Objective To understand the mutation characteristics of drug resistance-associated genes rpoB, katG and inhA in Mycobacterium tuberculosis (MTB) strains using gene chip method, and evaluate its clinical application value. Methods A total of 76 MTB strains were collected from Shijiazhuang area in 2013 to 2014. Gene chip was used to detect the mutations of rpoB, katG and inhA, and the L-J proportion drug susceptibility test was used as the gold standard to evaluate the overall concordance, sensitivity and specificity of gene chip. The consistency of microarray and phenotypic resistance was evaluated by Kappa test. Results Of all the 76 strains detected, 69 harbored mutations in katG/inhA. The predominant mutation site of katG was 315 codon with the mutation rate of 89.9%(62/69), and 5.8%(4/69) carried mutations at inhA-15(C→T), and 4.3%(3/69)carried combined mutations of katG 315 and inhA-15. The rpoB mutations were detected in 73 strains, of which 64.4%(47/73)carried mutations at codon 531, 15.1%(11/73)at codon 526, 12.3%(9/73)at 516 codon, 1.4%(1/73)at 513 codon, 1.4%(1/73)at 533 codon and 5.5%(4/73)had combined mutations. Compared with results from the L-J proportion method, the sensitivity, specificity and concordance rates of gene chip for RFP were 96.1%(73/76), 100%(50/50)and 97.6%(123/126). The sensitivity, specificity and concordance rates of gene chip for INH were 90.8%(69/76), 100%(50/50)and 94.4%(119/126). The sensitivity, specificity and concordance rates of gene chip for MDR-TB were 86.8%(66/76), 100%(50/50) and 92.1%(116/126). Conclusion The predominant mutation loci of MDR strains in Shijiazhuang area are katG315 and rpoB531. Gene chip is a fast and useful tool for clinical diagnosis of MDR strains.

Objective To investigate the changes of Treg cells,Th17 cells and related cytokines in pe?ripheral blood of patients with severe hand?foot?mouth disease( HFMD) in the initial stage of infection caused by Enterovirus 71 virus. Methods Thirty?five cases of severe HFMD children in the Fifth Hospital of Shijiazhuang from May 2013 to December 2013 were selected as the research subjects,including 27 cases of severe formed group and 8 cases of danger severe formed group. The frequencies of Th17 cells ( CD3+CD8?IL?17+) and Treg cells( CD4+CD25+Foxp3+) in peripheral blood were detected by flow cytometry in patients with severe HFMD and 31 healthy children(control group). Moreover the serum levels of interleukin 6(IL?6),interleukin 17(IL?17) ,interleukin 10( IL?10) ,interleukin 23( IL?23) ,and human transforming growth factorβ1 ( TGF?β1) were measured by ELISA. Results As compared with those in control group,the frequencies of Treg cells,ratio of Treg/Th17,serum levels of TGF?β1, IL?10 in severe HFMD groups were significantly decreased ( F=23. 23, 30. 88,10. 766,11. 680 respectively;P<0. 05) . However the frequency of Th17 cells,serum levels of IL?6,IL?17,IL?23 in severe HFMD groups were significantly increased( F=646. 81,5. 904,10. 557,3. 490 respectively;P<0. 05) . Conclusion The changes of Treg and Thl7 cells and related cytokines appear in peripheral blood of patients with HFMD in the initial stage of infection caused by Enterovirus 71 virus. The frequency of Treg cell is decreased,however,the frequency of Thl7 cells frequency is increased,as a result,which may spread inflammato?ry reaction and cause complication.

