glucose deprivation/reoxygenation(OGD/R)model of human umbilical vein endothelial cells(HUVEC)was constructed,and the cell viability was detected by cell proliferation kit(CCK-8 method)to explore the optimal modeling time of seven components;The release of lactate dehydrogenase(LDH)was detected by cytotoxicity kit;The expression of related cytokines was detected by enzyme-linked immunosorbent assay(ELISA);The mRNA expression of key proteins in the signaling pathway was detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Reoxygenation after 6 h of oxygen-glucose deprivation of HUVEC is the best modeling time.High-dose chlorogenic acid group,ferulic acid group,senkyunolide H,low-dose and medium-dose butylidenephthalide group,medium-dose and high-dose senkyunolide A and ligustilide groups significantly decreased LDH leakage rate(P<0.05,P<0.01);The expression of IL-6 in the cells of the partial dose group of chlorogenic acid,caffeic acid,butenylphthalide,senkyunolide H and senkyunolide A was significantly increased,the expression of IL-1 in the cells of the partial dose group of chlorogenic acid,ferulic acid and senkyunolide A was significantly decreased,the expression of VEGF,ICAM-1 and VCAM-1 in the cells of the partial dose group of chlorogenic acid,ferulic acid and senkyunolide H was significantly decreased,the expression of NF-κB in the cells of the partial dose group of chlorogenic acid,ferulic acid,senkyunolide H and ligustilide was significantly decreased,the expression of PAI-1 in the cells of ferulic acid and senkyunolide H partial dose group decreased significantly(P<0.05,P<0.01);The mRNA relative expression levels of ERK,VEGF,NF-κB,VEGFR2 and MMP9 were significantly down-regulated in the cells of chlorogenic acid,ferulic acid,caffeic acid,butylidenephthalide and senkyunolide A partial dose group,while the mRNA relative expression levels of AKT were significantly up-regulated in the cells of senkyunolide H and senkyunolide A partial dose groups(P<0.05,P<0.01).Conclusion The medicinal components of Danggui-Chuanxiong herb pair may play a role in IS by inhibiting the mRNA expression of adhesion factor,inflammatory factor and key protein of VEGF-PI3K-AKT/NF-κB signaling pathway in HUVEC.


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