This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

Objective To evaluate the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in ovarian cancer cell lines, and to investigate the biological effects of down-regulated MALAT-1 on OVCAR3 cells.Methods qRT-PCR analysis was used to examine the expression level of MALAT-1 gene in ovarian cancer cells, including ES-2, A2780, SKOV3 and OVCAR3 cell lines.For functional research, four shRNA oligos specially targeting MALAT-1 and a empty vector were designed and constructed into pGPU6/GFP/Neo, then transfected into OVCAR3 cells.qRT-PCR was used to confirm the effective suppression of MALAT-1.Changes of proliferation and adhesion of cells were analyzed by CCK-8 and adhesion assays.Wound-healing, transwell migration and invasion assays were used to examine migration and invasion of MALAT-l-silencing cells in vitro.Results The expression of MALAT-1 gene in OVCAR3 cells was high, and qRT-PCR results confirmed successfully the knockdown of MALAT-1 after transient transfection.After successful suppression of MALAT-1, the proliferation, wound-healing and adhesion ability in vitro were inhibited to some degree.In transwell migration assay, the number of migration cells in MALAT-1-silencing group was 52.17±4.48, which is much less than that in the negative and control groups (286.50± 12.23 and 295.67±6.96, respectively).In invasion assay, the number of invasion cells passing the transwell membrane in MALAT-1-silencing group (37.33±2.40) was also decreased significantly, compared to that in the negative and control groups (239.00±15.72 and 222.67±20.85, P ＜ 0.05).Conclusions shRNA-mediated silence of MALAT-1 can effectively inhibit the proliferation, adhesion, migration and invasion abilities of ovarian cancer cell line OVCAR3 in vitro, indicating MALAT-1 is expected to be a target gene for the treatment of ovarian cancer.

OBJECTIVE: To explore the molecular basis for a blood donor with an ABO subtype. METHODS: The proband and his family members were subjected to serological analysis. Their genotypes were determined by real-time PCR and sequencing of the coding regions of ABO gene. RESULTS: The proband was determined as an ABw subtype. By sequencing analysis, the proband was typed as A102/BW03. Compared with ABO*B.01, the proband was found to harbor a 721C>T variant (ABO*BW.03 allele) in exon 7 of the ABO gene, which caused substitution of Arginine at position 241 by Tryptophan resulting in a ABW phenotype. The blood type of the proband's sister was similar to that of the proband. The maternal serological pattern was B type, and the result of sequencing suggested that the genotype fit with B101/Bw03. CONCLUSION The 721C>T in the exon 7 of the ABO glycosyltransferase gene probably underlies the Bw03 phenotype. The ABO*Bw.03 variant of the proband and his sister were inherited from their mother.
ABO Blood-Group System ; genetics ; Amino Acid Substitution ; Female ; Genotype ; Humans ; Male ; Pedigree ; Whole Exome Sequencing

Objective:To investigate the application of mind map combined with daily mini-clinical evaluation exercise in standardized training of gynecological residents.Methods:A total of 100 trainees who received standardized training in Department of Gynecology, Women and Children's Hospital of Chongqing Medical University, were selected as subjects, and they were divided into control group (traditional teaching) and observation group (mind map combined with daily mini-clinical evaluation exercise) according to the order by which they entered the department for training, with 50 trainees in each group. After teaching, the two groups were compared in terms of assessment results of clinical practice exercise and degree of satisfaction with teaching. SPSS 22.0 statistical software was used for the t-test. Results:After the application of mind map combined with daily mini-clinical evaluation exercise in the standardized training of gynecological residents, compared with the control group, the observation group had significantly higher assessment results of inquiry ability, specialized physical examination, clinical diagnosis, diagnosis and treatment regimen, clinical practice ability, communication ability, clinical thinking ability, decision-making ability for clinical issues, and overall performance ( P<0.05). Compared with the control group, the observation group had significantly higher levels of mastery of clinical inquiry ability, specialized physical examination, development of diagnosis and treatment regimen, doctor-patient communication ability, and clinical practice ability, as well as a significantly higher overall teaching satisfaction score ( P<0.05). Conclusion:Mind map combined with daily mini-clinical evaluation exercise is a simple and feasible teaching method and can help to improve the comprehensive clinical practice ability of trainees receiving standardized residency training, and therefore, it holds promise for application in teaching.