Objective:To analyze the use status of antibiotics and the resistance of clinic isolate bacteria against the commonly used antibiotics before and after the intervention. Methods:Using the information retrieval systems, the consumption of antibiotics in the inpatients during the 1st quarter of 2012(before the intervention) and the same period of 2013(after the intervention) was com-pared. According to the defined daily dose ( DDDs) , the antibiotics were ranked, and the resistance rate against the commonly used antibiotics was analyzed. Results:Compared with the top ten before the intervention, the top ten after the intervention was changed sig-nificantly, however, cephalosporins was still the main species. After the intervention, the overall decline in DDDs was significant, the separation rate and distribution of bacteria remained stable. ESBLs enzyme production rate of Enterobacteriaceae Escherichia coli was re-duced by 7. 61%, and that of Klebsiella pneumoniae was reduced by 1. 34%, and the resistance rate against the commonly used antibi-otics was in an overall downward trend. The resistance rate of Gram-positive staphylococci against the commonly used antibiotics was de-creased, while that of Gram-positive enterococci showed notable difference. Conclusion:The DDDs of antibiotics and bacterial resist-ance rate are in an overall downward trend in our hospital after the intervention;however, there is still exception. Therefore, the clini-cal antimicrobial susceptibility tests should be performed as soon as possible to help the choice of antibiotics.

OBJECTIVE:To establish the method for the determination of mildronate in human plasma and urine,and to study the pharmacokinetic characteristics in healthy volunteers. METHODS:After precipitating plasma and urine sample,LC-MS/MS method was adopted. Dikma Diamonsil C18 column was used with mobile phase consisted of methanol-water(containing 0.2% for-mic acid,0.3% ammonium acetate)(31∶69,V/V)at the flow rate of 0.6 ml/min. ESI was adopted in MRM mode,by using nega-tive ion. The ion for quantitative analysis were m/z 147.10→58.20 (mildronate) and m/z 152.00→110.10 (internal standard,acet-aminophen). The pharmacokinetic parameters of mildronate with single administration and multiple administration were calculated by using DAS 2.1 software and compared. RESULTS:The linear range of mildronate in plasma were 0.02-20 ng/ml(r=0.999 3) and in urine were 0.05-40 ng/ml(r=0.998 2). The lowest limits of quantitation were 0.02 and 0.05 ng/ml. Precision and recovery met the requirements of biological specimen determination,and endogenous impurities hadn’t effect on the determination. The main pharmacokinetics parameters of low-dose,medium-dose and low-dose(250,500,750 mg)of mildronate in plasma with single ad-ministration were as follows:t1/2 were(3.39±0.81),(5.52±0.57)and(5.32±0.96)h;tmax were(0.80±0.45),(1.38±0.43)and (1.10±0.36)h;cmax were(4.17±1.46),(8.08±1.04)and(15.04±1.86)ng/ml;AUC0-36 h were(24.55±5.81),(45.50±7.07)and (85.60 ± 13.09)ng·h/ml. In the dose range,cmax,AUC0-36 h h had a linear relationship with dose (R2 were 0.974 5 and 0.968 3). The main pharmacokinetic parameters of low-dose of mildronate with multiple administration after keeping stable were as follows:cmin was(0.28 ± 0.10)ng/ml;AUCs was(38.78 ± 4.18)ng·h/ml;cs was(1.62 ± 0.17)ng/ml;DF was(3.81 ± 1.14);t1/2 was(6.17 ± 1.46)h;tmax was(1.20 ± 0.33)h;cmax was(6.46 ± 1.96)ng/ml;AUC0-36 h was(40.33 ± 4.65)ng·h/ml;accumulation factor of cmax and AUC were(1.73±0.90)and(1.64±0.40). Compared with single administration,t1/2,cmax and AUC of mildronate with multiple admin-istration after keeping stable all changed,and tmax had no signifi-cant difference. After single administration,26 h accumulative excretion rate of those groups were (0.004 009 ± 0.001 1)%, (0.004 026±0.001 01)% and(0.003 858±0.000 68)% respec-tively. CONCLUSIONS:Established method is sensitive,accurate and specific,and suitable for the determination of mildronate concentration in human plasma and urine and pharmacokinetics study. Mildronate capsule shows certain accumulation effect in healthy volunteers,and linear pharmacokinetic characteristics.

