Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology

A total of 1151 subjects were enrolled in this study.Metabolic syndrome (MS) was diagnosed according to the International Diabetes Federation (IDF) criteria.Significant differences in waist circumference,body mass index(BMI),diastolic blood pressure(DBP),systolic blood pressure(SBP),fat mass,Fat％ in different serum TSH levels were found.There were positive relation between fasting plasma glucose,DBP,SBP,and serum FT4 levels,between high density lipoprotein-cholesterol,DBP,SBP,waist circumference,fat mass,Fat％,and serum FT3 levels,even after adjustment for age and sex.Serum FT3 and FT4 levels were higher in the MS group than those in the control group.

Objective: To understand the survival status and influencing factors of HIV/AIDS patients with highly active antiretroviral therapy ( HAART ) among drug users in Yili Prefecture, Xinjiang from 2005 to 2019, so as to provide references for reducing AIDS mortality. Methods : The demographic information, clinical stage, baseline CD4+T lymphocyte ( CD4 ) level and treatment status of HIV/AIDS patients with HAART in Yili Prefecture from 2005 to 2019 were collected through AIDS Antiretroviral Therapy Information System. The survival rate was calculated by the life table method. The influencing factors for survival time were analyzed by Cox proportional hazard regression model. Results: Totally 1 935 patients were recruited, the median age receiving HAART was 37 years old and the median CD4 counts was 293/μL. The cumulative survival rates at 1, 5, 7 and 10 years were 97%, 78%, 73%, and 66%, respectively. The multivariate Cox proportional hazards regression analysis showed that the patients with body mass index of 18.5-<28.0 kg/m2 ( HR: 0.391-0.656, 95%CI: 0.234-0.958 ), baseline CD4>200/μL ( HR: 0.354-0.667, 95%CI: 0.232-0.841 ) , or missed medication in the last 7 days ( HR=0.009, 95%CI: 0.001-0.061 ) had lower risk of death; the patients with WHO clinical stage of Ⅱ-Ⅳ ( HR: 1.479-2.311, 95%CI: 1.004-3.288 ) or treatment delay ≥1 years ( HR: 1.287-1.388, 95%CI: 1.029-1.826 ) had higher risk of death. Conclusions The 5-year cumulative survival rate of HIV/AIDS patients with HAART in Yili Prefecture is 78%. Body mass index, baseline CD4 level, WHO clinical stage, treatment delay and missed medication in last 7 days were the influencing factors for survival time.

OBJECTIVETo investigate the effects and mechanism of cytokine-induced killer (CIK) cells in reversing multidrug resistance (MDR) and increasing intracellular concentration of adriamycin (ADR) in the K562/ADR cells.

METHODSPeripheral mononuclear cells (MNCs) were isolated from healthy donors and cultured with combined cytokines to generate CIK. The changes of cell phenotype and cytokines secretion of CIK were determined. K562/ADR cells were divided into three groups: ADR in combination CIK (group I), CIK alone (group II) and ADR alone (group III). The viability and proliferation of K562/ADR cells were assayed by MTT assay, the intracellular concentration of ADR and the expression of P-glycoproteins (P-gp) in K562/ADR cells by FCM.

RESULTSThe cytotoxicity of ADR in group I was higher than that in group II (P < 0.05). The cytotoxicity was increased with the E/T ratio increasing (P < 0.05) but had no relation with the concentration of ADR in group I (P > 0.05). The expression of P-gp was declined in group I and group II (P > 0.05). The intracellular concentration of ADR in group I was higher than that in group II (P < 0.05), and had no relation with the ADR concentration (P > 0.05).

CONCLUSIONPre-treatment with CIK can increase the cytotoxicity and the intracellular concentration of ADR and decrease the expression of P-gp in K562/ADR cells in the ADR and CIK combination group. Acute leukemia patients would be most likely to benefit from the combination of chemotherapy and CIK therapy.

Antineoplastic Agents ; pharmacology ; Cytokine-Induced Killer Cells ; immunology ; Drug Resistance, Multiple ; immunology ; Drug Resistance, Neoplasm ; immunology ; Humans ; K562 Cells

