OBJECTIVETo investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.

METHODSWhole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.

RESULTSMidazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.

CONCLUSIONMidazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.

Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; drug effects ; HEK293 Cells ; Humans ; Midazolam ; pharmacology ; Mutation ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology

Chromatography, High Pressure Liquid ; methods ; Humans ; Neonicotinoids ; Pyridines ; blood

Retinal vessel is the only visible vessels in human body and systemic microvascular lesions could be evaluated by the degree of retinal vessels. ln this article, the progress of retinal vascular caliber measuring method and its influencing factors were briefly reviewed.

Objective To investigate the effects ofTiaogan Lipi Huaji Prescription combined with high intensity focused ultrasound (HIFU) for the treatment of locally advanced pancreatic cancer.Methods Randomized, parallel controlled study was designed to select 60 patients with locally advanced pancreatic cancer, which were divided into treatment group and control group by random number table method, 30 cases in each group. The treatment group was givenTiaogan Lipi Huaji Prescription, one dose per day, twice a day, orally, 28 d as a treatment course, 6 courses in total; at the same time, HIFU was given to the treatment group, 30–60 min each time, once every other day, 2–3 times each week, and the tumor was completely covered for 2 times. The control group was given gemcitabine 1000 mg/m2, intravenous infusion, 1st, 8th d, 21–28 d for a cycle, a total of 6 cycles. The clinical benefit response, QOL-C30 score, survival status, progression-free survival (PFS), CA199 and CEA levels were observed.Results Clinical benefit rates of treatment group and control group were: the treatment group 1, 3, 6 months clinical benefit rate was 64.29%, 63.16%, and 50.00%, respectively; control group clinical benefit rate was 48.15%, 40.00%, and 44.44%, respectively, with statistical significance (P<0.05). The difference of QOL-C30 score between the two groups at the same time wasstatistically significant (P<0.05). During the treatment 1 to 6 months, CA199 in the two groups showed a downward trend, without statistical significance (P>0.05). CEA levels in the treatment group were lower than those in the control group at the same time with statistical significance (P<0.05), except for 2 and 6 months. The survival rates of treatment of 3, 6, and 12 months in the treatment group were 82.14%, 46.42% and 32.14%, respectively, and were 96.67%, 59.32% and 37.04%, respectively in the control group, without statistical significance (P>0.05). The survival time of the treatment group was (253.90±18.06)d in the control group and (246.77±17.31)d in the control group, without statistical significance (P>0.05). PFS was (136.73±16.22)d in the treatment group and (145.77±19.74)d in the control group, without statistical significance (P>0.05).ConclusionTiaogan Lipi Huaji Prescription combined with HIFU for the treatment of locally advanced pancreatic cancer has certain clinical efficacy, which can improve patients' life quality.

OBJECTIVE To observe the effects of glycogen synthase 3β (GSK-3β) in the regula-tion of NLRP3 inflammasome activation after acute myocardial infarction (MI) in Sprague Dawley(SD) rats. METHODS Ligation of the left anterior descending (LAD) in SD rats was used to establish an acute myocardial infarction model. SD rats were randomly divided into 3 groups (n=10, each group):sham group,MI group,and MI+SB group:the GSK-3β inhibitor(SB216763)was given 1 h by intrave-nous injection(0.6 mg·kg-1·d-1)before surgery.The serum and heart tissue were collected to measure lactate dehydrogenase (LDH) and IL-1β content and mRNA and protein levels of NLRP3, ASC, Cas-pase-1,IL-1β and GSK-3β after 2 days and 7 days operation,respectively.RESULTS The serum levels of LDH and IL-1β in the MI group were significantly higher than those in the sham group(P<0.01),and the MI+SB group was obviously lower than the MI group(P<0.01).In addition,mRNA and protein levels of NNLRP3, ASC, Caspase-1, IL-1β and GSK-3β expressions in MI group were clearly increased (P<0.01) compared with those in sham group.These indicators were significantly decreased in SB+MI group (P<0.01). Interestingly, the indicators were all higher at 7 days than 2 days. CONCLUSION GSK-3β inhibition induces cardioprotection via attenuating the activation of NLRP3 inflammasome after the acute myocardial infarction in rats.

Objective To evaluate the efficacy of L?Arabinose for bowel preparation before colonos?copy. Methods A total of 170 patients who underwent colonoscopy were randomized into 2 groups. The ex?perimental group (n=85) used L?Arabinose for bowel preparation, while the control group (n=85) used polyethylene glycol electrolyte solution ( PEG?ELS ) . The degree of comfort, adverse effects, and the visibility during colonoscopy were observed. Results Premedication of L?Arabinose for bowel preparation yielded to more comfort ( U=-4?349,P=0?000) , less adverse effects (χ2=29?27,P=0?000) , and similar visibility during colonoscopy ( U=-0?875,P=0?381) compared with PEG?ELS. Conclusion L?Arabinose is safe, comfortable, and effective for bowel preparation before colonoscopy.

