Objective To explore the effects of Dimethyloxalyl Glycine(DMOG)on isehemic acute renal failure(iARF)in mice and its relationship with activation of hypoxia inducible factor 1α(HIF-1α).Method Twenty five C57/BL male mice were divided into 5 groups randomly:control group,DMOG group,sham operation group,ischemia/reperfusion(I/R)group and DMOG pretreated group(DMOG+I/R).Ischemia/reperfusion injury was induced in mice by clamping both renal pedicles for 30 minutes.The expression of HIF-1α was determined by Western blot.Renal function was reflected by blood urea nitrogen(BUN)and serum creatinine(Scr).Morphologic changes were evaluated under light microscopy.Apoptosis in the kidney was detected by TUNEL staining.Expression of Vimentin,a marker of tubulointerstitial damage was detected by immunohistochemistry.Results The elvated levels of of BUN((65.8±2.6) vs (13.6±0.7),P＜0.01],and Scr[(229.5±11.2) vs (6.5±0.8),P＜0.01]andwere found morphological injury were induced by the ischemic insult in I/R group.Administration of DMOG dramatically improved renal function[BUN,(26.3±6.5)vs(65.8±2.6);Scr,(27.0±14.1)vs(229.5±11.2),P＜0.01]associated with amelioration of tubulointerstital damage.In the DMOG treated group,the protein level of HIF-1α in the kidney of mile was also up-regulated significantly.Conclusions The protection against iARF in mice by DMOG administration is mediated by activation of HIF-1α.

Objective To investigate the location and expression of hypoxia inducible factor (HIF) subunits in the remnant kidney of 5/6 nephrectomy rats. Methods Remnant kidneys were produced in adult male SD rats by 5/6 nephrectomy. The renal function and histopathological changes were evaluated at week 1, 2, 4, 6, 8 and 12 after operation. Tissues of remnant kidneys were collected to detect the location and expression of HIF-1α and HIF-2α by immunohistochemistry staining and Western blotting. The mRNA levels of HIF targeted genes vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1) were determined by RTPCR. Results (1) 5/6 nephrectomy rats underwent one week of acute renal failure at first[Scr (122.8±22.1) μmol/L] and then developed compensative chronic renal failure [(66.0±3.7)-(66.4±8.4) μmol/L], but the level of Scr increased quickly after week 6 [(66.4±8.4)-(127.8±22.7) μmol/L],concomitantly with progressive tubulointerstitial fibrosis in remnant kidney cortex. (2) In cortex, HIF-1α was expressed only in the atrophic and dilated tubular cells while HIF-2α was located in endothelial, interstitial fibroblasts, and vascular smooth muscle cells. The semiquantitative results of imunohistochemistry and Western blotting revealed that HIF-1α and HIF-2α were both gradually up-regulated during the early stage of remnant kidney, peaked at week 4 and 6, and then gradually down-regulated. (3) The mRNA levels of HIF targeted genes VEGF and HO-1 transiently peeked at week 4 and 6, and then decreased gradually. Conclusions The increased stabilization of HIF-αprotein and transcription of HIF targeted genes at the early stage of this model is a compensation reaction towards hypoxia. The mechanism of decreased expression of HIF-α at the end stage of chronic kidney disease deserves further investigation.

