Aim To investigate the effects of 4-aminopyridine (4-AP),K+ channel blocker, on the gastrointestinal function of murine. Methods Charcoal suspension was used to detect the effects of 4-AP on gastrointestinal motility of mice in vivo, contraction of isolated fundus longitudinal strips and duodenum of rats were studied in vitro,gastric acid secretion was measured by Gastric Secretion Test. Results 4-AP(5 mg?kg -1,ig)inhibited the gastrointestinal motility of mice. 4-AP(5 mmol?L -1) increased the maximum contractive force and minimum relaxation force, decreased the amplitude and frequency of the isolated duodenum peristaltic contraction. 4-AP(2.5 mg?kg -1,ip) significantly enhanced gastric acid secretion of rats. Conclusion 4-AP inhibited gastrointestinal motility and enhanced gastric acid secretion in murine.

Translational medicine is a novel concept about combination of basic research and clinical application. The aim of translational medicine is to realize the translation of basic research into clinical practice. microRNAs (miRNAs) are non-coding single-stranded RNAs with 21-25 nucleotides in length as newly discovered factors in regulating gene expression. Recently, the key regulatory role of miRNA in the cardiovascular system has been elucidated and amount of remarkable results has been achieved, particularly in the regulation of cardiac arrhythmias. A series of studies demonstrate that miRNAs are involved in the regulation of expression of a variety of proteins associated with cardiac electrical activity, and are the potential targets of occurrence of cardiac arrhythmias and anti-arrhythmic drugs. miRNAs as a therapeutic target regulate the stability of mRNAs of target genes or play an inhibitory role in the translation process. Stability of the corresponding miRNA expression levels in the target organ may be a new approach for the disease therapy. Regarding the dysfunction of miRNA, we employed miRNA re-expression strategy and anti-miRNA strategy to correct target protein function and provide a new entry for the therapy of arrhythmia. With the technology of miRNA mimics and antagomirs, miRNAs are expected to treat various cardiovascular diseases and will provide a fresh impetus to achieve transform medicine.

Aim To investigate the effects of K + channel blockers on arsenic trioxide-induced HeLa cell death. Methods Viability of HeLa cells was assessed by mitochondrial dehydrogenase activity using colorimetric MTT assay and the voltage-dependent K+ currents were recorded by using patch-clamp rest living cells after As2 O3 24 h-incubation showed significant increase of K + currents densities. At + 80mV, the densities of K+ currents (61 ± 18) pA/10 pF (n = 8) in As2O3 24 h-incubation group were significantly more than that in the control group (38 ± 10) pA/10 pF (n = 8, P ＜ 0. 05 ). The HeLa cells were prevented partially from As2 O3-induced cell death by co-application for 24 h with typical voltageeffects on HeLa cells. Conclusion Chronic treatment with As2 O3 increased voltage-dependent K+currents in HeLa cells and the cell death induced by As2O3 was reduced partially by voltage-dependent K +channel blockers, 4-aminopyridine or tetraethylammonium.

Aim To investigate effects of chlorzoxazone on survival and apoptosis of HepG2 cells.Methods The necrosis of HepG2 cells was evaluated by measurement of LDH release.The effects of chlorzoxazone on survival of HepG2 cells were assayed by MTT dyereduction.The effects of chlorzoxazone on cell apoptosis was analyzed by TUNEL method.The ultrastructure of HepG2 cells was observed by transmission electron microscope.Results Chlorzoxazone at concentrations of 100～500 ?mol?L-1 inhibited survival ratios of HepG2 cells in a dose-dependent manner significantly.Typical apoptotic changes were observed in HepG2 cells under the fluorescence microscope and transmission electron microscope.Apoptosis of HepG2 cells was induced after treatment of chlorzoxazone at concentrations from 100 ?mol?L-1 to 500 ?mol?L-1 for 48h,which showed obvious concentration-effect relationship.The apoptotic ratios of HepG2 cells were also increased when chlorzoxazone(100,200,300 and 500 ?mol?L-1) was treated for 24,48 and 72 h,which showed obvious time-effect relationship.Conclusion Chlorzoxazone inhibited HepG2 cells survival and induced cell apoptosis.

AIM To evaluate the integration method for analysis of voltage-dependent Ca2+-independent transient outward K+ currents (Ito) in pharmacology. METHODSThe inactivation phases of Ito were best fitted by the sum of two or three exponentials equations. The area under the raw current curves (AUC) was obtained by the integration of exponential equations. The AUC normalized to the cell capacitance represented the net K+ charge flow during any depolarized duration and was as the index for comparison. Calcineurin overexpression transgenic (TG) mice showed downregulation of Ito. These data were tested by the integration method. RESULTS AUC obtained from three or two exponentials fittings was calculated as: AUC=A1τ1+A2τ2+A3τ3+A0t-A1τ1e-t/τ1-A2τ2e-t/τ2-A3τ3e-t/τ3 or AUC=A1τ1+A2τ2+A0t-A1τ1e-t/τ1-A2τ2e-t/τ2. The 50% and 90% action potential duration (APD50, APD90) in ventricular myocytes of mice are about 10 ms and 30 ms, respectively. AUC at 10 ms (AUC50, AUC of 50% APD) and 30 ms (AUC90, AUC of 90% APD) in left ventricle cardiomyocytes of wild type (WT) and TG mice were normalized to the cell capacitance. The normalized AUC50 and AUC90 of WT group were significantly more than those of TG group, which was consistent to the prolongation of APD in TG mice and the previous published results(downregulation of components of Ito in TG mice). CONCLUSION The integration method was an ideal way for analysis of transient outward K+ currents in pharmacology.

