OBJECTIVE:To provide reference for improving the registration success rate of new drug research and develop-ment(R&D)enterprises after adjusting drug registration system in China. METHODS:The national drug policies,regulations and related documents were comprehensively studied and combed to explore the main contents of drug registration system adjustment and its effects on the R&D forms,drug patent and on-site verification. The suggestions were put forward. RESULTS & CONCLU-SIONS:The adjusted drug management system showed new definitions for new drugs and generic drugs in China,as well as de-tailed requirements and regulations for drug R&D conditions,process and on-site inspection. It enhanced the protection of patents and patentees. The new drugs should be assessed its market value and clinical advantages. Data contents and requirements for drug registration declaration were made the relevant adjustments. New drug R&D enterprises should develop drug listed license manage-ment system as early as possible based on the implementation of listed license management system pilot,improve its efficiency and benefit. The new drug R&D should notice the clinical efficacy and demand of market,focus on the drugs with good clinical effica-cy in common diseases,frequently-occurring diseases and major diseases;and those for treating rare diseases,the elderly and chil-dren disease can use easy access or fast track to accelerate the speed of drug registration. New drug R&D enterprises should im-prove the R&D conditions,and standardize the management of development process to ensure the effective and smooth develop-ment.

Objective To investigate the promoter methylation status of SFRP1 and SFRP2 gene in gastric cardia adenocarcinoma (GCA). Methods Methylation specific PCR (MSP) method was used to examine the methylation status of the 5' CpG island of SFRP1 and SFRP2 gene in tumors and corresponding normal tissues. Results Methylation frequencies of SFRP1 and SFRP2 gene in tumor specimens were 87.2 % (82/94) and 83 %(78/94), which was significantly higher than that in corresponding normal tissues (14.9 % and 55.3 %, respectively) (P <0.001). Methylation frequencies of SFRP1 in lymph node metastasis group (96.4 %) was significantly higher than that in no lymph node metastasis group (73.7 %). Methylation frequencies of SFRP1 and SFRP2 gene in poor differentiation group were all higher than that in moderate and poor-moderate differentiation groups, but both of them did not show significant difference(P >0.05). 63 cases of GCA showed both of SFRP1 and SFRP2 gene simultaneous methylation, which including 36 cases of lymph node metastasis group, 27 cases of no lymph node metastasis group. Simultaneous methylation frequencies of SFRP1 and SFRP2 gene in lymph node metastasis group was higher than that in no lymph node metastasis group, poor differentiation group was higher than that in moderate and poor-moderate differentiation groups, but both of them did not show significant difference (P >0.05). Conclusion Promoter methylation of SFRP1 and SFRP2 might be related with oncogenesis of GCA and hypermethylation of SFRP1 gene might be related with the malignant behavior of GCA.

Objective To evaluate clinical outcome and complications of mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse. Methods From Feb 2007 to Jan 2009, meshaugmented vaginal reconstructive surgery were performed on 66 women with pelvic organ prolapse stage Ⅲ-Ⅳ. Pre and postoperative symptoms, pelvic organ prolapse quantitation (POP-Q) stage and pelvic floor distress inventory-short form 20 (PFDI-20) measurements were studied to assess anatomic and quality-of-life outcome. Operative complications were also analyzed. Results Totally 65 patients underwent successful surgeries. The rate of follow-up was 97% (63/65) with a median follow-up of 17. 2 months. Subjective cure rate and objective cure rate were both 97% (61/63) at 6 and 12 months after surgeries, 51 women completed PFDI-20 measurements and scores were 102 ± 50 before surgery, 16 ± 21 at 6 months and 15 ± 20 at 12 months. It reached statistical difference when scores were compared before and after surgeries ( P ＜0. 05). Among 66 patients, 2 patients underwent organ injuries, 2 had recurrent prolapse, 4 had meshrelated complications and 1 had severe de novo stress urinary incontinence. Six patients underwent second surgery. Conclusions Mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapsed brought satisfied clinical outcome. The incidence of mesh-related complications was low and secondary operative interventions were effective.

Objective To explore the effects ofDanshen Tongluo Detoxication Decoction on the inflammatory response of rats with bone marrow stem cell (BMSC) transplantation in acute myocardial infarction (AMI); To discuss its mechanism of action.Methods The whole bone marrow adherent method was adopted for BMSCs separation and culture. The AMI model was established by closing the left anterior descending coronary artery of SD rats. After the modeling, SD rats were randomly divided into sham-operation group, model group and BMSCs group (BMSCs transplantation group),Danshen Tongluo Detoxication Decoction group, Danshen Tongluo Detoxication Decoction + BMSCs group, 10 rats in each group. BMSCs cell suspension was injected directly into the edge of the myocardial tissue infarction area; Chinese medicine or normal saline were administered for gavage. 4 weeks later, the contents of MCP-1 and sICAM-1 in each group were detected by ELISA. TLR-4 expression was measured by Western blot method, and HE staining was used to observe the myocardial tissue pathological changes.Results Compared with the model group, the contents of MCP-1 and sICAM-1 and the protein expression of TLR-4 in BMSCs group,Danshen Tongluo Detoxication Decoction group, andDanshen Tongluo Detoxication Decoction + BMSCs group decreased, Danshen Tongluo Detoxication Decoction group was better than BMSCs group (P<0.05,P<0.01), andDanshen Tongluo Detoxication Decoction + BMSCs group was better than BMSCs group andDanshen Tongluo Detoxication Decoction group(P<0.05,P<0.01).Conclusion BMSCs transplantation combined withDanshen Tongluo Detoxication Decoction can restrain the inflammatory response of AMI model rats and repair ischemic myocardium issue, which mechanism may be related to regulating TLR-4 induced inflammatory response.

