Research progress on the role of diphtheria toxin and its derivatives in targeted therapy of glioma / 中国肿瘤生物治疗杂志

@#[摘 要] 白喉毒素（DT）及其衍生物可通过受体介导的胞吞转运作用穿越血脑屏障（BBB），并将毒素或药物靶向递送至肿瘤细胞，是有前景的靶向治疗脑胶质瘤的策略之一。目前，用于靶向治疗脑胶质瘤研究的DT衍生物主要有CRM107、DT389-EGF、CRM197、DTAT/DTAT13/DTATEGF和DTEGF13。其中，CRM107和DT389-EGF已经进入临床Ⅱ期试验，其余衍生物尚处于临床前研究阶段。根据现有研究进展，CRM107和CRM197是最有希望在脑胶质瘤治疗中取得突破的两种衍生物，但关键在于降低其毒副作用和提高靶向性。因此，明晰DT及其衍生物在靶向治疗脑胶质瘤的关键作用机制及应用现状，可为促进开发高效低毒的脑胶质瘤治疗药物提供新的思路。

Evaluation of immune effect of diphtheria toxoid vaccine with chitosan as adjuvant on mice / 中国生物制品学杂志

@#Objective To evaluate the immune effect of the diphtheria toxoid(DT)vaccine using chitosan as adjuvant on mice,so as to provide an experimental basis for the preparation of novel adjuvant vaccines of DT.Methods A total of 30 male C57BL/6 mice were divided into mucosal immunization group and humoral immunization group,and each group was randomly divided into 6 groups:negative control group(PBS),positive control group(DT),aluminum adjuvant group,chitosan adjuvant group(final solution with 0.5% chitosan),aluminum adjuvant vaccine group and chitosan adjuvant vaccine group,with 5 mice in each group. Mucosal immunization group and humoral immunization group were inoculated with 500 μL PBS buffer,10 μg DT,500 μg aluminum adjuvant and 500 μL chitosan adjuvant per mouse by nasal drip and intraperitoneal injection respectively. The mice were observed for the status,collected for the eyeball serum before inoculation(0 d)and 7,21,35 d after inoculation,and collected for the nasal lotion simultaneously. The levels of IgG antibody in serum and sIgA antibody in nasal lotion were detected by ELISA.Results After intraperitoneal injection and nasal drip of chitosan adjuvant vaccine,the mental and behavioral state of mice was normal. Chitosan adjuvant vaccine effectively induced the IgG antibody against diphtheria in mice with not significant difference,compared with the classic aluminum adjuvant vaccine group(F = 127.926 > F_(0.05(1,8)),P > 0.05);It also induced the production of sIgA in mice,which was significantly higher than that in the classical aluminum adjuvant vaccine group 21 d after immunization(F =127.926 > F_(0.05(1,8)),P < 0.05).Conclusion Chitosan adjuvant DT vaccine can effectively stimulate the mucosal immunity and humoral immunity in mice with good safety,and has the potential to be an alternative to aluminum adjuvant for vaccine preparation,which can be considered as nasal drop vaccines.

Vitamina D, miR-21 y marcadores de apoptosis en pacientes con diabetes tipo I / Vitamin D, miR-21 and apoptosis markers in patients with type 1 diabetes

La diabetes Tipo 1 (DT1) es una compleja enfermedad autoinmune con una etiología aún desconocida. La vitamina D ha sido ampliamente estudiada debido a su potencial terapéutico en los potenciales nuevos casos de DT1. Por otra parte, los microARNs (miRs) han sido propuestos como posibles biomarcadores en diversos procesos biológicos como en la apoptosis e inflamación. El objetivo de este estudio fue evaluar el efecto de la suplementación con vitamina D sobre el perfil de expresión del miR-21 y marcadores de apoptosis tales como: BCL2, STAT3, TIPE2 y DAXX, en células mononucleares periféricas provenientes de pacientes con DT1 y sujetos controles. RESULTADOS: El perfil de expresión de miR-21 se encontró disminuido en los pacientes con DT1 en comparación con los controles. La expresión relativa de BCL2 se encontró aumentada en controles al comparar con pacientes DT1 en todas las condiciones experimentales. La expresión relativa de DAXX mostró un perfil de expresión diferencial al comparar pacientes con DT1 versus controles (p=0.006). CONCLUSIÓN: El estímulo con vitamina D parece tener un posible efecto regulador sobre los genes BCL2 y DAXX.

