Objective To evaluate the effects of fasudil on neointima hyperplasia in rat carotid artery balloon-injury model,and explore the potential molecular mechanisms of this effect.Methods Totally 30 male Sprague-Dawley (SD) rats were randomly divided into sham operation group,balloon injury group,2.5 ml/kg fasudil intervention group,5 ml/kg fasudil intervention group,10 ml/kg fasudil intervention group.The intima-to media(I/M) area ratio of neointima was calculated at 14th day after operation; the protein expression of proliferating cell nuclear antigen(PCNA) was measured by immunohistochemical and the integrated optical density (IA) was calculated.As the marker of oxidative stress,the levels of 8-hydroxy-2'-dcoxyguanosine (8OHdG) and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay (ELISA).The expressions of phosphorylated and non phosphorylated Ras,mitogen activated protein kinase kinase (MEK1/2) and extracellular signal regulated kinase (ERK1/2) were measured by Western blot.Results The I/M ratios were (0.22 ± 0.01) in sham operation group,(2.71 ± 0.23) in balloon injury group,( 1.72 ±0.24)in 2.5 ml/kg fasudil intervention group,(1.23±0.11)in 5 ml/kg fasudil intervention group,(0.85±0.12)in 10 ml/kg fasudil intervention group.As compared with sham operation group,I/M area ratio was increased in balloon injury group,and three fasudil intervention group inhibited neointima hyperplasia in a dose-dependent manner (all P＜0.01).The IA indexes were(15.11 ±1.42),(53.42±2.30),(45.25±1.62),(22.55±0.88) and(19.61±0.79) in the above five groups,respectively,showing the fasudil inhibited PCNA expression (all P＜0.01).Fasudil also inhibited the levels of 8-OHdG and MDA in a dose-dependent manner [8OHdG:(54.34±4.50)μg/kg,(106.81 ± 6.67)μg/kg,(94.21 ± 3.34) μg/kg,(65.58 ± 5.13) μg/kg,(51.32 ± 2.34) μg/kg; MDA:(19.94 ± 0.65 ) μmol/kg,( 58.83 ± 2.81 ) μmol/kg,(48.94 ± 1.35 ) μmol/kg,(40.62 ± 3.24 )μmol/kg,( 36.85 ± 0.91)μmol/kg (all P＜0.01)].Compared with balloon injury group,the relative expressions of Ras in three fasudil intervention group were 0.49±0.12,0.39±0.13,0.20±0.23 vs.0.62±0.10(P＜0.05 or,P＜0.01); MEK1/2 0.35±0.14,0.29±0.09,0.11±0.12 vs.0.56±0.1(P＜0.05 or,P＜0.01); ERK1/2 0.48±0.15,0.32±0.08,0.12±0.09 vs.0.64±0.13(P＜0.05 or,P＜0.01).The activations of ERK1/2,MEK1/2 and Ras were strongly suppressed in fasudil treated samples on day 14 after balloon injury.Conclusions Blockade of oxidative stress and Ras MEK1/2 ERK1/2 pathway is involved in the fasudil attenuating of balloon injury-induced neointima hyperplasia

OBJECTIVE:To investigate the effect of Shuxuening on interleukin 18 (IL-18) in patients with early diabetic nephropathy.METHODS:68 patients with early diabetic nephropathy were randomly divided into 2 groups (n=34).Both groups were given conventional diabetes therapy and oral dose of irbesartan (150 mg,qd).Treatment group were additionally treated with Shuxuening injection 20 mL and sodium chloride injection 250 mL (i.v.qd) for 3 weeks.The levels of IL-18 of 2 groups before and after treatment were determined by enzyme-linked immunosorbent assay,and the albumin excretion rate (UAER),fasting plasma glucose (FPG),serum creatinine (Scr) and other indicators were also detected.RESULTS:Compared with before treatment,the levels of IL-18 of 2 groups decreased after treatment (P0.05).CONCLUSION:Shuxuening can inhibit inflammatory cytokines IL-18 in peripheral blood of patients with diabetic nephropathy and have protective effects on kidney,which may be adjuvant therapy for diabetic nephropathy.

Objective To explore the value of diagnosis and treatment of conization of cervix to cervical intraepithelial neoplasia(CIN)Ⅱ-Ⅲ grade.Methods The data of 76 patients diagnosed as CIN Ⅱ-Ⅲ grade through pre-operative multiple-punch biopsies from July 1st 2006 to June 30th 2007 was retrospectively analyzed.Compared the pathohistology and treatment methods before and after conization of cervix.Results Accordance rate of diagnosis in pre-operative cervical biopsies under vaginoscopy was 48.68%,pathological up-grade were 24 cases(31.58%),among invasive carcinomas were 8 cases(10.53%),pathological down-grade were 15 cases(19.74%).Conclusion Diagnostic cervical conization could enhance the rate of diagnosis,and prevent the omission of invasive carcinomas for the patients with CIN Ⅱ-Ⅲ grade.

