OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

Aim To investigate the effect of recombi-nant glycoprotein hormone β5/α2(rCGH)on lipolysis in 3T3-L1 adipocytes,and explore the underlying mechanism.Methods 3T3-L1 preadipocytes were cultured and induced to differentiate into mature adipo-cytes,then treated with different concentrations of rCGH for 24 h in vitro.Cell viability of 3T3-L1 adipo-cytes was evaluated by CCK-8 assay,the levels of in-tracellular triglyceride(TG)and glycerol in the culture supernatant were measured by enzymatic method,and the changes of lipid droplets were observed by oil red O staining.The expression levels of HSL and ATGL lipo-lytic proteins in adipocytes were detected by Western blot.To carry out the intervention experiment with dif-ferent concentrations of rCGH with or without the PKA inhibitor,H89,on the mature 3T3-L1 adipocytes,the cultured cells were divided into the control group,H89 pre treatment group,1 μmol·L-1 rCGH group,and(1 μmol·L-1 rCGH+H89)combined intervention group.The contents of intracellular TG and free glycer-ol were measured by enzymatic method,and the ex-pression of CREB and lipolysis-related proteins was de-tected using Western blot.Results Different concen-trations of rCGH(0.25,0.5,1,and 2 μmol·L-1)had no significant effect on the cell viability of adipo-cytes(P＞0.05).Compared with the control group,the treatment with rCGH significantly decreased the size of lipid droplets and intracellular TG content,while significantly elevated glycerol concentration in cell supernatant.rCGH treatment also stimulated the protein expression of p-HSL,ATGL,and p-PKA.In addition,the addition of a PKA inhibitor,H89,atten-uated the effects of rCGH on free glycerol level,intra-cellular TG content,and the expression of p-HSL,p-PLIN1,and p-CREB.Conclusions rCGH enhances the lipolysis of 3T3-L1 adipocytes by up-regulating the activities of HSL,ATGL and PKA,promoting glycerol release,inhibiting TG synthesis and lipid accumula-tion,and its mechanism of action is related to the acti-vation of cAMP/PKA/CREB signaling pathway.

Aim To observe the changes in hippocam-pal 2A subunit of N-methyl-D-aspartate receptor(NR2A)before and after the learning and memory training,and then investigate the neuropharmacological effects of NR2A by microinjection of NVP-AAM077(NR2A specific antagonist)into the hippocampal den-teta gyrus,based on the spatial learning and memory behavior paradigm induced by Mirror water maze train-ing.Methods Three-month old SD rats were random-ly divided into the training and non-training group,and the rats in the two groups were randomly divided into control group and NVP-AAM077 group(NVP).The expressions of NR2A,brain-derived neurotrophic factor(BDNF),transcriptional activator 4(ATF4)and eu-karyotic transcription initiation factor 2 α(eIF2α)phosphorylation levels in denteta gyrus were detected by Western blot.Then,integrated stress response in-hibitor ISRIB was microinjected into the dentate gyrus after the NVP,the expression of ATF4 and p-eIF2αlevels,and the spatial memory abilities were detected.Results Compared with non-training,behavioral training promoted the expression of NR2A and BDNF of rats in denteta gyrus,and this effect could be inhibi-ted by NVP,which significantly increased the expres-sion of p-eIF2α and ATF4.Injection of ISRIB into denteta gyrus significantly inhibited the expression of ATF4,and reversed the spatial memory impairment caused by NVP.Conclusion NVP-induced hipp-ocampal dentate gyrus NR2A-mediated spatial learning and memory impairment in rats may be related to hipp-ocampal integrated stress response.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

Objective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.
Humans ; Metabolic Syndrome ; Overweight ; Coronary Artery Disease ; Retrospective Studies ; Cross-Sectional Studies ; Obesity ; Cholesterol, HDL ; Biomarkers

Seasonal influenza leads to a significant disease burden, and older people infected with influenza are susceptible to various complications. Influenza immunization can prevent infection effectively and significantly reduce the risk of complications and severe cases. Creating a supportive environment for vaccination is crucial in advancing the influenza vaccination rate among the elderly population. In China, the present environment for supporting influenza vaccinations among the elderly is primarily comprised of policies for free vaccination and expense reimbursement, which exhibit noteworthy regional variations across cities and regions. This study systematically analyses the supportive environment and regional disparities associated with influenza vaccination among the elderly in China. It aims to comprehend the opportunities for influenza prevention and control resulting from the current background of influenza vaccination and to identify potential health inequality challenges caused by regional differences. The findings should inform the introduction of relevant national policies and programs to protect the health and well-being of the elderly population.
Humans ; Aged ; Health Status Disparities ; Influenza, Human/prevention & control* ; China ; Cities ; Vaccination

Objective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.
Humans ; Metabolic Syndrome ; Overweight ; Coronary Artery Disease ; Retrospective Studies ; Cross-Sectional Studies ; Obesity ; Cholesterol, HDL ; Biomarkers

Seasonal influenza leads to a significant disease burden, and older people infected with influenza are susceptible to various complications. Influenza immunization can prevent infection effectively and significantly reduce the risk of complications and severe cases. Creating a supportive environment for vaccination is crucial in advancing the influenza vaccination rate among the elderly population. In China, the present environment for supporting influenza vaccinations among the elderly is primarily comprised of policies for free vaccination and expense reimbursement, which exhibit noteworthy regional variations across cities and regions. This study systematically analyses the supportive environment and regional disparities associated with influenza vaccination among the elderly in China. It aims to comprehend the opportunities for influenza prevention and control resulting from the current background of influenza vaccination and to identify potential health inequality challenges caused by regional differences. The findings should inform the introduction of relevant national policies and programs to protect the health and well-being of the elderly population.
Humans ; Aged ; Health Status Disparities ; Influenza, Human/prevention & control* ; China ; Cities ; Vaccination