OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism. METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture （CLP）. The 7-day survival rate， serum levels of tumor necrosis factor- α （TNF- α）， interleukin-6 （IL-6）， and IL-1β were determined in sham operation group， CLP group and calcitriol group （1 μg/kg）； the morphological changes of lung tissue in mice were observed. Lipopolysaccharide （LPS） tolerance macrophage models （representing sepsis-induced immunosuppression） were established using mice macrophage cell line RAW264.7 cells. The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， IL-18 and caspase-1 were assessed in culture medium group， LPS group， LPS tolerance group， and calcitriol （5 μmol/L） group. The following parameters were measured： propidium iodide （PI）-positive cell ratio， caspase-1 activity， lactate dehydrogenase （LDH） release， and Ca2+ levels. RESULTS Compared with CLP group， 7-day survival rate and serum levels of TNF-α， IL-6 and IL-1β were increased significantly in calcitriol group （P＜0.05）. Additionally， pulmonary tissue damage was markedly attenuated in calcitriol group. Compared with LPS tolerance group， the levels of TNF-α and IL-6 in cell supernatants， mRNA expressions of IL- 1β， NLRP3， IL-18 and caspase-1， PI-positive cell ratio， caspase-1 activity， LDH release， and Ca2+ levels were all increased significantly in calcitriol group （P＜0.05）. CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression， and the mechanism of action may be E-mail：yarfwy@163.com achieved by the binding of calcitriol to vitamin D receptor，which promotes the release of Ca2+ from the endoplasmic reticulum， thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Objective? To explore the process and experience of self-management among patients with schizophrenia by interview so as to provide examples and inspirations for clinical nursing and improving self-management among patients with schizophrenia. Methods? From February to April 2018, we collected information in 14 schizophrenia outpatients at a ClassⅢ Grade A psychiatric hospital in Beijing by semi-structured depth interview. The information was analyzed and summarized with the method of content analysis. Results? The interview results were divided into two aspects. On the one hand, the cognition of schizophrenia patients on self-management limited the self-management ability development of patients including lack of knowledge on self-management and family dysfunction. On the other hand, the experience of self-management also limited the ability involving lack of symptom management ability, skills and knowledge on treatment management, poor emotion management, low daily life management initiative, poor interpersonal management and inadequate social support resource use. Conclusions? Medical staff should actively understand the self-management of schizophrenia patients, strengthen training and education so as to improve disease self-management and promote recovery from disease.

OBJECTIVE:To provide reference for the improvement of Chinese patent medicine instruction.METHODS:The outpatients were selected randomly from a Third Grade Class A hospital.A questionnaire survey was conducted on the attention degree of the outpatients to Chinese patent medicine instructions when taking medicine orally.The concern content label of patients in 221 Chinese patent medicine instructions were counted,analyzed and graded according to survey results.RESULTS:A total of 515 questionnaires were distributed,and 498 effective questionnaires were collected with effective recovery rate of 96.7％.The results of questionnaire survey showed that the highest concern from the patients was usage and dosage (92.4％),followed by attentions and taboos (88.0％,70.3％).The following items were drug interaction,pregnant and lactating women medication,children medication and the elderly medication (56.2％,46.4％,45.2％,42.4％).Among the description of medication methods (usage and dosage) in 221 Chinese patent medicine instructions,203 prescriptions clearly marked medication times (91.9％),160 clearly marked drug dosage (72.4％) and 36 clearly marked medication course (16.3％).In matters of taboos (attentions,taboos,pregnant and lactating women medication,children medication and the elderly medication),124 prescriptions clearly marked population taboos (56.1％),82 clearly marked symptom taboos (37.1％) and 71 clearly marked diet taboos (32.1％).According to the scoring statistics of 221 Chinese patent medicine instructions,there were 52 instructions with score of 6,followed by 47 instructions with score of 8;there were only 4 instructions with full score (12).CONCLUSIONS:At present,related contents of medication methods highly concerned by the patients are well marked in Chinese patent medicine instructions,especially its guidance is basically able to meet the requirements in respect of medication times.The related contents of medication taboos,which is next only to attention degree of medication methods by patients,is poorly marked.Its guidance remains to be improved.

Objective: To investigate the association between ABCC2 gene polymorphisms and cyclosporine-induced liver injury in re-nal transplant recipients. Methods: The renal transplant recipients were divided into the liver injury group and the control group. Five single nucleotide polymorphisms ( rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) of ABCC2 were detected by high-throughput technique. The genotypes and haplotypes were analyzed between the groups. Results: There were 35 patients and 182 patients respectively in the liver injury group and the control group. No significant differences in alleles and genotypes were found between the groups (P>0. 05), and the SNP haplotypes showed no significant difference between the groups (P>0. 05). Conclusion: There is no association of ABCC2 polymorphisms (rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) with the liver injury induced by cy-closporine.