Objective To explore the clinical value of MRI in diagnosing and treating cesarean scar pregnancy (CSP).Methods A retrospective analysis was conducted on the clinical manifestations of 54 patients diagnosed with CSP between January 2009 to January 2013 in Peking University Third Hospital.Based on the patients' MRI image and other clinical datas,we did transvaginal operation on patients with CSP1,and transvaginal combined with abdominal operations on patients with CSP2.The intraoperative blood loss,operation time,postoperative hospital stay,and the length of time required for of serum hCG dropping to normal of the patients were analyzed.Results The average age of the 54 patients was (34±5) years and the average duration of gestation was (56± 16) days,all patients' vital sign were stable,the hCG level was 23-142 962 U/L before treatment.Twelve patients were diagnosed with CSP1 by MRI,and 5 of them had focus of 1-2 cm in diameter,the 5 patients' serum hCG level was 436-1 159 U/L and 23-32 days after drug administration,their hCG level returned to normal; the other 7 patients had focus of 2.0-4.4 cm in diameter,and their hCG level was 2 218-63 446 U/L,lesion resection was done on the 7 patients by hysteroscope or under B-uhrasound monitor.Forty-two patients were diagnosed with CSP2,and their focus were 1.0-7.1 cm in diameter,and serum hCG level were 23-142 962 U/L.We did bilateral uterine artery occlusion by laparoscope or laparotomy during operation for 22 patients or bilateral uterine artery embolization (UAE) before operation for 20 patients,then we did lesion resections.The blood loss during operation of CSP1 or CSP 2 was 50.1,267.2 ml; operation time was 30,128 minutes; postoperative hospital stay was 4.6,6.7 days;their serum hCG returned to normal 13-30 days after the surgery.All the 54 patients' uterus were preserved,and the patients undergoing operations were all cured without the second operation.Conclusion MRI is an effective method to conduct clinical treatment in CSP.

Objective To explore the qualitative evaluation of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant thyroid nodules (TNs).Methods Totally 110 outpatients with 132 TNs underwent CEUS were enrolled in this study in Jinling Hospitall Medical School of Nanjing University (Nanjing General Hospital of Nanjing Military).Nanjing General Hospital of Nanjing Military All the nodules underwent ultrasound guided fine needle aspiration biopsy (FNAB).113 TNs were histologically diagnosed,the characteristics of enhancement for each noudle were scored.The characteristicsof enhancement between benign and malignant TNs were compared by chi-square test.The receiver operating characteristic (ROC) curve analysis were conducted to determine the diagnostic values of thyroid CEUS.Results Contrast-enhanced patterns were significantly different between benign and malignant TNs in the degree,homogeneity of enhancement,enhanced ring and boundary,shape and size of the enhanced lesions (x2=23.85,P ＜ 0.001;x2=7.43,P=0.04;x2=34.54,P ＜ 0.001;x2=25.7,P ＜ 0.001;x2=53.10,P ＜ 0.001;x2=22.78,P ＜ 0.001;x2=30.90,P ＜ 0.001).Contrast-enhanced patterns were not significantly different between benign and malignant TNs in the process and completeness of enhancement.Malignant lesions had concentric (79.5％),inhomogeneous (89.0％) and low (71.1％) enhanced with irregular (79.5％) and unclear (64.4％) boundary and bigger size (63.0％).The typical CEUS feature of benign nodules was peripheral ring hyperenhancement (34.7％).According to ROC curve,the cut off value was 3.5 points.The area under the ROC curve (AUC) for CEUS was 0.862 (95％CI:0.797-0.927).The sensitivity,specificity and accuracy for CEUS were 80.8％,79.6％,80.3％ respectively.Conclusion The pattem of CEUS may assist in differential diagnosis of benign and malignant TNs.

Field operations,work and war on plateau is an important part of future war. It is necessary to study the early treatment and evacuation of scull injury. Research and survey were made in 7 field hospitals and hundreds of records were summaried before treatment criterion in early phase was put forward for patients on plateau as well as the evacuation in different level and stage,which aims to actively save patients' lives within limited time and reduce the death rate and prevent deformity. References are provided for war,training,and construction in battlefield.

