Objective To explore the significance of interleukin -35 (IL -35)in serum of patients with severe hepatitis.Methods Collected 39 cases of chronic hepatitis B(CHB)patients and severe hepatitis,and col-lected 19 cases of healthy control's(HC)peripheral blood at the same time.ELISA method was used to detect IL -35 levels.Results IL -35 in CHB and severe hepatitis group [(483.5 ±280.7)ng/mL and (277.9 ±248.7)ng/mL] were higher than HC group (50.5 ±47.8)ng/mL(t =2.089,3.303,P =0.044,0.002).In severe hepatitis group, the IL -35 levels in survivors group (305.3 ±301.2)ng/mL was higher than death group (78.7 ±33.2)ng/mL (P =0.012).IL -35 was positively correlated with ALT and AST,the correlation coefficient were 0.649 and 0.599. Conclusion IL -35 is involved in the pathogenesis of hepatitis B process,the low serum IL -35 levels in severe hepatitis patients may herald a bad prognosis.

Objective To evaluate the application value of hyperinsulinemic euglycemic clamp in the diagnosis and treatment of newly-onset diabetic patients. Methods Totally 11 newly-onset diabetic inpatients (10 patients with type 2 diabetes mellitus and 1 patient with latent autoimmune diabetes of adulthood) who were diagnosed in the Department of Endocrinology of Peking Union Medical College Hospital from January 2009 to August 2009 were included in this study. Hyperinsulinemic euglycemic clamp was applied to measure the glucose disposal rate (M value). Afterwards insulin pump therapy was applied and the total insulin dosage per day to get to the target of the fasting and postprandial blood glucose was calculated. Final]y the relationships between insulin dosage per day and the M value, body mass index (BMI) , fasting blood glucose, fasting insulin level were separately analyzed. Results The insulin dosage was only negatively correlated with M value (r = - 0. 83, P = 0. 003), and was not significantly correlated with BMI (r = 0.54, P = 0.106), fasting blood glucose (r = - 0. 16, P =0. 657) , and fasting insulin (r = 0. 16, P = 0. 659). The formula of insulin dosage and M value according to the mathematic model as follows: insulin dosage per day = - 3. 327 M + 49. 849. Conclusion Hyperinsulinemic euglycemic clamp can effectively evaluate the insulin sensitivity in the newly-onset type 2 diabetic patients, and thus can be a useful tool in deciding the clinical insulin dosage.

Optimization of sensor array is a significant topic in the application of electronic nose (EN). Stepwise discriminant analysis and cluster analysis combining with screening of typical index were employed to optimize the original array in the classification of 100 samples from 10 kinds of traditional Chinese medicine based on alpha-FOX3000 EN. And the identification ability was evaluated by three algorithm including principle component analysis, Fisher discriminant analysis and random forest. The results showed that the identification ability of EN was improved since not only the effective information was maintained but also the redundant one was eliminated by the optimized array. The optimized method was eventually established, it was accurate and efficient. And the optimized array was built up, that is, S1, S2, S5, S6, S8, S12.
Algorithms ; Biosensing Techniques ; methods ; Cluster Analysis ; Discriminant Analysis ; Drugs, Chinese Herbal ; classification ; isolation & purification ; Electronic Nose ; Medicine, Chinese Traditional ; Principal Component Analysis ; Reproducibility of Results ; Smell

