Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Ferroptosis ; Signal Transduction ; Brain Ischemia/metabolism* ; Cyclooxygenase 2/metabolism* ; RNA, Messenger ; Cerebral Infarction ; Reperfusion Injury/metabolism* ; Malondialdehyde ; Infarction, Middle Cerebral Artery

OBJECTIVE To observe the clinical efficacy of modified Chaihu Guizhi Decoction in treating stable angina pectoris with anxiety/depression in patients with coronary heart disease of qi stagnation and blood stasis type.METHODS 60 patients with stable angina pectoris and anxiety/depression caused by qi stagnation and blood stasis type of coronary heart disease were included in the study.They were randomly divided into a control group(n=30)and a treatment group(n=30).Both groups of patients received health education,psychological counseling,and routine treatment for coronary heart disease angina pectoris.The control group received droperidol melitracin tablets in addition to basic treatment,while the treatment group received modified Chaihu Guizhi Decoction in ad-dition to basic treatment for 4 weeks.The efficacy of traditional Chinese medicine(TCM)syndrome,total score of traditional Chinese medicine syndrome,angina symptom score,electrocardiogram treadmill exercise test,nitroglycerin withdrawal rate,self-rating anxiety scale(SAS),self-rating depression scale(SDS),and Seattle angina questionnaire(SAQ)scores between the two groups of patients were compared before and after treatment.At the same time,peripheral blood lipids and IL-6 levels were measured.RESULTS Af-ter treatment,the TCM syndrome score,angina symptom score,SAS,SDS score of both groups of patients decreased(P<0.01),and the scores of various dimensions of SAQ increased(P<0.01).The occurrence time of ST segment depression of 1mm in treadmill exer-cise test was prolonged,the occurrence time of angina was prolonged,and the recovery time of ST segment was shortened(P<0.01),and TC,TG,LDL-C,IL-6 were significantly reduced(P<0.05,P<0.01).Moreover,the treatment group was superior to the con-trol group in improving TCM syndrome scores,angina symptom scores,SAS,SDS scores,PL and TS scores in SAQ,apparent effective rate of TCM syndrome,nitroglycerin cessation rate,blood lipids(TC,LDL-C),and serum IL-6(P<0.05,P<0.01).CONCLU-SION Modified Chaihu Guizhi Decoction can significantly improve the clinical symptoms,anxiety and depression status of patients with stable angina pectoris and anxiety/depression of qi stagnation and blood stasis type of coronary heart disease,improve quality of life,reduce blood lipids and IL-6 levels.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To explore the influence of nutritional status on 90-day functional outcomes of stroke patients with acute large vessel occlusion in the anterior circulation after endovascular treatment (EVT). METHODS: We retrospectively analyzed the baseline, laboratory, surgical and 90-day follow-up data of patients with stroke resulting from acute large vessel occlusion in the anterior circulation, who underwent emergency endovascular treatment in our hospital from July, 2015 to December, 2020. A favorable outcome was defined as a modified Rankin scale score ≤2 at 90 days. Univariate and multivariate regression analyses were performed to explore the relationship between nutritional status and 90-day functional outcomes of the patients. RESULTS: A total of 459 patients (mean age of 68.29±11.21 years, including 260 males) were enrolled in this study. According to their prognostic nutritional index (PNI), the patients were divided into normal nutrition group (392 cases, 85.4%), moderate malnutrition group (44 cases, 9.6%), and severe malnutrition group (23 cases, 5.0%). Univariate analysis showed that the patients with good clinical outcomes had a lower proportion of malnutrition with a younger age, a lower rate of diabetes, lower baseline blood pressure, lower baseline NIHSS score, higher baseline ASPECT score, and higher rates of good collateral circulation and complete vascular recanalization. Multivariate analysis showed that in addition to age, diabetes, baseline systolic blood pressure, successful recanalization, baseline ASPECT score, baseline NIHSS score and collateral circulation, a greater PNI was a protective factor for a good 90-day outcome of patients after EVT (moderate vs severe: OR=0.245, 95% CI: 0.066-0.908, P=0.035; normal vs severe: OR=0.185, 95% CI: 0.059-0.581, P=0.004). CONCLUSION Nutritional status an important factor affecting the 90-day outcomes after EVT of stroke patients with acute large vessel occlusion in the anterior circulation.
Aged ; Brain Ischemia/etiology* ; Endovascular Procedures/methods* ; Humans ; Male ; Malnutrition/etiology* ; Middle Aged ; Nutritional Status ; Retrospective Studies ; Stroke/surgery* ; Thrombectomy/methods* ; Treatment Outcome

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine ; Percutaneous Coronary Intervention/adverse effects* ; Quality of Life ; Stroke Volume ; Ventricular Function, Left

