Bioavailable studies were performed based on plasma concentrations of captopril in 5 Beagle dogs and 5 male healthy volunteers after a single oral administration of captopril sustained-release tablet and sugar-coated tablet. A one-compartment model was adopted. Relative bioavailability of sustained-release tablet to sugar-coated one was 131.6% for dogs and 111.0% for humans. Their mean residence times (MRTs) were 4.52 h and 1.96 h in dogs, 4.28 h and 2.77 h in humans, respectively. The maximum concentrations were 995.9 ng/ml and 2470.8 ng/ml in dogs, 126.2 ng/ml and 251.2 ng/ml in humans for two kinds of tablets, respectively. The duration time, in which plasma concentration staved above 50% inhibitory concentration of angiotensin converting enzyme activity, was more than 10 h for sustained-release tablets and 6h for sugar-coated tablets at the same dose (37.5 mg). consequently, it could be expected that the sustained-release tablet dosed twice a day should have a greater efficiency than marketed sugar-coated tablet taken 3 times daily.

Objective To investigate the effects of Qi-Boosting Toxin-Resolving Formula (QBTRF) on CD4+CD25+ regulatory T cells and Th17 cells of patients with middle to late staged nasopharyngeal carcinoma (NPC). Methods Flow cytometry was performed to detect the ratio of CD4+CD25+ regulatory T cells and Th17 cells in the peripheral blood mononuclear cells (PMBC) among 18 patients with middle to late stage of NPC treated by QBTRF added to conventional therapy (treatment group), Foxp3 mRNA and ROR-γt mRNA in PMBC was determined by RT-PCR technique. Furthermore, serum levels of IL-6 and TGF-β were assayed by ELISA. Meanwhile, 15 patients with NPC treated by conventional therapy were taken as the control group. Results The ratio of CD4+CD25+ regulatory T cells to the total CD4+ T cells and the transcriptional level of Foxp3 mRNA in PMBC were significantly lower in treatment group than that of control group (P<0.05), the ratio of Th17 cells to the total CD4+T cells and the transcriptional level of ROR-γt mRNA in PMBC were significantly higher in treatment group than that of control group (P<0.05). However, the serum level of IL-6 was obviously higher in treatment group than that of control group (P<0.05), and the serum leve of TGF-βwas obviously lower in treatment group than that of control group (P<0.05). Conclusion QBTRF can significantly affect the number ratio and functional activity of CD4+CD25+ regulatory T cells and enforce the differentiation of Th17 cells among patients with middle to late staged NPC, which it may be reversed the immune tolerance of NPC through regulating the level of IL-6 and TGF-β.

Objective To investigate the implications of ratio of the CD4+ and CD25+ positive regulatory T cells (CD4+CD25+Tregs) in peripheral blood mononuclear cells (PBMC) and its associated regulatory factors such as forkhead transcription factor 3 (Foxp3) mRNA transcriptional activity in PBMC,serum levels of transforming growth factor beta-1 (TGF-β1),and interleukin 10 (IL-10) in the immunopathology of patients with middle to late staged nasopharyngeal carcinoma (NPC) based on a clinical trial.Methods In this study,18 NPC cases at middle to late stage as observing group and 10 healthy persons as control group were included to detect their ratio of the CD4+CD25+Tregs in the PBMC with flow cytometry (FCM) technique,transcriptional activity of Foxp3 with RT-PCR procedure,and serum levels of TGF-β1 and IL-10 with enzyme-linked immunosorbent assay (ELISA) method.A comparative analysis was used to explore their implications in the immunopathological correlation of NPC cases with their lesion.Results The ratio of the CD4+CD25+Tregs to total CD4+T cells in PBMC was significantly increased [(4.23 ±0.53)％ vs (2.65 ±0.31)％,t =8.60,P ＜0.01],accompanied with significantly elevated levels of Foxp3 transcription in PBMC (3.699 ± 0.309 vs 1.109 ± 0.146,t' =31.08,P ＜ 0.05],and serum contents of TGF-β1 [(645.56 ± 39.61) pg/ml vs (488.82 ± 36.91) pg/ml,t =10.27,P ＜ 0.01] and IL-10 [(1.27 ± 0.21) pg/ml vs (0.68 ± 0.08) pg/ml,t' =10.61,P ＜ 0.05] in these patients,when compared with that of healthy controls.Conclusions It may be true that CD4 + CD25 + Tregs,transcriptional regulatory factor Foxp3,and cytokines TGF-β1 as well as IL-10 altogether were composed of a regulating system in a positive feedback way to promote the developing process of immunotolerance phenomena in the tumor microenvironment and the initiation of immunoescape among patients with middle to late staged nasopharyngeal carcinoma.

