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

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cluster Analysis ; Diagnosis, Differential ; Female ; Humans ; Liver Diseases ; classification ; epidemiology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Yang Deficiency ; classification ; epidemiology ; Yin Deficiency ; classification ; epidemiology

Adult ; Brain Abscess ; Cholesteatoma ; surgery ; Endoscopy ; Female ; Humans ; Maxillary Sinus ; surgery

Objective To evaluate the left atrial function and to explore its determinants in patients with hypertrophic cardiomyopathy by three-dimensional echocardiography (3DE).Methods 46 patients with HCM (obstructive HCM:25 cases,nonobstructive HCM:21 cases) and 46 healthy cases (controls) were enrolled in this study.Time-volume curve of left atrium was acquired by 3DE in all subjects.Left atrial maximal volume (LAVmax),left atrial minimal volume (LAVmin) and left atrial presystolic volume (LAVp) were acquaired.Left atrial volume index (LAVI),left atrial expansion index (LAEI),left atrium emptying fraction (LAEF),left atrium passive emptying fraction (LAPEF) and 1eft atrium active emptying fraction (LAAEF) were calculated.Comparative analysis between two groups was taken .The Spearman correlation analysis and multiple linear regression analysis between left atrial volume index (LAVI) with interventricular septal thickness (IVSd),left ventricular outflow tract peak gradient (LVOT-PG),mitral regurgitation (MI), left ventricular diastolic function (LVDF) were analyzed respectively .Results Compared to the controls LAVmax (45.67 ±11.96)ml,LAVmin (20.48 ±6.80)ml,LAVp (24.48 ±9.31)ml,LAVI 25.63 ±6.52, LAEI (1.32 ±0.49)%,LAEF (55.25 ±8.06)%,LAPEF (35.90 ±7.00)%and LAAEF (30.20 ±10.13)%, the patient with HCM had a significantly larger LAVmax (81.45 ±24.24)ml,LAVmin (44.60 ±18.96)ml, LAVp (61.00 ±21.64) ml and LAVI 45.39 ±14.17,there were significant differences among the groups (t=8.978,8.123,9.227,8.436,all P<0.01),lower LAEI(0.95 ±0.43)%,LAEF (46.15 ±11.12)%, LAPEF (25.64 ±9.09)%,there were significant differences among the groups (t=-3.865,-4.493,-6.504,all P<0.01),and slightly lower LAAEF (28.20 ±9.26)%,there were no significant differences among the groups (t=-0.656,P>0.01).There were significant positive correlation between LAVI and IVSd,LVOT-PG,MI,LVDF respectively (r=0.704,0.517,0.640,0.701,all P<0.01).Multiple linear regression analysis demonstrated that IVSd , LVOT-PG, MI and LVDF were correlated factors of LAVI (absolute standardized coeffients =0.264,0.515,0.614,0.341,all P<0.05).Conclusions 3DE could evaluate the left atrial volume and function in patients with HCM , with increased left atrial volume and decreased reservioer,conduit and booster pump function .Mitral regurgitation,obstruction of left ventricular outflow tract,left ventricular diastolic dysfunction and the thickness of left ventricular wall contributed to left atrial dysfunction at different levels ,among which mitrial regurgitation contributed the most .

Objective: To study the antipyretic action of Dipseudoephedrine Glycyrrhizin and its effect on heart rate and blood pressure of rats.Methods: The model of pyretic rabbit was established by diphtheria-pertussis-tetanus triple vaccine,and to observe the effect of Dipseudoephedrine Glycyrrhizin on temperature of rabbit. Two-path physiological recorder was used to measure heart rate and blood pressure.Results: The experiment proved that Dipseudoephedrine Glycyrrhizin can decrease the anus temperature of pyretic rabbit obviously.Dipseudoephedrine Glycyrrhizanate had no remarkably effect on heart rate and blood pressure.Conclusion: Dipseudoephedrine Glycyrrhizin has antipyretic action and has no effect on heart rate and blood pressure within studied dose.

The high-copy-number plasmid pcDNA3.1+ is unstable within S almonella typhimurium. A novel plasmid pmcDNA3.1+ was constructed by removin g the promoter sequence of ampicillin resistance gene (bla gene) in plasmid pcDNA3.1+. In contrast to pcDNA3.1+, pmcDNA3.1+ was stable within Salmonel la typhimurium SL7207 in LB medium with or without ampicillin. Further experi ments showed the ?-lactamase activity of Salmonella typhimurium SL7207(pmc DNA3.1+) was apparently lowered than that of Salmonella typhimurium SL7207( pcDNA3.1+) and the high ampicillin concentration was maintained longer in LB me dium culturing Salmonella typhimurium SL7207(pmcDNA3.1+). When mice were a dministered with Salmonella typhimurium SL7207(pmcDNA3.1+) intraperitoneall y, more than 95% of Salmonella cells separated from the spleen still harbore d the plasmid pmcDNA3.1+ 7 days later; but 99% of Salmonella cells lost the plasmid pcDNA3.1+ at day 3 in mice innoculated with Salmonella typhimurium SL7207(pcDNA3.1+). By lowering the expression of bla gene, the rapid deco mposition of ampicillin in LB medium was avoided and the metabolic pressure was relieved for the host cells. This method offers a solution for the problem of t he instability of high-copy-number plasmid within Salmonella typhimurium.

OBJECTIVETo explore the distribution characteristics of basic syndromes and its related factors in patients with chronic functional constipation (CFC).

