The randomized controlled trials (RCTs) of treating diabetic nephropathy (DN) with alprostadil and valsartan were collected from CNKI,Wan fang date,VIP,PubMed,Embase,and Cochrane Library.The selected data was analyzed with RevMan 5.1 software.The effect of combination of valsartan and alprostadil in treating DN was evaluated.In 19 RCTs,675 cases were co-treated with alprostadil and valsartan and 670 were treated with valsartan.The results indicated that 24 h urine microalbumin excretion [WMD =-53.23,95％ CI (-67.55,-38.91),P＜0.01] and24 h urine protein[WMD=-0.38,95％ CI(-0.69,-0.07),P=0.02] in patients treated with combination of valsartan and alprostadil were reduced more markedly than in those treated with valsartan alone.There was no significant difference in blood urea nitrogen [WMD =-0.791,95 ％ CI (-20.62,4.79),P =0.22] and serum creatinine[WMD=-5.82,95％ CI(-19.22,7.58),P=0.39] between two kinds of treatment.These results suggest that combined treatment with valsartan and alprostadil shows advantageous effect on reducing urinary protein in DN.

Objective To investigate the role of miR-126 (micro RNA-126) in rat endothelial progenitor cells (EPCs) proliferation and migration and the starget gene of miR-126 by bioinformatics and experimental survey.Method EPCs were transfected with control oligoes and miR-126 mimics or inhibitor by electroporation.MTT was performed to evaluate the growth of EPCs subjecting to miR-126 overexpression.Cell migration analysis was done by wound healing and transwell assay.The target genes of miR-126 were predicted by TargetScan and validated by Western blot.Result (1) miR-126 mimics promoted EPCs growth at 24 h post cell transfection (P ＜ 0.01).In contrast,the EPCs growth was immue from miR-126 application at 48 and 72 h.(2) Both the wound healing and transwell assay show that miR-126 promotes EPCs migration (P ＜ 0.01) and miR-126 inhibitor inhibits EPCs migration (P ＜ 0.01).(3)It is predicted that KANK2 is the potential target gene of miR-126 by TargetScan online software.(4) The results of Western blot indicated that miR-126 mimics repress the expression of KANK2 compared with NC but miR-126 inhibitor enhances KANK2 expression.Conclusions miR-126 has a transient effect on the promotion of EPCc growth.miR-126 promotes EPCs migration and targets KANK2 protein.

OBJECTIVE To explore the effect and underlying mechanism of promethazine(PMZ) on proarrhythmia in guinea pigs. METHODS ① InvivoECG recordings were made to analyze effects of jugular intravenous(iv)injection of PMZ on ECG in guinea pigs. PMZ was injected in this order:3.83→7.67→15.33→38.33 mg·kg-1 cumulatively. ② In vitroECG recordings were made to analyze effects of PMZ on ECG in isolated hearts of guinea pigs. PMZ was perfused in such order:0. 1 → 1 → 10 →50 μmol·L-1 . ③ L-type Ca2+ currents from ventricular myocytes in guinea pigs were recorded to investi-gate the PMZ's blocking effect. PMZ was perfused in such order:0.1→1→10→50 μmol·L-1→washout.④ hNav1.5 and hERG currents were recorded to investigate the PMZ's blocking effects. PMZ-perfused in such order:1→3→10→30 μmol·L-1 for hNav1.5 current analysis,and 0.3→1→3→10 μmol·L-1 for hERG current analysis. RESULTS ① PMZ(15.33 mg·kg-1 )significantly prolonged QRS intervals in guinea pigs invivoECG(P﹤0.05). PMZ(38.33 mg·kg-1 )prolonged QRS,QTc,and P-R intervals but reduced the heart rate( P﹤0.05). PMZ(10 μmol·L-1 )reduced the heart rate of isolated guinea pig hearts. PMZ 50 μmol·L-1 prolonged QRS and QTc intervals and further reduced the heart rate(P﹤0.05).③ PMZ inhibited the L-type Ca2+ current from ventricular myocytes in guinea pigs in a concentration-dependent manner with the lC50 of(8.9±1.0)μmol·L-1 . ④ PMZ inhibited the hNav1.5 and hERG currents in a concentration-dependent manner with the lC50 of 6.1±1.5 and(1.6±0.2)μmol·L-1 ,respectively. CONCLUSION PMZ might cause arrhythmia at overdoses and incombination with other drugs which have potential blocking effect on /Na ,Ca2+ and /kr currents. The proarrhythmic effect of PMZ might be mediated by the blocking effect on /Na ,Ca2+ and /kr currents.

OBJECTIVETo investigate the effect of berberine on serum levels of TNF-alpha, IL-6 and adiponectin in obese mice induced by high fat diet and its potential molecular mechanisms.