OBJECTIVE:To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 (6986A>G,rs776746) gene polymorphisms. METHODS:One hundred and severty patients underwent renal transplantation receiving tacrolimus maintenance therapy after surgery were selected from our hospital during Jan. 1997-Dec. 2015,and then divided into Wuzhi capsules(+)group(74 cases)and Wuzhi capsules(-)group(96 cases)according to the use of Wuzhi capsules. Both groups received tacrolimus+mycophenolate mofetil+prednisone;Wuzhi capsules (+)group was additionally given Wuzhi capsules,one capsule each time,bid,for more than 12 months. Trough concentration of tacrolimus was detected by CMIA 0,1,3,6,12 months after medica-tion,and the blood concentrations(C0/D)were calculated at different time points after correcting daily dose. CYP3A5*3 gene polymor-phisms was detected by PCR-RFLP. The association of C0/D value with gene polymorphism was investigated by analysis of covariance. RESULTS:Among 170 patients,there were 65 cases of CYP3A5 GG genotype,83 cases of AG genotype and 22 cases of AA geno-type;genotype frequencies were 38.2%,48.8% and 12.9%,which was in line with Hardy-Weinberg balance (P>0.05). There was statistical significance in the distribution frequencies of GG,AG+AA genotype between Wuzhi capsules(+)group and Wuzhi capsules (-)group (P<0.05). After 1 month of medication,C0/D of tacrolimus in GG genotype was significantly higher in Wuzhi capsules (+)group than in Wuzhi capsules(-)group. After 1,3,6,12 months of medication,C0/D of tacrolimus in AG+AA genotype was sig-nificantly higher in Wuzhi capsules(+)group than in Wuzhi capsules(-)group,with statistical significance(P<0.05). There was no statistical significance in C0/D of tacrolimus in GG genotype between 2 groups after 3,6,12 months of treatment(P>0.05). CON-CLUSIONS:Wuzhi capsules can increase C0/D of tacrolimus in CYP3A5*3 AG+AA genotype,but have no significant effect on C0/D of tacrolimus in GG genotype;CYP3A5*3 genotype should be considered when using Wuzhi capsules as synergist of tacrolimus.

Objective To investigate the intensity of HBsAg and HBcAg expression in liver tissue of patients with chronic hepatitis B virus (HBV) infection and its clinical significance.Methods A total of 994 HBV infected patients underwent liver biopsy and histopathological examination.The expression of HBsAg and HBcAg in liver tissue was detected by histoimmunochemistry.Patients were divided into HBeAg (+)/HBVDNA(+), HBeAg(-)/HBV DNA(+) and HBeAg(-)/HBV DNA(-) groups according to HBeAg and HBV DNA levels;patients were divided into ＜2 × normal (ULN) group, 2-＜5 × ULN groupand ≥5 × ULN group according to the alanine aminotransferase (ALT) levels.The histologic activity (A), fibrosis (F), the expression of HBsAg and HBcAg in liver tissue and their correlations with clinical features were analyzed.Logistic regression analysis was used to study the factors affecting the expression of HBsAg and HBcAg in liver tissue.Results Among 994 HBV infected patients, 941 cases (94.67％) were intrahepatic HBsAg positive and 553 cases (55.63％) were intrahepatic HBcAg positive;403 cases (40.85％) were ≥A2 in histologic activity and 371 cases (36.09％) were ≥F2 in fibrosis.The degree of A and F was the highest in HBeAg (-) / HBV DNA (+) group, followed by HBeAg (-) / HBV DNA (-) group, and was the lowest in HBeAg (+) / HBV DNA (+) group.The intensity of intrahepatic HBsAg expression was significantly different among three groups (x2 =6.299, r =-0.760, P ＜ 0.05), however, the difference was not showed in pairwise comparisons.The difference of intrahepatic HBcAg intensity among three groups was statistically significant (x2 =282.995, r =-0.645, P ＜ 0.01), the intensity was the highest in HBeAg (+) / HBV DNA (+) group and the lowest in HBeAg (-) / HBV DNA (-) group.The constituent ratio of HBeAg positive and HBV DNA level were higher and the average age was lower in intrahepatic HBsAg positive group than those in HBsAg negative group.The constituent ratio of positive HBeAg, the levels of ALT, AST, PLT and HBV DNA were higher and the average age, the average FIB-4 level were lower in intrahepatic HBcAg positive group than those in HBcAg negative group.The HBV DNA level was an independent risk factor for intrahepatic HBsAg intensity, and the HBeAg positive and HBV DNA level were independent risk factors for intrahepatic HBcAg intensity.There were no significant differences in A and F among different groups of intrahepatic HBsAg intensity (x2 =1.943 and 2.630, both P ＞ 0.05).There was significant difference in F among different groups of intrahepatic HBcAg intensity (x2 =12.352, P ＜ 0.01), but not in A.The degree of F was the highest in intrahepatic HBcAg negative group.There was significant difference in intrahepatic HBcAg intensity among different groups of ALT level (x2 =16.349, P ＜ 0.01), but not in intrahepatic HBsAg intensity.The intrahepatic HBcAg intensity in ALT ＜ 2 × ULN group was lower than that in other two groups.Conclusions Most of patients with chronic HBV infection are intrahepatic HBsAg positive and more than half of them are intrahepatic HBcAg positive.The intrahepatic HBsAg intensity is not associated with A and F, but correlates with HBV DNA level.The intrahepatic HBcAg intensity is not associated with A, but it is negatively correlated with F and positively correlated with positive HBeAg expression, HBV DNA level and ALT level.

