According to the existing Provisions for Drug Registration (SFDA Order No. 28), applications for new drugs of traditional Chinese medicine are divided into two parts: the applications for drug clinical trial and for drug production (including new drug certificate). It will last for about 10 years from the application for drug clinical trial to get approving, and it also remains many problems and the low probability to succeed. From the sight of pharmaceutical review, there are mainly two aspects of regulatory compliance and technical issues, mainly for changes without approval of the competent authorities of the country. For example, sample preparation and approval of clinical trial process are significant changes. Technical problems are reporting incomplete data or information submitted does not comply with the technical requirements for review, such as: production process validation does not provide information, the preparation of samples for clinical trials and field inspection, production information, or the information provided does not meet the technical requirements. This paper summarizes the frequently asked questions and to make recommendations to advise applicants concerned, timely detection of problems, avoid risk, improving the quality and efficiency of the application for registration.
China ; Drug Approval ; legislation & jurisprudence ; Drug Evaluation ; legislation & jurisprudence ; Humans ; Legislation, Drug ; Medicine, Chinese Traditional

Objective To dynamically observe changes of IgG, its subclasses and IgE in sera of mice by immunization with mixed recombinant of BCG-Em Ⅱ/3 and BCG-Em14-3-3 vaccine of Echinococcus multilocularis (Era). Methods Forty Balb/c mice of 12-14 week old and 20-25 g weight were intranasally vaccinated by the vaccine, 4 mice were killed randomly by the weight on 0,2,4,6,8,10,12,14,16 and 18 weeks of immunization respectively, sera were gathered from the eyeball to measure IgG, its subclasses and IgE by routine ELISA. Results Levels of IgG, IgG2a and IgG2b in the sera of mice increased obviously on 2-18 weeks, reached the highest level on 10, 4 and 4 weeks respectively, the value was 0.095±0.033,0.022±0.001,0.023±0.003 respectively, as compared with the value on 0 week(0.030±0.013,0.012±0.004,0.013±0.004), the difference being statistically significant(q=2.95,4.87,2.81 respectively, P < 0.01 or P < 0.05); levels of IgG1, IgG3 and IgE in the sera of mice decreased remarkably on 2-18 weeks,came to the lowest level on 4,2,6 weeks respectively, the value was 0.031±0.004,0.136±0.002,0.114±0.002 respectively, as compared with the value on 0 week(0.192±0.007, 0.175±0.013,0.024±0.003), the difference being statistically significant (q =5.16,4.93,5.32 respectively, P < 0.01 or P < 0.05). Conclusion Helper T cell(TH) Ⅰ response is induced in mice by mixed recombinant of BCG-Em Ⅱ/3 and BCG-Em14-3-3 vaccine on early immunization.

Carcinoma, Papillary ; diagnosis ; pathology ; Female ; Humans ; Jugular Veins ; pathology ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Retrospective Studies ; Thyroid Neoplasms ; diagnosis ; pathology

[Objective] To explore whether necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion.[Method] Thirty-two healthy male Sprague-Dawley rats were randomly assigned into 4 groups (n--8):sham operation group (sham group),isehemia/ reperfusion group (I/R group),necroptosis inhibitor necrostatin-1 group (Nec-1 group) and solvent dimethyl sulfoxide (DMSO) group (DMSO group).Model of intestinal I/R injury was produced by clamping the superior mesenteric artery for 1.5 h followed by 6 h reperfusion in rats.Necrostatin-1 1.0 mg/kg was administered 30 min before occlusion in Nec1 group,while the equal volume of DMSO was given instead in DMSO group.The rats were sacrificed at 6 h of reperfusion and the lung tissues were removed for measurement of wet-dry ratio and microscopic examination and scored.The expression of receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3) in lung tissues was detected using Western-blot and immunohistochemistry.[Result] Compared with sham group,lung morphology score and wet/dry ratio in I/R,DMSO group raised (P ＜ 0.05).Lung morphology score and wet/dry ratio statistically declined in Nec-1 group compared with I/R and DMSO group (P ＜ 0.05),while there was no statistical difference of wet/dry ratio between sham group and Nec-1 group (P ＞ 0.05).As the result of westernblot and immunohistochemistry showed,the expression of RIP1 and RIP3 was up-regulated in I/R group and DMSO group (P ＜0.05),which was inhibited by Nec-1 in Nec-1 group (P ＜ 0.05).[Conclusion] Necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion,and Nec-1,the special inhibitor of RIP1,can reduce the injury.