METHODNormal male Kunming mice were randomly divided into two groups taking normal chow (NC, n = 10) and high fat diet (HF, n = 30), respectively. After 13 weeks, HF mice were continuously given high fat diet and divided into three groups, model group (BM), low-dosage of berberine group (BL) and high-dosage of berberine group (BH). Mice in BL and BH were administered berberine by gavage at the dosage of 50 mg x kg(-1) and 150 mg x kg(-1), respectively. Two weeks later, oral glucose tolerance test was performed. At the end of the experiment, the mice were killed and blood samples were collected. The epididymal fat tissue and liver were removed promptly and weighed. The serum cytokine was measured by ELISA. The levels of IkappaB kinase beta (IKK-beta) and IKK-beta (ser181) were detected by Western blotting.

RESULTSerum levels of TNF-alpha, IL-6 in mice of BM were significantly higher than those in NC (P < 0.05). After two-week treatment of berberine, serum levels of TNF-alpha, IL-6 in BL and BH were lower than those in BM (P < 0.05, respectively). However, there were no significant difference of adiponectin among four groups. The degrees of phosphorylation of IKK-beta (ser181) were decreased in liver and adipose tissue in BH in comparison to that in BM, although the expression of total IKK-beta did not change. Furthermore, the glucose tolerance was improved, while the body weight and epididymal fat were reduced in mice treated with berebrine. 9: Berberine is able to reduce inflammatory cytokines expression and inhibit activation of IKK-beta (ser181) in obese mice, which may partly explain the therapeutic effect of berberine on insulin resistance and abnormal glucose metabolism.

Animals ; Berberine ; administration & dosage ; Dietary Fats ; administration & dosage ; adverse effects ; Disease Models, Animal ; Glucose Tolerance Test ; Humans ; Inflammation Mediators ; blood ; Interleukin-6 ; blood ; Liver ; drug effects ; immunology ; metabolism ; Male ; Mice ; Mice, Obese ; Obesity ; blood ; drug therapy ; immunology ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; blood

The applications accepted and approved by general program, young scientist fund and fund for less developed region of national natural science funds in the discipline of Chinese materia medica, NSFC in 2011 have been introduced. The character and problems in these applications have been analyzed to give a reference to the scientists in the field of Chinese material medica.
China ; Foundations ; Materia Medica ; Natural Science Disciplines ; Research Support as Topic

Objective To investigate the metabolomics characteristic of neuromyelities optica spectrum disorder (NMOSD) in plasma and cerebrospinal fluid.Methods Ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify plasma metabolites in 16 patients with NMOSD and 8 healthy controls.At the same time,the identification of metabolites in cerebrospinal fluid of 8 NMOSD patients and 5 healthy controls was completed.Differential metabolites screening and metabolomic pathway analysis were performed by diversified data analysis methods.Results Compared with healthy control group,the content of 8 substances such as Cis.8.11.14.Eicosatrienoic acid in the plasma of NMOSD patients was increased.The content of 8 substances such as L-glutamine acid were decreased.There was no significant difference in the metabolites between Aquaporin 4 (AQP-4) antibody positive and negative NMOSD plasma.The content of 6 substances such as 3-hydroxybutyric acid in cerebrospinal fluid of patients with NMOSD was reduced.Conclusions The distribution of metabolites in plasma between NMOSD patients and healthy controls was significantly different.There was no significant difference in metabolites between AQP-4 antibody positive and negative NMOSD plasma.There are some differences in metabolites between cerebrospinal fluid of NMOSD patients and healthy controls.A variety of amino acid abnormalities,sphingomyelin dysfunction,energy metabolism and mitochondrial dysfunction were involved in the pathogenesis of NMOSD.

In obesity,insulin resistance (IR) in visceral adipose tissue is closely associated withmetabolic disease.The interaction between acquired immune cells,including T lymphocytes and B lymphocytes,and innate immune cells affects adipocyte function,contributesto the development of adipose tissue inflammation and IR.Here,we summarized the influence of acquired immune cells on adipose tissue inflammation and IR,providing a new direction and strategy for obesity-related.disease.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

This article summarizes Professor Shang Lili's experience in diagnosing and treating recurrent respiratory tract infections(RRTIs)in children based on the theory of"internal deficiency and external injury".Professor Shang believes that children are in the stage of growth and development,with delicate organs and insufficient vital energy,which is called"internal deficiency";external pathogens repeatedly invade the human body,resulting in clinical manifestations of both cold and heat,ultimately damaging the body's qi,blood,essence,and spirit,known as"external injury"."Internal deficiency and external injury"leads to repeated infections of pathogens in children and causes physical and mental distress,affecting their growth and development.The theory of"internal deficien-cy and external injury"emphasizes the influence of internal and external factors on RRTIs in children,reflecting the evolution of patho-genesis and guiding clinical staging treatment.During the acute infection period,the treatment of wind heat syndrome is based on the Xin Liang and Qing San methods,while the treatment of wind cold syndrome is based on the Xin Wen and Kai Bi methods.For the mixed deficiency and excess syndrome,various methods such as attacking,supplementing,harmonizing,and supporting should be used,and treatment should be based on syndrome differentiation,with adjustments made according to the symptoms;during the inter-mittent period of infection,Professor Shang aims to assist the righteous qi,taking into account the upper,middle,and lower Jiao,and adopting treatment principles such as nourishing the lungs,spleen,and kidneys.Professor Shang's experience provides useful ideas and methods for the treatment of RRTIs in children.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.