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract （COE） affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer （PLGC） by regulating the leucine-rich repeat containing G protein-coupled receptor 5 （Lgr5）/Wingless （Wnt）/β-catenin signaling pathway based on a gastric organoid injury model. MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG， 0.02 mg·L^-1）. Gastric organoid injury models were randomly divided into normal group， model group （0.02 mg·L^-1 MNNG）， low， medium， and high dose （5， 10， 20 mg·L^-1） groups of COE， and Wnt inhibitor Dickkopf-related protein 1 （DKK1） （0.5 mg·L^-1） group， and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium （MTT） assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin （HE） staining. The expression levels of Lgr5， Mucin2 （MUC2）， Mucin5AC （MUC5AC）， Mucin6 （MUC6）， Wnt， and β-catenin in gastric organoids under different drug concentrations were detected by Western blot （WB）. ResultCompared with the normal group， the number， volume， and activity of gastric organoids in the model group were decreased （P<0.01）， while the expressions of Lgr5， MUC2， Wnt， and β-catenin were significantly increased （P<0.01）. The expressions of MUC5AC and MUC6 were significantly decreased （P<0.01）. Compared with the model group， the number and volume of gastric organoids in the low， medium， and high dose groups of COE were all improved （P<0.01）， and the vitality of gastric organoids was significantly enhanced （P<0.01）. The effect was the most significant at a COE concentration of 20 mg·L^-1 （P<0.01）. The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced （P<0.01）， while the expression of MUC5AC and MUC6 were significantly increased in the low， medium， and high dose groups of COE （P<0.05， P<0.01）. Compared with the model group， Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids （P<0.05， P<0.01） and reduce the expression of MUC2， Wnt， and β-catenin. In addition， the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend （P<0.01）. ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5， MUC2， Wnt， and β-catenin and promoting the expression of MUC5AC and MUC6， thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.

Objective To survey the prevalence of greenhouse farmer's lung and related risk factors in part of rural areas of Liaoning Province.Methods Using uniform scheme,procedures and questionnaire,a survey for 5420 farmers(2660 men and 2760 women)with complete data who work inside greenhouses was performed in Shenyang,Xinmin,Chaoyang,and Jinzhou between August 2006 and June 2009.Pulmonary function tests was performed for every active farmer.Results Greenhouse farmer's lung was diagnosed in 308 cases,205 men(66.55%,205/308)and 103 women(33.44%,103/308),a prevalence of 5.7%(308/5420).The prevalence rate of greenhouse farmer's lung in males was significantly higher than that in females(?2=39.93,P0.05).In the 308 cases,the number of patiernts presented with fever chill,cough/sputum,chest tightness/shortness of breath were 180(58.44%),192(62.34%),160(51.95%)respectively,and the number of crepitations,radiological changes,spirometry abnormalities and serum IgE antibodies(+)was 164(53.25%),153(49.68%),147(47.73%)and 136(44.16%)at the time of the study.62.34%(192/308)of patients with greenhouse farmer's lung were mild and 38.66%(116/308)were severe.Conclusion The total prevalence rate of greenhouse farmer's lung in part of rural areas of Liaoning Province was 5.7% and multiple risk factors were associated with the disease.