Purpose To explore the effect of ultrasonic section,patient position and other factors on Young's modulus and shear wave velocity measurement of the muscle,and to study the consistency between Young's modulus and shear wave velocity on reflection of muscle hardness.Materials and Methods Shear wave elastography was used to detect 10 healthy young men and 10 women.Longitudinal and transverse detection of the Young's modulus and shear wave velocity of gastrocnemius and soleus were performed in natural ankle joint position,maximum plantar flexion and maximum dorsiflexion position.Results ① Comparison of the elasticity measurement between gastrocnemius and soleus.There were significant differences in the Young's modulus in the maximum plantar flexion and Young's modulus and shear wave velocity in maximum dorsiflexion position in longitudinal detection (P＜0.05) that gastrocnemius measurements were higher than soleus measurements.There were significant differences in Young's modulus and the shear wave velocity (P＜0.05) in natural position and maximum dorsiflexion position that soleus measurements were higher than gastrocnemius measurements.② In the positions of the ankle joints,the differences between longitudinal detection values and transverse detection values of gastrocnemius or soleus were statistically significant (P＜0.01) and longitudinal detection values were higher than transverse detection values.③ Comparison of the elasticity measurement of gastrocnemius and soleus muscle among different positions of the ankle joints.The measurement in natural position and in the maximum plantar flexion were evidently higher than that in the maximum dorsiflexion position (P＜0.01) in longitudinal detection.The maximum dorsiflexion position showed higher elasticity measurement.Only elasticity measurement in natural position and the maximum plantar flexion of the soleus was statistically different from that in the maximum dorsiflexion position (P＜0.01) that it was higher in the maximum dorsiflexion position.Conclusion The ultrasound elasticity measurements of gastrocnemius and soleus are related with the ultrasonic longitudinal or transverse section and the relative ankle positions.Moreover,there are some differences in elasticity measurements between these two muscles.should be given to all of these in quantitative evaluation of muscle hardness using shear wave ultrasound elastography.

Objective To explore an economic and effective management strategy for lumbar disc herniation (LDH) in community health center. Methods 62 LDH patients treated in Xujiahui community health center (observation group), 48 LDH patients treated in Huajing community health center (control group A) and 55 LDH patients treated in Shanghai 6th People's Hospital (control group B) were included.The observation group was managed by associate professor from Shanghai 6th People's Hospital and accepted different treatment strategy in mild, medium and heavy grades. The control groups A and B were managed routinely. 3 month later, costs of illness were computed and curative effects were accessed in 3 groups. Results There was no difference in curative effects between observation group and control group B (P>0.05), but better than control group A (P<0.05). The observation group cost the least among the groups (P<0.05). Conclusion Graded treatment strategy united with tertiary hospital is an economic and effective mode for LDH management in community health center.

OBJECTIVETo compare clinical effect of T-shaped locking internal fixation and external fixation in treating dorsal Barton's fracture,and investigate selective strategy of internal fixation.

METHODSFrom January 2008 to January 2013, 100 patients with dorsal Barton's fracture were randomly divided into two groups. In treatment group, there were 30 males and 20 females with an average age of (33.8±3.6) years old;30 cases were type B, 20 cases were type C;and treated with T-shaped locking internal fixation. In control group, there were 32 male and 18 females with an average age of (32.9±3.4) years old; 29 cases were type B, 21 cases were type C; and treated with external fixation. Volar tilt, ulnar deviation and radial height at 3 months after operation were detected and compared between two groups. Mechara functional evaluation were used to evaluate postoperative clinical effects. Clinical cure time, postoperative complications,joint mobility and function score were recorded and compared between two groups.

RESULTSIn treatment group,volar tilt was (11.9±2.7)°, ulnar deviation was (20.8+ 2.9)°,and radial height was (10.9±1.8) mm; while volar tilt was (9.1±1.6)°, ulnar deviation was (17.1±2.9)°, and radial height was (8.1±1.5) mm in control group. Treatment group was better than control group in volar tilt, ulnar deviation and radial height. Clinical cure time in treatment group was(12.0±2.3) weeks, shorter than control group (18.0±4.1) weeks. The incidence of complications in treatment group was lower than control group. According to Mehara functional evaluation,20 cases got excellent results, 25 good, 3 moderate and 2 poor in treatment group; 16 cases got excellent results, 14 good, 10 moderate and 10 poor in control group. Treatment group was better than control group in clinical effects.

CONCLUSIONT-shaped locking internal fixation with postoperative functional exercise for the treatment of dorsal Barton's fracture fits for biomechanics demands,and has advantages of stable fixation,rapid recovery, less complications and good functional recovery, it has better clinical effects.