The study on etiology and pathogenesis of coronary heart disease / thoracic obstruction has been carried on for a long time, and the understanding of TCM concept of blood stasis, heat and toxin was deeper and wider.A large quantity of clinical trials have proved that one of key pathogenesis of coronary heart disease / thoracic obstruction is the toxin induced by accumulation of blood stasis and heat, which damages heart blood or nutrient.In detail, the evil of blood stasis and heat were blocked or accumulated in human bodies to generate the toxic materials called toxin, which can damage collaterals of heart, burn out nutriment-blood of heart, block vessels of heart, and in the end, cause coronary heart disease / thoracic obstruction.Undoubtedly, the therapy of activating blood, clearing heat from the nutritive level, removing toxic substances has positive effectiveness.This article explains the relationship between the evil of blood stasis, heat and toxin with the occurrence and progress of coronary heart disease / thoracic obstruction, and discuss the theoretical basis of TCM therapy mentioned above directed at the evils.

Objective To investigate the association between serum total testosterone (TT ) levels and type 2 diabetes(T2DM )and any gender differences in elderly patients. Methods Based on the Aging Health database built from 2008 to 2012 ,935 elderly individuals over 60 years old with a mean age of 65.8 years receiving physical examinations were included.According to the 1999 WHO criteria for diabetes ,participants were assigned into four groups :a T2DM group(n＝298) ,an impaired fasting glucose(IFG)group(n＝26) ,an impaired glucose tolerance(IGT)group(n＝121) ,and a normal glucose regulation(NGR)group(n ＝ 490).We measured serum TT by ELISA and analyzed the distribution patterns in the groups.Furthermore ,we examined the gender-specific correlation of TT with T2DM and homeostasis model assessment of insulin resistance (HOMA-IR). Results The prevalence of T2DM in the participants was 31.9%(298/935).One-way ANOVA analysis showed that the TT level was higher in the NGR group than in the T2DM and IGT groups (PANOVA＝ 0.001) . Logistic regression analysis indicated a significant protective association between TT and T 2DM in the elderly.Every one unit of increase in the SD of the TT level was accompanied by a 23% reduction in the risk for T2DM (P＝ 0.001).Further gender-stratification analysis suggested that the protective role of TT against T2DM only existed in males (OR＝ 0.55 ,95% CI :0.44-0.68 ;P＜ 0.001).After adjustment for age ,blood pressure ,blood lipids ,and waist circumference ,the protective role of TT against T2DM in males still remained (OR ＝ 0.68 ,95% CI :0.53-0.86 ;P ＝ 0.002 ).Pearson correlation analysis also indicated a significant negative correlation between TT and HOMA-IR in older males(P＝0.002).As for older females ,no significant correlation of TT with T2DM and HOMA-IR was found. Conclusions The serum TT level might be an independent protective factor for T 2DM in older males ,as evidenced by its correlation with improved insulin resistance status ,which is not present in older females.

Objective To investigate the risk factors and appropriate screening methods for diabetic peripheral neuropathy (DPN ). Methods This research is a multicenter ,randomized ,cross-sectional study. Questionnaires ,physical examinations and laboratory tests were performed on 1054 elderly diabetic outpatients at 13 hospitals in urban and rural areas of Beijing. Patients were screened for DPN with the five physical examinations recommended by the Diabetes Branch of the Chinese Medical Association. They were divided into a confirmed DPN group(n=449 ,42.6％ ) ,a suspected DPN group(n=276 ,26.2％ ) ,and a non-DPN group(n=329 ,31.2％ ).Multivariate logistic regression was used to analyze risk factors for DPN.The sensitivity ,specificity ,Youden index ,and area under the receiver operating characteristic (ROC)curve were calculated and used for evaluating each test and their combinations in screening DPN and for choosing the opitmal test combination. Results The differences in age ,family income ,duration of diabetes ,glycated hemoglobin(HbA1c) ,hypoglycemia ,and dyslipidemia among three groups were statistically significant (all P<0.01). The decision whether or not to initiate metformin therapy ,metformin doses and DPN prevalence in patients on long-term metformin therapy showed statistically significant differences among three groups (all P<0.01). The differences in the prevalences of cerebral infarction ,diabetic retinopathy ,and peripheral vascular disease among three groups were statistically significant (all P< 0.05).Multivariate Logistic regression analysis suggested that levels of HbA1c ,hypoglycemia ,LDL cholesterol ,whether or not metformin use , metformin dose ,and duration of metformin use were risk factors for DPN in elderly diabetics (all P<0.05) . The combined methods of ankle reflex ,vibratory sensation and temperature sensation used for screening DPN showed the best results with a sensitivity of 94.1％ ,specificity of 75.3％ ,an area under the ROC curve of 0.847 ,and a Yoden index of 0.6945. Conclusions The prevalence of DPN in elderly diabetic outpatients at third-level referral hospitals in Beijing is high. Poor glycaemic control ,repeated episodes of hypoglycemia , metformin use and its daily dose and duration are risk factors for DPN in elderly diabetics.We should focus on strengthening the DPN screening and management of high-risk population.Symptoms of peripheral neuropathy plus ankle reflex ,vibratory and temperature sensations are simple ,rapid and reliable DPN-screening methods ,and can be promoted in outpatient department and primary hospitals.