Anti-Bacterial Agents ; adverse effects ; Azithromycin ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Humans ; Infusions, Intravenous

Objective To observe the curative effects and toxicity of low-dose bortezomib plus thalidomide and chemotherapy in treatment of multiple myeloma. Methods 35 patients with initial, refractory or relapsed MM received at least two cycles of treatment with bortezomib at 1.1 mg/m2 intravenously on days 0,3, 7, and 10, and by daily oral thalidomide escalated from 50mg to 150 mg and chemotherapy. The chemotherapy regimens included MP, VAD and AD regimen which was chosen according to the status of patients. Results After a median follow-up of 20 months, the overall response rate was 82.8 %, complete remission (CR)48.6 %, very good partial remission (VEPR) 17.1%, and partial remission 17.1%. The 3-year PFS and OS were 60.92 % and 72.41% separately. ORR and OS were same in initial and refractory or relapsed MM patients. Grade 3 or 4 adverse events including debility (3/35), nausing and vomiting (8/35), constipation (4/35), peripheral sensory neuropathy (3/35), neutropenia (10/35) and thrombocytopenia (12 %) were observed.Conclusion The regimen of low-dose bortezomib plus thalidomide and chemotherapy is a highly effective and safety regimen for MM patients. The maintenane therapy with thalidomide may prolong PFS.

OBJECTIVE:To analyze the rules and characteristics of adverse drug reactions(ADR)induced by Shuxuetong in-jection,and provide reference for clinical rational drug use. METHODS:ADR cases induced by Shuxuetong injection in Beijing collected by national ADR monitoring center in 2012 were retrieved,and 35 cases of the ADR were statistically analyzed. RE-SULTS:ADR induced by Shuxuetong injection had relatively high incidence in elder over 60 years old(68.57%);ADR might oc-curred after 5 min with off-label use and it mainly occured after 10 min-2 h(40.00%);clinical manifestations were mainly systemic damage and nervous system damage,and all patients were returned to normal after symptomatic treatment except one with unclear outcome. CONCLUSIONS:ADR induced by Shuxuetong injection is related to age and dosage. Clinical medication should be strict-ly in accordance with the instructions,strengthen medication monitoring and reduce incidence of ADR to ensure medication safety.

Mycotic vaginitis is a common and frequently-occurring gynaecopathia and easy to attack repeatedly, so painful to patients. In this study, the authors observed the clinical efficacy of Sophora gel combined with Fluconazole capsules in treating mycotic vaginitis, in order to seek an effective method for treating mycotic vaginitis. Totally 85 patients with mycotic vaginitis treated in our hospital between December 2012 and July 2014 were randomly divided into the treatment group (43 patients) and the control group (42 patients). The treatment group was given vaginally Sophora gel (one piece every night for 14 days) and orally Fluconazole capsules (150 mg, once every three days, four times in total); The control group was only administered with Fluconazole capsules. The total efficacy, cure rate, recurrence rate and clinical symptom improvements of the two groups were observed. The results show that the total efficacy, the cure rate and the recurrence rate of the treatment group vs. the control group were respectively 97.7%, 90.7% and 2.6% vs. 83.3%, 71.4% and 20.0%, with statistical significance in their differences (P < 0.05). The treatment group showed reduced leucorrhea, pruritus vulvae disappearance and earlier mucosal hyperemia disappearance than the control group, with statistical significance in their differences (P < 0.05). In conclusion Sophora gel combined with Fluconazole capsules can improve antifungal activity of drugs, relieve clinical symptoms, shorten the course of disease, enhance the cure rate and reduce the recurrence rate; So this therapy can be widely applied in clinic.
Adult ; Antifungal Agents ; administration & dosage ; Capsules ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Fluconazole ; administration & dosage ; Humans ; Mycoses ; drug therapy ; Sophora ; chemistry ; Treatment Outcome ; Vaginitis ; drug therapy ; Young Adult

Objective To study the relationship of abnormal family history in the first degree relatives and the clinical phenotype of patients with polyeystic ovary syndrome(PCOS).Methods Clinical data of first degree relatives of 139 women with PCOS were collected by questionnaires,including body mass index(BMI),waist hip ratio(WHR),and hursutism score.Follicle stimulating hormone(FSH), luteinizing hormone(LH),prolactin(PRL),testosterone(T),androstenedione(A),oral glucose tolerance test(OGTT)and insulin releasing test were measured.Results(1)Compared with patients with a negative family history of diabetes mellitus,for women with a positive family history,WHR(0.99?0.10 vs 0.79?0.08)and score of hirsutism(1.9?1.2 vs 1.8?1.2)were increased,the duration of menstruation was longer[(108?10)vs(92?19)days];A[(11?6)vs(8?5)nmol/L],homeostasis model assessment of insulin resistance(HOMA-IR,3.5?2.0 vs 2.7?1.6),area under curve(AUC) glucose[(836?245)vs(748?139)nmol?L~(-1)?min~(-1)],AUC insulin[(9670?4582)vs(7330?4311) mIU?L~(-1)?min~(-1)],fasting glucose[(5.0?1.1)vs(4.8?0.5)mmol/L]and fasting insulin[(15?8)vs (11?8)mIU/L]were increased,while early insulin secretion function index(?I60/?G60,32?22 vs 52?30),insulin sensitive index(ISI,0.019?0.011 vs 0.033?0.014)and disposition index(DI,18? 10 vs 30?22;P

