Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors / 药物分析学报

During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[M+10]+intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[M+10]+has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ioniza-tion.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a').Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

Effects of lead and manganese combined exposure on neurodevelopmental toxicity and JNK expression in zebrafish / 环境与职业医学

Background Lead and manganese are heavy metal pollutants widely existing in the environment, which can accumulate in the human body through the food chain, exert neurotoxicity, and cause neurodegenerative disorders. Especially in early childhood, the developing blood-brain barrier and nervous system are highly susceptible to environmental chemical pollutants. Most of the previous studies focused on the toxic effects of single heavy metal such as lead or manganese, while the studies on combined toxic effect are still scarce, and involved mechanisms are still unclear. c-Jun N-terminal kinase (JNK) is involved in neuronal development and regeneration, and some studies have found that JNK is involved in lead or manganese induced neurotoxicity. Its role in the toxicity of combined lead and manganese is unknown. Objective To understand the neurodevelopmental toxicity mechanism and to observe changes of JNK expression in zebrafish induced by combined lead and manganese exposure at environmentlly low concentrations. Methods Zebrafish embryos within 2 h post fertilization (hpf) were divided into four groups: control group, lead exposure group (0.1 mg·L−1 lead acetate), manganese exposure group (0.3 mg·L−1 manganous chloride), and lead-manganese combined exposure group (0.1 mg·L−1 lead acetate +0.3 mg·L−1 manganous chloride) and exposed to lead or/and manganese at designed levels for 7 d. Spontaneous movements and motor locomotion were observed, and mortality rate were calculated. The changes of JNK mRNA expression in zebrafish were evaluated. Results The experimental results showed that no significant effect of lead or/and manganese on spontaneous movements and mortality rate was found in zebrafish compared with the control group (P＞0.05). The results of locomotion analysis showed that compared with the control group, the activity counts and activity distance of zebrafish in the manganese exposure group were slightly increased (P＜0.01); the activity counts and activity distance of zebrafish in the lead exposure group were reduced by 50% and those in the lead-manganese exposure group were reduced by 80% (P＜0.01). Compared with the lead exposure group, the activity counts and activity distance of zebrafish in the lead-manganese combined exposure group decreased significantly by 60% (P＜0.05). The real-time quantitative PCR results showed that the JNK mRNA expression level was significantly increased in the lead-manganese combined exposure group compared with the control group(P＜0.01). Conclusion Lead exposure combined with manganese exposure at environmentlly low concentration can induce neurodevelopmental toxicity to zebrafish. JNK may be involved in neurodevelopmental toxicity induced by the combined exposure to lead and manganese.

The progress on the use of botulinum toxin type A therapy in Parkinson′s disease / 中华神经科杂志

Botulinum toxin type A (BTX A) has gain widespread use in various neurological conditions, characterized by safe injection and less side-effect. This review will examine the current research of BTX A in the following aspects: mechanism, location, dose and outcome, which manifests the safety and efficacy data of BTX A injection treatment to the symptoms of Parkinson disease, including refractory tremor, focal dystonia, loss of postural reflexes, sialorrhea, gastrointestinal symptoms and depressive disorder.

Research progress on the role of IDO signaling pathway in radiotherapy for non-small cell lung cancer / 中华放射肿瘤学杂志

Indoleamine 2, 3-dioxygenase (IDO) is one of the rate-limiting enzymes that degrade tryptophan (Trp) into kynurenine (Kyn). Inflammatory factor IFN-γ mediates tumor′s immune escape by activating the IDO signaling pathway, upregulating theKyn/Trp (K/T ratio) and suppressing the activity of both CD 8+T and regulatory T cells. Radiotherapy plays a major role in treating non-small cell lung cancer. It not only bi-directionally regulates immune response of the host, but also collaborates with immunosuppressive agents to kill tumors. Meanwhile, immune status of the host can affect the therapeutic effect of radiotherapy. In recent years, studies have shown that IDO activity levels change before and after radiotherapy and is related to clinical prognosis. Nevertheless, relevant mechanism remains unclear. This article aims to elucidate the application of IDO signaling pathway in radiotherapy for non-small cell lung cancer.