A series of adefovir mono-L-amino acid esters, mono non-steroidal anti-inflammatory drugs carboxylic ester prodrugs with more potent anti-HBV activity and lower nephrotoxicity were designed and synthesized. Adefovir bis (L-amino acid) ester was used as lead compound, according to pathological and pharmacological findings that non-steroidal anti-inflammatory drugs can effectively inhibit the organic anion transporter 1 (hOAT1)-mediated adefovir phosphonic acid pairs of anion transport across tubular basement membrane thereby reducing the nephrotoxicity of adefovir. Flatten design principle was used to introducing non-steroidal anti-inflammatory drugs structural fragments to design and synthesize target adefovir mixture ester prodrugs. HepG2 2.2.15 cell line was used as in vitro anti-HBV activity evaluation model. Five compounds exhibited antiviral activity, and compound 18 showed the most potent anti-HBV activity and relatively high selective index (EC50 3.92 micromol L(-1), SI 9.97). HK-2 cell line was used as in vitro model to evaluate nephrotoxicity. Results suggested the target compounds have lower cytotoxicity than the positive control. Moreover, by analyzing the primary structure and activity relationship of these compounds, it could suggest that mono-L-amino acid ester, mono non-steroidal anti-inflammatory drugs carboxylic ester prodrugs strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.
Adenine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Amino Acids ; chemical synthesis ; chemistry ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; chemical synthesis ; chemistry ; pharmacology ; Antiviral Agents ; chemical synthesis ; chemistry ; pharmacology ; Carboxylic Acids ; chemistry ; pharmacology ; Cell Survival ; drug effects ; Drug Design ; Hep G2 Cells ; drug effects ; Humans ; Kidney Tubules, Proximal ; cytology ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Molecular Structure ; Organophosphonates ; chemical synthesis ; chemistry ; pharmacology ; Prodrugs ; chemical synthesis ; chemistry ; pharmacology

Disease Management ; Humans ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; drug therapy ; surgery

OBJECTIVETo investigate the transcription of cytoskeleton protein genes in differentiation of neurons from mouse embryonic stem (ES) cells induced by all-trans retinoic acid (RA), and to explore the possibility of setting up a method to screen small molecules with promoting or inhibiting effect.

METHODSThe hanging drop method was employed for embryonic body formation to mimic embryo development in vivo. Reverse transcriptase PCR (RT-PCR) was performed to investigate mRNA expression of the neuron-specific cytoskeleton proteins including Mtap2, Nefm and beta-tubulin III which were regarded as the inducing effect indexes of RA. Morphological evaluation and immunocytochemistry staining were conducted to identify the neural derivatives. Moreover, the inducing effects of six synthetic molecules were further evaluated.

RESULTRA up-regulated the mRNA expression of Mtap2 and Nefm, especially Mtap2 increased by 1.27 times, which was consistent with the morphological alteration. However, there was no significant changes of beta-tubulin III expression. With addition of the six synthetic molecules, the transcription of Mtap2 was inhibited, while the Nefm mRNA expression was up-regulated in some degree, especially for molecule 1 and 3 that was increased by 1.4 and 1.2 times, which, however, was not parallel to the morphological changes.

CONCLUSIONThe transcriptional levels of Mtap2 and Nefm are both up-regulated in the RA-induced differentiation of ES cells towards neurons. The up-regulation of Mtap2 is consistent with the morphological alteration, which might be the key landmark in the RA-induced differentiation of ES cells into neurons.

Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Cytoskeletal Proteins ; genetics ; Embryonic Stem Cells ; cytology ; Gene Expression Regulation, Developmental ; Mice ; Microtubule-Associated Proteins ; pharmacology ; Neurofilament Proteins ; pharmacology ; Neurons ; cytology ; Transcription, Genetic ; Tretinoin ; pharmacology ; Tubulin ; pharmacology

OBJECTIVETo evaluate the potential reconsideration of curative operative treatment for patients with unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC).

METHODSFrom Jan. 1999 to Dec. 2002, 76 patients with unresectable stage IIIA (N2) NSCLC were entered in this study. They had all been proved by chest CT, chest film and fiberobronchoscopy. Twenty-one (27.6%) patients were examined by mediastinoscopy. All the patients received two cycles of chemotherapy with NVB (25 mg/m(2), D1, D5) and carboplatin (300 mg/m(2), D1). All the patients were staged again three weeks after induction chemotherapy. Sixty-four patients who achieved partial response (PR) or complete response (CR) were allowed to undergo surgery. Twelve patients who did not responde to chemotherapy received radiotherapy instead. Of the 64 surgically treated patients, 56 (84.7%) had a complete resection and then received 2 cycles of chemotherapy using the same regime, 8 patients had an incomplete resection and then received radiotherapy for the residual tumor.

RESULTSThe median survival for these 76 patients with unresectable stage IIIA (N2) NSCLC treated by either surgery or radiation after induction chemotherapy was 18.6 months with 1-, 2-, 3-year survival rate of 64.2%, 39.4% and 25.6%, respectively. The median survival for the 56 patients with a complete resection was 28.2 months with 1-, 2-, 3-year survival rate of 70.4%, 52.5% and 38.6%, respectively.