Type 1 diabetes (T1D) is a complex chronic autoimmune disease. Vitamin D has been one of the most studied therapeutic potential outbreaks related to T1D. Specific miRNAs have been proposed as potential biomarkers in several biological processes as apoptosis and inflammation. The aim of this study was to evaluate the effect of vitamin D on the expression profiles of miR-21 and apoptotic markers BCL2, STAT3, TIPE2 and DAXX, in PBMCs from T1D patients and control subjects. RESULTS: miR-21 expression was increased in controls regarding T1D patients. BCL2 was increased in controls compared to T1D patients in all experimental conditions. DAXX showed different expression patterns between T1D patients and controls (p=0.006). CONCLUSION: Vitamin D showed a possible regulation effect on apoptosis markers mainly through the regulation of BCL2 and DAXX

Dual-targeting nanovesicles enhance specificity to dynamic tumor cells

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two

Preformulation study on novel antischizophrenic drug DT-195 / 国际药学研究杂志

Objective: To perform a preformulation study for the novel antischizophrenic drug DT-195, so as to provide information for its formulation development. Methods: The scanning electron microscopy, X-ray powder diffraction, and the differential scanning calorimetry were used to characterize the appearance and crystalline form of DT-195, and the solubility was tested for DT-195 in different solutions. An HPLC method was established for the preformulation determination of DT-195. The apparent oil/water(O/W) partition coefficient of DT-195 and the equilibrium solubility of the drug under different pH conditions with high and low ion concentrations were determined using the established HPLC method. Results: DT-195 was an off-white crystalline powder, slightly soluble in water, with a good linearity with the peak area within the concentration range of 10-280 μg/ml(r=0.9997)in the HPLC analysis. DT- 195 was stable under acidic conditions and easily degradable under alkaline conditions. The apparent O/W partition coefficient of DT- 195 was 0.23. The solubility of DT-195 in solution decreased with the increase in the solution pH value or ion concentration. Conclusion: The established HPLC method is reliable for the determination of DT-195 and related substances with the high sensitivity, good specificity and the good separation of DT-195 and related substances. The present results have shown that DT-195 is a poorly soluble drug, and thus the improvement of DT-195 solubility in oral preparations will enhance the bioavailability in vivo.

Correlation of decayed, missing and filled teeth with risk factors for dental caries in children attending outpatient department in tertiary care hospital

Background: Oral health is of vital importance to humans' general health. Despite the marked improvement in oral health, caries occurs in both developed and developing countries worldwide. The patient's age is important for determining caries risk. Special attention must be paid to children's oral health when deciduous teeth start erupting and occlusion has formed in 2 to 3-year-old children. To assess the correlation of decayed, missing and filled teeth (dmft/DMFT) with risk factors for dental caries in children and with knowledge, attitude, and practices of parents regarding dental caries.Methods: Cross-sectional study included 96 children with dental caries attending paediatric outpatient department of Government Stanley Medical College, Chennai, Tamil Nadu, India between 2018 March to November. Clinical evaluation, dmft score, and knowledge, attitude and practices of parents were assessed using pre-formed questionnaire.Results: Patients with high dmft score were found to have low practice score with the Pearson correlation coefficient(r) value -0.41 and P value was 0.01. Corresponding values of knowledge and attitude were not statistically significant. Children who nap/sleep with bottle/pacifier have increased risk (P value-0.01).Conclusions: An oral health risk assessment should be done periodically by Paediatrician who has regular contact with children for early identification of dental caries, to impart healthy oral practices and make them aware of preventive measures.

