1.Regulation of organic anion transporting polypeptides expression and activity.
Manman ZHAO ; Dan LI ; Yan LI
Acta Pharmaceutica Sinica 2015;50(4):400-5
Organic anion transporting polypeptides (OATP), a member of solute carrier (SLC) superfamily, is considered as an important transmembrane uptake transporters. OATP is involved in the transport of a variety of endo- and xenobiotics (bile acids, bilirubin, prostaglandin, thyroid hormones, steroid hormone conjugates), drugs and toxins in a Na+ and ATP independent manner. Multiple factors (eg. hormones, proinflammatory cytokines, drugs) can affect the distribution, expression and activity of OATPs, leading to an altered accumulation of OATP substrates and related food-drug and drug-drug interactions. Changes in the distribution and expression of OATPs in malignant tissues may be related to the pathological process of cancer, while the modulation epigenetic mechanism also contributes to its distribution patterns. This review describes the factors that can affect the expression or function of OATPs, which may provide a valuable reference for drug development and the clarification of pathogenesis.
2.The possible mechanism of the relationship between adiponectin and intracranial atherosclerosis
Manman XU ; Yun XU ; Jingwei LI
International Journal of Cerebrovascular Diseases 2016;24(6):561-564
Different from Westerners,intracranial atherosclerosis (ICAS) is a main cause for acute ischemic stroke in Eastern population.Studies have shown that ICAS is associated with the risk factors including metabolic syndrome,dyslipidemia,diabetes mellitus,and inflammation.Adiponectin is involved in oxidative stress and glycolipid metabolism,its reduced level is the most important risk factor for metabolic syndrome and the most prominent inflammatory markers.Numerous studies have suggested that adiponectin is associated with cardiovascular diseases,and it is used as a preventive marker.In recent years,the relationship between adiponectin and ICAS has become a hot research topic.This article mainly reviews the roles of adiponectin in ICAS.
3.Diagnostic test of screening depressive disorders in general hospital with the Patient Health Questionnaire
Manman CHEN ; Li SHENG ; Shan QU
Chinese Mental Health Journal 2015;(4):241-245
Objective:Using a diagnostic test research,to explore the reliability and validity of the Patient Health Questionnaire (PHQ-9)on screening of depressive disorders in general hospital,and to determine the cut points for depressions with different severities.Methods:Three hundred and nineteen help-seekers (n =319)con-sulting the outpatient department of psychiatry in a general hospital were collected continuously.Among them,80 were people without any psychiatric diagnosis,239 were patients with mental disorders.All of subjects were asked to fulfill PHQ-9,and were assessed by psychiatrist with Mini-International Neuropsychiatric Interview (M.I.N.I.) and Hamilton rating scale for depression.M.I.N.I.was gold standard to diagnose depressive disorder,HRSD was used to assess the illness severity.Result:Factor analysis showed good structure validity of PHQ-9.46 patients were diagnosed depressive disorders.The area under the receiver operator characteristic analysis (ROC)of PHQ-9 was 0.94 (95%CI:0.91 -0.97)for depressive disorders.With 15 as the critical value for depression screening,the sen-sitivity was 0.83 and specificity was 0.90,respectively.By the result of HRSD as the standard to rank different lev-els of depression,the cut points of PHQ-9 for mild,moderate,and severe depression was 6,12,and 15.The consis-tency between results of PHQ-9 (with cut points of 6,12,15)and HRSD was moderate (with kappa =0.49).The kappa between results of PHQ-9 (with recommended cut points of 5,10,and 15)and HRSD was 0.46.Cronbach αcoefficient of PHQ-9 was 0.892.Conclusion:It suggests that PHQ-9 has satisfying reliability and validity,and is applicable for screening depression and assessment of its severity of outpatients in general hospital.The recommen-ded cut points of PHQ-9 are applicable to depressive outpatients in general hospital in China.
4.Effects of rosuvastatin therapy on short-term prognosis of myocardial infarction in patients with acute ST segment elevation
Dandan WANG ; Xiu LI ; Manman WANG ; Xiangli LIU
Tianjin Medical Journal 2017;45(3):314-317
Objective To investigate the therapeutic effects and adverse drug reactions of different doses of rosuvastatin in patients with acute ST segment elevation myocardial infarction (STEMI). Methods A total of 115 patients with STEMI were collected from Department of Cardiology, the Second Hospital of Tianjin Medical University. According to different oral doses of rosuvastatin, patients were divided into two groups including 5 mg/d rosuvastatin treatment group (low-dose group, n=44) and 10 mg/d Rosuvastatin treatment group (moderate-dose group, n=71). Patients of two groups were treated with Rosuvastatin at least 1 month after discharge. Data of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed and compared before and after treatment between two groups. The major cardiovascular adverse events (MACE) and adverse reactions were recorded in two groups of patients. Results There were no significant differences in blood lipid and liver function levels before and after one month treatment between the two groups. After one month treatment, levels of TC, LDL-C, ALT and AST were significantly decreased in both groups of patients compared with those before treatment (P<0.05). There were no significant differences in levels of TG, and HDL-C before and after treatment between two groups. The incidence of MACE (heart failure and angina pectoris) was significantly lower in moderate-dose group than that in low-dose group (P<0.05). There was no significant difference in the proportion of malignant arrhythmia between the moderate-dose group and the low-dose group (P<0.05). No target vessel repair and death were found in the two groups. No obvious adverse drug reactions were found during the follow-up period. Conclusion The hypolipidemic effects are epuivalent between 5 mg/d rosuvastatin and 10 mg/d on the basis of conventional treatment for STEMI patients, but the moderate dose can reduce the incidence of MACE and improve prognosis.
