With the rapid development of pharmacogenetics, more and more studies have shown evidence in the association between polymorphisms at the human leukocyte antigen (HLA) loci and severe adverse drug reactions (SADRs). Several HLA-B alleles proved to be associated with SADRs for drugs such as carbamazepine, allopurinol, lamotrigine, and lfucloxacillin. hTe USA Food and Drug Administration (FDA) has even recommended routine screening for HLA-B allele before the use of abacavir and carbamazepine. With the completion of human genome project and the Hapmapproject, several new pharmacogenetics approaches such as genome-wide association study (GWAS) have emerged. hTese newly developed methods will undoubtedly accelerate the identiifcation and clinical utilization of the pharmacogenetic biomakers. In addition, the immunogenetic mechanisms by which the HLA alleles cause SADRs are explored at the cellular and molecular level. hTis review focuses on the recent progresses in HLA alleles and ADRs regarding both the clinical translation and modern pharmacogenetic methods.

Objective To explore the expression of discoidin domain receptor 1 (DDR1) in rats with pulmonary fibrosis induced by paraquat (PQ) poisoning, and its relationship with the expression of transforming growth factor-β1 (TGF-β1). Methods 120 Sprague-Dawley (SD) rats were divided into control group and 20, 40, and 80 mg/kg PQ poisoning groups (each n = 30). Pulmonary fibrosis induced by PQ poisoning model was reproduced by one time administration of 20, 40, 80 mg/kg of 20% PQ, and the rats in control group were given 4 mL normal saline. Fifteen rats in control and different doses of PQ groups were sacrificed at 7 days and 21 days after intragastric administration, and lung tissues were collected. Pulmonary fibrosis was observed after hematoxylin-eosin (HE) staining. The immune-histochemical method was used to determine the expressions of DDR1 and TGF-β1. The relationship between the expression of TGF-β1 and DDR1 was analyzed by Pearson correlation analysis. Results The rats in control group were active, and no pathological changes in lung tissue were found. The rats in PQ groups became shortness of breath, bristles, and slow reaction etc. 0.5 hours after intragastric administration. After 7 days, the lung tissue was dark red, hard texture, appearance of yellow soil fiber nodules and obsolete hemorrhage, destruction of alveolar structure. The extent of lung injury increased gradually with the time of poisoning and the increase of PQ dose. It was shown by immune-histochemical staining that the control group had only a small amount of DDR1 and TGF-β1 positive expressions; in PQ groups, there were a large number of DDR1 and TGF-β1 positive expression particles in the alveolar wall, pulmonary interstitial and alveolar cavity. It was displayed by quantitative analysis that compared with the control group, DDR1 and TGF-β1 expressions were significantly increased in 20, 40, 80 mg/kg PQ groups with time- and dose-dependent [DDR1 (integral A value): 0.221±0.014, 0.249±0.021, 0.364±0.016 vs. 0.121±0.036 at 7 days; 0.247±0.025, 0.321±0.015, 0.432±0.027 vs. 0.139±0.021 at 21 days; TGF-β1 (integral A value): 0.230±0.016, 0.265±0.015, 0.339±0.016 vs. 0.129±0.032 at 7 days; 0.248±0.011, 0.295±0.016, 0.399±0.026 vs. 0.119±0.026 at 21 days; all P < 0.05]. It was shown by Pearson correlation analysis that DDR1 expression was positively correlated with TGF-β1 expression with the increase of PQ dose and poisoning time (DDR1 with TGF-β1: r = 0.996, P < 0.000; DDR1 with PQ dose: r = 0.985, P < 0.000; DDR1 with poisoning time: r = 0.989, P < 0.000; TGF-β1 with PQ dose: r = 0.992, P < 0.000; TGF-β1 with poisoning time: r = 0.972, P < 0.000). Conclusions The expression of DDR1 in the lung tissue in PQ poisoning rats showed a time- and dose-dependent change, and it was positively correlated with TGF-β1 expression. DDR1 may be involved in the process of pulmonary fibrosis induced by PQ poisoning.