OBJECTIVE:To study the bioequiavailability of two sertraline hydrochloride formulations in healthy volunteers.METHODS:A randomized, crossover study of 22 healthy volunteers receiving single oral dose of 50mg sertraline hydrochloride solution(test preparation) or sertraline hydrochloride tablets(comparator preparation) was conducted and the blood concentrations determined by LC/MS/MS.RESULTS: The pharmacokinetic parameters for the test sertraline and the comparator sertraline were as follows:t1/2 were (27.3?5.2)h and (26.3?3.0)h,respectively;Cmax were(9.56?2.49)?g?L-1 and(9.43?2.91)?g?L-1,respectively;tmax were(5.18?1.47)h and(6.00?1.07)h,respectively;AUC0～108 were(329?112)?g?h?L-1 and (297?111)?g?h?L-1,respectively;AUC0～∞ were(354?127)?g?h?L-1 and (316?122)?g?h?L-1,respectively.There were no significant differences in main pharmacokinetics parameters between the 2 preparations,except in tmax from analysis of variance and one-side & two-sides t tests.The relative bioavailability of the test sertraline was(115.5?26.7)%.CONCLUSION:These two sertraline hydrochloride formulations are bioequivalent.

Objective To detect and analyze the expression and significance of olfactory receptor family 2 subfamily W member 3 (OR2W3) in gastric adenocarcinoma,and to explore its correlation with cell proliferation and apoptosis. Methods From January 2013 to June 2014, 61 patients with gastric adenocarcinoma diagnosed in the Affiliated Hospital of North China University of Technology and undergoing radical operation were selected as the study subjects. Neoplasm tissue were selected as the observation group, normal gastric mucosa ( 61 cases) were selected as the control group. Immunohistochemistry was used to detect the expression of or2w3 and HER-2 in the two groups. Fish was used to detect the amplification of HER-2 gene in some of the patients with uncertain expression of HER-2. Western blot was used to detect the expression of PCNA and BAX in the observation group. Results Positive rate of OR2W3 was higher in the observation group ( 50. 8%, 31／61) than that in the control group ( 8. 2%( 5／61 )), and the difference between the two groups was statistically significant(χ2＝26. 63,P＜0. 05). The difference of the positive rate of OR2W3 in the maximum diameter(≥6 cm was 68. 8%(22／32),＜6 cm was 31. 0%( 9／29)),depth of invasion(seroas and beyond was 63. 4%(26／41),less serosa was 25. 0%(5／20)),vascular and lymphatic vessel involvement ( involvement was 78. 6%( 11／14),no involvement was 42. 6%( 20／47)), lymph node metastasis(metastasis was 82. 1%(23／28),no metastasis was 24. 2%(3／33)) and TNM staging(Ⅲ+Ⅳwas 78. 1%(25／32),Ⅰ+Ⅱ was 20. 7%( 6／29)) in observation group was statistically significant ( χ2 was 8. 423,7. 937,5. 559,20. 318,20. 080,respectively,all P＜0. 05). Expression of OR2W3 was correlated with survival time(X2＝5. 31,P＜0. 05). Positive correlation was found between OR2W3 and PCNA expression(r＝0. 54,P＜0. 05) . Negative correlation were found between OR2W3 and BAX expression ( r＝－0. 59, P＜0. 05). There were 8 cases of HER-2 positive and 53 cases of HER-2 negative. The difference of OR2W3 expression in tumors with different HER-2 expression was statistically significant ( χ2＝4. 957,P＜0. 05) . Conclusion The expression of OR2W3 in gastric adenocarcinoma tissue is significantly increased,which can promote the proliferation of cancer cells and inhibit apoptosis. OR2W3 is related to HER-2 expression. Detection of OR2W3 expression may be of some value in judging prognosis.

