Cl - ,ClC 3 chloride current can be inhibited by chloride channel inhibitor DIDS?tamoxifen and extracellular ATP. ClC 3 is modulated by cell volume and regulated by PKC.The present review discusses the expression, eletrophysiology,molecular properties,signal transduction of such channel.

AIM To study the effects of endothelin 1(ET 1) on ClC 3 chloride channel protein expression in cultured bovine cerebrovascular smooth muscle cells (CSMC). METHODS Cell culture and Western blot. RESULTS ① The endogenous ClC 3 expression was found in basilar artery, middle cerebral artery, and microvessel; ② The molecular weight of expressed ClC 3 chloride channel protein was about 95 ku; ③ ET 1 enhanced ClC 3 protein expression which was inhibited by nifedipine and SK&F96365. Cyclopiazonic acid(CPA) increased the expression of ClC 3 protein in a concentration dependant manner, and enhanced ET 1 effect on this protein expression. CONCLUSION ET 1 stimulated ClC 3 chloride channel protein expression in cultured bovine cerebrovascular smooth muscle cells. The intracellular Ca 2+ plays an important role on signal transduction pathway in ClC 3 protein expression process.

Objective To evaluate timing of tracheal intubation impact on the therapeutic effect of acute severe organophosphate poisoning( ASOPP) patients. Methods Retrospectively analyze 82 ASOPP patients with respiratory failure ( RF). The patients were divided into timely tracheal intubation group(n = 42) and delay tracheal intubation group (n =40) ,and compare the therapeutic effect of these two groups. Results Compared with timely tracheal intubation patients and delay tracheal intubation patients,total time of mechanical ventilation,hospital day decreased significantly (P<0.01) ,cure rate increased significantly (P<0.01) ,but complications [intermediate myasthenia syndrome (IMS) .pulmonary infection,cardiac damage and so on] had no significant difference(P>0.05). Conclusion It was exact that the therapeutic effect of timely tracheal intubation on rescuing the ASOPP patients, and the best time to tracheal intubation was in RF early period.

Objective To observe the effect of bisoprulol on malignant ventricular arrhythmia (MVA) and heart rate turbulence (HRT) in ambulatory electrocardiogram monitoring for twenty-four hours in patients with unsta-ble angina pectoris (UAP). Methods 40 UAP patients with premature ventricu]ar beats were observed. All patients were examined with ambulatory electrocardiogram monitoring for twenty-four hours before and after bisoprolol (5mg, Qd) was administered for 7 days. The number of patients with MVA、turbulence onset (TO) and turbulence slope (TS) were analyzed. Results After bisoprolol was administered for 7 days in patients with UAP,the number of pa-tients with MVA decreased by 14.2%. TO decreased and TS increased, and HRT was improved. Conclusions HRT had clinical prognostic value for malignant ventricular arrhythmia and sudden death in patients with UPA. Bisoprolol can improve HRT and reduce the incidence of MVA.

Objective To investigate the effects on anti-expression of Osteopontin (OPN) by an antisense oligodeoxynucleotide (ASODN) targeting to low free energy region of OPN mRNA and its effects on the proliferation and apoptosis of human breast carcinoma cell line MCF-7. Methods Designing and synthesizing an ASODN based on minimum free energy algorithm in vitro,which targets to the low free energy region of OPN mRNA. Transfecting it into breast carcinoma cell line MCF-7 which expresses OPN in high level. The cell proliferation-inhibitory rate was determined by MTT method;The morphologic change was observed through transmission electron microscope (TEM);The OPN mRNA expression level was checked by RT-PCR method;Cell cycle and apoptosis rate were detected by flow cytometry (FCM) after transfection respectively. Results OPN ASODN inhibited the proliferation of the cells by a time and concentration dependent manner (P