Subarachnoid anesthesia with ropivacaine combined with sufentanil in cesarean delivery / 中国基层医药

Objective:To investigate the efficacy of subarachnoid anesthesia with low-dose ropivacaine combined with sufentanil in cesarean delivery.Methods:A total of 120 women who were subjected to cesarean delivery in Tongxiang Second People's Hospital from May 2017 to April 2018 were included in this study. They were randomly assigned to undergo subarachnoid anesthesia either with low-dose ropivacaine plus sufentanil (observation group, n = 60) or low-dose ropivacaine alone (control group, n = 60) in cesarean delivery. The anesthesia effects, heart rate, mean arterial pressure, sensory block, 1-minute Apgar score, and the incidence of adverse reactions were compared between the two groups. Results:Time to anesthesia onset and time to pain recovery in the observation group were (2.07 ± 1.24) minutes and (51.29 ± 6.24) minutes, respectively, which were significantly shorter than those in the control group [(4.58 ± 1.69) minutes, (56.70 ± 7.91) minutes, t = 9.28, 4.16, both P < 0.05]. There was no significant difference in the duration of anesthesia between the two groups ( t = 0.76, P > 0.05). The heart rate, mean arterial pressure, and 1-minute Apgar score were (77.64 ± 6.20) beats/minute, (92.23 ± 1.38) mmHg, and (9.68 ± 0.70) points respectively in the observation group, which were significantly lower than those in the control group [(83.40 ± 5.93) beats/minute, (96.54 ± 4.06) mmHg, (7.59 ± 0.64) points, t = 5.20, 7.79, 17.07, all P < 0.05]. Time to onset of sensory block was significantly shorter in the observation group than in the control group [(52.07 ± 8.68) seconds vs. (64.30 ± 9.62) seconds, t = 7.31, P < 0.05]. Duration of sensory and motor block in the observation group were (161.75 ± 28.63) minutes and (86.26 ± 20.03) minutes, respectively, which were significantly longer than those in the control group [(130.29 ± 31.84) minutes, (78.60 ± 16.95) minutes, t = 5.69, 2.26, both P < 0.05]. The incidence of adverse reactions was significantly lower in the observation group than in the control group (5.00% vs. 16.67%, χ2 = 4.23, P < 0.05). Conclusion:Subarachnoid anesthesia with low-dose ropivacaine combined with sufentanil has satisfactory anesthetic effects in cesarean delivery. The combined therapy can stabilize hemodynamics, has little impact on newborns, and is highly safe.

Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

The role of pharmacogenomics in the personalization of Parkinson′s disease treatment / 中华神经科杂志

Parkinson′s disease (PD) is a common neurodegenerative disorder, which has a highly effective pharmacological symptomatic treatment. Levodopa is the most effective drug available for the symptomatic treatment of PD and is the gold standard with which other therapies must be compared. There are significant individual differences in clinical features, disease course, and response to pharmacological treatment in PD patients, not only attributed to disease process and environmental factors, but also genetic factors. Pharmacogenomics, also known as personalized medicine, is the study of how genetic variations in a person′s genome affect their response to drug therapies, which contribute to apply the patient with the best treatment plan, including the timing of dosing, the dose administered, and the most appropriate drugs. Pharmacogenomics accounts for 60%-90% variability in drug pharmacokinetics and pharmacodynamics. Major determinants of the pharmacogenomic outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. This article will summarize the impact of polymorphisms in genes encoding dopamine signaling pathway on drug response, and the impact of genetic polymorphisms on complications and prognosis associated with dopaminergic drug therapy.

Enlightenment of COVID-19 epidemic on function and layout of China-Africa friendship hospital: from global health governance perspective / 中华医院管理杂志

The globalized epidemic of the COVID-19 forced the international community to reconsider the importance and urgency of global public health in world peace and development. The authors analyzed the COVID-19 epidemic prevention and control situation in Africa, and discussed the functions and layout of China-Africa friendship hospitals from the perspective of global health governance. It was suggested that the functions of China-Africa friendship hospitals should be positioned as the high-level medical centers in Africa, regional medical and disease control linkage centers, regional health technology training centers, regional telemedicine collaboration center, and regional health policy research center.Furthermore, the layout of China-Africa friendship hospitals should respond to China′s assistance in the construction of Africa′s center for disease control and China-Africa′s cooperation plan for promoting the " one belt and one road" construction, and work together with the medical team to build a new pattern of medical integration and health care system for African disease prevention and control and medical treatment.

Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity / 医学前沿

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.

Association between monocyte-to-high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the association between monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and nonalcoholic fatty liver disease (NAFLD). MethodsA total of 208 patients who were admitted to Department of Gastroenterology, Zhongshan Hospital Affiliated to Dalian University, from January 2018 to October 2020 and were diagnosed with NAFLD by abdominal CT were enrolled as NAFLD group, and 210 healthy individuals were enrolled as control group. All subjects underwent routine blood test, biochemical examination, and abdominal CT examination, and serum MHR was calculated. In addition, according to abdominal CT findings, the patients with NAFLD were divided into mild NAFLD group with 148 patients and moderate-to-severe NAFLD group with 60 patients, and the variables such as white blood cell count (WBC) and MHR were compared between the three groups. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups; the Mann-Whitney U test was used for comparison of data with skewed distribution between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The fourfold table chi-square test was used for comparison of categorical data between two groups, and the R×C table chi-square test was used for comparison between three groups. A Spearman correlation analysis was used to investigate the correlation of MHR with metabolic markers and the severity of NAFLD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of MHR in predicting NAFLD. ResultsCompared with the control group, the NAFLD group had significant increases in body weight (t=-10.573, P＜0.001), body mass index (BMI) (t=-13.112, P＜0.001), smoking history (Z=14.667, P＜0.001), WBC (t=-7.359, P＜0.001), monocytes (Z=-9.932, P＜0001), low-density lipoprotein cholesterol (t=-3.394, P=0.001), triglyceride (TG) (Z=-11.737, P＜0001), cholesterol (t=-2.985, P=0.003), fasting blood glucose (FBG) (Z=-7.827, P＜0.001), alanine aminotransferase (ALT) (Z=-12.583, P＜0.001), and aspartate aminotransferase (AST) (Z=-9.514, P＜0.001) and a significant reduction in serum high-density lipoprotein cholesterol (HDL-C) (t=10.440, P＜0.001); in addition, MHR level had gender differences, and male patients had a significantly higher level than female patients (P＜0.001). Compared with the control group and the mild NAFLD group, the moderate-to-severe NAFLD group had a significant increase in serum MHR level (P＜0.001). The correlation analysis showed that serum MHR level was negatively correlated with HDL-C (r=-0.565, P＜0.001) and were positively correlated with smoking history, body weight, BMI, WBC, monocytes, TG, FBG, ALT, and AST (r=0.449, 0.482, 0.430, 0.478, 0.892, 0.333, 0.157, 0.386, and 0281, all P＜0.01). At the same time, MHR level was positively correlated with the severity of NAFLD (r=0.629, P＜0.001). The ROC curve showed that MHR had an area under the ROC curve of 0.846 (95% confidence interval: 0.810-0.882, P＜0.001), with a sensitivity of 77.9% and a specificity of 74.3%. ConclusionSerum MHR level is associated with NAFLD and can be used as a predictive index for evaluating the progression of NAFLD.

Clinical analysis of 82 cases of brucellosis with first symptom of joint pain / 中华地方病学杂志

Objective:To understand the characteristics and diagnosis and treatment of brucellosis with joint pain as the first clinical manifestation, and summarize the clinical classification of brucellosis complicated with joint pain, so as to provide reference for clinical diagnosis and treatment.Methods:Cases of brucellosis with first symptom of joint pain diagnosed in the 940th Hospital of PLA Joint Logistic Support Force from January 2015 to January 2020 were selected. The main clinical features, laboratory examination, diagnosis and treatment were analyzed.Results:A total of 82 patients with joint pain of the first symptom were selected, including 61 males and 21 females. Joint pain was the main complaint of the patients, 63.4% (52/82) of the patients visited spine surgery department, 17.1% (14/82) visited minimally invasive orthopedics department, 12.2% (10/82) visited rheumatic immunology department, and 7.3% (6/82) visited traditional Chinese medicine department. Brucellosis patients with cervical lesions accounted for 22.0% (18/82), combined with lumbar lesions accounted for 51.2% (42/82). The patients with elevated C-reactive protein accounted for 68.3% (56/82), abnormal liver function accounted for 52.4% (43/82), anti "O" positive accounted for 3.7% (3/82), abnormal autoantibodies accounted for 6.1% (5/82), and human leukocyte antigen-B27 (HLA-B27) positive accounted for 12.2% (10/82). Four patients with HLA-B27 positive had sacroiliac arthritis. All patients were cured after standard and full course therapy.Conclusion:Joint pain may be the first symptom of brucellosis, and the lumbar spine and cervical spine are the most vulnerable parts.