Objective The study was designed to evaluate the clinical efficacy of azithromycin in lung function of patients with IPF.Methods Randomized controlled trials were searched in CNKI,data-base of Wanfang and WeiPu,where azithromycin was used to patients with IPF.We extracted all data on lung functions,standardized mean difference (SMD)with 95% confidence intervals (CI )were pooled with Stata 11.0.Results Seven unique trials with 516 participants were identified.Be compared to pred-nisone,the patients with IPF received azithromycin experienced no improvement in FVC% [SMD = -2.00,95% CI =(-2.05,-1.95)],but it was found that azithromycin was superior to prednisone in in-crease the percentage of carbon monoxide diffusing [SMD =1.16,95% CI =(-2.83,5.16)]and de-cline the percentage of residual volume[SMD =3.00,95% CI =(1.04,4.96)].Azithromycin combined with prednisone were statistically superior to prednisone alone in improvement of FEV1 %[SMD =7.80, 95% CI =(5.92,9.67)],FVC%[SMD =7.23,95% CI =(4.89,7.56)]and lung carbon monoxide diffusion function[ml/(min·kpa))][SMD =40.62,95% CI =(38.96,42.28)].Conclusions Our study suggests that azithromycin significantly improvement pulmonary diffusion function in patients with IPF. Azithromycin combined with prednisone were more effective in improvement of FEV1 %,FVC% and lung diffusion function.

Objective To investigate the mutation characteristics and genotype of hepatitis B virus resistance gene in Nantong area,and provide scientific basis for clinical rational drug.Methods A total of 158 cases of chronic hepatitis B (CHB)pa-tients who were received with nucleos (T)ide analogues therapy for at least 2 years as the research object,and 30 cases of CHB patients who were not received nucleos (T)ide analogues for the treatment as the control group.PCR-sequencing method was used to detect the HBV P resistant gene and genotype,meanwhile,observe the relationship between three main mutation model and the levels of ALT and HBV DNA was also investigated.Results B genotype was detected in 42 (26.58%)out of 158 CHB patients,and 116 cases (73.42%)were C genotype.A total of 131 patients with different site mutations in P region,the mutation rate were 82.91%.There were totally 11 HBV mutation sites,including the main muta-tion site:M204I,L180M,M204V,A181V and A181T,the frequency of drug resistance were 41.14%,37.34%,22.15%, 11.39% and 10.13%,respectively.Moreover,11 mutation sites had 21 mutation patterns.In lamivudine (LAM)resistance associated mutations,the L180M and M204V sites were mainly co-occurrence,followed by M204I alone.In adefovir dipivoxil (ADV)resistance associated mutations,A181V was the main mutation site.Whereas,the drug resistance rate of entecavir (ETV)was low.Conclusion The main genotypes of HBV were type B and C in Nantong area,and C type was the dominant genotype.The resistance mutations mainly concentrated in LAM and ADV resistance associated mutations,while the resist-ance rate of ETV was low.Multi-locus drug-resistant mutation detection may help to detect viral resistance and guide clinical treatment better.

Objective To investigate the risk factors and biomarkers for early diagnosis and treatment for myocardial ischemia during endoscopic retrograde cholangiopancreatography (ERCP) in patients aged ≥75 years,in order to improve the effectiveness and security of ERCP.Methods A total of 82 patients undergoing ERCP in our hospital from Jan.2013 to Dec.2014 were divided into the elderly group (n =42,aged≥75 years) and the non-elderly group (n =40,aged ＜75 years).The pre-and post-operative ECG findings,laboratory serological indexes,ERCP operating parameters and post-operative complications were compared between two groups.Results ASA grade was increased in elderly patients as compared with the non-elderly group.The intraoperative hypothermia,preoperative infection and jaundice,and hypertension were risk factors for myocardial ischemia during ERCP.The biochemical indexes including myeloperoxidase,creatine kinase and cardiac troponin Ⅰ were the biomarkers for early diagnosis of myocardial ischemia in patients with non-specific changes of ST-T wave.The indications of anesthesia meeting operation,the consecutive and close anesthesia monitoring,application of nitroglycerin,thermal insulation during operation,oxygen inhalation can effectively relieve myocardial ischemia during ERCP operation.Conclusions The early discovering and effectively treating myocardial ischemia during ERCP can ensure the safe and effectiveness of ERCP in elderly patients aged ≥75 years.