5.Effect of the general practitioners training in northern Anhui province
Dongxiao LI ; Fang QI ; Lingxia XIA ; Manman YIN
Chinese Journal of Medical Education Research 2017;16(9):942-945
Objective To understand the effect of the general practitioners training in northern An-hui province, so as to provide a scientific basis for improving training strategies and measures. Methods In accordance with the requirements of Implementation of General Practitioners Training Program in Anhui Province, the training courses was designed, which includes the differences between general medicine and special medicine, general medicine service psychology, ethics related skills, general teaching skills, general clinical skills, and general practice policies, with a total of 32 credit hours. Participants were examined through the self-designed electronic questionnaire before and after the training. A total of 118 participants were involved in the training, and 109 of them were examined before the training, with a recovery rate of 92.4%. After the training, they were examined again, and the recovery rate was 100%. All data were analyzed by SPSS 17.0 software, and P<0.05 was considered statistically significant. Results Scores of the general medicine knowledge and skills after the training were higher than that before the training, and the difference was statistically significant (P<0.05). As for the course evaluation, the average score was over 4 in organiza-tion and management, training facilities, teacher knowledge, training materials, training methods and skills, while the average score was no more than 4 in training content and helping teaching. Conclusion The training achieves good results, and in the future, we should strengthen the training of teaching ability, thus further improving the effect of general practitioners training. Also, we should design the training content reasonably and pay attention to improve the quality and effectiveness of individual courses accordingly. What's more, we can use diversified teaching methods to further improve the teaching ability of general practitioners.
6.Clinical diagnosis of tetralogy of Fallot children with concurrent DiGeorge syndrome
Bin LI ; Manman HU ; Lei SHI ; Taibing FAN
Chinese Journal of Applied Clinical Pediatrics 2015;(18):1409-1411
Objective To explore the clinical diagnosis of tetralogy of Fallot( TOF) children with concurrent DiGeorge syndrome ( DGS ) . Methods Retrospective analyses were conducted for the clinical characteristics of 715 TOF children with concurrent DGS at Henan Provincial People′s Hospital and the Third Affiliated Hospital of Zheng-zhou University from January of 2008 to October of 2014. Among them,there were 78 definite cases of thymic aplasia (DGS group),including 45 boys and 33 girls with an age range of(9. 12±4. 35) months and a body mass range of (7. 28±2. 34) kg. And the remainder was designated as non-DGS group(NDGS group),including 387 boys and 250 girls with an age range of(8. 21±5. 61) months and a body mass range of(8. 19±3. 47) kg. In DGS group,genetic screening uncovered 10 cases of chromosome 22q11. 2 gene deletion. And based upon this result,DGS group was fur-ther divided into genetic and clinical diagnosis subgroups. The genetic diagnosis group had 10 cases,including 6 boys and 4 girls with an age range of(8. 12±4. 15) months and a body mass range of(6. 28±2. 74) kg,the clinical diagnosis group had 68 cases,including 39 boys and 29 girls with an age range of(8. 19±4. 37) months and a body mass range of (7. 05±2. 39) kg. Results No statistical difference existed in age,body mass or preoperative developmental status of pulmonary vasculature between DGS group and NDGS group(P>0. 05). And the preoperative incidence of recurrent pneumonia was obviously higher in DGS group than that in NDGS group(P<0. 001). The probability of concurrent hy-pocalcemia and facial malformation was higher in DGS group than that in NDGS group. However,there was no statistical difference(P>0. 05). And an inter-group comparison of T lymphocyte immunity defect had no statistical difference(P>0. 05). The duration of on-machine and intensive care unit stay was markedly longer in DGS group than that in NDGS group(P<0. 001). And the probability of concurrent hypocalcemia and facial malformation was higher in genetic diag-nosis subgroup than that in clinical diagnosis subgroup. However,there was no statistical difference(P>0. 05). And an inter-group comparison of T lymphocyte immunity defect had no statistical difference ( P>0. 05 ) . Conclusions With diverse clinical manifestations,DGS patients may have non-specific findings of cellular immunity defect,hypocalcemia or facial malformation. TOF children with concurrent thymic aplasia should raise an alert so that effective interventions may be adopted to boost their long-term quality of life.