T cell immune receptor with Ig and ITIM domains (TIGIT), a promising new target in cancer immunotherapy, plays a critical role in limiting adaptive and innate immunity against tumors. The extracellular domain of human TIGIT was used to immune BALB/c mice, and a new anti-human TIGIT chimeric antibody (c7D3) was developed. The mice in this study were used in accordance with the international guidelines for the care and use of laboratory animals, and the animal study was approved by the Institutional Animal Ethics Committee of AbMax Biotechnology. The biological activity of c7D3 was studied. The results showed that c7D3 exhibited high affinity for TIGIT and effectively inhibited the interaction between TIGIT and its ligands. Cell-based assays indicated that c7D3 induced strong luciferase signaling in TIGIT/CD155 signaling reporter assay and enhanced cytokine secretion in a T cell stimulation assay. The data showed that c7D3 has high binding affinity and excellent blocking bioactivity, supporting the further advancement for therapeutic application.

Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg · kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg · kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism.
Animals ; Energy Metabolism ; drug effects ; Glucosides ; pharmacology ; Heme Oxygenase-1 ; genetics ; Lipopolysaccharides ; pharmacology ; Male ; Membrane Proteins ; genetics ; Mice ; Mice, Inbred BALB C ; Monoterpenes ; pharmacology ; Oxidative Stress ; drug effects ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVE:To study the effects of 10 kinds of nephrotoxic TCM on three main subtypes(Oat1,Oat2 and Oat3) of kidney organic anion transporter(Oats)in mice. METHODS:A total of 1 840 SPF NIH mice were randomly divided into nor-mal control group(isovolumic pure water),probenecid group(30 kg/mg),sodium carboxymethyl cellulose(CMC)group,Pulsa-tillae radix,Corydalis rhizoma,Aconiti kusnezoffii radix,Aconiti radix,Angelicae pubescentis radix,Gleditsiae spina,Polygo-num cuspidatum,Kansui radix,Platycladi cacumen,Aucklandiae radix high and low dose groups. Mice were treated twice a day for 5 d,ig. After 1 h of the last dosing,they were iv given PAH in tail(30 mg/kg). The PAH pharmacokinetic parameters of the kidney homogenate were determined and the PAH intake in kidney tissue at the time point of 1,5,10,15 and 20 min was detect-ed. The PAH in blood was analyzed by DAS 2.0 software. The grouping and dosing were the same as before,after 1 h of the last dosing,kidney slices were made and put into PAH-buffer. The PAH intake of kidney slices was determined. RESULTS:Compared with normal control group,the t1/2β in C. rhizoma high dose group,A. kusnezoffii high and low dose groups,A. pubescentis high dose group,P. cuspidatum high and low dose groups and P. cacumen group were increased;Vd were all decreased in 10 kinds of TCM high and low dose groups;except for A. pubescentis low dose group,G. spian low dose group and K. radix low dose group, the CL was decreased and AUC0-20 min was increased in all other groups,with significant difference (P<0.01 or P<0.05). Com-pared with normal control group,the content of PAH in kidney tissue in P. radix high dose group,C. rhizoma high dose group,A. kusnezoffii high dose group,A. radix high and low dose groups,A. pubescentis high and low dose groups,G. spina high and low dose groups,P. cuspidatum high and low dose groups,K. radix high and low dose groups,P. cacumen high and low dose groups and A. radix high and low dose groups were increased,with significant difference (P<0.01 or P<0.05). Compared with normal control group,the intake of PAH in kidney slices in C. rhizoma high dose group,A. kusnezoffii high and low dose groups,G. spi-na high and low dose groups,K. radix high dose group,P. ca-cumen high and low dose groups and A. radix high dose group were decreased,with significant difference (P<0.01 or P<0.05). CONCLUSIONS:The 10 kinds of nephrotoxic TCM probably induced kidney injury through inhibiting the Oat1,Oat2 and Oat3 of Oats.

