BACKGROUND: Glucose metabolism disturbance, one of clozapine's adverse effects, has received increasing attention from endocrinologists. Insulin resistance is believed to be associated with clozapine-induced glucose metabolism disturbance. Does it have direct effects on secretion function of islets?OBJECTIVE: To investigate the effects of different concentrations of clozapine on the secretion function of pancreatic islets in vitro.DESIGN: A completely randomized controlled design for the experimental study.SETTING: Department ofPsychiatry, People's Hospital of Wuhan University.MATERIALS: The experiment was conducted in the Laboratory Center of Stomatology Hospital of Wuhan University from September 2003 to January2004. Three healthy male Wistar rats of clean grade were used.METHODS: [1] Classical collagenase digestion method was used to isolate and purify the rat islets of Langerhans. [2] Hank's solution containing 2 g/L bovine serum albumin and 3.3 mmol/L glucose was added for preincubation for 30 minutes. The supernatant was removed. The wells were divided into five groups with 12 wells in each group. The control group was added with 1 g/L dimethyl sulphoxide (DMSO) and 3.3 mmol/L or 16.7 mmol/L glucose, 1 mL per well. The four experimental groups were added with 1 mL 0.2 μmol/L, 1 μmol/L, 5 μmol/L, or 10 μmol/L clozapine apart from the above DMSO and glucose. Six wells in each group were incubated for 1 hour, and another six wells were incubated for 4hours. The supernatants of the different groups were collected and stored at-20℃ in the refrigerator for later testing. The above procedures were repeated three times. The insulin released into the medium supernatant was examined by radioimmunoassay. [3] One-way ANOVA was used to compare the differences between the experimental groups and control group; LSD-t test was used for multiple comparison.MAIN OUTCOME MEASURES: The level of insulin secretion in the supernatants in culture solution containing 3.3 mmol/L or 16.7 mmol/L glucose which was incubated for 1 hour or 4 hours.RESULTS: [1] At 3.3 mmol/L glucose, no difference in insulin secretion was found between the four clozapine groups and control group after 1-hour incubation (P ＞ 0.05). After 4-hour incubation, the level of insulin in clozapine groups decreased significantly [(0.92±0.4), (1.02±0.3),(1.06±0.4), (0.74±0.2), (1.66±0.4) mU/IEQ, P ＜ 0.05]. There was no significant difference in the volume of insulin among the four clozapine groups with different concentrations (P ＞ 0.05). [2] At 16.7 mmol/L glucose, the level of insulin at the four concentrations of clozapine did not differ from that of control group either after 1 hour or 4 hours of incubation (P ＞ 0.05).CONCLUSION: Clozapine inhibits basal insulin secretion, but the effect is not correlated with its dosage.

In recent years,the United States analyzing the aging of the population brought by the increase in cardiovascular diseases such as medical equipment and its impact on the U.S. market-oriented role,combined with the present condition of population and medical device market of China,the trend of aging is pointed out and that there is a great potential market of medical device for cardiovascular disease in China,but some problems still exist,such as high price,low public acceptance,etc. According to relevant policies,corresponding suggestions were proposed for domestic medical device companies to enhance their R&D capability and adaptability to the medical system reform.

Objective To report operative course and relative complications in a group of patients who underwent Excessive Pressure Regulation System (Ex-PRESS) glaucoma shunt implantation in the real world,and discuss the ralated factors and possible interventions in clinical practice.Methods Preferred Ex-PRESS glaucoma shunt implantation were performed on 11 eyes with deverse types of glaucoma.Operative course and relative complications were analyzed from recorded tapes and documents.The correlations between complications,types of glaucoma,and previous procedures were analyzed,the complications were appropriately managed.Results 11 patients with diverse types of glaucoma who underwent Ex-PRESS glaucoma shunt implantation were recruited for the study.Among them,2 patients had combined phacoemulcification surgery,1 patient had repeat shunt implantation.During the procedure,1 patient had dislocated shunt into anterior chamber;1 patient had shunt entirely inserted into anterior chamber with plunger.4 patients had hypotony and flat anterior chamber,2 of them had hyphema,2 experienced subchoroid detachment.1 patient had intraocular lens pupil clamping after combined cataract and glaucoma surgery;4 cases had flat filtering blebs and uncontrolled intraocular pressure during the follow-up period,2 of them had blocked drainage and proliferative anterior synechia around the head,which was found in the patients with primary angle-closure glaucoma who had previous operation history.The common long-term complication was external ostium occlusion (4/11).The complications of drainage are related to the type of glaucoma and the history of operation.Conclusions Other than the complications which present commonly in trabeculectomy procedure,there were some complications related to the Ex-PRESS glaucoma shunt.History of ocular surgery,surgical techniques and the type of disease were associated with the incidence of complications.

Objective:To collect the current status and healthcare needs of people living with HIV (PLHIV) in China during the COVID-19 outbreak to inform quick response from government and communities.Methods:During February 5 th to 10 th, 2020, a national anonymous survey was conducted using an online questionnaire among PLHIV at least 18 years of age and had started antiretroviral treatment (ART) to collect the information on COVID-19 prevention, HIV-related health services and the needs on psychosocial support. Current status and needs of people living with HIV were analyzed in Hubei and other regions. Results:A total of 1 014 valid questionnaires were collected, with PLHIV respondents cross the country. The survey revealed that 93.79% of the respondents could obtain information regarding the prevention of COVID-19 from their communities or villages. Respondents were concerned with HIV-specific protective measures and personal protective equipment shortage. 32.64% of all respondents were not carrying sufficient antiretroviral medicines (ARVs) to meet the needs under traffic and travel restrictions, and some could face stock-outs in the coming month. In Hubei province where 53 respondents needed ARV refill, 64.15% reported difficulty accessing ARV due to the "blockage" . 28.93% respondents were in need of sociopsychological support, and 85.31% anticipated further improvement of the out-of-town ARV refill process from the government.Conclusion:PLHIV wants to know HIV-specific protective measures against COVID-19 outbreak. PLHIV who returned to their home-towns and affected by the lock-downs reported challenges with refills. We should undertake a more systematic study on impacts of the COVID-19 on PLHIV to develop preparedness capacity for future public health emergency.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.