Objective:To identify the epitope of mAb15A11 which is specific against RA associated autoantigen cartilage oligomeric matrix protein ( COMP ).Methods: A filamentous phage library displaying random linear dodecapeptides was used to mapping the epitope of mAb15A11.After three rounds of screenings,40 phage clones were selected at random and sequenced.The specificity of phages was confirmed by enzyme immunoassays.Homology search by ClustalW2 and structure analysis by PyMol to identified the epitope amino acid sequence.Western blot analysis of COMP and ELISA analysis of COMP-derived peptides were used to confirm epitope′s characterization.Results: After repeated screenings using bio-panning method, 2 clones were identified, which interacted specifically with mAb 15A11.Homology search did not find succession consensus sequence within COMP molecular,which indicated that the epitope was not linear.PyMol Structure analysis identified the rationality of conformational epitope.Western blot analysis and ELISA of EDTA-treated COMP further prove an conformational structure of the epitope recognized by mAb 15A11.ELISA analysis of COMP-derived peptides demonstrated both disulfide bonds between 229 C-243 C and 237 C-253 C and every epitope amino acid of 232 G,238 H,240 H,241 A,244 V,247 R and 251 R were essential to the binding of mAb 15A11 with COMP.Conclusion: In this study, the potential B cell antigentic epitopes of mAb 15A11 was identified by phage display library.The epitope amino acids sequence and char-acterization were also recognized.It may have important theoretical value for the study of reaction mechanism of COMP antibody and antigen and may also show application significance in the detection of rheumatoid arthritis.

Objective: To investigate the diagnosis and treatment of adult small bowel torsion in order to improve early diagnosis and improve prognosis. Methods: Clinical data of 43 cases of small bowel torsion from January 2012 to December 2017 were collected. All of them were confirmed by surgery as small bowel torsion. After admission, white blood cell count > 18 × 10⁹/L was found in 5 patients; and hemoglobin<100 g/L was found in 5 patients; abdomen CT examination in 39 patients showed 33 cases had intestinal torsion; 14 cases suggested possible mesenteric and root torsion. Results: All patients underwent surgical treatment. During the operation, there were 11 cases with intestinal torsion ≥ 720°; 13 cases underwent simple bowel torsion in surgical operation; 4 cases underwent decompression combined with reduction of the bowel; 1 case was treated with reduction and jejunostomy; and small intestine resection was performed for intestinal necrosis. Twenty-two patients had small bowel resection and jejunostomy was performed in 3 cases. The small intestine was resected 7-240 cm, with an average of about 66 cm. Conclusions Small bowel torsion should be diagnosed and operated as soon as possible. The suspected necrotic bowel should be removed and more healthy intestine should be reserved. The patient′s vital signs should be observed dynamically after operation to prevent the occurrence of intestinal necrosis and septic shock, to avoid excessive intestinal necrosis that would lead to postoperative short bowel syndrome, and to improve the patient's cure rate and reduce hospital stay.

Objective:To evaluate the effect of dexmedetomidine mixed with dexamethasone on efficacy of ropivacaine for popliteal sciatic nerve block in the patients undergoing ankle surgery.Methods:A total of 120 patients of either sex, aged 30-64 yr, with body mass index of 19.6-29.7 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective ankle surgery, were divided into 4 groups ( n=30 each) by a random number table method: control group (group C), dexmedetomidine group (group DD), dexamethasone group (group DM), and dexmedetomidine plus dexamethasone group (group DD+ DM). In group C, 0.5% ropivacaine 30 ml was injected around the popliteal sciatic nerve guided by ultrasound combined with a nerve stimulator.Dexmedetomidine 1 μg/kg, dexamethasone 10 mg and dexmedetomidine 1 μg/kg plus dexamethasone 10 mg were added to 0.5% ropivacaine in group DD, group DM and group DD+ DM, respectively.The analgesic time, consumption of sufentanil and adverse reactions were recorded after popliteal sciatic nerve block. Results:Compared with group C, the analgesic time was significantly prolonged, the consumption of sufentanil was reduced, and the incidence of nausea and vomiting was decreased in group DD, group DM and group DD+ DM ( P<0.05). Compared with group DD and group DM, the analgesic time was significantly prolonged, and the consumption of sufentanil was reduced in group DD+ DM ( P<0.05). No itching, drowsiness, hypotension, bradycardia or respiratory depression occurred in each group. Conclusion:Dexmedetomidine mixed with dexamethasone can effectively enhance the efficacy of ropivacaine for popliteal sciatic nerve block in the patients undergoing ankle surgery.

OBJECTIVETo investigate the expression of interleukin-9 (IL-9) in colon cancer tissues and its clinical significance.

METHODSImmunohistochenmistry and qRT-PCR were used to detect the expressions of IL-9 protein and mRNA in 92 colon cancer tissues and paired adjacent normal tissues. The correlation of IL-9 expressions with the clinicopathological features and prognosis of the patients was analyzed.

RESULTSIL-9 protein and mRNA expressions were significantly higher in adjacent normal tissues than in the colon cancer tissues ( < 0.001). In colon cancer patients, IL-9 expression was significantly correlated with TNM stage (=0.013), Ducks stage (=0.025) and lymph node metastasis (=0.004) but not with gender, age, tumor size, differentiation or hepatic metastasis ( > 0.05). The survival time of colon cancer patients with positive IL-9 expression was significantly longer than that of patients negative for IL-9 expression (=0.015).

CONCLUSIONSIL-9 expression is lowered in colon cancer tissues compoved with in the adjacent normal tissues. IL-9 expression is negatively correlated with TNM staging, Ducks staging and lymph node metastasis but positively with good prognosis, suggesting its important role in the tumor microenvironment of colon cancer.

Our previous work found that DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl]quinoline) was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II) (CDDP)-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU)-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.