The association of subjective oral health awareness with dental caries, dental prostheses, periodontal status of Korean adults / 대한구강보건학회지

OBJECTIVES: In order to aid the development of practical oral health improvement programs for adults, this study examined whether a correlation exists between oral health indices assessed by experts and self-perceived oral health status. METHODS: Raw data from the second year (2013–2015) of the sixth Korea National Health and Nutrition Examination Survey were analyzed. Among those surveyed, adults over the age of 19 were designated as research subjects. RESULTS: The DT indices, prosthetics indices, and Community Periodontal indices were higher when the subjective oral health status was “Bad.” CONCLUSIONS: The results of this study demonstrated the consistency between subjective and objective oral health status. Thus, self-perceived oral health status is a reliable index to evaluate adult oral health projects for improving the quality of life of adults, improving their oral health, and evaluating future oral health services.

Food poisoning infection caused by Salmonella spp / Монголын Анагаах Ухаан

Background@#We aimed to study the etiology and transmission route of diseases introducing the modern, rapid and high-sensitivity molecular genetic diagnostic methods for salmonellosis.@*Material and Method@#In the study, we collected 680 stool samples and defined organisms of food intoxication by identification of bacteria, polymerase chain reaction (PCR) and determined serotype and antibiotic resistance.@*Result@#Salmonella spp was detected from the stool of 25 (42.3%) patients out of 59 outpatient clinic and of 170 (27.4%) patients out of 621 inpatient clinic with diagnosis of food intoxication. In total there was detected 195 salmonella spp, and out of this isolated Sal. typhimurum in 193 (98.9%), and Sal. enteritidis was in 2 (1.1%) patients, respectively. We defined Sal. typhimurum in selected 32 cultures and did not detect resistant gene DT-104 ACS-SuT by PCR.@*Conclusion@#As resulted in the survey, we defined 195 (28,6) Salmonella typhimurum among the 680 patients who were suffered from food intoxication, and revealed fast foods, animal derived foods such as chicken, fish caused the food intoxication. Sal. typhimurium not resistance to antibiotics.

A Novel Run-length based wavelet features for Screening Thyroid Nodule Malignancy

Abstract: Thyroid nodules are cell growths in the thyroid which might be for in one of two categories benign or malignant. Nodular thyroid disease is common and because of the associated risk of malignancy and hyper-function; these nodules have to be examined thoroughly. Hence diagnosing thyroid nodule malignancy in the early stage can mitigate the possibility of death. This paper presents an intelligent thyroid nodules malignancy diagnosis using texture information in run-length matrix derived from 2- level 2D wavelet transform bands (approximation and details). In this work, ANOVA test has been used to for feature selection to reduce for feature selection about 45 run-length features with and without wavelet generated, before feeding those features which clinical importance to the Support Vector Machine(SVM) and Decision Tree (DT) classifier to perform the automated diagnosis. The validation of this work is activated using 100-thyroid nodule images spliced equally between the two categories (50 Benign and 50 Malignant). The proposed system can detect thyroid nodules malignancy with an average accuracy of about 97% using SVM classifier for the run- length matrix, features derived from spatial domain while the average accuracy is increased to 98% in case of hybrid feature derived from spatial domain and 2-level wavelet decomposition. For the other proposed classifier (DT), the average accuracy in case of spatial domain based features is 93% whereas the average accuracy of the hybrid features system is 97%. Hence the proposed system can be used for the screening of thyroid nodules.