CONCLUSIONPreoperative induction chemotherapy with NVB plus carboplatin should be seriously considered for the patients with unresectable stage IIIA (N2) NSCLC, It is suggested that, whenever possible, surgery should be taken as the first choice for the patients who show down-staged benefits that complete resection can be attempted.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; surgery ; Chemotherapy, Adjuvant ; methods ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Lung Neoplasms ; drug therapy ; surgery ; Male ; Mediastinoscopy ; Middle Aged ; Preoperative Care ; Vinblastine ; administration & dosage ; analogs & derivatives

Objective To observe the expression ofmicroRNA-134 (miR-134) in the mouse brain tissue with FMR1 gene knockout during the different development periods and its expression characteristic, and explore whether the deficiency of fragile X mental retardation protein (FMRP) can induce the changes of miR-134 transcription. Methods FVB strain male mice, including FMR1 gene knockout (KO, n=15) and their wild type (WT, n=15) counterparts were chosen in the experiment. The expressions of miR-134 in the brain tissues of these KO mice that were 0 d, 4 and 6 w old and the age-matched WT mice were detected by qRT-PCR. Results The transcriptional level of miR-134 in the brain tissue of KO mice had no significant difference as compared with that of age-matched WT mice (P＞0.05). The transcriptional levels of miR-134 in 6-w-old KO and WT mice were significantly decreased as compared with the newbom and 4-w-old same genotype mice (P＜0.05). Conclusion The absence of FMRP does not influence the transcription of miR-134 and the transcriptional level of miR-134 in the brain tissues maintains a high level during the developmental stage of the nervous system and gradually decreases to a low level after grow-up, demonstrating its important role in regulating the development of nervous system.

AIM To investigate the ameliorative effects of Schisandrol A(Sol A)in Suhuang antitussive capsule on post-infectious cough(PIC).METHODS The in vivo mouse PIC model was established by intratracheal instillation of lipopolysaccharide(LPS)combined with cigarette smoke exposure.The mice were randomly divided into the control group,the model group,the Suhuang antitussive capsule group(14 g/kg),the montelukast sodium positive control group(3 mg/kg),and low and high dose Sol A groups(10,30 mg/kg).The in vitro PIC model was established by stimulating human bronchial epithelial cells(BEAS-2B)with LPS.The cells were divided into the control group,the model group,the Suhuang antitussive capsule group(10 μg/mL)and low and high dose Sol A groups(3,10 μmol/L).HE and Masson staining were used to detect the pathological changes of the lung and bronchial tissues.ELISA was used to detect the levels of IL-1β,IL-6,TNF-α,ROS,MDA,SOD and GSH in the lung tissues.RT-qPCR was used to detect the IL-1β,IL-6 and TNF-α mRNA expressions in BEAS-2B cells.And Western blot was applied to detect the protein expressions of p-PI3K,p-Akt,NOX4,SIRT1,p-ERK,Fibronectin,E-cadherin,Vimentin and α-SMA in mouse lung tissue and BEAS-2B cells.RESULTS Compared with the model group,the groups intervened with Sol A or Suhuang antitussive capsule displayed prolonged cough latency(P＜0.01);reduced cough frequency(P＜0.01);relieved pulmonary inflammatory cell infiltration and collagen deposition in PIC mice;decreased pulmonary levels of IL-1β,IL-6,TNF-α,ROS,MDA and protein expressions of Fibronectin,Vimentin,α-SMA,p-ERK,p-PI3K,p-Akt,and NOX4(P＜0.05,P＜0.01);increased pulmonary levels of SOD and GSH and protein expressions of E-cadherin and SIRT1(P＜0.05,P＜0.01);decreased ROS level,IL-1β,IL-6,TNF-α mRNA expressions and p-ERK,p-PI3K,p-Akt,NOX4 protein expressions in vitro(P＜0.05,P＜0.01);and increased SIRT1 protein expression in vitro as well(P＜0.01).CONCLUSION Being the main antitussive component of Suhuang antitussive capsule upon the PIC model,Sol A inhibits the inflammation via SIRT1/ERK signaling pathway and relieve the oxidative stress via PI3K/Akt/NOX4 signaling pathway.

AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.