Objective To explore whether albumin corrected anion gap (ACAG) is associated with long-term mortality of sepsis patients.Methods Adult patients with a diagnosis of sepsis within the first 24 hours (from December 2013 to December 2014) admitted to the intensive care unit (ICU) were included via the Sepsis database of West China Hospital Sichuan University. To record their long-term survival, patients were followed up by telephone interview one year after enrollment. ACAG was calculated according to the anion gap (AG) level within the first 24 hours admitted to ICU, and patients were divided into normal ACAG group (ACAG 12-20 mmol/L) and high ACAG group (ACAG > 20 mmol/L), and clinical characteristics and 1-year mortality were compared between groups. Patients were also divided into survivors and non-survivors according to the 1-year survival outcome, and multivariate logistic regression analysis was conducted to find independent risk factors for long-term mortality of sepsis patients.Results A total of 296 sepsis patients were enrolled in the study, with 191 (64.5%) in the high ACAG group and 105 (35.5%) in the normal ACAG group. There were no significant differences in age, gender, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), Charlson cormobidity index (CCI) and other background variables between groups. Compared with the normal ACAG group, patients who suffered from multiple organ dysfunction syndrome (MODS) in the high ACAG group were more prone to develop renal and gastrointestinal injury (43.5% vs. 25.7%, 52.9% vs. 33.3%, respectively), had significantly higher serum creatinine [SCr (μmol/L): 89.0 (61.0, 148.0) vs. 67.1 (48.0, 86.0)], greater need for continuous renal replacement therapy (CRRT, 16.8% vs. 6.7%), and significantly shorter length of ICU stay and hospital stay [days: 11 (5, 22) vs. 16 (18, 31), 21 (14, 39) vs. 28 (20, 47)], with statistically significant differences (allP < 0.05). It was shown by Kaplan-Meier survival analysis that 1-year cumulative survival for the high ACAG group was significantly lower than that of the normal ACAG group (55.0% vs. 67.7%,P = 0.046). It was shown by multivariate logistic regression that ACAG [odds ratio (OR) = 1.201, 95% confidence interval (95%CI) = 1.115-1.293,P = 0.000], APACHE Ⅱ (OR = 1.053, 95%CI = 1.011-1.098, P = 0.014), the incidence of septic shock (OR = 2.203, 95%CI = 1.245-3.898,P = 0.007), fungus infection (OR = 3.107, 95%CI = 1.702-5.674,P = 0.000), acute renal failure (OR = 2.729, 95%CI = 1.134-6.567,P = 0.025) and complicated with malignancy (OR = 2.929, 95%CI = 1.395-6.148,P = 0.005) were independent risk factors contributing to increased 1-year mortality among sepsis patients.Conclusion ACAG was an independent risk factor for 1-year mortality of sepsis patients.