Objective To observe the influence of spine kyphotic deformity on postmenopausal osteoporosis patients' pulmonary function and physical activity,and then provide a guide for the rehabilitation training of patients with osteoporosis and a kyphotic spine.Methods Sixty postmenopausal women with osteoporosis were recruited from the osteoporosis outpatients of the Third Hospital of Peking University.Half of them suffered from spine kyphosis (the spine kyphosis group) and the other half did not (the non-spine kyphosis group).There was no significant difference in the average ages and body mass indexes of the two groups.The research applied Cobb's angle and wall-occiput distance (WOD) to assess kyphosis severity,a visual analogue scale (VAS) to evaluate the patient's pain level,plus pulmonary function assessments and thoracic expansion assessments in both groups simultaneously,and the 6-minute walking test (6-MWT) to assess the patients' physical activity.Results The spine kyphosis group said they experienced significantly more pain than the non-kyphosis group,and they had worse pulmonary function and poorer physical activity.These differences were statistically significant.Pulmonary function was significantly correlated with the severity of spine kyphosis,back ache,thoracic expansion as well as physical activity.Conclusion Spine kyphosis deformity can aggravate back ache among postmenopausal osteoporosis patients,and affect their pulmonary function and physical activity.When planning clinical exercise training for such patients,physicians should pay attention to respiratory function training so as to improve the patients' pulmonary function,physical activity and endurance as much as possible,and thus improve their quality of life.

Objective To explore the effects of fasudil on inhibiting vascular smooth muscle cells (VSMCs) proliferation in vitro,increasing cell apoptosis,and inhibiting the Ras-MEK 1/2-ERK 1/2 pathway.Methods Healthy male SD rats (80～100 g) were selected.VSMCs were separated by the thoracoabdominal aortic vascular membrane dissection.Cultured VSMCs were randomly divided into 5 groups:serum-free group; serum group; serum + 1 μmol/L fasudil intervention group; serum + 10 μmol/L fasudil intervention group; serum + 100 μmol/L fasudil intervention group.The proliferation and migration of VSMCs were detected by MTT method and wound healing assay.Cell cycle and apoptosis of VSMCs were examined by flow cytometric analysis.The mRNA expressions of pro-apoptotic protein (Bax) and anti-apoptotic protein(Bcl-2) were determined by RT-PCR method,and the ratio of Bax/Bcl 2 was calculated.Western blot were performed to detect the protein expressions of Ras,MEK1/2,ERK1/2 and Akt in VSMCs.Results Fasudil inhibited rat VSMCs proliferation and migration,and blocked FBS-induced progression from the G0/G1 phase to S phase in a dose-dependent manner.Fasudil inhibited the early and late apoptosis in VSMCs,increased Bax mRNA expression and inhibited Bcl 2 mRNA expression.Fasudil significantly inhibited the protein expressions of FBS-stimulated intracellular Ras,phosphorylated MEK1/2,ERK1/2 in a dosedependent manner,but did not affect the protein expression of phosphorylated Akt.Conclusions Fasudil can attenuate VMSCs proliferation by blocking Ras-MEK1/2-ERK1/2 pathway and increasing cell apoptosis.

Pegylated interferon (PEG-IFN) combined with ribavirin (PR regimen) has been used in China for more than 10 years.With the development of direct-acting antiviral agents (DAAs),the therapeutic regimens for hepatitis C has become more and more diverse.In the regimen of DAAs combined with PR regimen,IFN helps to benefit the long-term prognosis of patients with chronic hepatitis C (CHC),and the addition of DAAs may improve therapeutic effect,shorten the course of treatment,and further improve the current status of treatment of CHC.This article introduces the advantages and disadvantages of PR regimen,DAAs combined with PR regimen,and oral regimen with DAAs,in order to investigate the therapeutic regimens suitable for different CHC patients and provide a reference for clinical practice.

Objective To study the methods of preparing samples, analyse free radical in smoke of cigarette and the relationship between free radical and the other harmful components in the cigarette smoke. Methods The contents of two types of free radical in smoke of 13 kinds of cigarettes were determined with electron spim resonance(ESR) and the self-made equipment. Results The analytic results showed that the main component was the free radical in gas state in all cigarette samples and it was about 10-30 times higher than the content of free radical in solid state. The content of free radical in gas state of cigarette made in China was lower than that made in foreign country. Conclusion The analysis method using ESR and the self-made equipment will be easily used in the related experiment; The level of free radical in gas and solid state is positively related to the level of tar and nicotine in the cigarette sample of same trademark but it is not the same in the samples of different trademark. Therefore, we can not to infer the content of free radial in cigarette smoke by the content of tar and nicotine in it,especially for the content of free radial in gas state. Using charcoal filter is benefit to reduce the level of free radical in cigarette smoke.