Objective To investigate the risk factors for heart failure in patients with coronary atherosclerotic heart disease and to analyze the influence of different blood pressure levels on the risk of heart failure.Methods A total of 826 coronary atherosclerotic heart disease patients admitted to the Department of Cardiovascular Medicine of First Hospital of Qinhuangdao from October 2018 to October 2020 were selected as the research subjects.The patients were divided into the heart failure group(n=27)and the non-heart failure group(n=799)based on whether heart failure occurred.The clinical data of patients in the two groups were collected,and the risk factors for heart failure in patients with coronary atherosclerotic heart disease were analyzed by using the univariate and multivariate logistic regression.According to the history of hypertension,the patients were divided into the hypertension history group(n=522)and the normal blood pressure group(n=304),and according to the blood pressure levels,the patients were further divided into the normal blood pressure group(n=304),grade 1 hypertension group(n=102),grade 2 hypertension group(n=254)and grade 3 hypertension group(n=166).The cumulative incidence of heart failure of patients was compared among all groups,and the impact of hypertension history and blood pressure levels on the occurrence of heart failure in patients with coronary atherosclerotic heart disease was analyzed by using the multivariate Cox proportional hazards regression model.Results Univariate analysis showed that there were statistically significant differences in the proportion of advanced age,history of hypertension,history of smoking,coronary artery disease,hemoglobin level,proportion of left atrial enlargement,and proportion of left ventricular hypertrophy between the heart failure group and the non-heart failure group(P＜0.05);and there was no significant difference in gender,history of hyperlipidemia,body mass index,history of diabetes,albumin level,and serum creatinine level between the two groups(P＞0.05).Multivariate logistic regression analysis showed that the history of hypertension,advanced age,multivessel coronary artery disease(≥2 vessels),and left ventricular hypertrophy were risk factors for heart failure in patients with coronary atherosclerotic heart disease(P＜0.05).The cumulative incidence of heart failure in the hypertension history group and the normal blood pressure group was 3.63％(19/522)and 2.63％(8/304),respectively;and the cumulative incidence of heart failure in the hypertension history group was significantly higher than that in the normal blood pressure group(x2=6.792,P＜0.05).The cumulative incidence of heart failure in the normal blood pressure group,grade 1 hypertension group,grade 2 hypertension group,and grade 3 hypertension group was 2.63％(8/304),2.94％(3/102),3.54％(9/254),and 4.22％(7/166),respectively,showing an increasing trend,and there was a significant difference between each group(P＜0.05).In the Cox proportional hazards model,model 1(unadjusted for confounding factors),model 2(adjusted for age factors),and model 3(adjusted for confounding factors such as the history of hypertension,history of smoking,coronary artery distase,hemoglobin level,left atrial enlargement,and left ventricular hypertrophy on the basis of model 2)all showed that the history of hypertension was the risk factor for heart failure in patients with coronary atherosclerotic heart disease,and the higher the blood pressure level,the higher the risk of developing heart failure(P＜0.05).Conclusion The history of hypertension,advanced age,multi vessel coronary artery disease(≥2 vessels),and left ventricular hypertrophy are risk factors for heart failure in patients with coronary atherosclerotic heart disease,among which the history of hypertension has the greatest influence,and the probability of developing heart failure increases as the blood pressure grade increases.

This article presented the maternal and infant outcomes of glycogen storage disease type Ⅲa (GSDⅢa) in a woman with full-term pregnancy. The woman exhibited symptoms of hypoglycemia when she was three months old, which were alleviated with intravenous glucose infusion. At the age of 19, during surgical treatment for scoliosis, she was found with liver cirrhosis, splenomegaly, and thrombocytopenia. Glycogen debranching enzyme deficiency was detected through liver biopsies, leading to the clinical diagnosis of GSDⅢ (unspecified genotype). The patient was admitted after conceiption due to "irregular lower abdominal pain for 1 day" at 34 weeks and 3 days. Through multidisciplinary management in the late pregnancy, which included medication adjustments, dietary instruction, and platelet transfusions both at half an hour before and during the operation, the patient underwent a cesarean section at 37 +1 weeks of gestation and delivered a healthy boy with normal Apgar scores at 1, 5, and 10 min. The mother followed a high-protein diet postpartum and the newborn experienced hypoglycemia after birth. Intravenous glucose was supplied to the infant, restabilizing his blood glucose. Maternal and neonatal blood glucose both remained stable. Postpartum whole-exome sequencing identified compound heterozygous variants in the mother, which were in the AGL gene at chr1:100379102-100379103 with gene variant information of NM_000642.2:c.3971_3972delAT(p.Tyr1324*) and at chr1:100345603 with gene variant information of NM_000642.2:c.1735+1G>T, confirming the diagnosis of GSDⅢa. The newborn carried a heterozygous variant in the AGL gene at chr1:100379102-100379103 with gene variant information of NM_000642.2:c.3971_3972delAT(p.Tyr1324*). Postpartum follow-ups showed stable blood glucose levels for the mother and normal growth and development for the newborn.

Abstract Gut flora undergoes a dynamic colonization and development process at different stages of human life. Sex specific gut flora development begins during puberty, which is influenced by sex hormone levels. The potential relationship between sex hormone levels, which suggests that there may be a two way interaction between intestinal flora and sex hormones. In addition, evidence is emerging for bidirectional effects of the microbiome in human health. Therefore, the review presents the dimorphism of intestinal flora, the characteristics of intestinal flora during puberty and the latest research progress, explores the close relationship between intestinal flora and precocious puberty and reproductive system diseases, and further explains the influence mechanism and treatment measures of considering gender factors in intestinal microflora, precocious puberty and reproductive system related diseases.

OBJECTIVE To explore the role and underlying mechanism of tournefolic acid B （TAB） on the improvement of glucose metabolism and renal function in diabetic nephropathy （DN） model mice. METHODS DN model mice were established by high-fat diet combined with streptozotocin， and then randomly divided into model group， positive control group （vitamin E， 20 mg/kg）， TAB low-dose， medium-dose and high-dose groups （1， 2， 4 mg/kg）， with 12 mice in each group； normal control group was given regular diet. Each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. The glucose metabolic function was estimated by fasting blood glucose， glucose tolerance test， insulin tolerance test and serum insulin concentration. The renal coefficients and biochemical indicators related to renal function [serum uric acid， blood urea nitrogen， creatinine levels， and ratio of urine microalbumin to creatinine] were detected in mice； the contents of biochemical indicators related to oxidative stress [superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， 8-hydroxydeoxyguanosine （8-OHdG）] were determined in renal tissue of mice； the pathological morphology of renal tissue was observed； the expressions of extracellular matrix （ECM） deposition related factors [transforming growth factor β1 （TGF- β1）， fibronectin （Fn）， type Ⅳ collagen （Col Ⅳ）] and protein kinase B （Akt）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway related proteins were determined in renal tissue of mice. RESULTS Compared with normal control group， fasting blood glucose， area under glucose tolerance curve， area under insulin tolerance curve， serum insulin content， the levels of uric acid， urea nitrogen and creatinine @qq.com and ratio of urinary microalbumin to creatinine in serum， the contents of MDA and 8-OHdG and the protein expressions of TGF-β1， Fn and Col Ⅳ were increased significantly in model group （P＜0.05）， while the contents of SOD， GSH-Px and the protein expressions of p-Akt， Nrf2， HO-1 in renal tissue were decreased significantly （P＜0.05）； the significant thickening of the basement membrane， accumulation of mesangial matrix， glomerulosclerosis and interstitial fibrosis of the renal tubules were all found. Compared with model group， above indexes of mice were all reversed significantly in TAB groups （P＜0.05）， and pathological changes were alleviated in a dose-dependent manner. CONCLUSIONS TAB can improve blood glucose metabolism and kidney function and alleviate renal tubulointerstitial fibrosis in DN model mice， the mechanism of which may be associated with activating the Akt/Nrf2/HO-1 signaling pathway and suppressing ECM deposition.

3-iodothyronamine（T1AM）is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ，slowing heart rate ，promoting lipolysis ， reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine，but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger ， T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM，in order to provide new therapeutic drugs of cardiovascular ，metabolic diseases and nervous system diseases.

Objective : To explore the material basis and mechanism of Yindan Xinnaotong soft capsule( YD) in treating myocardial ischemia⁃reperfusion injury (MIRI) based on network pharmacology , so as to provide theoreti⁃ cal reference for the treatment of MIRI. Methods : The main active components and action targets of YD were searched by TCMSP , SwissTargetPrediction and China knowledge Network . The disease targets of MIRI were screened by GeneCards database. The“ drug⁃component⁃disease⁃target ”network relationship was constructed by fication was carried out between the top three main active components and the top six targets in PPI network. Human myocardial AC⁃16 cells were constructed hypoxia/reoxygenation (H/R) model to initially verify the core target. Using CCK⁃8 assay was usedto detect cell viability and explore the optimal drugconcentration. The influence of YD on cell morphology was observed by using optical microscope. LDH content was detected to assess the integrity of cell membrane ; Western blot was used to detect the expression of STAT3 , p ⁃STAT3 , PI3K , AKT1 and p ⁃AKT1 . Results : A total of 105 active components , 382 drug targets , 1223 MIRI disease targets and 160 drug⁃disease common targets of YD were obtained. The key targets involved AKT1 , STAT3 , VEGFA , TNF , MAPK8 , PIK3CA and so on. GO analysis mainly involved apoptosis , lipolysis , muscle cell proliferation , cytokine⁃mediated inflammation , oxidative stress and so on. The results of molecular docking showed that VEGFA , APP and PIK3CA could bind to quercetin , luteolin and kaempferol. Our results showed that 200 mg/L YD could significantly promote the proliferation of AC⁃16 cells and reduce LDH leakage. Western blot results showed that YD could activate STAT3 and PI3K⁃AKT1 signaling pathways and protect myocardium. Conclusion YD can protect MIRI through multi⁃components , multi⁃targets and multi⁃pathways.

OBJECTIVE: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing. RESULTS: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors. CONCLUSION Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.

Objective To analyze HIV-1 drug resistance gene mutations in AIDS patients who failed first-line antiviral therapy in Hubei Province from 2017 to 2018, and to provide references for clinical treatment. Methods Plasma samples of HIV patients who had received first-line antiviral treatment for more than 12 months and had a viral load greater than 103 copies / ml were collected in Hubei Province, and drug resistance genotypes were detected. The prevalence and characteristics of drug resistance were analyzed. Results A total of 198 patients were selected, and 182 target gene sequences were successfully detected. The gene subtypes were mainly CRF01_{_}AE, with a total drug resistance rate of 69.23%. The proportion of NRTIs, NNRTIs and PIs resistance mutations was 46.15%, 65.38% and 0.55%, respectively. The occurrence of cross resistance mutations of NRTIs and NNRTIs reached 40.66%. The mutation sites related to NRTIs were mainly M184V and K65R, while the mutation sites related to NNRTIs were mainly V179D, K103N and Y181C. There was only one case of PIs related mutation at the site of M46I. Conclusion HIV-1 genotyping demonstrated a high proportion of drug resistance in the HAART failure population in Hubei Province, and multi-drug resistance occurred frequently. It is necessary to strengthen the monitoring of drug resistance, implement timely adjustments to antiviral treatment programs, and reduce the occurrence and spread of drug-resistant strains.