Objective To study the clinical effect of specific immune therapy for children with allergic rhini-tis(AR)and its influence on the level of serum IL -17 and IL -35.Methods 174 children with AR were chosen as the research group,who were used specific immune therapy for 24 months.In same period,110 cases of healthy chil-dren were selected as the control group.Curative effect was evaluated by rhinitis symptoms total score(TRSS)points rate.quality of life was evaluated by nasal conjunctivitis related quality of life questionnaire(RQLQ)score.Pulmonary function before and after treatment,serum Eos counting,IL -17,IL -35 were detected.Results (1 )In research group,the total effective rate after treatment of 2 years was 89.66%,which was significantly higher than 71.26% after treatment of 1 year,there was statistically significant difference(χ2 =18.716,P <0.05).(2)In the research group, TRSS score and RQLQ score after treatment of 1 year and 2 years were lower than that before treatment(t =28.360, 42.850,7.749,42.850,all P <0.05 ),and the data after treatment of 2 years were less than that after treatment 1 year(t =19.207,10.558,all P <0.05).(3)In the research group,FEV1 /predictive value after treatment of 1 year and 2 years elevated compared to that before the treatment,the airway resistance value /forecast and Eos count were lower than that before the treatment(t =15.972,27.811,48.780,62.211,10.930,62.211,all P <0.05).FEV1 /pre-dicted value after treatment of two years was higher than that after treatment of 1 year,airway resistance value /forecast and Eos counts were less than that after treatment of 1 year(t =8.728,14.707,16.488,all P <0.05 ).(4)In research group,serum IL -17 after treatment of 1 year and 2 years reduced,while IL -35 rose (t =9.162,14.522, 10.235,14.522,all P <0.05).And IL -17 after treatment of 2 years was lower than that after treatment of 1 year,IL-35 was higher than after treatment of 1 year(t =5.795,7.731,all P <0.05).(5)Correlation analysis showed that the serum IL -35 and the level of IL -17 showed a negative correlation(r =-0.36,P <0.05).Conclusion Effect of specific immune treatment on children with allergic rhinitis is better,specific immune treatment can improve the clinical symptoms,inhibit IL -17,promote IL35 and improve lung function and quality of life of patients.

Objective To investigate the activity of recombinant Vibrio vulnificus hemolysin (rVvhA) on the apoptosis of J774A.1 cells and the related mechanism. Methods The cytotoxic effect of rVvhA on the growth of J774A.1 cells was identified by MTT, celluar and mitochondrial morphology were observed by transmission electron microscopy, apoptosis or necrosis and mitochondrial membrane potential in J774A.1 cells were measured by flow cytometry, activities of caspase-3 ,-8,-9 were detected by spectrophotometry. Results The viability of J774A.1 cells exposed to rVvhA was inhibited, and it is dependent on dose. Celluar and mitochondrial uhrastructure both occurred to change obviously observed by transmission electron microscopy in J774A.1 treated by 2.0 HU/ml and 3.0 HU/ml rVvhA after 8 hours; and 3.0 HU/ml rVvhA group had a better cytotoxic effect on J774A.1 than that of 3.0 HU/ml rVvhA group. The percentage of apoptosis is (7.80±0.62)%, (12.33±0.12)%, respectively. Besides, the mitochondriai membrane potential also reduced, because the rate of fluorescence which is green increase 1.0% (normal) to 9.8% (2.0 HU/ml rVvhA) and 39.2% (3.0 HU/ml rVvhA). At the same time, the caspase-3, -9 activity increased gradually, but caspase-8 remained unchanging. In J774A.1 cells treated by 3.0 HU/ml rV-vhA + caspase-3 inhibitor(Ac-DEVD-FMK) or caspase-9 inhibitor(Ac-LEHD-FMK), The apoptosis of was reduced to(6.23±3.95)% ,(9.60±3.14)%, and the activity of caspase-3, -9 reduced, too. Conclusion The rVvhA has cytotoxic effect on J774A.1. Mitochondria-mediated apoptosis pathway which is dependent on caspase may be related to apoptosis induced by rVvhA in J774A.1.

Objective To investigate the clinical manifestations and imaging features of dural arterio-venous fistula of super petrosal venous drainage and treatment. Methods From May 2013 to September 2014,9 patients with petrosal vein drained dural arteriovenous fistula at the Department of Neurosurgery, Xuanwu Hospital,Capital Medical University and the Department of Neurosurgery,Beijing Haidian Hospital were enrolled retrospectively. The patients were treated with endovascular embolization or microsurgery,and the MRI and DSA examinations were improved,and the scores of the modified Aminoff&Logue scale (ALS) were performed before and after treatment. Results In the 9 patients,there were 3 females and 6 males. They all had different degrees of limb sensory and motor abnormalities,7 of them also had urination and/or bowel disorders,4 had cranial nerve dysfunction,including hoarseness,bucking,hiccup,and paralysis. Six patients received embolization treatment,3 received microsurgery,and they all achieved anatomic cure. The preoperative ALS score was 6. 0 ± 2. 7,and the score at 3 months after procedure was 2. 8 ± 1. 7. There was significant difference between before and after treatment (t=4. 816,P<0. 05). Conclusions The petrosal vein drained dural arteriovenous fistula is a kind of rare cerebrovascular malformation. The lesion involves a wide range. The clinical manifestations are severe. Both endovascular embolization and microsurgery can achieve a more ideal therapeutic effect. If the vascular condition is permitted,the interventional embolization treatment should be preferred.

