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Objective:To observe the clinical efficacy of Shenqi Dihuang Decoction combined with conventional western medicine in the treatment of stage Ⅲ Diabetic Nephropathy (DN).Methods:A total of 96 patients with stage Ⅲ diabetic nephropathy with syndrome of deficiency of qi and yin in our hospital, from January 2019 to January 2021, who met the inclusion criteria, were divided into 2 groups by random number table method, 48 in each group. The control group was given the conventional western treatment. The observation group was given Shenqi Dihuang Decoction on the basic of the control group treatment. Both groups treatment lasted for 3 months. Before and after the treatment, the changes of TCM Syndrome Scores were observed. The levels of soluble intercellular adhesion molecular-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were detected by double antibody sandwich ELISA. The levels of BUN, SCr, SOD and Hcy were detected by automatic biochemical analyzer, collect 24-hour urine, 24-hour urine total protein quantity (24 UTP) was detected by immunoturbidimetry, and eGFR was calculated by CKD-EPI formula to evaluate the clinical efficacy.Results:After the treatment, the total effective rate in the observation group was 83.3% (40/48), and the control group was 66.7% (32/40) and the difference was statistically significant ( χ2=3.56, P=0.049). After the treatment, TCM Syndrome Scores in the observation group was significantly better than that of the control group ( t=4.05, P<0.01). After treatment, the systolic blood pressure in the observation group was significantly lower than that of the control group ( t=4.29， P<0.01). After treatment, the levels of 24 hUTP [(1.43 ± 0.54) g vs. (1.86 ± 0.50) g, t=4.05], serum sICAM-1[(396.07 ± 50.61)μg/L vs. (480.11 ± 63.01)μg/L, t=7.20], Hcy [(27.41 ± 3.42) μmol/L vs. (29.76 ± 5.80) μmol/L, t=2.42] in the observation group were significantly lower than those in the control group ( P<0.05), and the levels of SOD [(168.32 ± 41.26) U/ml vs. (143.11 ± 37.02) U/ml, t=3.15] was significantly higher than that of the control group ( P<0.01). Conclusions:Shenqi Dihuang Decoction combined with conventional western medicine can reduce 24 hUTP quantity and kidney damage, delay the development of Ⅲ DN, improve clinical effect and protect the kidney function, and sICAM-1 for the Ⅲ DN patients with the syndrome of qi and yin deficiency combined with blood stasis.
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OBJECTIVE：To study the efficacy and safety of sacubitril valsartan sodium tablets combined with Bailing capsules in the treatment of chronic left heart failure with renal insufficiency ，and to provide reference for clinical drug use. METHODS ： Totally 96 patients with chronic left heart failure with renal insufficiency who sought medical care in our hospital from Nov. 2018 to Nov. 2019 were divided into group A ，B and C according to table of random numbers ，with 32 cases in each group. Group A received conventional heart failure treatment and and Bailing capsules （2 g each time ，3 times a day ）；group B received conventional heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）；group C was given with heart failure treatment and Sacubitril valsartan sodium tablets （50 mg each time ，twice a day ）and Bailing capsules （2 g each time，3 times a day ）. 3 groups received consecutive 6 months of treatment. Clinical response rates of 3 groups were compared. Left heart function indexes [left ventricular end systolic diameter （LVESD），left ventricular end-diastolic diameter （LVEDD），left ventricular ejection fraction （LVEF）] and serological indexes [interleukin 1（IL-1），IL-6，N terminal brain natriuretic peptide precursor，glomerular filtration rate （GFR）] were detected before and after treatment. The occurrence of ADR were observed and recorded. RESULTS ：During this study ，a total of 6 patients fell off ，and eventually 90 patients completed the study ，including 29 cases in group A ，30 cases in group B and 31 cases in group C. Before treatment ，there was no statistical significance in left heart function indexes or serological indexes among 3 groups（P＞ 0.05）. After 6 months of treatment ，clinical response rate of group C was significantly higher than those of group A and B 163.com （P＜0.05）. Compared with before treatment ， LVEDD， LVESD and serological indexes of 3 groups were decreased significantly after treatment （P＜0.05），while LVEF and GFR were increased significantly （P＜0.05）；the changes of above indexes （except for IL- 1 level in serum ） in group C were significantly better than group A and B ，the changes of above indexes in group B （except for GFR ）were significantly better than group A （P＜0.05）. No significant ADR were observed in 3 groups. CONCLUSIONS ：Sacubitril valsartan sodium tablets combined with Bailing capsules can significantly decrease the level of serum inflammation factors ，and improve cardiac and renal function in patients with chronic left heart failure with renal insufficiency ，with good safety.