Effect of topical steroid treatment on children with severe phimosis / 中国医师杂志

Objective To investigate the clinical efficacy of 0.1％ mometasone furoate cream in the treatment of phimosis in children.Methods A prospective study was carried out over two years period on an outpatient which basis on two groups of patients with severe phimosis.598 children with severe phimosis (Kikiros classification 4-5) aged from 2 years old to 11 years old and 8 months were selected.311 cases in the observation group and 287 cases in the control group.The observation group applied a steroid cream the foreskin twice a day for 4 weeks,and the control group used local handling of the foreskin twice a day for 4 weeks.The effects of the two groups after 2 and 4 weeks of treatment were compared.Results 29 cases in the observation group and 47 cases in the control group were loss of follow up.In the steroids group which including 282 patients,68.8％ of patients (194 cases) showed a complete response (full retraction of the foreskin) to the therapy.The total efficiency rate of the 4 stage phimosis group is higher than the 5 grade phimosis group.Patients who had a history of balanoposthitis or urinary tract infection showed poorer improvement in preputial retraction.A total of 28 out of 240 patients (11.7％) in the control group showed a complete response to the therapy.The total efficiency rate of the observation group was significantly higher than the control group (x2 =173.121,P ＜ 0.01).There were 4 cases of discomfort in the observation group and 6 cases of foreskin injured in the control group.Conclusions Topical application of 0.1％ mometasone furoate cream in the treatment of severe phimosis in children is an effective,safe and simple non-invasive treatment with less adverse reactions.

Crystalloid or colloid for goal-directed fluid therapy in cesarean section under combined spinal epidural anesthesia / 中国医师杂志

Objective This study will compare crystalloid to colloid for goal-directed fluid therapy (GDFT) in cesarean section under combined spinal epidural anesthesia,and to discuss which type of fluid is more effective to prevent perioperative hypotention.Methods We randomly assigned 60 patients (ASA Ⅰ-Ⅱ) scheduled undergoing cesarean section into two groups:colloid group and crystalloid group.The colloid group received balanced 6％ HES (130/0.4,Volulyte) and Lactated Ringer's solution (LR),while the crystalloid group just received LR as haemodynamic optimization fluid.The primary outcomes included the incidence of maternal hypotension,and vasopressor doses prior to delivery.The secondary outcomes included umbilical blood gas abnormalities,neonatal Apgar grade and adverse events.Results The impact fluid volume,total liquid volume and urine volume in the crystalloid group were more than those in the colloid group (P ＜ 0.05).No statistical difference was seen in the number of patients who showed hypotension,vomiting and nausea between two groups.And there was no significant difference in the incidence of neonatal adverse effects between two groups.Conclusions No evidence showed that colloid had more advantages in GDFT for patients received cesarean section under combined spinal epidural anesthesia,except that the volume of colloid input was less than crystalloid.

Next-generation ALK-TKI in NSCLC patients / 中国医师杂志

Objective The aim of the study is to investigate the therapeutic efficacy of next-generation anaplastic lynphoma kinase-tyrosine kinase inhibitor (ALK-TKI) in advanced non-small cell lung cancer (NSCLC).Methods The clinical data and outcomes of 22 patients with advanced non-small cell lung cancer who received the next generation of ALK-TKI from 2014 to 2017 in our hospital were retrospectively analyzed.Results 22 patients were included for survival analysis with 15 males and 7 females.The median age was 48 and all of them were adenocarcinoma patients.There were 12,2,7 and 1 patients received ceritinib,alectinib,brigatinib and lorlatinib,respectively.A total of 14 patients could be evaluated,including complete response (CR) in 2 cases,partial response (PR) in 3 cases,stable disease (SD) in 6 cases,progressive disease (PD) in 3 cases.The ORR and DCR were 35.7％ and 78.6％,respectively.The median progression free survival (PFS) of the 22 NSCLC patients was 8.7 months.Progression pattern can be analyzed in 17 patients.Among them,10 patients underwent primary progression (lung),occurring at the leading frequency (accounting for 58.8％) and followed by central nerve system (CNS) progression (accounting for 29.4％).Conclusions Next-generation ALK-TKI provide a reasonable choice for crizotinib-resistant patients.Primary progression (lung) is the leading cause for treatment failure.Multi-disciplinary integration may provide a potential choice for prolonging administration of next-generation ALK-TKI.