METHODSThe complete data of 538 patients with CFC were collected and initial database was established with Epidata 3. 0. TCM syndrome typing was performed. The distribution characteristics of basic syndromes were analyzed using SPSS 17. 0 Software. The univariate and multivariate Logistic regression analyses were performed with SPSS 17. 0 Software to determine basic syndrome related factors such as age, engaged professionals, sleep quality, depression, mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation, and so on.

RESULTSThe TCM syndrome frequency of CFC patients was sequenced from high to low as qi deficiency syndrome (380 cases, 70.6%), qi stagnation syndrome (337 cases, 62.6%), blood deficiency syndrome (234 cases, 43.5%), yin deficiency syndrome (220 cases, 40.9%), yang deficiency syndrome (197 cases, 36.6%), and others(58 cases, 10. 8%) . Most patients were complicated with complex syndromes, and the most common complex syndromes were qi deficiency complicated qi stagnation syndrome (275 cases, 51.1%) and qi deficiency complicated blood deficiency syndrome (222 cases, 41.3%). Aging, work fatigue, and exercise conditions were main related factors for qi deficiency syndrome (P <0. 01, P <0. 05). Poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, defecation barriers constipation were main related factors for qi stagnation syndrome (P <0.01). Sleep quality and poor emotional (depression and anxiety tendencies) were main related factors for blood deficiency syndrome (P <0. 01, P < 0.05). Stimulating beverages were main related factor for yin deficiency syndrome (P <0.05). Engaged in mental work and slow transit constipation were main related factors for yang deficiency syndrome (P < 0. 01, P <0. 05).

CONCLUSIONSCFC is featured as complex syndromes. The most common complex syndromes were qi deficiency complicated qi stagnation syndrome and qi deficiency complicated blood deficiency syndrome. Basic syndrome related factors such as age, engaged professionals, sleep quality, poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation were associated with the distribution of CFC syndromes.

Anxiety ; complications ; Constipation ; complications ; diagnosis ; psychology ; therapy ; Depression ; complications ; Diagnosis, Differential ; Factor Analysis, Statistical ; Fatigue ; Humans ; Medicine, Chinese Traditional ; Qi ; Stress, Psychological ; complications ; Syndrome ; Yang Deficiency ; diagnosis ; Yin Deficiency ; diagnosis

Adolescent ; Angiofibroma ; surgery ; Endoscopy ; Humans ; Male ; Nasopharyngeal Neoplasms ; surgery ; Nose ; surgery ; Otorhinolaryngologic Surgical Procedures ; methods

Objective To identify changes in the occurrence of endemic fluorosis in order to provide scientific basis for making countermeasures. Methods Five villages from 14 counties of mild, moderate and severe fluorosis affected areas were selected by stratified cluster sampling every year in the whole province during 2006 - 2010. Water and urinary fluorine were determined by ion selective electrode method(GB/T 8538-1995); dental fluorosis of children 8-12 years old was diagnosed with Dean method; skeletal fluorosis was diagnosed according to "clinical indexing standards of endemic skeletal fluorosis "(GB 16396-1996), between 2006 and 2008, and "clinical diagnosis standard of endemic skeletal fluorosis"(WS 192-2008) between 2009 and 2010. Results A total of 25 diseased villages were surveyed, 14 with water sources changed, covered a resident population of 8005 people, beneficiary population 7154, and accounting for 89.37% of the resident population; not changed villages 11. In accordance with the "State drinking water health standards", in the 14 changed villages the fluoride in drinking water was qualified (≤ 1.20 mg/L), there were 3 schools whose water fluorine content exceeded the standard; among the 11 villages that did not change water sources 7 drinking water samples fluorine content exceeded the standard. Of the 8 to 12 years old children in villages with changed water sources, 363 of them were checked and 142 dental fluorosis were found, the detection rate of dental fluorosis was 39.12% (142/363); in villages with water sources not changed, 303 children were checked, the detection rate of dental fluorosis was 43.89%(133/303). Of sixteen and elder adults in water source changed villages, 6424 people were checked and 403 skeletal fluorosis were found, skeletal fluorosis detection rate was 6.27% (403/6424); 3572 people were checked in not changed villages, the detection rate of skeletal fluorosis was 13.89%(496/3572). In water sources changed areas, geometric mean of urinary fluoride was in the normal reference value(WS/T 256-2005, 1.40 mg/L)or less. Conclusions Endemic fluorosis is decreased in water improved areas, but in unimproved areas the disease is still severe, and control of endemic fluorosis is still an arduous task.

The purpose of this study was to evaluate the impact of callus induction and culture conditions on secondary metabolic diversity of the callus cell lines of traditional Chinese medicinal plant Glycyrrhiza sp. (Glycyrrhiza) by combined chemical analysis and HPLC fingerprint. These callus induction conditions included two Glycyrrhiza species, two types of explants, light and dark conditions, and two combinations of hormones. The evaluation was firstly based on the contents of total flavonoids in the callus by chemical analysis and one way ANOVA. The content of total flavonoids in callus was significantly (P < 0.05) influenced by Glycyrrhiza species, light condition, and the combination of hormones. The callus was further evaluated using diversity factor based on the comparison of HPLC fingerprints of these callus cell lines. Diversity factor varies significantly for calli induced under different conditions, with the highest being at 0.45 under light condition and combination of hormones. These results provide important knowledge for the selection of suitable callus cell lines for the production of pharmacologically important secondary metabolites or bioactive fractions by in vitro culture of Glycyrrhiza sp.
Cell Culture Techniques ; methods ; Cell Line ; Darkness ; Flavonoids ; biosynthesis ; Glycyrrhiza ; cytology ; drug effects ; metabolism ; radiation effects ; Plant Growth Regulators ; pharmacology ; Plant Roots ; metabolism