Objective:To explore the effects of human recombinant erythropoietin (rhEPO) on inflammation of hyperoxic lung injury in neonatal rats.Methods:Seventy-two neonatal rats were randomly divided into 4 groups: control group, BPD group, hyperoxia + low-dose recombinant erythropoietin [EPO(L)]group, and hyperoxia + high-dose recombinant erythropoietin [EPO(H)]group.The neonatal rats in BPD group, hyperoxia + EPO(L)group and hyperoxia + EPO(H)group were exposed to 850 mL/L oxygen.Then the neonatal rats in hyperoxia + EPO(L)group and hyperoxia + EPO(H)group were given 800 IU/kg and 2 000 IU/kg rhEPO by subcutaneous injection respectively at 1 d, 3 d and 7 d, while the control group and BPD group were given the same amount of 9 g/L saline water.Initially, the body weight of each group was recorded at 3 d, 7 d and 14 d. The morphological structure changes of lung tissues were observed by HE staining under light microscope, and the radial alveolar count(RAC) in lung tissues were detected.The expression of nuclear factor kappa B(NF-κB) was detected by immunofluorescence staining; Western blot was applied to determine the protein expression of phosphorylated NF-κB(pNF-κB), inhibitor protein(IκB) and Caspase-3 in lung tissues; and the expression of interleukin-1β(IL-1β) in bronchoalveolar lavage fluid was determined using enzyme linked immunosorbent assay (ELISA).Results:(1) On the 14 th day, the body weight of neonatal rats in the BPD group was lower than that in the control group [(18.97±3.21) g vs.(27.97±2.30) g], and the difference was statistically significant( P<0.01); however, the body weights of neonatal rats in the hyperoxia+ EPO(L)group and hyperoxia+ EPO(H)group[(24.16±2.15) g, (26.04±1.97) g] was much heavier than that in the BPD group, and the differences was statistically significant(all P<0.05). (2) The morphological structure of lung tissues which was observed by HE staining showed that in the BPD group, there were a few inflammatory cells infiltration in alveolar septum on the 3 rd day, the inflammatory response was more evident on the 7 th day, when exudation could be seen in the alveolar cavity; and on the 14 th day, the number of pulmonary alveoli decreased, pulmonary bulla formed, and septa were thickened.Besides, it was also observed that compared with control group, RAC was significantly decreased in BPD group on the 14 th day(5.50±1.29 vs.14.33±2.80), and the difference was statistically significant( P<0.01). Pathological changes were ameliorated and the infiltration of inflammatory reaction cells was reduced in the hyperoxia+ EPO(L)group and hyperoxia + EPO(H)group.RAC was remarkably higher in the hyperoxia+ EPO(L)group and hyperoxia+ EPO(H)group than that in the BPD group on the 14 th day, and the differences were statistically significant (all P<0.05). (3)Immunofluorescence results showed that: the number of NF-κB p65 positive cells increased significantly and fluorescence intensity increased in the BPD group, while EPO could greatly reduce the number of NF-κB p65 positive cells and lower the fluorescence intensity.(4)Western blot results indicated that compared with the control group, the expressions of pNF-κB p65 and Cleaved Caspase-3 was significantly increased, and the differences were statistically significant (all P<0.05); and IκB was significantly lower, and the difference was statistically significant ( P<0.05). The expression of NF-κB p65 and Cleaved Caspase-3 was significantly lower, but IκB was significantly higher in the hyperoxia+ EPO(L)group and the hyperoxia+ EPO(H)group than those in the BPD group, and the differences were statistically significant (all P<0.05). (5) ELISA results revealed that the expression of IL-1β in the BPD group was significantly higher than that in the control group, and the difference was statistically significant ( P<0.05); Compared with BPD group, the expression of IL-1β was significantly lower in the hyperoxia+ EPO(L)group and hyperoxia+ EPO(H)group, and the differences were statistically significant (all P<0.05). Conclusions:EPO can reduce hyperoxia-induced lung tissue apoptosis and protect newborn rats against hyperoxic lung injury by decreasing the inflammatory response of cells through the NF-κB pathway on BPD.

Objective To explore the method of three-dimensional reconstruction of fetal bilateral renal artery and its application value of three-dimensional visualization model.Methods One case of 31 weeks fresh fetal bilateral kidney specimens was infused with epoxy resin-titanium dioxide and then casted.Obtained the original two-dimensional CT image data sets through CT thin layer scanning of the casting mold.Reconstructed the three-dimensional model of fetal bilateral renal artery with the Mimics 17.0 software, and the model was compared with the casting mold specimen.Results The casting mold specimen of fetal bilateral renal artery clearly showed the shallow blood vessels, but it was difficult to observe the deep renal arteries.On the contrary,the three-dimensional model of fetal bilateral renal artery could help to observe and measure the deep renal arteries accurately,but it failed to show the shallow blood vessels clearly.Conclusion Based on the advantage of the three-dimensional model fetal bilateral renal artery and casting mold specimens,the direction and distribution of fetal bilateral renal arteries could be displayed with stereoscopic multi-level through the combination of virtual and reality,which may provide a reliable morphological data for anatomy teaching and fetal basic medical research information.