Grape seed proanthocyanidin extract improves myocardial function in rats with myocardial infarction by inhibiting PARP-1 activity / 中国医师杂志

Objective To observe the improvement effect of grape seed proanthocyanidin extract (GSPE) on myocardial function in rats with myocardial infarction and to explore its mechanism.Methods Myocardial infarction model rats were randomly divided into five groups:model group,GSPE low,middle and high group,poly ADP-ribose polymerase-1 (PARP-1) inhibitor BSI-201 group,with 15 rats in each group,and another 15 rats were as the sham operation control group.Rats in GSPE low,medium and high dose groups were administrated with 100 mg/ml GSPE,200 mg/ml GSPE and 400 mg/ml GSPE respectively;BSI-201 group was given 120 μmol/L BSI-201 of gavage,and the control group and model group were treated with equal volume of normal saline of gavage,1 times a day for 4 weeks.Doppler echocardiography was used to evaluate cardiac function in rats;myocardial infarction volume was detected by three-phenyl tetrazolium chloride (TTC) staining;hematoxylin and eosin (HE) staining was used to detect histopathological changes of myocardial tissue;terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of myocardial cells;Western blot was used to analyze the expressions of Bax,cleaved-caspase3,Bcl-2 and PAR in myocardial tissue.Results Compared with the control group,the heart rate,left ventricular end diastolic pressure,myocardial infarction area and cell apoptosis rate were significantly increased in the model group,and the mean arterial pressure and left ventricular systolic pressure were decreased significantly (P ＜ 0.05);Myocardial cells were broken and necrotic,irregular fibers arranged in the myocardium,and a large number of inflammatory cells were infiltrated;the protein expressions of Bax,cleaved-caspase3 and PAR in myocardial tissues were increased significantly (P ＜ 0.05),and the protein expression of Bcl-2 was significantly decreased (P ＜ 0.05).Compared with the model group,the heart rate,the left ventricular end diastolic pressure,myocardial infarction area and cell apoptosis rate in the GSPE low,middle and high dose groups and the BSI-201 group were significantly decreased,and the mean arterial pressure and the left ventricular systolic pressure were increased significantly (P ＜ 0.05);the degree of histopathological damage was alleviated;the expressions protein of Bax,cleaved-caspase3 and PAR in myocardial tissues were decreased significantly (P ＜ 0.05),and the protein expression of Bcl-2 was increased significantly (P ＜ 0.05).Conclusions Grape seed proanthocyanidin extract may inhibit cardiomyocyte apoptosis and improve myocardial function of rats with myocardial infarction by inhibiting PARP-1 activation.

Effects of different concentrations of aluminum hydroxide adjuvant and adsorption methods on the immunogenicity of diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine / 中华微生物学和免疫学杂志

Objective To investigate the effects of different concentrations and adsorption methods of aluminum hydroxide adjuvant produced by different manufacturers on the immunogenicity of the diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine ( DTaP-sIPV) . Methods Five anti-gens of DTaP were adsorbed onto different concentrations (0. 42 mg/ml, 0. 47 mg/ml and 0. 52 mg/ml) of aluminum hydroxide from different manufacturers through sequential and separate adsorption. Adsorbability, anti-pertussis toxin ( PT)/filamentous hemagglutinin ( FHA)/pertactin ( PRN)/diphtheria toxoid ( DT)/tet-anus toxoid ( TT) antibodies and the potency of vaccines were detected. Results The adsorbability of alu-minum hydroxide adjuvant slightly decreased with the reduction of concentration. No significant difference in potency and antibody level was observed between sequential and separate adsorption. Moreover, no signifi-cant difference in antibody level was observed between vaccines prepared with aluminum hydroxide adjuvant produced by General Chemical Corp and our institute. Conclusion Aluminum hydroxide adjuvant produced by our institute at the concentration of 0. 52 mg/ml and separate adsorption method are suitable for prepara-tion of DTaP-sIPV.

Fusion proteins of DT390 linking TMTP1 for targeted therapy of ovarian cancer / 中国肿瘤临床

Objective:To investigate targeted therapy of ovarian cancer with new fusion proteins that were produced by fusing the first 390 amino acids of diphtheria toxin(DT390)to the TMTP1 peptide.Methods:The cisplatin-resistant cell line,C13*,and cisplatin-sensi-tive cell line,OV2008,were selected as models and divided into control,TMTP1,DT390-TMTP1,DT390-biTMTP1,and DT390-triTMTP1 groups.Laser scanning confocal microscopy was used to observe nuclear morphology.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide(MTT)and flow cytometry assays were used to detect cell survival and apoptosis,respectively.The formation of subcu-taneous tumors in nude mice following injection of C13*cells was used to observe the formation and growth of ovarian cancer.Apop-tosis of cells in the subcutaneous tumor tissue was detected by the terminal deoxynucleotidyl transferase dUTP nick-end labeling(TU-NEL)assay.Results:Laser scanning confocal microscopy showed that DT390-biTMTP1 and DT390-triTMTP1 induced nuclear shrinkage and fragmentation.The MTT assay showed that cell survival was obviously reduced with increasing concentrations of DT390-biTMTP1 and DT390-triTMTP1. Flow cytometry revealed that DT390-biTMTP1 and DT390-triTMTP1 significantly increased cell apoptosis (P<0.05).The apoptosis rates of the DT390-biTMTP1 and DT390-triTMTP1 groups were 66.0%±12.0% and 72.9%±4.6%,respectively.These were higher than the 55.5%±8.9% and 65.1%±9.8% obvserved in OV2008 cells.DT390-biTMTP1 and DT390-triTMTP1 significantly in-hibited the tumor formation (P<0.01) and growth (P<0.05), and increased apoptosis (P<0.05) of subcutaneous tumors. However, DT390-TMTP1 had insignificant effects on C13*and OV2008 cells.Conclusions:DT390-biTMTP1 and DT390-triTMTP1 preferentially tar-geted and inhibited ovarian cancer cells.These fusion proteins may be a promising strategy for clinical therapy of ovarian cancer.

Association of XPD Asp312Asn single nucleotide polymorphisms with oxaliplatin based chemotherapy / 中国医师杂志

Objective This study was to determine the role of the Xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism in predicting response to Oxaliplatin based chemotherapies and survival in patients with metastatic colorectal cancer.Methods This study enrolled a total of 106 patients treated with FOLFOX4 (n =72) or XELOX (n =34) regimen.The genotype of XPD Asp312Asn was analyzed by TaqMan probe based real-Time polymerase chain reaction (PCR).Logistic regression was used to predict the response to the treatments.Cox proportion hazards models and Kaplan-Meier method were applied to predict the survival.Results The effective rate of chemotherapy in 106 patients with colorectal cancer was 57.6％ (61/106).There was no significant difference in the distribution of G/G,G/A and A/A genotypes between the two groups (P ＞ 0.05).Multivariate survival analysis showed that the survival time of patients with A/A genotype,carcinoembryonic antigen (CEA) (＞5 ng/ml) and age (＞65 years) was relatively short,with statistical significance (P ＜ 0.05).Conclusions XPD Asp312Asn single nucleic acid polymorphism can be used as a predictor of survival in patients with metastatic colorectal cancer,but it is not associated with oxaliplatin sensitivity and needs further study.