Adult ; Bone Plates ; Case-Control Studies ; Female ; Fracture Fixation ; instrumentation ; Fracture Fixation, Internal ; instrumentation ; Humans ; Male ; Radius Fractures ; surgery ; Wrist Injuries ; surgery

OBJECTIVETo study the bone mineral development and the factors influencing the development in preterm infants.

METHODSNinety preterm and 90 term infants followed up by the child health care service were randomly enrolled. Tibia quantitative ultrasound measurements were used to evaluate bone mineral density described as supersonic speed of sound (SOS) and Z scores at 6 months old (corrected gestational age for preterm infants). The factors influencing bone mineral development were investigated by questionnaire.

RESULTSThe SOS values and Z scores in term infants were significantly higher than those in preterm infants at 6 months old. In the preterm group, the SOS values and Z scores were significantly different in infants with different birth weights or gestational ages (P<0.05). The SOS values in preterm infants with different weaning time were significantly different. The Z scores in female preterm infants were significantly higher than that in males (P<0.05). Multiple regression analysis indicated that weaning time and daily time of outdoor activities were independent factors influencing SOS values in preterm infants.

CONCLUSIONSIt is helpful to promote bone mineral development by an appropriate weaning time or increasing the time of outdoor activities in preterm infants.

Bone Density ; Breast Feeding ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; physiology ; Male ; Regression Analysis ; Sex Characteristics

OBJECTIVETo determine whether lactic acid bacteria as probiotics is efficacious in the primary prevention of infantile eczema or atopic eczema.

METHODSFor this meta analysis of randomized controlled trials (RCT) describing the efficacy of probiotics in infants with eczema or atopic eczema at ages of ≤2 years, a comprehensive search in the databases was performed up to January 2010. Three reviewers independently evaluated the studies for methodological qualities. RevMan 5.0.2 software was used for meta analysis.

RESULTSTwelve RCTs on the preventive effects of lactic acid bacteria as probiotics on infantile eczema were included, and 7 of the 12 RCTs reported the preventive effect of lactic acid bacteria on atopic eczema. The meta analysis showed that there was an overall significant reduction in infantile eczema and atopic eczema favoring lactic acid bacteria compared with placebo. The relative risk (RR) ratios for eczema and atopic eczema were 0.80 (95%CI: 0.70-0.90; P<0.01) and 0.78 (95%CI: 0.64-0.97; P<0.01), respectively. Lactic acid bacteria combined with other probiotics decreased significantly the incidence of eczema, with a RR ratio of 0.79 (95%CI: 0.68-0.93; P<0.01). The use of lactic acid bacteria alone did not result in a reduction in the incidence of eczema, with a RR ratio of 0.85 (95%CI: 0.69-1.05; P>0.05).

CONCLUSIONSThe data from this meta analysis suggest that lactic acid probiotics combined with other probiotics play a role in the prevention of infantile eczema. There is insufficient evidence to recommend single use of lactic acid bacteria for prevention of eczema. Further studies are required to determine whether the findings are reproducible.

Child ; Child, Preschool ; Dermatitis, Atopic ; prevention & control ; Humans ; Lactobacillus ; Lactococcus ; Probiotics ; therapeutic use ; Randomized Controlled Trials as Topic ; Streptococcus thermophilus

OBJECTIVETo establish an experimental animal model of Alzheimer's disease (AD) with clinical and pathological specificity conformed to AD in human, and to observe the effect of Zhinao Capsule (ZNC) on learning, memory and patho-morphological parameters in the model.

METHODSThe experimental AD model of rats was improved and established by combined injection of beta-amyloid protein (beta-AP) to lateral ventricle and transforming growth factor beta 1 (TGF beta 1) to brain. The learning and memory function of the model rats were tested by step-through test and water-maze test, and the number and cross area of beta-AP deposited macula in cerebral cortex and CA1 region of hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis.

RESULTSThe improved AD animal model showed both the specificity of behavior (learning and memory impairments) and the typical pathological specificity (beta-AP deposited macula). ZNC could effectively improve the impairment of learning and memory and reduce the number and cross area of beta-AP deposited macula in cerebral cortex and hippocampus CA1 region in the AD model rats.

CONCLUSIONThe AD rat model induced by the combined injection of beta-AP and TGF beta 1 is a good animal model simulated to the clinical reality, which could be used to screen and evaluate the anti-dementia agents. ZNC could display anti-dementia effect of the AD model rats.

Alzheimer Disease ; drug therapy ; physiopathology ; Amyloid beta-Peptides ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Learning ; Male ; Memory ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta