OBJECTIVETo establish the analytical method for the release kinetic (RK) of Aconitum Brachypodum gel based on the nonlinear mixed effect model (NLMEM), in order to rationally evaluate the drug release process and explain the release mechanism.

METHODThe zero-order kinetic model containing for non-corroded drug system with the random effect was taken as the base model. The fixed effect and random effect factors impacting the drug release were analyzed by PROC NLMIXED of SAS to establish the final typical model. Subsequently, 10 training subsets were randomly extracted from the primary data to respectively their RK models, calculate the corresponding predicted root-mean-square error and average relative error, and evaluate the model stability and prediction accuracy.

RESULTThe burst effect F0 had a very significant effect on the RK model. Among the component factors, carbopol 940 showed an obvious effect on the inherence release speed constant k0 and the concentration gradient change constant a, with different variations on the basis of dosage range. The random effect factors of k0 and a had a significant impact. The final RK model was proved to be stable, effective and reliable in the cross validation.

CONCLUSIONThe drug release kinetic analysis method could be used to rationally evaluate the drug release process and explain the release mechanisms.

Aconitum ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Gels ; Kinetics ; Monte Carlo Method ; Nonlinear Dynamics

Objective To explore the optimal HbAlc diagnostic cutpoint in different glucose tolerance populations in the plateau region.Methods (1) 472 diabetes mellitus (DM) patients and highrisk groups accepting diabetes screening in the First Affiliated Hospital of Kunming Medical College (217 males and 255 females,≥20 years old,median age 54 years old) were collected,oral glucose tolerance test (OGTT) and HbAlc were tested.(2) the research subjects were divided into normal glucose adjustment group (NGT),Impaired fasting glucose group (IFG) and (or) Impaired glucose tolerance IGT group and diabetes mellitus (DM) group.The receiver-operating characteristic curve (ROC) was explored to determine the optimal HbA1c diagnostic cut point for IFG,IGT and DM status respectively.Results The average HbA1 c values of NGT,IFG and (or) IGT,DM groups were (6.06 ± 0.11) ％,(6.63 ± 0.11) ％,(8.70 ± 2.08)％ respectively,for IFG and IGT groups,the optimal HbA1c diagnostic cut points were 6.7％ and 6.6％,respectively; If use either FBG or 2 h PG to diagnose DM,the corresponding optimal HbA1 c diagnostic cut point was 7.1％ ; If use anyone of FBG or 2hPG to diagnose DM,the corresponding optimal HbA1c diagnostic cut point was 7.0％ ; If both FBG and 2hPG were used to diagnose DM,the corresponding optimal HbA1 c diagnostic cut point was 7.1％.Conclusion Preliminarily confirm the optimal HbA1c diagnostic cut point in different glucose tolerance populations in the plateau region of Kunming,and provide the evidence for further clinical application of HbA1c.

Objective To study the immediate conservative breast surgical reconstruction by trans-ferring the same lateral latissimus dorsal myocutaneous flap (LDM) for the treatment of stage Ⅱ and stage Ⅲ breast cancer, combined with neoadjuvant chemotherapy. Methods Breast cancer patients in stage Ⅱ and Ⅲ with pathological diagnosis by core needle biopsy, had undergone immediate conservative breast reconstruction surgery with transferring the latissimus dorsal myocutaneous (LDM). We scored the reconstructed breast twice at one month after operation and completion of radiation. The final score was decided using the mean value of the twice evaluating score. Kaplan-Meier survival was used to analyze the survival of 18 cases with traditional mastectomy. Results The tumor size ranged from 30 mm to 55 mm before neoadjuvant chemotherapy, and ranged from 25mm to 45 mm after neoadjuvant chemotherapy. The median weight of the tumor specimens in breast conservative operation was 140 g (90 g to 220 g). A-mong the 18 patients, 16 cases had more than 3 scores with satisfied cosmetics (93.33 % ). Dorsal subcu-taneous seroma in donation area was observed in 5 of 18 patients (27.78 %) and dorsal incision dehiscence was observed in 2 of 18 patients (11.11%). None of the patients developed recurrence except that 1 pa-tient (5.55 %) had distance metastasis (bone metastasis} in a mean 22-months follow-up. The Kaplan-Meier survival curve in breast conservation reconstruction patients had no different from that of traditional mastectomy patients at the same time. Conclusions Immediate conservative breast surgical reconstruction by using the same lateral latissimus dorsal myocutaneous flap is an effective method for stage Ⅱ and stage Ⅲ breast cancer patients combined with neoadjuvant chemotherapy, which can increase satisfactory breast so that cosmetic outcome can be reached.

Objective To evaluate the relationship between Henoch-Schonlein purpura (HSP) accompanying renal impairment and helicobater pylori(Hp) infection.Methods This study consisted of 304 patients with HSP.The patients were divided into 2 groups(group A and group B) based on Hp infection or not(91 cases in group A and 213 cases in group B).Compared with the rates of accompanying renal impairment in 2 groups.And observed the recovery from renal impairment between the patients who were turned into negative(group C)and patients still were positive after the anti-Hp therapy(group D).Numeration data were analyzed by ?2 test.Results Group A which was with Hp infected,the accompanying renal impairment ratio was 65.9%.Group B which was without Hp infected,the ratio was 35.2%.There was significant difference between 2 groups(?2=24.378 P

Objective To investigate the relationship between genetic single-nucleotide polymorphisms of ligase Ⅳ (LIG4) and heat shock protein B1 (HSPB1) and prognosis in nasopharyngeal carcinomas.Methods DNAs were extracted by phenol-chlorofrom method from peripheral blood samples of 168 nasopharyngeal carcinoma patients.Genetic single-nucleotide polymorphisms were divided by Taqman realtime polymerase chain reaction (PCR).All statistical analyses were performed with statistical product and service solutions v13.0.A p-value of less than 0.05 was confirmed as statistical significance.Single-factor and multiple-factor logistic analyses were used to calculate odds ratio (OR) and 95％ confidence interval (CI).Long-rank test and COX were also used.Results No relationship was found between the recurrence,metastasis and overall survival of nasopharyngeal carcinoma and genetic single-nucleotide polymorphisms of LIG4 and HSPB1 with single-factor and multiple-factor logistic analyses.Conclusions LIG4 rs1805388 and HSPB1 rs2868371 had no relationship with prognosis of nasopharyngeal carcinomas.

Animals ; Fatigue ; prevention & control ; Female ; Gardenia ; chemistry ; Hypoxia ; prevention & control ; Male ; Mice ; Mice, Inbred Strains ; Plant Extracts ; pharmacology ; Thuja ; chemistry ; Ziziphus ; chemistry

OBJECTIVETo evaluate the reliability, validity, and responsiveness of traditional Chinese medicine (TCM) clinical outcomes rating scale for heart failure (HF) based on patients' report.

METHODSTCM clinical outcomes rating scale for HF (TCM-HF-PRO) were evaluated based on 340 HF patients' report from multiple centers. The completion of the investigation was recorded. Cronbach's α coefficient and split-half reliability were used for reliability analysis, and factor analysis was used to assess the construct validity of the rating scale. Pearson correlation analysis was then used for criterion validity analysis. Discriminant analysis was used to assess the responsiveness of the scale. All 340 HF patients having complete TCM-HF-PRO data were assigned to the treatment group and the control group by central randomization. The total TCM-HF-PRO scores of the two groups were compared using paired t-test to reflect the longitude responsiveness of the scale before treatment and at week 2 after treatment.

RESULTS(1) The recycling rate of the scale was 100.0%. One of them was not filled completely, which was rejected thereby. So the completion rate was 99.7%. The completion time for TCM-HF-PRO scale ranged 15 to 25 min. (2) The Cronbach's α coefficient of rating scale was 0.903, split-half reliability was 0.844 and 0.849. (3) Confirmatory factor analysis showed that 7 factors and items formed according to maximum load factor basically coincided with the construct of the rating scale, 7 factors accumulated contribution rate was 43.8%. TCM clinical outcomes rating scale for HF based on patients' report was relatively better correlated with the Minnesota living with HF questionnaire (r = 0.726, P < 0.01). (4) Discriminant analysis showed that the rating scale correctly classified more than 78.8% of case studies having confirmed initial differential diagnosis by experts. The total scale of the rating scale decreased more in the two group after treatment, with significant difference as compared with before treatment (P < 0.01.

CONCLUSIONTCM clinical outcomes rating scale for HF based on patients' report had good reliability, validity and responsiveness, hence it could be used to assess clinical efficacy for HF patients.

Diagnosis, Differential ; Discriminant Analysis ; Factor Analysis, Statistical ; Heart Failure ; diagnosis ; Humans ; Medicine, Chinese Traditional ; methods ; standards ; Reproducibility of Results ; Surveys and Questionnaires

Objective To explore the clinical significance of the blood lactic dehydrogenase(LDH), ?_2-microglobulin(?_2-MG),D-dimer measuring in the diagnosis and treatment of Non-Hodgkin lymphoma. Methods In 40 cases with NHL,LDH was measured by L-P continuous monitoring method,?_2-MG was measured by luminescent immunoassay,D-dimer was measured by immunoturbidimettic assay.Results The levels of the blood LDH,?_2-MG and D-dimer in patients with NHL were higher than those of in the controls(P 0.05).Con- clusion The levels of blood LDH,?_2-MG,D-dimer can be taken as an auxiliary clinical index to diagnose, classify the phase,evaluate the effectiveness of treatment and prognosis in the NHL patients,and have impor- tant clinical significance.

Objective To analyse MMACHC mutations for 45 pedigrees with combined methylmalonic aciduria and homocyctinuria by Sanger sequencing, and to discuss the utility of prenatal genetic diagnosis for these pedigrees.Method Peripheral blood was collected from 45 probands and their parents from 2012-2015 in Genetic Counselling Clinic of the First Affiliated Hospital of Zhengzhou University, and the DNA were extracted from the blood.Then the coding sequence of MMACHC gene was amplified by PCR, and the PCR products were further sequenced to detect mutations for each pedigree.For 12 families, chorionic villus sampling was performed on the pregnant women to make prenatal genetic diagnosis.Result There were 14 distinct mutations detected in the 45 pedigrees, and the most frequent mutations are c.609G>A(W203X),c.658-660delAAG(K220del)and c.80A>G (Q27A).Two of those mutations have not been reported before:one is a splicing site mutation c.81+1G>A;while the other is a missense mutation c.665A>G,p.Y222C.Most mutations were found in exon 4.Among the 12 pedigrees who received prenatal diagnosis, 2 fetuses were normal, 7 fetuses were carriers of heterozygous mutation, and the other 3 fetuses were patients with compound heterozygous mutation or homozygous mutation.The couples whose fetuses were normal or carriers continued the gestation, while the couples whose fetuses were patients decided to terminate the pregnancy.After delivery, the outcome of the fetuses was the same as the prenatal diagnose results.Conclusion Two novel mutations of MMACHC were identified and prenatal genetic diagnosis helps to avoid the delivery of combined methylmalonic aciduria and homocyctinuria patients.

OBJECTIVETo investigate the effect of total flavonoids of astragalus on the expression of endoplasmic reticulum chaperone, calumenin and connecxin 43 (CX43) in suckling mouse myocardium with myocarditis caused by coxsackievirus B3 (CVB3).

METHODSThe primary culture of suckling mouse myocardium cells were randomly divided into control group, CVB3 infected group and total flavonoids of astragalus group. Firstly, to confirm the identity of the suckling mouse myocardium, α-SMA was monitored by immunohistochemistry method. Then the protein expression changes of endoplasmic reticulum chaperone-glucose regulatory protein 78 ( GRP78), calumenin and CX43 were detected by Western blot.

RESULTS(1) Compared with that of the control group, the GRP78 expression level in CVB3 infected group was improved, the expression levels of calumenin and CX43 were all reduced. (2) Compared with that of CVB3 infected group, GRP78 expression level was decreased, and the expression levels of calumenin and CX43 were increased in total flavonoids of astragalus group.

CONCLUSIONCVB3 infection may cause endoplasmic reticulum stress of rat myocardium cells by increasing the expression of GRP78 and decreasing the expression of calumenin and CX43. On the other hand, total flavonoids of astragalus can reduce the expression of GRP78 and increase the expression of calumenin and CX43.The results of this experiment may be closely related to the effects of anti-arrhythmia with viral myocarditis caused by CVB3.

Animals ; Astragalus Plant ; chemistry ; Blotting, Western ; Calcium-Binding Proteins ; metabolism ; Cells, Cultured ; Connexin 43 ; metabolism ; Coxsackievirus Infections ; drug therapy ; Endoplasmic Reticulum ; metabolism ; Endoplasmic Reticulum Stress ; drug effects ; Flavonoids ; pharmacology ; Heat-Shock Proteins ; metabolism ; Mice ; Myocarditis ; drug therapy ; virology ; Myocardium ; cytology ; Myocytes, Cardiac ; drug effects ; virology ; Rats