AIM To study the effects of protein tyrosine kinase inhibitor and protein tyrosine phosphatase inhibitor on cultured bovine cerebrovascular smooth muscle cells (CSMC) Ca 2+ store operated Ca 2+ influx. METHODS Cell culture and single intracellular free Ca 2+ concentration was measured in fura 2/Am flueorescence probe by MetaFluor Fluorescence ratio imaging system. RESULTS (1) protein tyrosine kinase inhibitor (genistein,2.5,5,10 ?mol?L -1 )decreased Ca 2+ influx significantly induced by endothelin 1(ET 1),ATP,cyclopiazonic acid(CPA) in concentration dependent manner; (2) Protein tyrosine phosphatase inhibitor (vanadate,2,4,8 ?mol?L -1 ) increased Ca 2+ influx significantly induced by ET 1,ATP,CPA in concentration dependent manner. CONCLUSION Protein tyrosine kinase inhibitor and protein tyrosine phosphatase inhibitor have effects on Ca 2+ store operated Ca 2+ influx induced by ET 1, ATP, CPA. Protein tyrosine phosphorylation participats in the signal transduction of Ca 2+ store operat Ca 2+ influx in cerebrovascular smooth muscle cells.

AIM: To explore the effects of exendin-4 (EX-4) on endoplasmic reticulum stress (ERS)-mediated insulin resistance in the 3T3-L1 adipocytes.METHODS: In vitro 3T3-L1 pre-adipocytes were differentiated into adipocytes, and the cells were treated with tunicamycin (TM), tauroursodeoxycholic acid (TUDCA) or EX-4, respectively.The cell viability was measured by MTT assay.The glucose consumption was determined by glucose oxidase assay to evaluate insulin sensitivity of the 3T3-L1 adipocytes with different interventions.The protein levels of p-Akt, Akt and endoplasmic reticulum stress markers, including inositol requiring enzyme-1 (IRE1), p-IRE1, JNK, p-JNK, protein kinase R-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic initation factor 2 alpha (eIF2a), p-eIF2a, activating transcription factor-6(ATF-6) were detected by Western blot.RESULTS: The insulin-stimulated glucose consumption and the protein level of p-Akt were inhibited by TM at 5 mg/L for 5 h (P<0.05), while they were increased when the cells were treated with TUDCA at 1 mmol/L or EX-4 at 100 nmol/L for 24 h (P<0.05).The effects above induced by TM (5 mg/L for 5 h) were also blunted by pretreating with TUDCA at 1 mmol/L or EX-4 at 100 nmol/L for 24 h (P<0.05).The protein levels of ERS markers such as p-IRE1, p-JNK, p-PERK, p-eIF2a and ATF-6 were significantly increased by treating with TM at 5 mg/L for 5 h, whereas 24 h pre-treatment with TUDCA or Ex-4 alleviated the ERS of the 3T3-L1 adipocytes induced by TM.The expression of total IRE1, JNK, PERK and eIF2a was not changed in different groups.CONCLUSION: Exendin-4 improves endoplasmic reticulum stress mediated insulin resistance in 3T3-L1 adipocytes.

