Objective To establish an LC-MS/MS method for determination of S-071031 B, a novel antidepressant , in rat plasma and to study its pharmacokinetic profiles .Methods An LC-MS/MS method was established to determine S-071031B in rat plasma, and L-8021 was employed as the internal standard .The analytes were separated on a C18 column with a mobile phase consisting of water-acetonitrile containing 0.1%(v/v) formic acid at a flow rate of 0.3 ml/min.The mass spectrometer was operated in a selected reaction monitoring ( SRM ) mode with a positive electrospray ionization (ESI) interface.The plasma concentration-time curve was drawn and pharmacokinetic parameters were calculated by DAS 2.0.Results The linear range was from 2 to 1000 ng/ml with a sensitivity of 2 ng/ml as the lower limit of quantification . The intra-day and inter-day precisions , recoveries and matrix effects at three spiked levels were all suited to the determina-tion of biological samples.After oral administration of S-071031B, the Cmax of S-071031B was (287.2 ±50.8) μg/L and the Tmax was (0.8 ±0.3) h, with a t1/2of (2.9 ±0.6) h and an AUC(0-∞)of (1372.6 ±255.3) μg/L· h.Conclusion This method is sensitive and specific enough for determination of S-071031 B in rat plasma to facilitate the study of its phar-macokinetics .

Objective To develop a HPLC method for the determination of chlorogenic acid in xiaoaiping injection in human plasma.Methods The analytical column was packed with Hypersil ODS C18 (250 mm×4.6 nm,5 μm).The mobile phase was acetonitrile-0.4% phosphoric acid solution(13:87).The flow rate was 1 ml/min,and detection wave length was set at 327 nm.Results The linear ranges were 2.5～60.0 mg/L chlorogenic acid in human plasma,with the correlation coefficients of 0.9996.The Low limit of detection was 0.25 μg/ml.The method and extraction recovery were 100.1%～102.6%and 78.6%～80.3%.The relative standard deviation value for the within-day and between-day precision were less than 3.9%.Conclusion The method is simple,sensitive for the determination of chlorogenic acid in xiaoaiping injection in human plasma.

AIM: The aim of this study was to reveal the regulatory role of glutathione (GSH) in the transcriptional activity of activating transcription factor-2 (c-Jun/ATF-2) and nuclear factor-?B (NF-?B) of macrophages induced by angiotensin Ⅱ(AngⅡ). METHODS: Macrophage intracellular GSH was determined by fluorophotometry, and buthionine-[S,R]-sulfoximine(BSO)was used for depletion of intracellular GSH. The phosphorylation of c-Jun/ATF-2 and expression of NF-?B p65 were determined by immunoblot, and the activity of NF-?B was determined by electrophoresis mobility shift assay (EMSA). The c-Jun/ATF-2 was also determined by Immunohistochemical staining. RESULTS: The GSH content in the macrophage was decreased in cells that were lipid-peroxidized with AngⅡ (1.0 (?mol/L)) for 30 min and 60 min, respectively, followed by an adaptive GSH increase in the presence of AngⅡ (1.0 (?mol/L)) for longer time. In parallel, exposure to AngⅡfor 60 min also decreased macrophage GSH content in a dose-dependent manner. The GSH of RAW 264.7 cells were depleted by BSO, a specific inhibitor of GSH synthesis, and incubation for 18 h with 0.5 mmol/L BSO was sufficient for complete depletion of intracellular GSH. The phosphorylation of c-Jun/ATF-2 could be induced by the AngⅡ (1.0 (?mol/L)), whereas it did not occur in glutathione-depleted RAW 264.7 macrophages. The activation of NF-?B could also be induced by the AngⅡ (1.0 (?mol/L)), but it did not occur in glutathione-depleted RAW 264.7 macrophages. CONCLUSION: These data provide evidences that the intracellular glutathione redox may participate in the regulation of transcription activity of c-Jun/ATF-2 and NF-?B in macrophages. [