Transcription factor is one of the key factors in the regulation of gene expression at the transcriptional level. It plays an important role in plant growth, active components biosynthesis and response to environmental change. This paper summarized the structure and classification of bHLH transcription factors and elaborated the research progress of bHLH transcription factors which regulate the active components in plants, such as flavonoids, alkaloids, and terpenoids. In addition, the possibility of increasing the concentration of active substances by bHLH in medicinal plants was assessed. The paper emphasized great significance of model plants and multidisciplinary research fields including modern genomics, transcriptomics, metabolomics and bioinformatics, providing the contribution to improve the discovery and function characterization of bHLH transcription factors. Accelerating the research in the mechanism of bHLH transcription factors on the regulation of active components biosynthesis will promote the development of breeding and variety improvement of Chinese medicinal materials, also ease the pressure of resources exhaustion of traditional Chinese medicine home and abroad.

Objective To investigate the clinicopathological characteristics and prognostic factors of hepatolithiasis associated with intrahepatic cholangiocarcinoma (HLAIHCC).Method A ret rospective study was conducted on 36 patients who suffered from histopathologically confirmed HLAIHCC.These patients received surgical resection of the tumor from June 2006 to September 2009.Results The overall 1,3,5 year survival rates for patients with HLAIHCC were not significantly better than those patients with ICC (63.6％,36.4％,and 30.3i％ vs.65.4％,34.3％,and 28.6％,P=0.57).For the patients who received curative resection,the 1-,3-,and 5-year survival rates (81.4 ％,61.7 ％,and 58.6 ％) were significantly better than those who received palliative resections (x2 =20.426,P＜0.001).The white blood cell count was significantly higher in the HLAIHCC group than in the ICC group (x2 =19.70,P＜0.001) and tumor size was significantly smaller in the ICC group than in the HLAIHCC group (P=0.04).Serum CA19-9 level (P=0.049) and resection margin (P=0.019) were independent risk factors of prognosis.Conclusions This study showed HLAIHCC to have different clinicopathological characteristics from ICC.Curative resection was the optimal surgical treatment for HLAIHCC.Serum CA19-9 level and resection margin were independent risk factors of prognosis.

Objective Toanalyzetheclinicalcharacteristicsandtreatmentoutcomesofspinalfilum terminalevascularmalformation.Methods Theclinicaldataof6patientswithfilumterminalevascular malformation diagnosed and treated from January 2008 to December. 2013 were analyzed retrospectively. The definition of filum terminale vascular malformation is anterior/posterior spinal artery feeding arteriovenous fistula or arteriovenous malformation and located below conus medullaris,and does not complicate with spinal vascular lesions in the other part. The Aminoff & Logue score and MRI of spinal cord function were performedatoneyearaftermicroneurosurgeryand/orendovascularembolization.Results Allpatients were males. Their clinical presentations were the weakness of both lower extremities and sphincter disturbance. The mean course of disease was 17. 1 ± 5. 2 months. The pathological type of the 6 patients were all arteriovenous fistulas. The feeding arteries included lumbar artery,internal iliac artery,and median sacral artery. Two of the 6 patients underwent Onyx glue embolization,3 were treated with microneurosurgery,and 1 was treated with embolization in combination with microneurosurgery. They were all achieved anatomic cure. The Aminoff & Logue scores were improved after 1 year (3. 8 ± 1. 9 scores before procedure,2. 8 ± 2. 0 scores after procedure),there was no significant difference (P >0. 05). The myodynamia scores were improved in 3 patients,2 did not change,1 got worse. The urinary and bowel functions were improved in 2 patients,and4didnotchange.Conclusion Filumterminalevascularmalformationisararevascular malformation of spinal cord. Both embolization and surgical treatment can achieve anatomic cure. Although the spinal cord function can be only partially restored,but continuous deterioration can be prevented.