Objective To examine the association between residual renal function at initiation of dialysis and prognosis in maintenance dialysis patients.Methods Incident patients with end-stage renal diseases initiating dialysis between 1 January 2005 and 30 September 2009,followed up to 31 March 2010 were enrolled in this study.Residual renal function was evaluated using eGFR estimated by the abbreviated MDRD equation.Patients were classified into four groups according to eGFR of ≥10.5,8 to ＜10.5,6 to ＜8,＜6 ml·min-1·(1.73 m2)-1.The outcome was all-cause and cardiocerebral vascular mortality.Results (1) A total of 562 patients were included.The median eGFR at initiation of dialysis was 5.60 (2.26-12.62) ml·min-1·(1.73 m2)-1.The median follow-up time was 17 (0-58) months from initiation of dialysis and 141 patients died within this period.The median survival time was 45.48 (43.05-47.90) months.With eGFR declined,Scr,BUN,serum uric acid,serum prealbumin,phosphorus,calcium and phosphate product,iPTH,mean arterial pressure (MAP) at initiation of dialysis increased (P＜0.05),and hemoglobin,proportion of male,proportion of diabetes comorbidity,proportion of the Charlson comorbidity index ≥5 decreased (P＜0.05).Though there was no significant difference among the four groups,the proportion of left ventricular hypertrophy comorbidity increased when eGFR declined.(2) There was no significant difference of all-cause mortality among four groups using Kaplan-Meire survival curve.Cox regression model indicated no significant difference of all-cause mortality in levels of eGFR (HR=1.012,95％CI 0.961-1.065,P=0.654).Without patients died in the first 3 months,the multivariate Cox regression model indicated eGFR at initiation of dialysis was the protective factor to 1 year survival (HR=0.791,95％CI 0.669-0.935,P＜0.01).(3) The multivariate Cox regression model indicated the risk of overall and 1 year cardiocerebral vascular death decreased with eGFR at initiation of dialysis increased (HR=0.868,95％CI 0.777-0.971,P＜0.05; HR=0.937,95％CI 0.851-0.992,P＜0.05,respectively).(4) The multivariate Cox regression model indicated eGFR at initiation of dialysis was benefit to survival of patients treated by peritoneal dialysis,with all-cause death risk decreased by 10％ when eGFR increased by 1 ml·min-1·(1.73 m2)-1 (HR=0.90,95％CI 0.81-0.99,P＜0.05).In hemodialysis patients,Kaplan-Meire survival curve was significantly different among the four groups (Log-rank test,P=0.047); the survival of the group of 8 to ＜10.5 ml·min-1·(1.73 m2)-1 was lower as compared to the groups of 6 to ＜8 (Log-rank test,P=0.033) and ＜6 ml·min-1(1.73 m2)-1 (Log-rank test,P=0.005); but the multivariate Cox regression model indicated no relationship between survival and eGFR.In the subgroup of chronic glomerulonephritis as primary renal disease,the eGFR at initiation of dialysis was the benefit factor,with all-cause death risk decreased by 16.6％ (HR=0.834,95％CI 0.736-0.946,P＜0.01) and cardiocerebral vascular death risk decreased by 18.2％ (HR=0.818,95％CI 0.669-0.999,P＜0.05) when eGFR increased by 1 ml ·min-1 ·(1.73 m2)-1.In the subgroup of chronic glomerulonephritis treated by peritoneal dialysis,the all-cause death risk decreased by 32.1％ with eGFR increased by 1 ml·min 1·(1.73 m2)-1 (HR=0.679,95％CI 0.535-0.862,P＜0.01).Conclusions Early initiation of dialysis may not be associated with improved overall survival,but may reduce cardiocerebral vascular and 1 year all-cause mortality,improve the survival of chronic glomerulonephritis patients and peritoneal dialysis patients.

Objective To study the prevalence,treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control.Methods We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female.Hypertension was defined as systolic blood pressure(SBP) ≥ 140 and/or diastolic blood pressure (DBP) ≥90 mm Hg ( 1 mm Hg = 0.133 kPa).Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey.Hypertension control was defined as blood pressure ＜ 140/90 mm Hg before each dialysis session.Results The prevalence of hypertension in the hemodialysis patients was 86.3%.The treatment rate and control rate in those patients were 96.8% and 25.5% respectively.More than half (50.4% ) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more.Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin Ⅱ receptor blockers ( 56.4% ), centrally acting anti-hypertensive agent ( 26.4% ), beta blockers and alpha, beta-blockers( 14.0% ).The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease.The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension.The hypertension control rate elevated significantly with the adequate hemodialysis.Conclusions There is a very high prevalence of hypertension in maintenance hemodialysis patients.Although the treatment rate is high, the control rate is unsatisfactory.So the control of hypertension in hemodialysis patient is still a clinical challenge.Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.

Objective:To observe the effect of gait training assisted by an end-effector-based robot on the gait, balance, walking and general lower limb motor functioning of stroke survivors.Methods:Thirty-nine stroke survivors were randomized into a training group ( n=21) and a control group ( n=18). In addition to routine hemiplegia rehabilitation, the control group was given medium frequency electrical stimulation while the training group underwent 20 minutes of gait training assisted by an end-effector-based robot six days a week for 4 weeks. Before and after the intervention, both groups were evaluated using the functional ambulatory categories (FAC), the Fugl-Meyer lower extremity assessment, the Wisconsin Gait Scale and the Berg balance scale (BBS). Results:There were no significant differences between the groups before the intervention. Afterward significant improvement was observed in both groups in all measurements, with the training group scored better in terms of FAC and BBS.Conclusion:Using an end-effector-based robot in gait training might be more advantageous for improving the gait, balance, walking and general lower limb functioning of stroke survivors.

OBJECTIVE：To provide referen ce for improving commission management system of medical insurance in China. METHODS：By analyzing the problems of commission management system of medical insurance in China ，studying the specific types，responsibility division and its features of basic medical insurance contractors in the United States ，the suggestions were put forward for improving corresponding system in China. RESULTS & CONCLUSIONS ：There are some problems in the entrusted management of medical insurance in China ，including that the fair competition mechanism has not been established ；the operation and management of social security fund lacks of supervision mechanism ；the role of the government is unclear and inexperienced ； the imperfect supervision mechanism causes follow-up problems ；it is still uncertain whether the entrusted management system can improve the efficency of medical insurance management. In the United States ，the way of entrusted management of medical insurance was to introduce the third-party management. The contractors employed by the Centers for Medicare and Medicaid Services in the United States mainly included medical insurance contractor ，zone program integrity contractor ，comprehensive error rate test review contractor and statistical contractor ，supplemental medical review contractor ，qualified independent contractor and so on ，among which medical insurance contractor was in the core position. Each contractor had a clear division of labor in handling medical claims ，preventing medical fraud ，reviewing the correctness of payments ，evaluating medical records and handling appeals. This mode greatly reduced the work pressure of the government ，improved the efficiency of medical insurance management and operation，and promoted the continuous improvement of the whole system. It is suggested that China should expand the scope of social agency management ，clarify the responsibilities of government and social resources ，introduce various types of social economic organizations and establish a complete and effective performance supervision and management system in order to improve the modernization level of China ’s medical insurance governance.