7.Preparation and Quality Control of Loxoprofen Sodium Patches
Manman HU ; Jinlai LIU ; Xiaohui LI ; Zhong LIN
China Pharmacist 2014;(5):755-757
Objective:To study the preparation and quality control of loxoprofen sodium patches and develop an HPLC method for the determination of loxoprofen sodium. Methods:Loxoprofen sodium patches were prepared with CMC-Na and PVP as the adjuvants, and an HPLC method was used to determine the content of loxoprofen sodium. Results:The linear range of loxoprofen sodium was 4-24μg·ml-1(r=0. 999 7), the average recovery was 99. 99%(RSD=0. 99%, n=6). Conclusion:The preparation method is reason-able, simple and stable. The developed HPLC method is specific to determine the content of loxoprofen.
8.Preparation and in vitro evaluation of borneol and folic acid co-modified doxorubicin loaded PAMAM drug delivery system.
Jingjing LI ; Manman GUO ; Shunping HAN ; Yue SUN ; Weidong FEI ; Xiuiing XU ; Fanzhu LI
Acta Pharmaceutica Sinica 2015;50(7):899-905
A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
9.Construction of vibrio vaccine strain and expression of antigen gene:attenuated Listeria monocytogenes as vaccine vector
Chengchao DING ; Guowei CHEN ; Manman XIE ; Liang GUO ; Jie LI ; Jingjuan SUN ; Qing LIU
Chinese Journal of Immunology 2017;33(9):1281-1285,1290
Objective:To provide a potential platform for transferring specific antigen against fish bacterial diseases based on attenuated Lm (EGDe-ΔactA/ΔinlB).Methods: Attenuated Lm (EGDe-ΔactA/ΔinlB) was used to express outer membrane protein K (Ompk),a conserved and effective vaccine candidate in vibrio.The identification of recombinant strains and detection of antigen genes were operated with PCR and RT-PCR,respectively.Results: The results of PCR showed that Lm-Ompk (L-O),Lm-Lmo0576-Ompk (L-L-O) and Lm-P-Ompk (L-P-O) were constructed successfully.The identity of foreign gene was 100% compared with sequence of NCBI.The analysis of transcription showed that the expressions of Ompk in L-O,L-L-O and L-P-O were significant (P<0.001).Moreover,the expression of Ompk in the condition of antibiotic was higher than that in the BHI without antibiotic (P<0.05).Conclusion: Lm-Ompk (L-O),Lm-Lmo0576-Ompk (L-L-O) and Lm-P-Ompk (L-P-O) were constructed successfully.
10.Anti-tumor effect and its mechanism of co-administration of fusion proteins hVEGF121/βhCG and mGM-CSF/βhCG
Liangliang JING ; Zitao MIAO ; Manman LI ; Jia YE ; Liang JIN ; Rongyue CAO ; Jun LONG
Journal of China Pharmaceutical University 2017;48(1):102-109
This study aimed at investigating the inhibitory effects and the anti-tumor mechanisms of co-adminis-tration of fusion proteins mGM-CSF/βhCG ( GC ) and hVEGF121/βhCG ( VC ) on RM-1 prostatic cancer and B16 F10 melanoma in the C57 BL/6 J mouse model. Two recombinant stains containing pET-28 a-mGM-CSF-X10-βhCGCTP37 and pET-28 a-VEGF-M2-X10-βhCG-CTP37 were induced by lactose to express fusion proteins. The fusion proteins were separated and purified to prepare the anti-tumor protein vaccines ( VC protein vaccine and GC protein vaccine) , which were then mixed to prepare a combined protein vaccine named VGC protein vac-cine. The prostatic cancer and melanoma tumor-bearing mice C57 BL/6 J were immunized with described vac-cines, then the growth of each tumor was measured;splenocyte proliferation of immunized mice was detected;and the cytotoxic effects of the vaccine on tumor cells were tested. After that, the in vivo concentrations of IFN-γ and anti-hVEGF antibodies were investigated by ELISA. The difference between each experimental group and normal saline group ( NS) was statistically significant in both tumor-bearing mouse models ( P <0. 05) respectively. Besides, VGC group exhibited significantly better anti-tumor effect compared with the GC and VC groups with the anti-tumor rate ( 41. 7 ± 0. 83)% and ( 46. 4 ± 1. 27)% for prostatic cancer and melanoma tumor, respectively. The co-administration of the two proteins, VC and GC, could inhibit the growth of RM-1 prostatic tumor and B16F10 melanoma effectively via anti-tumor immunity and anti-tumor angiogenesis.