Relationship between blood lipid level and Parkinson's Disease:A Meta-analysis / 中国医师杂志

Objective Although multiple lines of evidence suggested that serum lipid is related to Parkinson's disease ( PD) , it has been controversial. The aim of this study is to conduct a systematic review and meta-analysis to analyse the relationship between serum lipid levels and PD risk. Methods Pertinent studies were identified by a search in Pubmed, Medline, Web of Science, Cochrane Library, Wanfang data-base, the Wiper database and China National Knowledge Infrastructure (CNKI) up to July, 2018. All sta-tistical analyses were conducted using STATA version 12. 0. Results Eleven related articles met our selec-tion criteria and a total of 1424 PD patients and 7250 healthy controls were included in further analysis. Through meta-analysis, low triglyceride ( TG) level appeared to increase risk of developing PD [ standard-ised mean difference (SMD) = -0. 31, 95％ CI ( -0. 40, -0. 21), P=0. 318, I2 =14. 7％], while no significant association was identified between total cholesterol ( TC) [ SMD= -0. 09, 95％ CI ( -0. 40, 0. 22), P=0. 000, I2 =94. 0％], low density lipoprotein cholesterol (LDL-C) [SMD= -0. 10, 95％ CI ( -0. 40, 0. 19), P=0. 000, I2 =92. 3％] and high density lipoprotein cholesterol (HDL-C) [SMD=-0. 09, 95％ CI ( -0. 22, 0. 05), P=0. 103, I2 =45. 5％] with PD. The similar conclusion was ob-tained by subgroup analysis in both Asian and non-Asian. Conclusions Our results indicate that TG were associated with the risk of PD, while TC, LDL-C and HDL-C maybe not associated with the risk of PD. However, this conclusion needs further confirmation.

Feasibility of single hole thoracoscopy of pleural fibreboard end-arterectomy in treatment of chronic tuberculous empyema / 中国内镜杂志

Objective To discuss the feasibility of single hole thoracoscopy of pleural fibreboard endarterectomy surgical treatment on chronic tuberculous empyema. Methods Retrospective analysis of minimally invasive treatment of 52 cases of chronic tuberculous empyema form January 2013 to May 2016, 50 cases applied single hole thoracoscopy surgery, video-assisted mini-thoracoscopy for another 2 cases. Results There was no death, operation time 60 ~ 240 min, average 160 min, bleeding 150 ~ 2000 ml, average 350 ml, postoperative chest tube drainage time 3 ~ 21 d, average 7 d, postoperative persistent leakage in 3 patients, 3 cases of atelectasis, incisional infection in 1 case, pleural effusion in 1 case, 3 cases of arrhythmia. All the cured patients are received the corresponding treatment, the follow-up of 3 ~ 36 m, the chest CT scan show no atelectasis. Conclusion Under the condition of strict selection of indication, single hole thoracoscopy of pleural fibreboard endarterectomy in treatment of chronic tuberculous empyema is safe and feasible, so it is worthy of making further clinical promotion and application.

Evaluation of the significance of EBV nucleic acid and serology tests in the management of EBV-related diseases / 中华检验医学杂志