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OBJECTIVE：To observe the clinical effect and safety of recombinant human brain natriuretic peptide （rhBNP） combined with levosimendan in the treatment of acute decompensated heart failure （ADHF）complicated with renal insufficiency. METHODS：A total of 156 patients with ADHF complicated with renal insufficiency admitted to the Dept. of Cardiology in the Affiliated Hospital of Southwest Medical University during Jan.-Dec. 2019 were randomly divided into rhBNP group ，levosimendan group and combination group ，with 52 patients in each group. All patients received rountine treatment. On this basis ，rhBNP group was given rhBNP for injection [after 1.5 μg/kg intravenous pulse injection，intravenous dripping for 24 h with 0.007 5 μg（/ kg· min）]；leosimendan group was given Leosimendan injection 12.5 mg [intravenous dripping for 1 h with 6-12 μg（/ kg·min），then intravenous dripping for 23 h with 0.1 μg（/ kg·min）]. Combination group received drug combination according to the administration method of single drug group. Three groups received treatment for consecutive 7 d. Cardiac function indexes [heart rate （HR），left ventricular ejection fraction （LVEF），left ventricular end-diastolic diameter （LVEDD）]，mean arterial pressure （MAP），pulmonary capillary pressure （PCWP），renal function indexes [estimated glomerular filtration rate （eGFR），serum creatinine （Scr）]，serum levels of cystatin C （Cys-c）and amino-terminal brain natriuretic peptide precursor （NT-proBNP）were observed in 3 groups before and after treatment. Clinical efficacy and the occurrence of ADR were recorded. RESULTS ：Three cases withdrew from the study in rhBNP group and 1 case in levosimendan group ；152 cases completed the study. Before treatment ，there was no statistical significance in cardiac function indexes ，MAP，PCMP，renal function indexes or serum levels of Cys-C and NT-proBNP among 3 groups（P＞0.05）. After treatment ，the HP ，MAP，PCWP and serum level of NT-proBNP in 3 group as well as serum level of Cys-C in combination group were decreased significantly （P＜0.05）；the LVEF in 3 group as well as the eGFR and Scr level in levosimendan group and combination group were significantly increased （P＜0.05），compared with before treatment ；above indexes of combination group were significantly better than those of rhBNP group and levosimendan group （P＜0.05）. Total effective rate of combination group was 94.23％ ，which was significantly higher than those of rhBNP group （77.55％）and levosimendan group （76.47％）（P＜0.05）. There was no significant difference in the incidence of ADR among 3 groups（P＞ 0.05）. CONCLUSIONS ：rhBNP combined with levosimendan in the treatment of ADHF complicated with renal insufficiency can significantly increase the clinical efficacy ，and improve cardiac and renal function but don ’t increase the incidence of ADR.
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Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.
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Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.
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OBJECTIVE： To observe the effects of nicorandil on vascular endothelial function and angina pectoris recurrence in patients with unstable angina pectoris after percutaneous coronary intervention （PCI）. METHODS： Totally 195 patients with unstable angina pectoris were collected from Sichuan Provincial People’s Hospital during Jan. 2016-Mar. 2018， and then divided into control group （97 cases） and observation group （98 cases） according to random number table. Both groups received PCI， and then given basic treatment as Enoxaparin sodium injection， Isosorbide mononitrate sustained-release tablets， Aspirin enteric-coated tablets， Clopidogrel sulfate tablets and Atorvastatin calcium tablets after PCI. Observation group additional received Nicorandil tablet 5 mg， tid， on the basis of control group. Both groups were treated for 6 months. The levels of vascular endothelial function related indexes （FMD， ET-1， NO）， myocardial injury markers （cTnⅠ， CK-MB） and inflammatory factors （hs-CRP） were observed before and after PCI. The recurrent angina pectoris， the occurrence of MACE and ADR were recorded. RESULTS： 6 patients of control group and 4 patients of observation group withdrew from the study. One day before operation， there was no significant difference in the levels of vascular endothelial function， myocardial injury markers or inflammatory factors between 2 groups （P＞0.05）. One day after operation， the levels of FMD and NO in both groups decreased significantly， while the levels of ET-1， cTnⅠ and CK-MB increased significantly （P＜0.05）. The levels of FMD and NO were increased significantly in the 1st and 6th months after surgery， and the observation group was significantly higher than the control group； the levels of ET-1， cTnⅠ， CK-MB and hs-CRP were decreased significantly， and the observation group was significantly lower than the control group （P＜0.05）. The incidence and times of recurrent angina pectoris， duration， the proportion of grade Ⅲ angina pectoris and total incidence of MACE in observation group were significantly lower， less or shorter than control group （P＜0.05）. There was no statistical significance in total incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Additional use of nicorandil can improve vascular endothelial function， relieve the myocardial injury and inflammatory response， reduce the occurrence of recurrent angina pectoris and MACE after PCI and doesn’t influence the safety of routine treatment.
