Objective To analyze the characteristics of methadone-related poisoning cases and provide a reference for forensic identification.Methods A total of 71 cases of methadone-related poisoning re-ported from 1998 to 2023 in China and 26 cases of methadone-related deaths reported from 2013 to 2018 in Italy were retrieved from databases including PubMed,Wanfang and CNKI.The general infor-mation,forensic pathological and toxicological characteristics were analyzed.Results Among the 71 methadone-related poisoning cases in China,there were 54 cases(76.06%)of poisoning without death and 17 cases(23.94%)of death from poisoning.There were 54 male cases(76.06%),and 51 cases(71.83%)aged 19 to 39 years old.There were 35 cases(49.30%)of poisoning caused by methadone alone,and 32 cases(45.07%)were poisoning caused by methadone combined with other substances or drugs including heroin and benzodiazepines.Most of the poisoned showed coma,respiratory depres-sion and miosis.Signs of asphyxia were often found by autopsy.The mass concentration of methadone detected in the blood of 6 deceased ranged from 0.112 to 3.000 mg/L.Among the 26 methadone-related deaths in Italy,22 cases were male(84.62%).There were 6 cases(23.08%)caused by methadone alone,and 20 cases(76.92%)died from methadone combined with other substances or drugs.The mass concentration of methadone in blood ranged from 0.181 to 4.059 mg/L.Conclusion The propor-tions of poisoning cases caused by methadone alone and methadone combined with other substances or drugs are comparable in China.The majority of deceased caused by methadone poisoning shows typi-cal triad of coma,respiratory depression and miosis,which helps forensic experts determine the cause of death related to methadone.Additionally,it is necessary to increase the routine testing of the con-centration of methadone and its combined substances or drugs in deceased,and collect data for the in-terpretation of the results of related cases.

The cobalt sulphide nickel ternary material(NiCo2S4)prepared by hydrothermal method in this work was combined with multi-walled carbon nanotubes(MWCNT)for constructing an electrochemical sensor for quantitative detection of rutin.The morphology and crystal of the electrochemical materials were characterized by scanning electron microscopy and X-ray diffractometer,and the electrochemical behavior of the glassy carbon electrode(GCE)modified with NiCo2S4/MWCNT composites was investigated.The experimental results showed that the electrochemical redox process of two electrons and two protons occurred on the surface of modified electrode NiCo2S4/MWCNT/GCE.Under the optimized conditions,the linear range for detection of rutin by square-wave voltammetry(SWV)using this sensor was 0.06-14.8 μmol/L and the detection limit was 14.3 nmol/L.The electrochemical sensor was sensitive,simple and low-cost,with good reproducibility and reliable stability,and could be used for detection of rutin in real samples such as compound rutin tablets and color chrysanthemi tablets,with spiked recoveries of 99.5%-102.0%.

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

【Objective】 To explore the attention and its relationship with anxiety in patients with glaucoma.【Methods】A prospective case-control study was done on 20 primary open angle glaucoma（POAG）patients and 28 normal subjects. Response time with and without disturbance was examined by using Matlab software. Anxiety was assessed with State Anxiety Inventory（S- AI）and Trait Anxiety Inventory（T- AI）. Response time and inhibiting effects between two groups were compared by t test and Mann- Whitney U test ，respectively. Spearman correlation analysis was applied to determine the relationship between inhibiting effect and anxiety.【Results】The scores of S-AI and T-AI in POAG group were significantly higher than those in normal subjects（t = -3.912，P = 0.001；t = -2.127，P = 0.042）. There were statistically significant differences in the scores between groups even after gender was adjusted by using line regression model（β = 9.449，P = 0.000；β = 7.089，P = 0.018）. The average response time in POAG group（0.84±0.15）s was significantly longer than that in normal participants（0.75±0.14）s（t = -2.127，P = 0.039）. The difference was statistically insignificant when gender was adjusted by using line regression model（β = 0.063，P = 0.210）. The inhibiting effect in POAG group（0.126±0.089）s was longer than that in normal subjects（0.085±0.066）s（Z = -1.715，P = 0.086）. The inhabiting effect wasn′ t statistically significantly correlated with scores of S- AI and T- AI（P＞0.05）.【Conclusions】Patients with POAG showed severer anxiety than normal subjects but attention was comparable. There was no significant correlation between attention and anxiety.

OBJECTIVETo describe the characteristics and factors associated with long-term retention for methadone maintenance treatment (MMT) patients.

METHODSThis study was conducted in eight MMT clinics located in Sichuan, Yunnan, Guangxi, Guizhou and Zhejiang provinces. Five hundred and thirty-nine MMT patients who enrolled in MMT clinics in 2004 and retained in treatment by June 2010 were selected as study subjects. Chi-square tests were used to compare the demographics and drug abuse history at enrollment and treatment characteristics during the follow-up period between continuous treatment patients and discontinuous treatment patients.