Objective To investigate the effect of dexmedetomidine (DEX) on early cognitive dysfunction after hepatic lobectomy by regulating microRNA-182-5p/brain-derived neurotrophic factor (miR-182-5p/BDNF) axis in rats. Methods Sixty specific pathogen free(SPF) SD male rats were randomly divided into control group, model group, DEX low dose treatment group (25 μg/kg), DEX medium dose treatment group (50 μg/kg), DEX high dose treatment group (100 μg/kg), and DEX+ miR-182-5p mimic group, with 10 rats each group. The rats in the model group were anesthetized with sevoflurane and then underwent partial hepatectomy. The rats in DEX low-, medium-, and high-dose treatment groups were injected with DEX (25, 50, and 100 μg/kg) intraperitoneally and inhaled sevoflurane for 30 minutes before partial hepatectomy. DEX + miR-182-5p mimic group rats were treated with the same method as DEX high-dose treatment group, and miR-182-5p mimic (50 μg) was injected through tail vein every 2 days after operation. Rats in the control group were intraperitoneally injected with 2 mL/kg normal saline, then anesthetized by inhalation of sevoflurane for 2 hours. Morris water maze test and Neurological Severity Scale (NSS) were used to evaluate the postoperative cognitive function and neurological function damage of rats in each group. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the level of miR-182-5p in rat hippocampus. The protein expression level of BDNF in hippocampus was determined by western blot. The binding region of miR-182-5p and BDNF 3'UTR was analyzed by bioinformatics, and the targeting relationship between miR-182-5p and BDNF was detected by dual luciferase reporter gene assay. Results The results showed that compared with the control group, the escape latency of Morris water maze test in the model group was significantly prolonged at 2 to 5 days after operation (P < 0.05), and the NSS scores in the model group were significantly increased at 1, 3 and 7 d after operation (P < 0.05). Compared with the model group, the rats in the DEX treatment group had significantly shorter escape latency of Morris water maze test at 2 to 5 days after operation, and significantly lower NSS scores at 3 and 7 days after operation in a dose-dependent manner (P < 0.05). Compared with the DEX high-dose treatment group, the DEX + miR-182-5p mimic group had significantly prolonged escape latency of Morris water maze test at 2 to 5 days after operation, and significantly increased NSS scores at 3 and 7 days after operation (P < 0.05). Compared with the control group, the level of miR-182-5p in the hippocampus of the model group was significantly increased, and the level of BDNF was significantly decreased (P < 0.05). Compared with the model group, the DEX treatment group had a significant reduction in the level of miR-182-5p and a significant increase in the level of BDNF in the hippocampus after surgery in a dose-dependent manner (P < 0.05). Compared with the DEX high-dose treatment group, the DEX + miR-182-5p mimic group had a significant increase in the level of miR-182-5p and a significant reduction in the level of BDNF (P < 0.05). The dual luciferase reporter gene assay verified the targeted binding of miR-182-5p to BDNF. Conclusion DEX improves early cognitive dysfunction in rats after hepatic lobectomy by inhibiting miR-182-5p and increasing BDNF levels.

Objective To assess the efficacy of transvaginal three-dimensional power Doppler ultrasound(3D-PDU)in predicting pregnancy outcomes after mild and moderate transcervical resection of adhesion(TCRA).Methods Sixty-six patients with mild and moderate intrauterine adhesions(IUA)who had fertility issues and underwent TCRA surgery in Tongde Hospital of Zhejiang Province from January 2020 to December 2021 were chosen,31 successful pregnancy patients were included in pregnancy group,and 35 unsuccessful pregnancy patients were included in non pregnancy group.3D-PDU examination was performed before and 3 months after surgery.The measurements of endometrial thickness(ED),uterine volume(EV),endometrial vasculogenesis index(VI),blood flow index(FI),and vasculogenesis-blood flow index(VFI)were taken.The pregnancy was followed up for 1 year to observe the prognostic value of the above related indicators on postoperative pregnancy.Results The ED,EV,VI,FI and VFI levels of patients post-operation were significantly higher than those before the operation(P＜0.05),the improvement of pregnant group patients was better than that of non pregnant group patients(P＜0.05),and area under the receiver operating characteristic curve were 0.80,0.84,0.68,0.65 and 0.88 respectively.Conclusion 3D-PDU can effectively predict the postoperative pregnancy outcome of TCRA in patients with mild to moderate IUA by measuring ED,EV,VI,FI,and VFI before and after surgery,providing reference for efficacy evaluation and guiding subsequent treatment.

Objective To investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer.Methods A total of 48 BRCA mutation carriers(16 with BRCA1 and 32 with BRCA2)and 78 age-matched non-carriers were included in this study.Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues.The FOXP3 RNA expression in 39 BRCA1,36 BRCA2,and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombin-ation deficiency scores were evaluated to validate the immunohistochemistry results.Results The FOXP3 positive rate was 43.8%(7/16)in BRCA1 mutation carriers,59.4%(19/32)in BRCA2 mutation carriers,and 9.0%(7/78)in non-carriers.The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers(P=0.002;P<0.001).TCGA-BRCA results showed that the FOXP3 RNA level in BRCA1/2 mutant breast cancer was significantly higher than that in non-carriers(P=0.02,P=0.004).The FOXP3 RNA level was positively correlated with the homologous recombination deficiency score(Spearman R=0.30,P<2.2e-16).Conclusion Patients with BRCA1/2 mutant breast cancers have higher FOXP3expression than non-carriers,and may be more sensitive to immunotherapy.