Abstract: Objective　To analyze the serotype distribution, drug resistance rate and drug resistance gene carrying of Streptococcus pneumoniae isolates in hospitalized patients, and evaluate the coverage of the vaccine to the serotype of Streptococcus pneumoniae in this area, so as to provide reference for the rational use of antibiotics in clinic. Methods　A total of 150 strains of non-repetitive Streptococcus pneumoniae isolated from inpatients from January 2015 to December 2019 were collected for serotyping and antimicrobial sensitivity test. The carrying rates of pbp2b, ermB and tetM were detected by PCR. Results　The PCR classification rate of 150 strains of Streptococcus pneumoniae was 93.1%, and the classification rate of capsular swelling test was 100%, and a total of 19 serotypes were divided, mainly 19F and 6B. Children's serotypes were predominantly 19F, 6B, and 15A; adult serotypes were predominantly 19F, 14, and 23F. The coverage rates of the PCV7, PCV10, PCV13 and PPV23 vaccines were 36.8%, 42.1%, 57.9% and 68.4%, respectively. Strains with serotypes of 19F, 6B, 3, and 23F had higher rates of resistance to antimicrobials. The sensitivity of Streptococcus pneumoniae to penicillin was greater than 96.0%. Antimicrobials with significant differences in resistance rates between invasive and non-invasive strains were penicillin, moxifloxacin, and levofloxacin. The percentage of strains carrying both ermB and tetM resistance genes was 96.0%, and the concordance rate between pbp2b, ermB and tetM resistance genes and the resistance phenotype was >98.0%. A total of 10 multi-resistance combinations were detected, with a multi-resistance rate of 62.6%, and the multi-drug resistance pattern of Streptococcus pneumoniae was mainly concentrated in the 19F and 6B serotypes. Conclusion　There are significant age differences in the serotypes of Streptococcus pneumoniae in this area. The vaccine currently used has low coverage in this region and therefore offer limited protection to the population. The drug resistance rates of Streptococcus pneumoniae varied significantly among serotypes. Erythromycin and tetracycline are not recommended for clinical treatment of Streptococcus pneumoniae. Penicillin can still be used as the first choice for clinical treatment of Streptococcus pneumoniae infection.

ObjectiveTo investigate the value of a digital three-dimensional reconstruction technique in the treatment of hepatic alveolar echinococcosis (HAE).MethodsThe computed tomography scan data for 13 patients with HAE who were admitted to the First Affiliated Hospital of Xinjiang Medical University from February 2011 to October 2011 were reconstructed and analyzed by a three-dimensional reconstruction system to assess resectability,and to facilitate surgical planning and individualized virtual surgery.The results of preoperative analysis were compared with the results of actual operations.ResultsThe three-dimensional models of the liver were reconstructed successfully,and intrahepatie lesions and vessels were clearly displayed.One patient received an autologous liver transplantation,10 underwent hepatectomy,and 2 received percutaneous transhepatic cholangial drainage.Virtual operation planning was carried out for 11 patients using the three-dimensional reconstruction system.The mean volume of the liver to be resected was predicted to be 920 ml (range,339-2678 ml),and the mean percentage of liver to be resected to the total liver volume was predicted to be 45％ ( range,23％ -68％ ).The mean volume o[ the actual liver resection was 834 ml (range,315-2250 m[),and the mean percentage of actual liver resected to the total liver volume was 42％ (range,22％ -70％ ),which was consistent with the results of preoperative three-dimensional reconstruction.All patients were followed up for 2-8 months,and no severe complications such as liver failure,hemorrhage and bile leakage were detected.ConclusionDigital three-dimen-sional reconstruction is helpful in the diagnosis and treatment of HAE and effectively reduces surgical risks.

Objective To study the incidence of stroke among elderly people in China's longevity area and its association with diseases such as hypertension,diabetes and heart disease.The differences in the following common hematological indicators in subjects with stroke and non-hypertension,diabetes,heart disease and stroke were studied:superoxide dismutase (SOD),malondialdehyde (MDA),hypersensitive c-reactive protein (hsCRP),albumin (propagated) glucose (GLU),cholesterol (CHO),triglyceride (TG),high-density lipoprotein cholesterol (HDLC),glycosylated serum protein (GSP) urea nitrogen (BUN),creatinine (CREA) and uric acid (UA).Methods Residents who participated in the project of biomedical research of aging population conducted in 2014 were selected from 8 longevity Areas in China.2 315 people aged 40 and over attended the study,including 22 aged 40 and over,238 aged 60 and over,490 aged 70 and over,629 aged 80 and over,518 aged 90 and over,418 aged 100 and over.Using the self-designed questionnaire to collect information about the characteristics of social demographics,the clinical doctors used the unified inspection tool to examine the subjects.The fasting blood samples were collected by vacuum tube at early morning.The contents of plasma SOD,MDA,hsCRP,ALB,GLU,CHO,TG,HDLC,GSP,BUN,CREA and UA were detected and compared among these elderly who were classified into different genders and different age groups and different healthy groups.Results The prevalence of high blood pressure,diabetes,heart disease and stroke increased with age,reaching a peak and then slowly decreasing.The age of peak was 90 ～ 99,60 ～ 69,70～ 79 and 80～ 89.The prevalence of hypertension was 71.62 ％ and 60.54 ％ respectively for stroke subjects and non-cerebral apoplexy subjects,and the difference was statistically significant.The prevalence of diabetes was 18.92％ and 11.35％ respectively,and the difference was statistically significant.The prevalence of heart disease was 20.98％ and 5.26％,respectively,and the difference was statistically significant.The rates of non-hypertension,non diabetic and non-heart disease were 4.73％ and 33.41％ respectively,and the difference was statistically significant.In the groups of Stroke subjects and Non-high blood pressure,nomdiabetic,non-heart disease subjects the following indicators were Compared,values of SOD were 55.76±8.27 and 57.16±8.00 U/ml respectively,the difference between groups were not statistically significant (t=0.341,P=0.053),values of MDA were 5.81 ± 3.82 and 5.67± 3.16 μmol/L respectively,the difference between groups were not statistically significant (t=0.329,P =0.661),values of hsCRP were 4.15 ± 12.33 and 2.94 ± 6.25 mg/L,respectively,the difference between groups were not statistically significant (t=0.026,P=0.080),values of ALB were 41.60±4.51 and 42.08±3.94 g/L respectively,the difference between groups were not statistically significant (t=0.032,P=0.194),values of ALB were 41.60 ± 4.51 and 42.08± 3.94 g/L respectively,the difference between groups were not statistically significant (t =0.032,P=0.194),values of ALB were 41.60 ± 4.51 and 42.08 ± 3.94 g/L respectively,the difference between groups were not statistically significant (t =0.032,P=0.194),values of GLU were 5.89 ± 2.67 and 4.90 ± 0.90 mmol/L respectively,the difference between groups showed statistically significant (t=0.000,P=0.000)),values of CHO were 4.81 ± 1.00 and 4.71±1.02 mmol/L respectively,the difference between groups were not statistically significant (t =0.670,P=0.318),values of TG were1.33±0.69 and 1.14±0.57 mmol/L respectively,the difference between groups showed statistically significant (t=0.012,P=0.000),values of HDLC were 1.29±0.35 and 1.41±0.40 mmol/L respectively,the difference between groups showed statistically significant (t=0.004,P=0.001),values of GSP were 259.10±60.90 and 246.75±24.52 μmol/L respectively,the difference between groups showed statistically significant (t =0.000,P =0.000),values of BUN were 6.84±± 3.53 and 6.62 ± 2.20 mmol/L respectively,the difference between groups were not statistically significant (t=0.110,P=0.338),values of CREA were 84.92 ± 33.00 and 80.14 ± 24.64 μmol/L respectively,the difference between groups showed statistically significant (t=0.013,P=0.044),values of UA were 296.73±91.34 and 288.12±80.47 μmol/L respectively,the difference between groups were not statistically significant (t=0.123,P=0.247).Conclusion Diabetes,hypertension,and heart disease are risk factors for stroke.Abnormal blood glucose and lipid metabolism:the increase of GLU,TG and the decrease of HDLC are important common biochemical index of stroke.Patients with cerebral apoplexy have certain renal impairment.