OBJECTIVE:To explore the effects and safety of atorvastatin combined with probucol on the vascular elasticity in patienits with hypertension. METHODS:246 hypertensive patients were randomly divided into control group and observation group,123 cases in each group. All patients received conventional antigypertensive treatment,based on it,control group was given 10 mg Atorvastatin tablet,qd;observation group was additionally given 0.25 g Probucol tablet,qd,on the basis of control group. They were treated for 1 year. Clinical efficacy,lipid levels(total cholesterol,triglyceride,low density lipoprotein cholesterol,high density lipoprotein cholesterol),cystatin C (Cys-C),C-reactive protein (CRP),elastic parameters of common carotid artery and lower limb artery(stiffness,pressure-strain elastic modulus,compliance,augmentation index,pulse wave velocity)before and af-ter treatment in 2 groups were observed,and the incidence of adverse reactions was compared. RESULTS:Before treatment,there were no significant differences in lipid levels,Cys-C,CRP and elastic parameters of common carotid artery and lower between 2 groups (P>0.05);after treatment,the above-mentioned indexes were significantly improved,and the improvement degree in ob-servation group was superior to control group,the differences were statistically significant(P<0.05). And there were no severe ad-verse reactions during treatment in both 2 groups. CONCLUSIONS:Atorvastatin combined with probucol can improve lipid level and elasticity of common carotid artery and lower limb artery,with good safety.

Objective To investigate the distribution of breast invasive ductal carcinoma with different molecular subtypes ,and to study the relationship between molecular subtypes and clinical pathological features in Xinjiang area .Methods A total of 621 patients with IDC from January 2013 to January 2014 was classified into Luminal A type,Luminal B type,HER-2 overexpression type and Basal -like type,different molecular subtypes according to the estrogen receptor(ER),progesterone receptor(PR),epidermal growth factor receptor -2(HER-2) and Ki-67,and compared the statistics combining with the clinical pathological characteristics of IDC .Re-sults The result showed that Luminal B type accounted for 53.1%,Luminal A type,HER-2 overexpression type and Basal-like type accounted for 14.5%,15.9%,16.4%,respectively.There were significant differences between the molecular subtypes and tumor size ,histological grade ,tumor pathological stage ,the expression of ER , PR and HER-2(P<0.05 for all).There were no correlations between the molecular subtypes and age ,as well as lymph node metastasis(P>0.05).Conclusion There is a close relationship between invasive ductal carcino-ma of different molecular subtypes and clinical pathological characteristics .The molecular subtypes are beneficial to treatment guidelines for clinical individual .

Objective Delayed xenograft rejection (DXR) is a major barrier to the long-term xenograft survial.This study evaluated the interaction between human peripheral blood mononuelear cells (PBMC) and porcine endothelial cells (PEC),and the effects of new generation of rabbit antihuman leukocyte polyclonal antibody (newRALG) inhibiting xenogeneic cell-mediated immune responses.Methods newRALG was obtained from rabbits after immunization with activated lymphocytes and monoeytes.PEC were isolated from aorta,and human PBMC were isolated from peripheral blood.Co-cultures of PKH-26 labeled PEC with PBMC were established,newRALG,thymoglobulin,isotype Ig and scavenger receptor (SR) ligand poly G were added into the co-cultures.Cells were collected,then FACS analysis was carried out to detect the up-take of PEC membrane by monocytes and the expression of costimulatory molecules.Lymphocyte proliferative responses to PEC with or without antibody were evaluated by a xenogeneie mixed lymphocyte-endothelial cell reaction (xMLER).Results FACS analysis revealed that monocytes from PBMC-PEC co-cultures became positive for PKH-26 following their interaction with PKH-26 labeled PEC,indicating that they engulfed PEC membranes during activation.PKH-26 positive monocytes up-regulated the CD40 and CD80 expression.Furthermore,SR blockade with poly-G prevented PEC membrane up-take by monocytes,newRALG greatly reduced SR-mediated PEC membrane up-take.The effects of thymoglobulin in inhibiting PEC membrane uptake were limited.xMLER demonstrated strong lymphocyte proliferation in response to PEC,and lymphocyte proliferation was dramatically inhibited by newRALG but not isotype Ig at a dosmdependent manner.Conclusions Monocytes play an important role in xenogeneic immune responses.SR ligand poly G inhibits PEC membrane up-take.newRALG inhibits PEC membrane up-take by monocytes,suggesting that newRALG blocks SR.Additionally,newRALG inhibits lymphocyte proliferation in response to PEC.These results suggest that this new polyclonal preparation may thus impair the initiation of xeno-specific immune responses and prevent xenograft rejection.