OBJECTIVE：To pro vide reference f or resolving structural imbalance of “supply and demand dislocation ”in each stage of new drug R&D funds in China. METHODS ：Through analyzing the fund demand in each stage of new drug R&D and the problem of “supply and demand dislocation ”in detail ，a financing scheme matching the fund demand of each stage was designed ， and analyzed with the financing process of “Wanke”. RESULTS & CONCLUSIONS ：In the basic stage of new drug R&D ，there was a large demand for funds ，but there were great technical risks ，transformation risks and investment risks ，little attention and support from investors ，resulting in the lack of R&D funds in this stage. It is suggested to increase the investment of R&D enterprises themselves. In the stage of new drug discovery ，the risks of R&D and investment were still high ，more funds were needed and funds were in short supply. It is suggested to attract more venture capital into this stage. From preclinical stage to clinical stage Ⅱ，there was a greater demand for funds. It is suggested that this stage should mainly rely on venture capital and pledge financing with patents. From the clinical stage Ⅲ to pre-marketing ，R&D had entered the mature stage with less investment risk. Therefore ，more venture capital could be obtained in this stage ，and there was a situation of excess capital. At this time ，in addition to venture capital ，R&D enterprises can also choose listing financing. In the post-marketing stage ，the sales right of a certain region in the product sales link could be transferred to provide new reserve funds for the next round of new drug R&D ，so as to achieve a virtuous circle of R&D activities. One of the reasons for the success of “Wanke”R&D financing lied in the combination of various financing methods in the financing process. It is suggested that China should improve the financial financing system and patent value evaluation system at the national level ，so as to promote the drug patent pledge financing in China as soon as possible. Finally ，new drug R&D institute must establish the concept of independent innovation ，speed up the output of technological innovation results ，so as to achieve the improvement of China ’s independent R&D capability.

OBJECTIVE： To provide reference for the improvement of OTC drug management system in mainland China. METHODS： By analyzing the classification， registration management， conversion procedures and supporting measures， instructions and packaging management of OTC drugs in Taiwan area of China， and considering the current situation and problems of OTC drug management in mainland China， suggestions for improving OTC drug management system in mainland China were put forward. RESULTS & CONCLUSIONS： OTC drugs of Taiwan area could be divided into drugs instructed by physicians and pharmacists （hereinafter referred to as “instructed drugs”） as well as patent drugs. The registration management of instructed drugs was implemented in accordance with the Criteria for the Review of Instructed Drugs. The criteria not only regulated the active ingredients， dosage forms， indications， usage and dosage， side effects， matters needing attention and warnings of instructed drugs， but also stipulated the requirements for labeling， instructions and outer-of-the-box printing of instructed drugs. Taiwan area had also established a mechanism for evaluating drug conversion to expand the variety range of prescription drugs converted to OTC drugs， and had equipped a series of supporting measures to reduce the safety risks arising from drug conversion. In 2016， Taiwan area also formulated the Format and Relevant Standards for Outer-of-the-Box of Generic Western OCT Drug， and revised the drug instructions and the outer-of-the-box. The format was more standardized and the terminology was easier to understand， which made it easier for the public to read. It is suggested that mainland China should refer to the experience of Taiwan area， set up special registration channels for OTC drugs and simplify the requirements for examination and approval， pay attention to and improve the matching measures for the conversion of prescription drugs to OTC drugs， encourage brand building and improve intelligibility of OTC drug instructions， so as to build an effective OTC drug management system.

OBJECTIVE：To provide reference for deepening the reform of medical insurance payment mode in China. METHODS：By analyzing the specific reform process and driving factors of American Medicare ，and considering the background of current payment reform in China ，then some suggestions were put forward to promote the reform of medical insurance payment mode in China. RESULTS & CONCLUSIONS ：The payment mode of Medicare in the United States had undergone three stages ， which were post-payment system ，pre-payment system and value-based payment system. The payment modes included payment by service items ，payment by disease diagnosis related groups （DRGs）and payment by service value. The change was the result of the comprehensive effect of the three systems of technology ，politics and social culture in the United States. The demand for reasonable treatment and control fees drove the change from post-payment system to pre-payment system ，while the crisis of service quality ， the rise of service cost and the contradiction between doctors and patients drove the change to value-based payment. Payment mode reform had a positive impact on Medicare in the United States ，reducing medical expenditure and improving the quality of service. It is suggested that China should draw lessons from the experience of the United States in reforming the prepayment system nationwide on the basis of the current DRGs pilot projects. Meanwhile ，in order to avoid the medical quality crisis in the later period of the United States ，it is necessary to introduce the concept of value-based payment ，establish incentive and restraint mechanisms and strengthen the construction of the regulatory supporting system for the whole process.