RESULTSOf the 539 patients, 110 (20.4%) were continuous treatment patients whereas 429 (79.6%) were discontinuous treatment patients. Of these 429 discontinuous treatment patients, 84.1% (361/429) had 2-4 treatment episodes whereas 15.9% (68/429) had 5 or more episodes during follow-up period. When continuous treatment patients were compared with discontinuous treatment patients, living with family members or friends (88.2% (97/110), 78.5% (337/429)), age of first drug use under 25 (61.8% (68/110), 71.3% (306/429)), low urine morphine positive test results (67.3% (74/110), 38.2% (164/429)) and living within 5 kilometers of the MMT clinic (72.7% (80/110), 61.3% (263/429)) were positively associated with higher possibility of continuous treat retention (P < 0.05). Demographics and drug abuse characteristics at enrollment, including gender, age, employment status, family relationship, injection, needle sharing, criminal behavior, contacts with drug users, MMT daily dosage and family members receiving MMT were not significantly associated with treatment retention (P > 0.05).

CONCLUSIONIllicit drug use during the treatment and longer distance travelling to MMT clinic might have negative impact on patients' continuous treatment retention. Mobile MMT vehicles and expanded MMT service sites could be introduced to improve compliance of treatment retention of MMT patients.

Adult ; Female ; Humans ; Longitudinal Studies ; Male ; Methadone ; administration & dosage ; therapeutic use ; Patient Compliance ; statistics & numerical data ; Substance-Related Disorders ; drug therapy ; Treatment Outcome

Objective To evaluate the long-term effectiveness of the first set 8 methadone maintenance treatment (MMT) clinics in China. Methods Repeated cross-sectional surveys were conducted on the first month after the enrollment and 5 years later,among drug users who received MMT,using a standard questionnaire.Data on demographic characteristics,HIV-related high-risk bchaviors,criminal records associatcd with drug use and related family/social functions were collected and analyzed.Results There were 252 and 195 participants being interviewed at the baseline and the 5-year surveys,respectively,.Of them,66 participants were involved in both surveys.There was no significant differences on factors as ethnicity,level of education,working status,marital status and living status (P＞0.05) between the baselinc and the 5-year surveys.Compared with data from the baseline survey,participants' behavior on drug abuse (100.0％ vs.24.1％,P＜0.001 ),needle sharing behavior ( 19.4％ vs.0.0％,P ＜ 0.001 ),and exchanging sex for drugs ( 34.5 ％ vs.0.0％,P＜0.001 ) had significant decreases at the 5-year survey.Rates on condom use ( 10.6％ vs.25.0％,P=0.004),and having jobs (27.8％ vs.47.7％,P＜0.001 ) had been improved significantly,while self-reported criminal cases related to drug use (15.1％ vs.1.5％,P＜0.001) and the contacts with drug users (88.9％ vs.31.3％,P＜0.001) had been significantly reduced after joining the MMT program.Conclusion MMT could play an active role in reducing the HIV-related high-risk behaviors,criminal cases associated with drug abuse as well as enhancing the family and social functions of the MMT patients.Providing high quality service to the MMT clinic and trying to keep the drug users stick to the program remain difficult.It was also important to improve the training programs for staff working at the MMT clinics.

Objective To develop and optimize the molecular detection assays for recently identified human coronavirus (HCoV) infection.Methods Based on the 208 base pair(bp) sequence of novel HCoV reported by HPA of UK,we designed and obtained several pairs of primer(F-1,R-1 ;F-2,R-2) and Taqman probes(TZ1,TZ2) for detection of novel HCoV.Two of probes were modified with LNA(LNA-TZ1,LNA-TZ2).Then,RT-PCR and various real time RT-PCR assays were developed and optimized in this study.We also compared our assays with the real time RT-PCR assays reported recently by Europe team based on upE or ORF1b target.Results The RT-PCR or real time RT-PCR assays for novel HCoV were developed without cross-reactivity with other HCoV and several common respiratory viruses using clinical specimen panel.The analytical sensitivity of assays were less than 50-500 copies per reaction and the detection was improved when Taqman probe modified with LNA-tagged,compared to no LNA-tagged in real time RT-PCR assays.The upE and LNA-TZ1 based assays were better than others.Conclusion The molecular detection sensitivity and specificity of TaqMan-based real time PCR assay could be improved when probe tagged with LNA.The upE or LNA-TZ1 based real time RT-PCR assay was recommend for detection of novel HCoV.This study laid a foundation for improving the performance of novel HCoV detection.