OBJECTIVE:To evaluate the bioequivalence of the domestic pidotimod granules with the imported pidotimod syrup as control.METHODS:20 healthy male volunteers were treated with a single dose(800 mg)of pidotimod granules(test formulation)or pidotimod syrup(reference formulation)by a randomized crossover design,with plasma concentrations of pidotimod determined by HPLC and pharmacokinetic parameters of pidotimod computed,and the bioequivalence between two formulations was evaluated using DAS2.0 program.RESULTS:The pharmacokinetic parameters of the reference formation vs.the test formulation of pidotimod were expressed as follows:t1/2(2.70?0.80)h vs.(2.62?0.84)h;Cmax(4.04?0.59)?g?mL-1 vs.(3.87 ?0.66)?g?mL-1;tmax(2.28?0.44)h vs.(2.13 ?0.43)h;AUC0～14(22.11?4.20)mg?h?L-1 vs.(23.00?4.25)mg?h?L-1;AUC0～∞(22.85?4.42)mg?h?L-1 vs.(23.83?4.52)mg?h?L-1.The relative bioequivalence of the test formulation as against the control was(106.08?22.05)%.CONCLUSION:The pidotimod granules and pidotimod syrup are bioequivalent.

Objective To study the variations of microorganism indexes of barrelled purified water during its preservation period of 90 days. Methods The total count of bacteria, the mould and yeast count, the conductance rate and pH value in water samples collected from the fresh products of barrelled purified water at the same day of production and then at the 5th, 10th, 20th, 40th, 60th and 90th days after the production date respectively were determined. Results The total count of bacteria of barrelled purified water reached peak at the 5th and 20th days during the observed preservation periods, and then decreased gradually. No significant variations of mould and yeast count, decrease of pH value (6.3 to 6.0), increase of conductance rate (4.2 to 5.8 ?s/cm) were observed in the barrelled purified water during the whole 90_day preservation period. Conclusion The total count of bacteria of barrelled purified water was fluctuated obviously in the observation period. A suggestion was made that the time limit of quality guarantee for preservation period of barrelled purified water must be within 30 days.

Objective To investigate the effect of Bmal1 on proliferation in gastric cancer cells and the molecular mechanism, and to provide theoretical and experimental basis for further research targeting circadian therapy for gastric cancer. Methods Applying RNAi technique to silence Bmal1 gene in BGC823 was regarded as experimental group. The normal BGC823 was as control group. The inhibitory effect of the cell line was measured by MTT assay. The mRNA expression of p53, c-Jun and c-Fos was evaluated by real-time RT-PCR. Results Comparing with the data of control group,the inhibitive rates of cell growth in experimental group after 6 h,12 h,24 h were 5.78%(P=0.001),9.20%(P=0.00)and 83.08%(P=0.00)respectively. Down-regulation of Bmal1 decreased p53 (P<0.05), while increased c-Fos and c-Jun expression (P > 0.05). Conclusion RNAi targeting Bmal1 has effects on gastric cancer proliferation by down-regulating p53 mRNA.

Objective To study the value of combined parenteral and enteral nutrition support with chemotherapy for advanced gastrointestinal cancer in elder patients.Methods Totally 79 patients admitted from 2006 to 2011 were randomly divided into two groups using random number table:the treatment group (n=42) was provided with combined parenteral and enteral nutrition support and chemotherapy,the control group(n =37) was treated with chemotherapy only.Nutritional risks were screened at admission.After two cycles of chemotherapy,the nutritional status,Karnofsky performance score,toxic reaction,and nosocomial infection rate were compared betweeen these two groups.Results After 2 cycles of chemotherapy,the body mass index[(19.00±3.31) kg/m2 vs.(18.24±1.98) kg/m2,P=0.04],albumin [(33.90±1.50) g/Lvs.(29.90±2.38) g/L,P=0.02],prealbumin [(28.19±1.50) g/Lvs.(25.51 ±8.38) g/L,P=0.01],hemoglobin [(107.0 ± 6.90) g/L vs.(104.20 ± 9.70) g/L,P =0.02],and lymphocyte levels [(2.99 ±0.55) × 109/L vs.(2.63 ±0.20) × 109/L,P =0.03] were all significantly higher in the treatment group.The incidence of myelosuppression in the treatment group was 28.57％,significantly lower than that in the control group (83.78％,P =0.00) ; such difference was also detected in patients with nutritional risk in the 2groups (31.03％ vs.95.45％,P =0.00).The incidences of nosocomial infection in the treatment group were significantly lower than in the control group after both the first and the second cycle of chemotherapy (0 vs.10.81％,P=0.03; 2.38％ vs.27.03％,P=0.02).Conclusions Combined enteral and parenteral nutrition support with chemotherapy in elderly patients with advanced gastrointestinal caner could improve nutritional status,reduce toxic reaction,and prevent nosocomial infection.Therefore combined nutrition support is a safe and effective approach for elderly patients with advanced gastrointestinal cancer.