Protective effects of shenfu injection on cerebral ischemia reperfusion injury in rats / 中国医师杂志

Objective To study the protective effect of shenfu injection on cerebral ischemia reperfusion injury in rats.Methods 120 male Sprague Dawley (SD) rats(320-350 g) were randomly divided into sham operation group,model control group,Nimodipine injection group,low,medium and high dose group of shenfu injection according to gender weight.20 males in each group were given medicine once a day for 7 days before operation.The cerebral ischemia model was established by thread embolization after 5 days of administration.In the sham operation group,the other operations were the same as those in the model group except for carotid artery ligation and thread insertion.After 24 hours of perfusion,the neurological score,abdominal aorta blood flow,malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione (GHS) levels in brain tissues were measured.Triphenyltetrazolium chloride (TTC) staining was used to calculate the area of cerebral infarction and pathological examination of brain tissues.Results Compared with the model control group,the middle and high dosage of shenfu injection could obviously improve the nerve function and increase the percentage of cerebral infarction area (P ＜ 0.05);the high dosage group of shenfu injection could obviously decrease the whole blood viscosity (P ＜ 0.01);the middle and high dosage of shenfu injection could obviously reduce the level of MDA in rat brain tissue (P ＜ 0.01) while increasing the levels of SOD and GSH (P ＜0.01),finally could significantly improve the pathological changes of brain tissues such as mild swelling of nerve fibers,mild neuronal degeneration,inflammatory interstitial edema and inflammation.Conclusions Shenfu injection has obvious protective effect on cerebral ischemia reperfusion model in rats.

Correlation between UGT1A6 rs2070959 gene polymorphism and VPA metabolism in epileptic patients / 中国医师杂志

Objective To investigate the relationship between uridine diphosphate glucuronosyltransferases (UGT) 1A6 rs2070959 polymorphism and serum concentration of valproic acid (VPA) in patients with epilepsy.Methods We selected 200 cases of epilepsy patients treated in our hospital from June 2014-January 2017.All the patients were treated with VPA monotherapy ＞ 3months.When the VPA of patients reached steady state,we detected the VPA blood level.The genotypes and allele frequencies of UGT1A6 rs2070959 in 200 epilepsy patients were determined.The average standard deviation of 1-fold VPA was used as high VPA group and vice versa as low VPA group.The genotype and allele frequencies of UGT1A6 rs2070959 were compared between the two groups,and the influencing factors of VPA concentration in epileptic patients were analyzed.Results The frequencies of A genotype,AG genotype and GG genotype were 77.01％,18.39％ and 4.60％ in the high VPA group,67.26％,19.47％ and 13.27％ in the low VPA group,with no significant difference between the two groups (P ＞ 0.05);the allele G frequency in the high VPA group was significantly lower than that in the low VPA group (13.79％).The age and weight of the high VPA group were significantly higher than those of the low VPA group (P ＜ 0.05),and the gender composition of the high VPA group was not significantly different from that of the low VPA group (P ＞0.05).Logistic regression analysis showed that age and weight gain were positively correlated with VPA concentration (P ＜ 0.05),allele G expression was negatively correlated with VPA concentration (P ＜0.05).Conclusions Allele G expression at UGT1 A6 rs2070959 is associated with decreased VPA concentration in epileptic patients,which may require a higher dose of VPA.

The effects of bitter gourd saponins on the expression of podocin and nephrin in renal tissues of rats with renal damage induced by salt-sensitive hypertension / 中国医师杂志