This systematic review aims to evaluate the efficacy and safety of Wenxin Granules in the treatment of chronic heart failure with atrial fibrillation. Databases,such as CNKI,Wan Fang Date,VIP,PubMed,Cochrane Library,were electronically retrieved for relevant randomized controlled trials of Wenxin Granules in the treatment of chronic heart failure with atrial fibrillation. Two researchers independently screened out the literatures,extracted data according to the inclusion criteria,and conducted a quality assessment by the risk bias assessment tool in the Cochrane evaluation manual. Cochrane systematic evaluation software Rev Man 5. 3 was used for data analysis. Totally 11 randomized controlled trials,including 941 subjects. The intervention measures were the conventional treatment recommended by the guidelines combined with Wenxin Granules; and the control measures were the conventional treatment recommended by the guidelines alone. The results showed that compared with conventional treatment alone,Wenxin Granules combined with conventional treatment can better reduce the BNP level in patients with heart failure with atrial fibrillation( MD =-258. 18,95% CI[-464. 06,-52. 30],P= 0. 01) or NT-proBNP level,better improve left ventricular ejection fraction( MD = 6. 72,95%CI[4. 61,8. 84],P<0. 000 01),I~2= 65%,And the ventricular rate decreased more significantly( MD =-11. 66,95% CI[-15. 79,-7. 54],P<0. 000 01),and the cardiac function was improved more efficiently( RR = 1. 20,95%CI [1. 11,1. 31],P<0. 000 1),I~2= 23%.In conclusion,compared with the single administration of conventional Western medicine,the combined administration of Wenxin Granules has better effects in reducing the level of BNP or NT-proBNP,slowing down the ventricular rate,and improving the left ventricular ejection fraction,with fewer adverse reactions. However,due to the small sample size and the low quality of literatures included in this systematic review,it is shall be carefully applied in clinic. More rigorous randomized controlled trials shall be conducted to determine the efficacy of Wenxin Granules in improving cardiac function in the treatment of chronic heart failure with atrial fibrillation.
Atrial Fibrillation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/drug therapy* ; Humans ; Randomized Controlled Trials as Topic ; Stroke Volume ; Ventricular Function, Left

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2–3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.
Adult ; Asian Continental Ancestry Group* ; China ; Comorbidity ; Developed Countries ; Developing Countries ; Diagnosis* ; Epidemiologic Studies ; Epidemiology ; Global Health ; Humans ; Hypersensitivity* ; Prevalence ; Rhinitis, Allergic*

Objective: To understand the changes of serum transient receptor potential channel 1(TRPC1) in patients with vascular depression. Methods: 58 patients with vascular depression, 49 patients with major depressive disorder and 38 healthy controls were recruited.The TRPC1 of all subjects were detected by ELISA.Patients with vascular depression and patients with primary depression were scaled by HAMD-17.The level of TRPC1 was contrasted in different ages groups and in different nosogenesis (cerebral infarction, ischemic cerebrovascular disease, old cerebral hemorrhage, cerebral microbleeds, vascular risk factors, etc.) of vascular depression.The relationship between TRPC1 level and severity of depressive symptoms was further analyzed. Results: (1)The level of TRPC1 of serum((643.76±118.43)pg/ml) was decreased in patients with vascular depression compared with that in healthy controls ((712.48± 98.75) pg/ml). The level of TRPC1 in patients with vascular depression over 60 years ((601.43±113.55)pg/ml)was lower than that in patients with major depressive disorder over 60 years ((626.32±125.46)pg/ml) and healthy controls over 60 years((721.84± 99.62)pg/ml) .(2) Among the various causes of vascular depression, the level of TRPC1 in patients with cerebral infarction, ischemic cerebrovascular disease and cerebral microbleeds was significantly lower (P<0.05). (3) The levels of TRPC1 in the patients with vascular depression (r=-0.962, P<0.05) and patients with major depressive disorder (r=-0.674, P<0.05) were negatively correlated with HAMD-17 score. Conclusion The level of TRPC1 is lower in patients with vascular depression, which is more obvious in patients with cerebral infarction, ischemic cerebrovascular disease, and cerebral microhaemorrhage.The lower the level of TRPC1, the more severe the depression.The neuroprotective effect of TRPC1 is reduced in patients with vascular depression.The TRPC1 can be used as a biomarker for vascular depression.