OBJECTIVETo investigate the effect of hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major.

METHODSFifteen beta-thalassemia major patients with a median age of 3. 5 years (range 1 - 10 years) received allogeneic HSCT. According to the Pesaro's classification for thalassemia, 12 patients were grade I - II, and 3 grade III. The bone marrow transplantation (BMT) plus peripheral blood stem cell (PBSC) transplant mobilized by granulocyte colony-stimulating factor (G-CSF) was used when donor is low body-weight.

RESULTOf the fifteen patients, nine were disease-free survival (DFS) at a median follow-up of 2.5 years (range 6 - 54 months). Of eight grade I - II patients received HLA identical sibling BMT, seven were DFS, and of two received HLA mismatched marrow from their mother, one DFS, another not engrafted. Two patients received unrelated cord blood HSCT were both not engrafted. Two patients received PBSC transplantation alone were not engrafted, but one of them soon received BMT from the same donor and was DFS. The incidences of grade I - II and grade III acute graft-versus-host disease (aGVHD) were 20% (3/15) and 6.7% (1/15), respectively. Interstitial pneumonia occurred in 4/15 (26.7%) patients. There were no long-term complications in the survivors.

CONCLUSIONGrade I - II beta-thalassemia major patients received HLA identical sibling BMT had higher DFS. It was propitious for engraftment to use BMT plus PBSC, but with a higher incidence of acute and chronic GVHD.

Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Male ; Transplantation, Homologous ; Treatment Outcome ; beta-Thalassemia ; therapy

To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose Chemistry, Pharmaceutical ; Excipients ; chemistry ; Hydrophobic and Hydrophilic Interactions ; Surface-Active Agents ; chemistry ; Tablets ; Water ; Wettability

OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo, as well as the potential mechanisms. METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats. The effects of lapachol on C6 cell proliferation, apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/ phenazinemethosulfate (PMS) assay, hoechst 33358 staining, annexinⅤ-FITC/PI staining, and comet assay. Effects of lapachol on topoisomerase I (TOP I) and topoi?somerase Ⅱ (TOP Ⅱ) activities were detected by TOP Ⅰ and TOP Ⅱ mediated supercoiled pBR322 DNA relaxation assays and molecular docking. TOPⅠ and TOPⅡ expression levels in C6 cells were also determined. RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats (P<0.05). It was showed that lapachol could inhibit proliferation, induce apoptosis and DNA damage of C6 cells in dose dependent manners. Lapachol could inhibit the activities of both TOPⅠ and Ⅱ. Lapachol-TOPⅠ showed relatively stronger interaction than that of lapachol-TOPⅡ in molecular docking study. Also, lapachol could inhibit TOPⅡ expression levels, but not TOPⅠ expression levels. CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro, which might be related with inhibiting TOPⅠ and TOPⅡ activities, as well as TOPⅡ expression.