Objective To study the therapeutic effect of bitter gourd saponins on salt-sensitive kidney injury induced by high salt diet and its possible mechanism.Methods 50 Sprague Dawley (SD) rats were randomly divided into normal group,model group and low-dose,middle-dose and high-dose treatment group after 10 days of adaptive feeding.Each group had 10 rats.Except the normal group,the other four groups were given high salt diet (4.0％ high salt diet) to induce salt-sensitive kidney damage in rats.The normal group and the model group were given 1.0 m/(kg · d) normal saline,and the three dosage groups of total saponins of balsam pear were given 10 mg/(kg · d),20 mg/(kg · d) and 40 mg/(kg · d) respectively.After 8 weeks of treatment,rats were sacrificed and collect the 24-hour proteinuria,creatinine.Serum creatinine,serum aldosterone,serum sodium and serum potassium were measured,and renal histopathology and the expression of podocin and nephrin were detected.Results Pathological examination of model group showed obvious glomerular sclerosis and renal interstitial fibrosis,and glomerular sclerosis in the treatment group was obviously improved by bitter gourd saponins;The systolic pressure in the model group was 170 mmHg,significantly higher than that of the normal and treatment groups,the systolic blood pressure of the treatment groups were obvious decreased when treated by bitter gourd saponins (P ＜ 0.05);Compared with normal group,serum creatinine and 24 h proteinuria / urine creatinine in model group were significantly increased (P ＜ 0.05),while creatinine clearance rate and aldosterone were significantly decreased (P ＜ 0.05),and the above indexes in bitter gourd saponins treatment group were significantly improved;Compared with the model group,the protein and mRNA expression of podocin and nephrin were significantly decreased (P ＜ 0.05),while the two indexes can be revered by bitter gourd saponins in treatment group (P ＜ 0.05).Conclusions The bitter gourd saponins can significantly improve the symptoms of salt-induced hypertensive nephropathy in rats,which may be related with the expression of podocin and nephrin in renal tissue,thereby inhibiting glomerulosclerosis and improving renal interstitial fibrosis.

The basic research of Xuezhikang combined with rosuvastatin lipid-lowing therapy for atherosclerosis renal artery stenosis / 中国医师杂志

Objective To observe the therapeutic effects and adverse effect of different lipid-lowering regimens in Atherosclerosis renal artery stenosis (ARAS) rat model and select the optimal treatment.Methods 90 Wister rats were randomly divided into sham operation group (group F) and operation group.The operation group was divided into normal feed group (group N) and high-fat feed group (group T).We established the rat model in operatino group by narrowing the renal artery with acupuncture needle and 8 weeks of high-fat feeding.According to the different lipid-lowing therapeutic schedules,the T group rats were randomly divided into five groups:the blank group (T0 group),the Xuezhikang group (T1 group),the rosuvastatin group (T2 group),the regular dose of rosuvastatin combined with Xuezhikang (T3 group),the low dose of rosuvastatin combined with Xuezhikang (T4 group).Mter 6 weeks of intervention,the serum lipids [total cholesterol (TC),triglyceride (TG),high density lipoprotein-cholesterol (HDL-C),low density lipoproteincholesterol (LDL-C)],liver function [alanine aminotransferase (ALT),aspartate aminotransferase (AST)],kidney function [blood urea nitrogen (BUN),serum creatinine (Scr)] and pathological changes of aorta and kidney were detected before and after treatment.Results (1) The blood pressure,BUN and Scr were significantly increased in N group and T group compared with F group (P ＜ 0.05).TC,TG,LDL-C were significantly increased (P ＜ 0.05) and HDL-C were significantly decreased (P ＜ 0.05) in T group compared with N,T group.According to the pathological section,the aorta in T group had visible atherosclerosis change,the renal tubules were atrophied and decreased.All above,the rat model of ARAS was successfully established.(2) After 6 weeks of drug intervention,compared with prior treatment,TC,TG,LDL-C,BUN and Scr were significant decrease (P ＜ 0.05),while HDL-C was significantly increased (P ＜ 0.05) in all treatment groups,and the most remarkable change was in T3,T4 group,T3 group was better than T4 group but with no significant difference between T3 and T4 group (P ＞ 0.05).We found that ALT and AST were significantly increased in T2 and T3 group (P ＜ 0.05) after treatment.Compared with T0 group,pathological lesions of aorta and kidney were reduced best in T3 and T4 group.Conclusions Low dose of rosuvastatin combined with Xuezhikang can achieve ideal lipid-lowing effects.At the same time,it has a protective effect on kidney,and has little damage to liver function.