BACKGROUNDAbnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide (H2S) on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow.

METHODSThirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt + propargylglycine (PPG), 11-week control, 11-week shunt and 11-week shunt + sodium hydrosulfide (NaHS) groups. Rats in 4-week shunt, 4-week shunt + PPG, 11-week shunt and 11-week shunt + NaHS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt + PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt + NaHS group were intraperitoneally injected with NaHS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining.

RESULTSFour weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P < 0.01), but expression of bcl-2 increased significantly (P < 0.01). PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 (P < 0.01), but increased the expression of bcl-2 (P < 0.01). After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P < 0.01), but expression of bcl-2 increased obviously (P < 0.01). NaHS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2.

CONCLUSIONSH2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.

Alkynes ; pharmacology ; Animals ; Apoptosis ; drug effects ; Blood Flow Velocity ; physiology ; Blotting, Western ; Glycine ; analogs & derivatives ; pharmacology ; Hemodynamics ; drug effects ; Hydrogen Sulfide ; pharmacology ; Hypertension, Pulmonary ; etiology ; physiopathology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Pulmonary Artery ; cytology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

【Objective】 To supervise the clinical blood use of 19 hospitals, covering a district of Shanghai, during two years, and discover the problems in the process of blood transfusion, so as to put forward suggestions for corrective methods in grades and promote continuous improvement of clinical transfusion management. 【Methods】 A total of 19 hospitals were supervised in terms of hardware facilities, management level, professional and technical level, and blood typing test on the site, according to the Administrative Blood Management Measures for Medical Institutions, Technical Specification for Clinical Transfusion and Shanghai Medical Quality Supervision Score Statistical Table.All data were analyzed. 【Results】 These hospitals can properly perform clinical blood transfusion, but there were obvious differences.Tertiary hospitals were relatively better, yet need to strengthen the management of medical documents.Secondary hospitals remained to be improved, mainly in insufficient construction of Blood Transfusion Department (blood bank), the lack of management and maintenance of key equipment and the lack of standardization in medical documents writing.However, flaws in the supervision were general in private hospitals (most of which were affiliated hospitals), so the management of clinical blood use should be further strengthened. 【Conclusion】 For secondary hospitals or above, routinized writing of medical documents and promoted construction of Blood Transfusion Department (blood bank) should be strengthened.For private hospitals, especially affiliated hospitals, the management of clinical blood use should be further improved, including the examination rules corresponding to the blood use process and strict access and exit mechanism, so as to improve the overall management level of clinical blood use and ensure the safety of clinical blood use.

To systematically review effectiveness and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice. A systematic retrieval was performed throughout China National Knowledge Infrastructure( CNKI),Wan Fang,VIP,Sino Med and PubMed,Medline,Cochrane Library databases from the establishment to April 2019. Randomized controlled trials of Yinzhihuang Oral Liquid in treatment of neonatal hyperbilirubinemia were retrieved. Clinical studies in line with the inclusion criteria were involved for data extraction,and the quality of the included literatures was evaluated by the risk bias assessment tool in the Cochrane review manual. Finally,Meta-analysis was performed by Rev Man 5.3 software. A total of 30 studies were involved,involving 3 923 child patients,including1 940 in observation group and 1 983 in control group. According to the results of Meta-analysis,the total effective rate( RR = 1. 22,95%CI[1. 18,1. 26],P<0. 000 01),level of TBi L after treatment( MD =-38. 78,95%CI[-48. 38,-29. 18],P<0. 000 01),time to jaundice resolution( MD =-1. 76,95% CI[-2. 10,-1. 41],P < 0. 000 01) and daily average decrease value of bilirubin( MD =11. 67,95%CI[8. 89,14. 45],P<0. 000 01) of observation group were significantly better than those of control group,with statistically significant differences. Adverse reactions were reported in nine studies,mainly including diarrhea,vomiting,fever,rash and other symptoms,which did not affect the treatment effect. The effectiveness of Yinzhihuang Oral Liquid combined with conventional therapy in treating neonatal jaundice was better than conventional therapy alone,with little adverse reactions. However,most of literatures included had a low research quality,which impacted the reliability of the conclusion. Therefore,it is suggested to conduct more largesample-size,multicenter,scientifically designed,strictly implemented high-quality randomized controlled trials in the future,in order to study the efficacy and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice.
China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Infant, Newborn ; Jaundice, Neonatal/drug therapy* ; Reproducibility of Results

OBJECTIVE: To analyze the changes of blood biochemical index and the pathological changes of myocardium and kidney in type 2 diabetic mouse at different time points, which can provide the basis for the selection of type 2 diabetic modeling time for later research. METHODS: After 6 weeks of feeding with high-fat diet, 24 healthy male ICR mice were injected with streptozocin (STZ, 30 mg/kg) intraperitoneally for 5 days to establish diabetic models. After 9 days, a random blood glucose ≥ 11.1 mmol / L was measured as diabetic mice. 4, 6 and 8 weeks after successfully preparing the diabetic mouse, 8 diabetic mice (a group)would be sacrificed each time. Then the biochemical and pathological conditions were analyzed: ① the indexes of heart and kidney were calculated. ②the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr) and blood urine nitrogen (BUN) were determined. ③ Histopathological changes of myocardium and renal tissues were observed by hematoxylin and eosin (HE) staining. Masson staining was used to observe the fibrosis of myocardium. PAS staining was adopted to observe the pathological changes of renal tissue. In addition, 8 ICR male mice were taken as the control group. RESULTS: At the 4, 6 and 8 week, cardiac organ coefficient, the values of LDH and CK were all increased compared with the control group. Cardiomyocyte hypertrophy and myocardial fibrosis could be observed. Renal organ coefficient, the values of Cr and BUN were increased. Glomerular hypertrophy, basement membrane thickening and atrophy could be perceived. CONCLUSION At the 6 week, related biochemical and pathological changes in diabetic mice were comparatively obvious and breeding time was relatively short. Thus, 6 weeks after the preparation of the diabetic mice would be the optimal time for type 2 diabetes mellitus modeling, proper for inventions of drugs and other research purposes including pathology, physiology, biochemistry, etc.
Animals ; Diabetes Mellitus, Experimental ; pathology ; Diabetes Mellitus, Type 2 ; pathology ; Disease Models, Animal ; Kidney ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Streptozocin

Aim To use microdialysis technology combined with ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology to study the effect of Achyranthes bidentata saponins (ABS) on rheumatoid arthritis (RA) and its mechanisms. Methods SD rats were randomly divided into adjuvant arthritis (AA) model group, blank control group and ABS administration group. AA rat model was induced by Freund's complete adjuvant. UPLC-Q-TOF/MS was used to collect joint cavity microdialysis fluid sample information of each group of rats. Results On 6th day after administration of ABS, an inhibitory effect on the paw swelling, improved the arthritis score (P < 0. 05), and better the pathological morphology of the synovial tissues were found in AA rats. Nineteen potential biomarkers were discovered and identified. Pathway enrichment analysis revealed that they mainly involved purine metabolism, pyrimidine metabolism, fatty acid biosynthesis and steroid hormone biosynthesis pathway. Conclusions Microdialysis combined with metabolomics can reveal the metabolic mechanism of ABS intervention on RA, laying a foundation for further study of the mechanism of ABS.