Objective To determine the adherence to and its determinants of methadone maintenance treatment (MMT) among heroin addicts in Dehong prefecture in Yunnan province from 2005 to 2009. Methods A dynamic cohort analysis was conducted with the time of treatment initiation as the time of cohort entry, to calculate the proportion of adhering to the treatment at different time points after initiation of the treatment, and to study the determinants of adherence.Results A total of 3758 had been treated. Among them, 95.8% were males, 75.8% aged between 20-39 years, 90.4% were peasants or unemployed, 57.0% were ethnic minorities, 35.0% were single and 55.5% were married with spouses, 43.9% were illiterate or educated at most primary school. The age of first using drugs averaged at 23.93 years. About 96.3% of the study subjects had used heroin and 21.7% were HIV-infected. The minimum time under MMT was less than 1 month and the maximum 61 months. The median methadone dose at first delivery was 25 ml, with the minimum 1 ml and the maximum 330 ml. By the end of the study or observation period, a total of 1798 patients had withdrawn from treatment and 1960 were still under treatment. The proportions of adherence to or still being under the treatment after 1,3,6,9, 12,24, 36,48 and 60 months treatment were 0.919,0.847,0.756, 0.690, 0.637, 0.519, 0.417, 0.360 and 0.321, respectively. Multiple regression analysis using Cox proportional hazard model indicated that withdraw from the methadone maintenance treatment was significantly associated with location of the treatment clinics, year of treatment initiation, marital status, HIV infection status, methadone dose of first delivery and the result of last urine test for heroin use. Conclusion MMT attendants in Dehong prefecture had a relatively high withdraw rate and low adherence rate. More efforts are needed to provide tailored counseling and education to MMT attendants, to provide family and community support, appropriate methadone dose at first delivery, and to better coordinate with local police department.

Objective To determine the incidence and risk factors of HIV infection among heroin addicts receiving methadone maintenance treatment(MMT)in Dehong prefecture,Yunnan province.Methods All heroin addicts who were HIV negative at the initiation of MMT in June 2005 and through June 2011,in Dehong prefecture were included in the cohort analysis.HIV incidence was calculated and related risk factors determined by using Cox proportional hazard regression model.Results A total of 3154 MMT clinic attendants were qualified for this cohort study.By June 2011,1023(32.4％)of them had never received any follow-up HIV testing so were thus referred as loss to follow-up.The other 2131(67.6％)members had received at least one follow-up HIV testing and were observed for a total of 4615.86 person-years.During the period,22 new HIV infections or seroconverters were identified,making the overall HIV incidence as 0.48/100 person-years.The HIV incidence was higher among those who were unemployed,never married,self-reported being injecting drug users(IDUs)and HCV positive at entry into the MMT program.None of those who were always negative on follow-up-urine-testing of morphine was discovered as HIV newly infected during the follow-up period.Data from multiple regression analysis under Cox proportional hazard model indicated that after controlling for confounding variables,non-IDUs at the entry point for the MMT program,were less likely to be HIV newly-infected or seroconverted than IDUs(HR=0.29,95％CI:0.11-0.76).Conclusion MMT prograqm in Dehong prefecture was demonstrated to be fairly effective in reducing HIV transmission through drug use.Those HIV negative attendants at the MMT clinic who were IDUs or keep using drugs during the treatment,were at higher risk of HIV seroconvertion.More efforts were needed to improve the follow-up and HIV testing programs for the MMT clinic attendants.

Objective To determine the proportion of heroin use among patients who were involved in community-based methadone maintenance treatment (MMT) program and to identify the risk factors associated with heroin use. Methods This study was conducted in 9 MMT clinics within 3 provinces. Thirteen hundred and one patients who met the study criteria were selected from each of the five groups with different dosages of methadone users. An administrative questionnaire was applied to explore the demographics,drug abuse-related behaviors and MMT services received by the clients,etc. The prevalence of depression and anxiety among the clients were also collected by SAS and SDS. Urine samples were collected as a biological marker to indicate if heroin had been used. Results Of the 1301 patients,76.2% were males. The mean age was (34.6±6.5) years while 71.7% had an education level of primary school or below. The average daily dosage of methadone was (48.1±29.4) mg and self-satisfied evaluation score on treatment was 8.6. On average,27.7% urine samples showed positive opiate evidence. Marital status,employment status,treatment retention,self-satisfied evaluation score on dosage and dropout history were found to be significantly associatedwith heroin use,while gender,education level and dosage had no significant association with heroin use. It seemed that risk factors that associated with heroin use were different from areas to areas. Conclusion High quality MMT clinic services,high self-satisfied score,longer treatment retention and low dropout rate seemed to have the effects of reducing the risk of ongoing heroin abuse under the methadone maintenance treatment program.