Objective To evaluate the safety, performability and long-term clinical efficacy of stenting angioplasty for treating symptomatic internal carotid artery (ICA) stenosis in the origin part in elderly patients. Methods Stenting angioplasty was performed on 29 patients with symptomatic ICA stenosis in the origin part. Results 29 stents were placed in 29 patients. Operations were performed 100%successfully. After an average 24 months of follow-up visits, restenoses were detected in 2cases reexamined by DSA 6 months after stenting, both presented with less than 50% stenoses. 1 case was found not regularly taking statins and antiplatelet drugs after stenting, severe restenosis occurred 6 months later, stent implantation performed again, no recurrence of transient ischemic attack (TIA) was noted during 2 years′follow-up visit. Cerebral ischemic strokes occurred in 2 cases , and both of them had balloon dilatation after stenting. 1 case was completely recovered after treatment and 1 was left with weakness in right extremities, unabling to walk. No cases of posterior circulation ischemia, death and myocardial infarction were detected. Conclusions Stenting angioplasty can be performed in treating symptomatic internal carotid artery stenosis in elderly patients. It showed a relatively good mid-long-term clinical effects and can be a secondary prevention option.

Objective: To observe the clinical effect of Tongfu granules(通腑颗粒) on the gastro- intestinal dysfunction in patients with multiple organ dysfunction syndrome(MODS).Methods: The trial was prospective,multi-centric and clinically controlled.One hundred and forty patients with MODS who had been selected were randomly divided into two groups: mosapride citrate group and Tongfu granules group.Respectively at 0 hour,the 48 th hour,the 7 th day or before death, the following scoring systems were calculated: the intestinal dysfunction score,acute physiology and chronic health evaluationⅡ((APACHEⅡ)) score and Marshall score.The duration of mechanical ventilation,hospitalization in intensive care unit(ICU) and the prognosis within 28 days were recorded.Results: After treatments,the intestinal dysfunction score,(APACHEⅡ) score and Marshall score of all patients decreased,at the same time,the therapeutic effects of Tongfu granules group were more significant than those in mosapride citrate group(P20 scores.The mortality was elevated with the increased number of dysfunction organs.Conclusion: Tongfu granules can ameliorate the severity of the disease situation andimprove the prognosis of patients with MODS.

AIM:To explore the therapeutic effect and possible molecular mechanisms of prednisone combined with icariin(ICA)on hormone resistant nephrotic syndrome(SRNS).METHODS:In the in vi-vo experiment,rats were divided into control group,SRNS group,prednisone group,and P+I group.Each group was given corresponding drugs for 6 weeks.Detection of 24-hour urinary protein in rats using CBB;The blood biochemistry analyzer de-tects rat albumin,total cholesterol,triglycerides,creatinine,and urea nitrogen;HE and Masson were used to detect morphological changes in rat kidney tissue;Immunohistochemical detection of GR-α,GR-β,NLRP3,caspase-1,GSDMD,IL-1β.In the in vi-tro experiment,HK-2 cell injury model with doxoru-bicin,divided into control group,SRNS group,pred-nisone group,P+l group.GR-α,GR-β,NLRP3,cas-pase-1,GSDMD were detected by Rt-PCR and West-ern blot.RESULTS:In the in vivo experiment,com-pared with the control group,the SRNS group showed weight loss,increased 24-hour urine pro-tein,decreased albumin,increased total cholester-ol,triglycerides,creatinine,and urea nitrogen,renal tubular atrophy,increased renal interstitial area,sig-nificant infiltration of inflammatory cells,fibrous tis-sue proliferation,and GR-β,NLRP3,caspase-1,GSD-MD,IL-1 β in renal tissue decreased(P＜0.01);Com-pared with the SRNS group,the combined group showed weight gain,decreased 24-hour urine pro-tein,increased albumin,decreased total cholester-ol,triglycerides,creatinine,and urea nitrogen,re-duced renal tubular atrophy,reduced interstitial in-flammatory cell infiltration,reduced fibrosis,and and GR-α,NLRP3,caspase-1,GSDMD in renal tissue decreased increased(P＜0.01).In vitro experiments,compared with the control group,the model group showed GR-β,NLRP3,caspase-1,and GSDMD in-creased(P＜0.01),GR-α decreased(P＜0.01);Com-pared with the SRNS group,GR-β,NLRP3,caspase-1,and GSDMD decreased(P＜0.01),GR-α increased in the P+I group.CONCLUSION:The combination of prednisone and ICA has a protective effect on the kidneys of SRNS rats and can improve the therapeu-tic effect.The mechanism may be related to the NL-RP3/Caspase-1/GSDMD pathway.