OBJECTIVE To investigate the resistance of Pseudomonas aeruginosa strains to 5 ?-lactams.METHODS Susceptibility of 218 P.aeruginosa strains isolated from Anhui Province in 2005 to ceftriaxone,cefotaxime,ceftazidime,aztreonam,and piperacillin were tested by agar dilution method.RESULTS The resistance rate to ceftriaxone,cefotaxime,aztreonam,piperacillin,and ceftazidime were 59.2%,57.3%, 56.0%,51.8%,and 39.0%,respectively.There was statistically significant difference between ceftazidime and other 4 ?-lactams(P0.05).CONCLUSIONS Ceftazidime is the most susceptible antibiotic to P.aeruginosa strains among 5 ?-lactams tested.

Objective To establish a method for simultaneously measuring L-citrulline and L-arginine concentration in plasma using reversed-phase high performance liquid chromatography (RP-HPLC)with ultraviolet detection,and the novel method is applied to the patients with digestive system tumor.Methods Plasma samples were deproteinized by trichloroacetic acid with heating method.Phenylisothiocyanate (PITC)was used as derivatization reagent and a gradient elution was adopted. The feasibility verification of method was carried out by detecting plasma L-citrulline and L-arginine acid concentration in 21 cases of advanced digestive tract malignant tumor patients,21 cases of non malignant tumor patients and 39 cases of healthy people.Results The linearity for L-citrulline and L-arginine ranged from 0 to at least 1 000 μmol/L.r=0.999 95 for both. The lower limits of quantification for L-citrulline and L-arginine were 0.240 μmol/L and 0.448 μmol/L respectively.The in-traday and interday coefficients of variation (CVs)were less than 3.4% and 7.2%,respectively.The average recovery rate was from 95.2% to 104.1%.The ratio of plasma L-citrulline/L-arginine in patients with digestive cancar was significantly higher than that in the healthy control group,t-test,P =0.009.The sensitivity and specificity of plasma L-citrulline/L-argi-nine ratio in the malignant tumor of digestive system were 81% and 71.4% respectively.Conclusion This method can pro-vide a reliable and efficient method for the clinical determination of the L-citrulline and L-arginine concentration in plasma. The ratio of plasma citrulline/arginine increased obviously in patients with digestive cancer,suggesting that this ratio is a more sensitive index than single concentration of L-citrulline or L-arginine when evaluating patients with digestive tumor.

Objective To investigate the psychological condition of the rural residents with HIV/AIDS.Methods Totally 192 subjects with HIV/AIDS residing in countryside of Henan Province(China)were investigated with questionaire and Symptom Check list 90(SCL-90).Results SCL-90 total score,the number of positive items and the score of each factor for the 192 subjects with HIV/AIDS were higher than those of Chinese normal(P

Objective To explore the construction and application of cloud-based healthcare information system (CHIS).Methods The process of CHIS employment and implementation for primary-level medical and healthcare institutions was elaborated by the example of a city after the analysis and comparison of mode difference between traditional and cloud construction.Results CHIS integrated regional medical resources and realized integrated application of medical and public healthcare resources,mobile integration of regional operation and continuous innovation in construction mode,and facilitated uniformed management,high-efficiency running and maintenance as well as business development.Conclusion CHIS contributes to enhancing medical inforrnatization in primary institutions,promoting continuous medical innovation and innovating medical informatization mode.