OBJECTIVETo investigate the effect of compound Coptidis Rhizoma capsule (CCRC) on unbalanced expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway in rats with early diabetic nephropathy (DN), and discuss CCRC's effect on DN rats with early diabetic nephropathy and its possible mechanism.

METHODDN model rats were established by injecting streptozotocin (STZ). The rats were randomly divided into seven groups: the normal group, the model group, the enalapril treatment group, the xiaoke pill treatment group and three CRCC treatment groups. They were orally administered once a day for five weeks. The fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), insulin (Ins), 24 h urinary protein (24 h Upro) and 24 h urinary microalbumin (24 h UmAlb) were tested. The pathological changes in renal tissues were examined by optical microscopy. Immuno- histochemical measures were used to detect the expressions of TGF-β1, BMP-7, Smad2/3, Smad1/5, and Smad7 protein, and RT-PCR was used to detect TGF-β1 mRNA and BMP-7 mRNA in renal tissues.

RESULTCompared with model group, BUN, Scr, Ins, 24 h Upro and 24 h UmAlb levels decreased at different degrees in CCRC treatment groups; the abnormal pathomorphology in renal tissue was improved; immunohistochemistry results showed that the expression of TGF-β1 and Smad2/3 were reduced, while the expression of BMP-7, Smad1/5 and Smad7 increased in CRCC treatment groups; the expression of TGF-β1 mRNA were reduced, but the expression of BMP-7 mRNA had no obvious change in CRCC treatment groups.

CONCLUSIONCRCC can improve the early renal function, delay the progression of chronic renal pathology and maintain the dynamic balance of TGF-β1/BMP-7 expression in renal tissues of DN rats. The mechanism may be related to down-regulation of renal TGF-β1 and up-regulation of BMP-7 through Smad signaling pathway.

Animals ; Bone Morphogenetic Protein 7 ; genetics ; metabolism ; Coptis ; chemistry ; Diabetic Nephropathies ; drug therapy ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Signal Transduction ; drug effects ; Smad Proteins ; genetics ; metabolism ; Transforming Growth Factor beta1 ; metabolism

A new teaching method was developed in the curriculum of Harmful Microorganisms Control Technology.It is characterized by students’ self-learning followed by student’s instruction.Both students and teacher have succeeded in this model after four stages of practice,in which a pleasant learning atmosphere was created in the classroom.An effective interaction between teacher and students was achieved.Students are viewed as main objects in the classroom and they are encouraged to ask questions,to formulate their own ideas,or to find things out for themselves.Thus,students’ abilities including presentation,communication,competition,and cooperation were enhanced.By adapting their role to the new teaching method,teachers have also improved their teaching skill and strategies.

Objective:To investigate the clinic effect of r-MHT and hematoma aspiration on the traumatic intracerebral hematoma.Methods:89 cases with traumatic intracerebral hematoma were given hematoma aspiration,47 of them were given r-MHT and hematoma aspiration,the clinic effect on the 1st,7th,14th day after treatment were evaluated by NIHSS,the hematoma volume before treatment on the 1st,7th,14th day after treatment were counted by Dotian formula.Results:The effective rate of treatment group was 93.6％,which was significantly higher than that of the control group (P＜0.05).The NIHSS score of treatment group was significantly higher than that of the control group(P＜0.05) on the 1 st day,1st,2nd week after treatment (P＜0.05).Conclusion:r-MHT and hematoma aspiration couldn effectively reduce the brain damage,improve the patient's neurological fumction in treating traumatic intracerebral hematoma.

Objective To investigate whether preoperative proton pump inhibitor (PPI) would increase the risk of bacteremia after endoscopic ultrasonography guided fine needle aspiration (EUS-FNA).Methods Dogs were randomly divided into experimental group ( n = 8) to take 20mg of omeprazole orally twice a day for 3 days before EUS-FNA, and control group (n = 10) to take placebo.EUS-FNA was performed to puncture the pancreas, and blood was collected before and after the procedure for culture.Bacteremia incidence of the two groups were compared.Results Bacteria culture was positive in 11 edogse.After excluding contamination, 1 dog in experimental group and 3 in control group were authentical bacteremia.There was no significant difference on the incidence of bacteremia between 2 groups based on Fisher test ( P = 0.383).Conclusion Aplication of PPI before EUS-FNA is not likely to increase the incidence of bacteremia.