Objective To prepare micronized nimodipine push-pull osmotic pump (PPOP) controlled release tablets . Methods The nimodipine as a model drug ,micronization technique was applied to the PPOP method .Designed and prepared the controlled release of the nimodipine tablet for 12 hours in vitro .The factor f2 was used to evaluate the similarities of differ-ent dissolution profiles ,and the optimal formulation was performed .Results The micronized nimodipine PPOP controlled re-lease tablets were successfully prepared with excellent zero-order release characteristics .The PPOP tablet′s release behavior was close to the zero-order release equation (r= 0 .998 4) .Conclusions The controlled-release formulation was prepared suc-cessfully .Micronized technique combined with the PPOP method significantly increased the release of the nimodipine tablet , the poorly soluble drug ,in vitro .

Objective To analyze the correlation between liver pathology and clinical characteristics in a large series of patients with chronic HBV infections , so as to provide the data base for non-invasive medical diagnosis .Methods Liver pathology and clinical characteristics of 1 397 patients with chronic HBV infections were retrospectively analyzed . Ridit analysis and Spearman correlation analysis were performed to investigate the correlations of clinical characteristics with liver pathology of patients .Results In 1 397 patients, there were 604 patients (43.24%) with liver inflammation grading ≥G2 and 504 patients (36.08%) with fibrosis stage ≥S2.Inflammation grade and fibrosis stage of liver tissues were both higher in male patients than those in females (u=3.093 and 2.854, P<0.01).Inflammation grade and fibrosis stage of liver tissues in patients aged ≤30 years were lower than those in patients aged >30-40 years and >40 years (r=0.259 and 0.303, P<0.01;F=4.199 and 12.226,11.610 and 24.359, P<0.05 and <0.01).Patients with HBeAg( -) and HBV DNA≥103 copies/mL were of higher degrees in liver tissue inflammation compared with those with HBeAg ( +) and those with HBeAg ( -) but HBV DNA <103 copies/mL (F=8.788 and 5.635, all P<0.01);while the fibrosis stage in patients with HBeAg (-) and HBV DNA≥103 copies/mL was only higher than that in HBeAg ( +) patients (F=12.886, P<0.01). Liver tissue inflammation and liver fibrosis aggravated with the increase of ALT ( r=0.537 and 0.517, P<0.01).There was no significant difference in liver tissue inflammation among different age groups of patients with ALT (1-<2) ×ULN and HBV DNA≥103 copies/mL (χ2 =4.365, P >0.05),but there was significant difference in liver fibrosis in patients between aged >40 years and ≤30 years ( F=3.177,P<0.05).Conclusions Liver biopsy and antiviral therapy should be considered in chronic HBV infected patients with age of >30 years, lightly elevated ALT levels , HBeAg(-) and detectable HBV DNA levels , especially in male patients .Screening for liver fibrosis should be considered in patients with HBeAg ( -) and low HBV DNA levels .

Objective To assess the liver biopsy and the clinical characteristics of inactive HBsAg carriers.Methods One hundred and ten inactive HBsAg carriers,including 76 males and 34 females aged (38.9 ± 9.4) years (21-66),underwent liver biopsy from January 2011 to September 2015,the histopathological findings and clinical features were analyzed.Among 110 cases the inflammation activity (A) was ＜ A2 in 73 cases and ≥A2 in 37 cases;the fibrosis (F) ＜ F2 in 63 cases and ≥F2 in 47 cases.The upper limits of normal (ULN) for ALT was defined as 30 U/L for men and 19 U/L for women according to World Health Organization (WHO) standard,and 50 U/L for men and 40 U/L for women according to Chinese national standard.There were 59 cases with ALT ＜ 1 × ULN of WHO standard and 110 cases with ALT ＜ 1 × ULN of Chinese standard.Results In 110 inactive HBsAg carriers,there were 100 cases (90.9％) ≥A1 and 37 cases (33.6％) ≥A2,84 cases (76.3％) ≥F1 and 47 cases (42.7％) ≥F2.The severity of A and F were both higher in males than that in females,especially that of F (U =2.162,P =0.032;x2 =5.315,P =0.021).But there were no statistical differences between WHO standard group and Chinese standard group (U =0.951,0.435;P =0.341,0.663).Along with the increase of age,the degrees of A and F aggravated (F =3.705,5.915;P =0.014,0.001).The average ages in ≥ A2 group and ≥F2 group were (41.7 ± 9.6) years and (38.7 ± 8.1) years,respectively.The independent risk factors for severity of A and F were age,gender (male) and age,respectively.Conclusion There may be histological damages of varying degree in liver tissues of most inactive HBsAg carriers,and for those aged 40 years and over,especially males screening of liver histological activity and fibrosis would be necessary.