To study the regulating effect of total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. on the intestinal flora and short-chain fatty acids in spontaneous type 2 diabetic nephropathy mice, db/db mice were taken as the research object, and were treated with the total phenolic acid of Salvia miltiorrhiza Bge. Animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine Drug Safety Evaluation Research Center. Fresh feces and cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. Gas chromatography was used to detect short-chain fatty acids in fresh feces and cecal content. Then the correlation analysis of the two results was made. Compared with the normal group, the most significant decreased differential flora in the model group were g_Rikenellaceae_ RC9_gut_group and g_Bacteroidales_S24-7_group, while the most significant increased were g_unclassified_f__ Coriobacteriaceae and g_unclassified_p__Firmicutes. Compared with the blank group, the contents of isovaleric acid and valeric acid in fresh feces and the contents of 6 short-chain fatty acids in the cecal contents of the model group were significantly reduced (P < 0.01). After drug intervention, the intestinal flora disorder and the reduction of short-chain fatty acids were improved to varying degrees, and the effect of the total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. was slightly better than that from the roots in regulating some flora and short-chain fatty acids. The results of correlation analysis showed that g_Rikenellaceae_RC9_gut_group was moderately positively correlated with acetic acid and isobutyric acid in the cecal contents (r > 0.4). It is suggested that the total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. can improve the intestinal flora disorder of mice with type 2 diabetic nephropathy, and can regulate the content of short-chain fatty acids in the intestine via adjusting the content of some short-chain fatty acid-producing bacteria, thereby helping to restore normal.

Objective:To explore the effective components， targets， and possible mechanisms of Wenshen Yangxue prescription in improving endometrial receptivity of aged female mice based on network pharmacology and experimental verification. Method:Based on Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine， the components and targets of Wenshen Yangxue prescription were retrieved， and the targets of ovulatory dysfunctional infertility were collected from the Online Mendelian Inheritance in Man （OMIM） and GeneCards with "anovulatory sterility" and "anovulatory infertility" as keywords. The protein-protein interaction （PPI） network was constructed based on STRING and the core targets of Wenshen Yangxue prescription against ovulatory dysfunctional infertility were screened by Cytoscape， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the core targets in DAVID database. Then， the "medicinal-component-target-pathway" network was established and the core targets were verified by animal experiment. Result:A total of 253 components and 326 targets of Wenshen Yangxue prescription， 819 disease targets， and 74 common targets were screened out. The common targets were mainly involved in the biological processes such as positive regulation of nitric oxide biosynthetic process， positive regulation of cell proliferation， response to estradiol， aging， response to oxidative stress， and angiogenesis. The GO term of response to oxidative stress and five of the top 20 KEGG pathways were analyzed. According to the "medicinal-component-target-biological process/pathway" network， 41 chemical components in 20 medicinals participated in hypoxia inducible factor-1 （HIF-1） signaling pathway， tumor necrosis factor （TNF） signaling pathway， forkhead box O （FOXO） signaling pathway， Toll-like receptor （TLR） signal pathway， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway by affecting 35 targets. The results of animal experiment showed that the prescription could increase the expression of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， forkhead box O3A （FoxO3A）， and phosphorylated FoxO3A （p-FoxO3A） in uterus of aged female ICR mice. Conclusion:Wenshen Yangxue prescription interferes with oxidative stress and PI3K/Akt/FoxO3A signaling pathway by influencing Akt1， dual oxidase 2 （DUOX2）， epidermal growth factor receptor （EGFR）， heme oxygenase-1 （HMOX1）， myeloperoxidase （MPO）， and other targets， thereby improving endometrial receptivity of aged female mice.

Objective: To analyze the effect of acupuncture versus hormone replacement therapy (HRT) for premature ovarian insufficiency (POI). Methods: China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Web of Science, Cochrane Library, PubMed, and Excerpta Medica Database (EMBASE) were searched up to January 31st, 2019 to identify randomized controlled trials (RCTs) evaluating the effect of acupuncture for POI. The primary outcome was the level of basal serum follicle- stimulating hormone (FSH). Secondary outcomes included serum levels of luteinizing hormone (LH), estradiol (E2) and anti-Müllerian hormone (AMH). Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane's tool. Meta-analysis was conducted by RevMan version 5.3. Results: Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis. The pooled results showed that there was a significant reduction in the basal serum FSH level (MD=-5.82, 95％CI:-9.76 to -1.87, I2=82％, P=0.004) and a remarkable elevation in the basal E2 level (SMD=0.93, 95％CI: 0.34 to 1.52, I2=88％, P=0.002) in the acupuncture group when compared with the control. Subgroup analysis showed that compared with HRT, a significant decrease in the FSH level was observed in both acupuncture alone (MD=-4.53, 95％CI:-8.96 to -0.10, I2=73％, P=0.04) and acupuncture plus HRT (MD=-9.60, 95％CI:-17.60 to -1.61, I2=50％, P=0.02), while a remarkable elevation of E2 was only found in acupuncture plus HRT (SMD=1.43, 95％CI: 1.03 to 1.82, I2=0％, P<0.00001). There was no significant difference in the LH level between acupuncture and HRT (MD=-3.16, 95％CI:-9.41 to 3.10, I2=0％, P=0.32), only one trial reported AMH, and no significant difference was found between acupuncture and HRT. Conclusion: The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI. However, evidence supporting the finding is limited due to the small sample size, potential methodological flaws and significant heterogeneity. Hence, this conclusion still needs to be verified by high-quality RCTs.

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 10/L to 1.08 ± 0.62 × 10/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 μ g/L (P<0.05), 3 months with 33.56 ± 15.28 μ g/L (P<0.05), and 6 months with 36.78 ± 11.92 μ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 μ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, μ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, μ g/L, P<0.05). CONCLUSION QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.