Objective:To compare the effects of modified incision drainage combined with thread-drawing and precise minimally invasive surgery in the treatment of anal fistula on anal defecation function and complications.Methods:A total of 105 patients with anal fistula who were diagnosed and treated in Xin′an International Hospital from December 2018 to December 2020 were collected. The patients were divided into the observation group (58 cases) and the control group (47 cases) according to surgical methods. The observation group received modified incision drainage combined with thread-drawing surgery. The control group received precise minimally invasive anal fistula surgery. The treatment outcome, anal defecation function and complications were compared between the two groups.Results:The operation time, intraoperative blood loss, first defecation time after operation, normal eating time after operation in the two groups had no significant differences ( P>0.05). The hospital stay in the observation group was significantly longer than that in the control group: (5.29 ± 1.53) d vs. (4.02 ± 1.16) d, there was statistical differences ( P<0.05). After operation, the resting pressure of the anal canal, resting rectal pressure, length of the tube high pressure belt, the maximum systolic pressure of the anal canal between the two groups had no significant differences ( P>0.05). The excellent and good rate of anal defecation function and complication rate between the two groups had no significant differences ( P>0.05). Conclusions:Modified incision drainage combined with thread-hanging surgery in the treatment of anal fistula is equivalent with precision minimally invasive surgery. Both can effectively improve the anal defecation function. The postoperative safety is good and there is no recurrence. However, the hospital stay of patients with precision minimally invasive surgery for anal fistula is relatively shorter.

Objective To investigate the effects of CD4+CD25high regulatory T cells(Treg)and the imbalance of helper T lymphocyte subsets(Th1/Th2)on the immunological mechanism of IgA nephropathy(IgAN)patients. Methods The percentage of Treg and helper T cells subpopulation (Th1/Th2)in the peripheral blood of IgAN patients and healthy controls was examined by flow cytometry.The FOXP3 expression was detected through intracellular staining.The correlation of Treg or Th1/Th2 with clinical parameters of IgAN was analyzed by Spearman or Pearson rank correlation test. Results The percentages of Treg and Th2 cells were significantly higher in peripheral blood of IgAN patients compared to that of healthy controls[Treg (2.14±0.82)%vs[1.59±0.53)%,Th2(2.57±0.72)%vs(1.81±1.10)%,all P＜0.05].Th1/Th2 ratio was significantly reduced in IgAN patients(5.75±1.89 vs 12.73±9.79,P＜0.05).The percentage of circulating Treg cells was positively correlated with serunl IgA concentration(r=0.397,P＜0.05),and was negatively correlated with eGFR(r=-0.376,P＜0.05).The percentage of circulating Th2 cells was positively correlated with serum IgA(r=0.468,P＜0.05). Conclusions There is a disorder of T lymphocyte population in the peripheral blood of IgAN patients.The increased Treg and Th2 cells may play an important role in the pathogenesis of IgAN.

Objective To analyze the efficacy and cosmetic results of intensity modulate radiation therapy (IMRT) for breast cancer after breast-conserving surgery.Methods From 2003 to 2006, 117 patients with breast cancer, after breast-conserving surgery followed by 4 - 6 cycles of chemotherapy,received intensity modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT).The radiation dose was 50 Gy in 25 fractions to the whole breast and 10 Gy boost to the tumor bed.Patients with positive hormone receptors then received endocrine treatment.Results The follow-up rate was 94.0% until September 2009.114 and 91 patients were followed up to 3 and 5 years, respectively.The 3-and 5-year overall survival rates were 99.1% and 96%.The 5-year disease free survival and local recurrence rates were 88% and 3.6%.Cosmetic results were satisfied.Severe radiation toxicities, such as radiation pneumonitis, pulmonary fibrosis and heart injury were not found.Conclusions Patients treated with IMRT after breast-conserving surgery have a satisfied prognosis as well as cosmetic results.

OBJECTIVE To evaluate the clinical features of tumors primarily in the pterygopalatine fossa, and the efficiency of surgical management for these lesions. METHODS The clinical data of 7 cases with tumors primarily in the pterygopalatine fossa were retrospectively studied. Three of them were primary diseases, i.e. fibrous histiocytoma, neurofibroma and cholesteatoma. The other 4 cases were secondary tumors mainly located in pterygopalatine fossa. There were 1 case with epithelial-myoepithelial carcinoma, 1 case with adenoid cystic carcinoma , 1 case with recurrent inverted nasal papilloma, 1 case with recurrent malignant fibrous histiocytoma. Approaches to tumors in pterygopalatine fossa lesions included lateral rhinotomy, and transnasal or transantrum approaches under the nasal endoscope. RESULTS The patient suffered from adenoid cystic carcinoma developed local recurrence 4 months after operation, and extended resection of the recurrent tumor with laser was performed again. No further recurrence was found after following-up for 3 years. Neither local recurrence nor regional metastasis was found in the remaining 6 cases with a follow-up period of 2 to 4 years. The main complication was oronasal fistula. CONCLUSION CT scan or MRI is the main method to the early diagnosis of pterygopalatine fossa tumors. Lateral rhinotomy, endoscopic trasnnasal or transantrum approaches are feasible procedures to resect the tumors.