OBJECTIVETo screen the HIV-1 entry inhibitors targeting HIV-1 gp120 from the IBS natural product database by virtual screening based on the binding mode of the neutralizing antibody VRC01 with HIV-1 gp120 and investigate the anti-viral activities of the inhibitors and their action mechanisms.

METHODSThe binding interaction of the candidate molecules binding gp120 and changes of the binding free energy were analyzed by MM-PBSA calculation. The anti-HIV-1 activities of the tested compounds were detected by HIV-1 pseudotyped virus, laboratory-adapted HIV-1 and a cell-cell fusion assay. The cytotoxicity of the studied molecules was examined by XTT colorimetric assay. The mechanisms of the anti-viral activities of the candidate molecules were analyzed using enzyme-linked immunosorbent assay.

RESULTSA total of 19 molecules with distinct reduction of the binding free energy after binding with gp120 were screened from 40000 molecules. Among them, NC-2 showed anti-HIV-1 activities against HIV-1 pseudotyped virus and laboratory-adapted HIV-1, and was capable of blocking HIV-1 envelope-mediated cell-cell fusion. The IC50 of NC-2 for inhibiting HIV-1IIIB and pseudotyped HIV-1JRFL infection were 1.95∓0.44 µmol/L and 10.58∓0.13 µmol/L, respectively. The results of ELISA suggested that NC-2 could inhibit the binding of HIV-1 gp120 to CD4 without blocking the formation of gp41 six-helix bundle in vitro.

CONCLUSIONThis computer-based virtual screening method can be used to screen HIV-1 entry inhibitors targeting gp120. Using this virtual screening approach combined with anti-viral activity screening, we obtained a potent HIV-1 entry inhibitor NC-2 with novel structure.

Anti-HIV Agents ; pharmacology ; Antibodies, Monoclonal ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Binding Sites ; Cell Fusion ; Cell Line ; Drug Discovery ; Drug Evaluation, Preclinical ; HIV Antibodies ; pharmacology ; HIV Envelope Protein gp120 ; antagonists & inhibitors ; HIV-1 ; drug effects ; Humans ; Microbial Sensitivity Tests

GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.

BACKGROUNDThe high blood homocysteine (Hcy) levels found in patients with hyperhomocysteinemia (HHcy) have been implicated in an increased risk of cardiovascular disease morbidity and mortality in end-stage renal disease (ESRD). This study investigated the association of HHcy with progression of IgA nephropathy.

METHODSWe analyzed 108 participants newly diagnosed with IgA nephropathy between August 2005 and August 2007 in the Department of Nephrology, Chinese People's Liberation Army General Hospital. The association between clinicopathological factors and the Hcy levels were analyzed by Logistic regression and those with ESRD risk were analyzed by Cox regression.

RESULTSPatients were aged (35.71 ± 10.73) years and included 45.71% women and 12.04% patients with HHcy. In multivariate Logistic regression analysis, HHcy was associated with arterial lesions (OR 2.60; 95% CI 1.55 ± 4.34; P < 0.001) even when age, body mass index, estimated glomerular filtration rate, mean arterial pressure, and initial proteinuria were taken into account. Mean follow-up was (67.37 ± 16.21) months. HHcy was also associated with worse ESRD-free survival (HR 4.71; 95% CI 1.45 to 15.31; P = 0.010).

CONCLUSIONHHcy is associated with the risk of intrarenal arterial lesions and may be useful for estimating the prognosis of IgA nephropathy.

Adult ; Body Mass Index ; Female ; Glomerular Filtration Rate ; physiology ; Glomerulonephritis, IGA ; etiology ; physiopathology ; Humans ; Hyperhomocysteinemia ; complications ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Retrospective Studies