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Objective To investigate the effect of sertraline on the viability and the expression of tyrosine hydroxylase (TH) and phosphorylated ERK1/2 in NGF-induced rat pheochromocytoma (PC12) cells.Methods NGF-induced PC12 cells were pretreated or directly treated with different concentrations of sertraline for 24 or 48 hours and the pretreated groups were then subjected to serum withdrawal condition. Then cell viability was determined by the cell counting Kit-8 (CCK-8). The expression of Tyrosine hydroxylase (TH) and pERK1/2in NGF-induced PC12 cells was determined by immunohistochemistry and western blot respectively. Results The viability of NGF-induced PC12 was improved after administration with sertra]ine. After 24h sertraline administration, the cells activity of PC 12 cells at 20μM ( 1.32 ± 0. 11 ) , 10μM ( 1. 17 ± 0.05 ) of direct effect, and 20μM ( 1.15 ±0.11 ) of protect effect increased dramatically as compared with control group. But high dose ( 50μM )sertraline express high toxic effect to PC12 cells. The expression of TH was increased by sertraline 20 μM at both 24h(ratio of TH/β-actin = 1.27 ±0.05) and 48h(ratio of TH/β-actin = 1. 23 ±0.08) compare with control group,and the expression of pERK1/2 also increased dramatically by sertraline 20 μM at both 24h (ratio of (pERK1/2)/β-actin = 1.41±0.05) and 48h( ratio of (pERK1/2)/β-actin = 1.40 ±0.06) compare with control group(P＜0. 01, P ＜ 0. 05). Immunohistochemistry showed similar results. Conclusion These data suggest that the neuroprotective effect of sertraline may play an important role in depression therapy, and this effect might be mediated by TH and pERK1/2 up-regulation.
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To identify metabotropic glutamate receptor 4 (mGluR4) modulators by Ca2+ influx assay, we developed the functional cell-based high throughput-screening (HTS) assay. The human mGluR4 cDNA was transfected into HEK-293 stably expressing promiscuous G-protein (Ga alpha15) cells. Recombinant stable mGluR4 cell line was selected under Zeocin and validated by Ca2+ influx assay. The assay was optimized on loading time of Fluo Calcium Indicator, Dimethyl sulfoxide (DMSO) tolerance and sodium hydroxide (NaOH) tolerance using agonist (L-Glutamic acid (L-Glu)) of mGluR4. The rank order of the agonist potency for the stable human mGluR4 cell line was L-(+)-2-Amino-4-phosphonobutyric acid (L-AP4) > L-Serine-O-phosphate (L-SOP) > L-Glu, and of the antagonist potency was (RS)-alpha-Methylserine-O-phosphate (MSOP) > (RS)-alpha-Methyl-4-phosphonophenylglycine (MPPG). Z' factor value of the cell line in 96- and 384-well plate format was 0.80 and 0.65. Our data indicate a successful development of functional human mGluR4 recombinant stable cell line that was suitable for high throughput screening to identify mGluR4 agonist/antagonist.
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Humans , Aminobutyrates , Pharmacology , Cell Line , DNA, Complementary , Genetics , Drug Evaluation, Preclinical , Kidney , Cell Biology , Embryology , Phosphoserine , Pharmacology , Plasmids , Genetics , Receptors, Metabotropic Glutamate , Genetics , TransfectionABSTRACT
Objective To study the effects of monocyte chemotactic protein-1(MCP-1) on the growth of human umbilical vein endothelial cells (hUVEC). Methods hUVEC were cultured in vitro and identified. hUVEC that grew vigorously were stimulated for 24 h or 48 h respectively with MCP-1(0.1, 1.0, 10, and 100 ?g/L). The survival rate of hUVEC was first detected by MTT assay. The cell cycle and DNA content were detected and analyzed by flow cytometry. Results hUVEC were isolated from human umbilical veins and cultured, and then identified by immunofluorescence and immunohistochemistry with factor Ⅷ and KDR. MCP-1 induced the apoptosis of hUVEC in a dose-dependentmanner and a time-dependentmanner (P
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Objectives:To explore the influnce of nutritional support treatment on the prognosis in patients with severe acute nectrotizing pancreatitis. Methods:The patients were divided into experimental group (35 cases of 1995 1999) and control group (33 cases of 1990~1994).The biochemical indicators complications and mortality rate were retrospectiverly analyzed between groups. Results:After treatment of 3 days,the amylase,transaminase,BUN,WBC and glucose in experimental group decreased significantly.TLC after treatment in experimental group was significantly different( P