Objective:To observe the clinical effect on patients of invasive ductal carcinoma of the breast by neoadjuvant chemotherapy, and to analyze the changes of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki67 in neoplasm.Methods:A total of 83 patients which were treated by neoadjuvant chemotherapy in breast invasive ductal carcinoma diagnosed were selected in North China University of Science and Technology Affiliated Hopital from January 2014 to December 2020. There were 30 cases of Luminal type A, 31 cases of Luminal type B, 10 cases of HER-2 positive type and 12 cases of triple negative type. To observe the clinical effect of different molecular subtypes, detect the expression of Er, PR, HER-2 and Ki67 in pathological tissues before and after neoadjuvant chemotherapy, and conduct a retrospective case-control study. Comparison between the two groups use χ2 test, matched χ2 and accurate probability method. Results:Fifty-eight cases were clinically effective, the total effective rate was 69.8% (58/83), and 9 cases were pathological complete response (pCR), accounting for 10.8% (9/83). After neoadjuvant chemotherapy, the highest clinical efficacy was luminal type B in 26 cases, and the highest PCR was triple negative type in 3 cases. The pathological results showed that the expression of ER (6 cases of positive expression were increased, χ2=1.03, P=0.310), PR (8 cases of positive expression were increased, χ2=1.56, P=0.210) and HER-2 (2 cases of positive expression were decreased, χ2=0.10, P=0.748) was not different before and after neoadjuvant chemotherapy. The expression of Ki67 was decreased in 25 cases (30.1%) after chemotherapy compared with 59 cases (71.1%) before chemotherapy (34 cases of positive expression were decreased, χ2=27.85, P<0.001). Five cases were added among Luminal type A after chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 (>0.75), the consistency rate was 91.9%. The consistency was idea before and after chemotherapy. Five cases were added after Luminal type A chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 ( P>0.75), and the consistency rate was 91.9%,The consistency before and after chemotherapy was good. After chemotherapy, HER-2 expression remained unchanged in 59 cases (clinically effective in 48 cases), up-regulated in 9 cases (clinically effective in 4 cases) and down regulated in 15 cases (clinically effective in 6 cases)( χ2=12.82, P=0.002). Ki67 expression remained unchanged in 35 cases (20 cases were clinically effective), up-regulated in 7 cases (2 cases were clinically effective) and down regulated in 41 cases (36 cases were clinically effective)( χ2=14.63, P=0.001). Conclusion:The clinical effect of neoadjuvant chemotherapy in the treatment of breast invasive ductal carcinoma is ideal. The clinical effective rate of Luminal B type is the highest, and the pCR rate of triple negative type is the highest.And it can significantly reduce the expression of Ki67. The down-regulation of HER-2 and Ki67 is significant for clinical efficiency.

The clinical data of two children with refractory/relapsed acute B-lymphoblastic leukemia (ALL-B)treated with Blinatumomab in Department of Pediatrics, Peking University People′s Hospital from September 2019 to May 2021 were retrospectively analyzed.After 1 course of Blinatumomab infusion, both children achieved complete hematologic remission.During the infusion process, grade 2 cytokine release syndrome (CRS) was observed, and there were no fatal adverse reactions.One case underwent bridging hematopoietic stem cell transplantation after remission and achieves disease-free survival currently.The other case is still alive after subsequent consolidation chemotherapy.As a novel bispecific antibody, Blinatumomab has a good response rate to refractory/relapsed ALL-B and induces fewer adverse events, so it can be used as a candidate immunotherapy for patients with high tumor burden.

Objective To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. Methods A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was chosed as controlled drug. The duration of treatment was 7-14 days in both groups. Results A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for perprotocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS)population were 79.7% and 77.4%, the effective rates were 95.2% and 96. 7%, and the bacterial clearance were 96. 7% and 97. 5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety.The drug adverse events occurred both in 10. 1%, and drug adverse reactions accurred in 7. 8% and 7.9%patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prologation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P＞0.05).Conclusions Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

Objective:To observe and analyze the application effect and value of problem based learning (PBL) combined with team-based learning(TBL) in the teaching of New Drug Clinical Research. Methods:Postgraduate students were randomly divided in-to two groups(n=20):"PBL+ TBL" group and lecture based learning(LBL) group. After the end of the teaching,the teaching ef-fectiveness survey and theory test of the groups were performed,and the results were compared. Results:The combined teaching meth-od (PBL+TBL) could stimulate learning enthusiasm, improve learning efficiency, and enhance the abilities of self-study, literature retrieval and analyzing and solving problems. Totally 90% of students thought the new teaching method had good application value in clinical teaching. Furthermore,the excellent rate of the theory test scores in the combined teaching group was better than that in the traditional teaching group (P<0.05). Conclusion: PBL combined with TBL can overcome the disadvantages of traditional teaching method,which provides higher interest,improved ability of self-study as well as higher teaching quality of medical students. The meth-od is worthy of promotion in postgraduate teaching.