OBJECTlVE To investigate the inhibition of Radix lsatidis and its major constituents indigo and indirubin on three principal subtypes of organic anion transporters ( OATs) , Oat1, Oat2 and Oat3 in vivo in mice. METHODS Granules of Radix lsatidis ( GRl) 0.615 and 2.46 g·kg-1 , decoction of Radix lsatidis ( DRl) 1.6 and 6.4 g·kg-1 , indigo 0.008 and 0.64 mg·kg-1 and indirubin 0.0192 and 1.536 mg·kg-1 were ig given to the NlH mice (60 mice per group), twice a day, for 5 d while four control groups were set up, including vehicle of water, 0.5%sodium carboxymethyl cellulose ( CMC) , positive control probe-necid (0.05 g·kg-1) and additives of sucrose plus dextrin (1.5 g·kg-1 each) groups. After the last dosing of the test samples, para-aminohippuric acid ( PAH) clearance test was conducted. All the mice were iv given PAH 0.03 g·kg-1 and 1, 2.5, 5, 7.5, 10 and 20 min later before 10 mice per group were euthanized to collect whole blood and the kidneys were quickly removed. Each right kidney was homoge-nized to analyze the PAH accumulations and each left kidney to extract total mRNA for analysis of Oat1, Oat2 and Oat3 gene expressions using quantitative real-time PCR. The concentrations of PAH in sera and in kidney homogenates were determined by the method of Kiguchi. Major pharmacokinetic parame-ters of PAH in sera were calculated by pharmacokinetic software ( DAS2.0) . PAH uptake test for kidney slices was performed on another group of NlH mice according to the method of Nakakariya. RESULTS There was no significant difference between water control group and 0.5%CMC group in all the examined items. Compared with the vehicle control groups ( water and 0. 5%CMC group ) , elimination half time ( t1/2β) of PAH in GRl 2.46 g·kg-1 ,indigo 0.64 mg·kg-1 and indirubin 1.536 mg·kg-1 groups was signifi-cantly prolonged (P<0.05), the total clearance (Cl) and volume of distribution (Vd) were obviously reduced ( P<0.01) and the area under the curve ( AUC0-20 min ) of PAH in all the tested groups was signifi-cantly increased ( P<0.01) . AUC0-20 min obtained from renal PAH accumulations within the checked time was significantly higher ( P<0.05, P<0.01) than in the vehicle control group. But there was in no signifi-cant difference between all the study groups in kidney-to-plasma AUC ratios. PAH uptake results by kidney slices were significantly lower ( P<0. 05, P<0. 01 ) than in vehicle control group in every two dosages of all the four samples tested. Compared with vehicle control group, the mRNA expressions of Oat1, Oat2 and Oat3 were obviously ( P<0.05, P<0.01) and abnormally regulated in the groups of GRl 2.46 g·kg-1, DRl 6.4 g·kg-1, indigo 0.64 mg·kg-1 and indirubin 1.536 mg·kg-1. CONCLUSlON The renal Oat1, Oat2 and Oat3 of mice are significantly inhibited by GRl, DRl, indigo and indirubin. The inhibitory function of Radix lsatidis probably stems from indigo and indirubin contained in it.

Objective To explore the feasibility of excluding oral 75 g glucose tolerance test (OGTT)in pregnant women with fasting plasma glucose (FPG) ＜4.4 mmol/L in middle and late trimester.Methods From February 1,2012 to August 31,2013,18 851 pregnant women without pre-gestational diabetes mellitus who received 75 g OGTT in Maternal and Child Health Hospital of Hubei Province,China,at 24-28 weeks of gestation were enrolled.The criteria for gestational diabetes mellitus (GDM) were FPG ＞5.1 mmol/L and/or 1 h plasma glucose ＞10.0 mmol/L and/or 2 h plasma glucose ＞8.5 mmol/L in OGTT.The values of FPG in predicting GDM were analyzed with receiver operating characteristic (ROC) curve.The differences of detection rates for GDM among women of different ages,women with different FPG levels,and those with or without risk factors of GDM were compared by x2 test and Fisher's exact test.Results The overall detection rate of GDM was 9.11％(1 718/18 851).The detection rate of GDM was lower in women aged ＜ 25 years than women aged 25-,30-and ≥ 35 years [4.77％ (137/2 875) vs 7.76％ (803/10 350),12.43％ (552/4 440)and 19.06％ (226/1 186),respectively,x2=30.53,120.24 and 210.66,all P＜0.01].The sensitivity and specificity were 55％ and 68％,respectively,when the cutoff value of FPG was 4.4 mmol/L,and the Youden index was 0.23 and the area under the ROC curve was 0.61 (95％CI:0.59-0.63,P＜0.01).The sensitivity and specificity were 40％ and 80％,respectively,when the cutoff value was 4.5 mmol/L,and the Youden index was 0.20 and the area under the ROC curve was 0.61 (95％CI:0.59-0.63,P＜0.01).The missed diagnosis rate was lower when the cutoff point of FPG was defined as 4.4 mmol/L.The detection rate for GDM was 3.45％ (384/11 121) in women with FPG ＜4.4 mmol/L,significantly lower than in those with FPG ≥ 4.4 but ＜5.1 mmol/L and ≥ 5.1 mmol/L [8.06％ (561/6 957) and 100.00％ (773/773),x2=183.66 and 7 672.08,all P＜0.01].When FPG was ＜4.4 mmol/L or ≥ 4.4 but ＜5.1 mmol/L,the detection rate for GDM was significantly higher in women with GDM risk factors than in those without [5.09％ (118/2 318) and 10.75％ (184/1 712) vs 3.02％ (266/8 803) and 7.19％ (377/5 245),x2=23.56 and 22.06,P＜0.01].Conclusion OGTT may not be included in GDM screening in the pregnant women with FPG＜4.4 mmol/L and without GDM risk factors in the areas lack of medical resources.