Objective To investigate the relationship between Epstein-Barr virus (EBV) DNA and EBV serology markers and evaluate the clinical application values in different diseases.Methods Plasma samples from 397 diagnosed EBV infection-associated patients and 120 health donors from May 2014 to November 2015 in Wuhan Tongji Hospital were collected.Real-time fluorescent quantitative PCR was performed to detect the levels of EBV-DNA in peripheral blood mononuclear cell and plasma.ELISA was used to detect VCA IgA,VCA IgM,VCA IgG,EA(D) IgG and EBNA IgG antibodies in plasma.The positive rate of EBV-DNA and EBV antibodies were counted in each group according to the detection threshold.Kappa statistic and Spearman sank correlation test were used to analysis the correlation and uniformity between EBV-DNA and EBV serology indicators.Results The positive rate of VCA IgG in patient and health control was 94.2% (374/397) and 93.3% (112/120) respectively (χ2=0.125,P=0.67);The positive rate of EBNA IgG in patient and health control was 95.4% (379/397) and 95.0% (114/120) respectively (χ2=0.045,P=0.807);but the positive rate of VCA IgM was 5.5% (22/397) and 0% (0/120) respectively (χ2=6.9,P<0.01);The positive rate of VCA IgA was 43.3% (172/397) and 9.2% (10/120) respectively (χ2=49.5,P<0.01);The positive rate of EA(D) IgG was 42.0% (167/397) and 7.5% (9/120) respectively (χ2=49,P<0.01).The positive rate of EBV-DNA was 65.5% (260/397) and 16.7% (20/120) respectively (χ2=88.5,P<0.01);The positive rate of EBV-DNA in plasma was 45.8% (182/397) and 5.0% (6/120) respectively (χ2=66.4,P<0.01).Furthermore,the uniformity and Spearman correlation analysis showed that there was no significant correlation between EBV-DNA and EBV serology indicators.The correlation analysis between PBMC EBV-DNA and VCA IgM,VCA IgA,EA(D) IgG showed the Kappa was 0.073,0.147,0.073,respectively;the correlation analysis between plasma EBV-DNA and VCA IgM,VCA IgA,EA(D) IgG showed the Kappa was 0.144,0.369,0.288,respectively.Thus,the patients were divided into different groups according to the discharge diagnosis,it was observed that the positive rates of EBV-DNA is more than 90% in extra-nodal NK/T cells lymphoma,EBV-associated hemophagocytic lymphoid tissue hyperplasia,chronic active EBV infection and infectious mononucleosis.In nasopharyngeal carcinoma patients,the positive rate of EBV antibodies (VCA IgA and EA(D) IgG) were higher than the detection of EBV-DNA.Conclusions There was no significant correlation between EBV-DNA and EBV serology markers for the same sample.The clinical application values of EBV DNA and EBV serology markers were not identical in nasopharyngeal carcinoma,extra-nodal NK/T cells lymphoma,infectious mononucleosis and EBV-associated hemophagocytic lymphoid tissue hyperplasia.

Analysis on the size and income of off-staff medical workers at county-level hospitals in China / 中华医院管理杂志

Objective To learn the size and income of off-staff medical workers in a survey of public county-level general hospitals in China.Methods Human resources investigation of public county-level general hospitals,with SPSS data analysis of the outcomes.Results From 2011 to 2013,the proportion of off-staff medical workers increased from 31.44% to 36.69%,of whom the highest proportion was found in China′s western region,accounting for 40.69%;the ratio of off-staff practicing physicians increased from 14.24% to 16.64%,of whom China′s central region accounted for 19.92%;the ratio of off-staff nurses increased from 43.03% to 49.77%,of whom China′s western region accounted for 55.88%.In 13.7% of the hospitals,income of off-staff medical workers was less than a half of that for permanent staff;41.32% and 26.31% of the hospitals surveyed were fully covered with social insurance and housing fund account respectively.Conclusions Off-staff labor is a distinct feature at such hospitals,making imperative a HR system reform of public hospitals.The discriminative income and welfare between permanent and off-staff medical workers calls for a fundamental change to the income and welfare system.

Assessing the quality of rodent laboratory animals in Beijing area by pathological diagnosis in October 2014 / 中国比较医学杂志

Objective To assess the health status of rodent laboratory animals by pathological diagnosis, our lab has being take apart in investigating the quality of laboratory animals in Beijing area for years and offer some advices for standardized breeding to ensure accurate results of scientific research.This paper focuses on the analysis of laboratory rodent samples that collected in October 2014.Methods We collected the heart, liver, spleen, lung, kidney, large intestine and small intestine, and put these organs into 10%Calcium formaldehyde solution for fixation, and then prepared into two different sections for optical microscopy observation including all paraffin specimens stained with H&E and the frozen sections stained with Oil Red-O and PAS.Results The vast majority of laboratory rodents were up to standard, but there still a problem in individual units.The main problem is liver and lung disease.The rate of Hepatocyte swellingis 6%(mouse), 2.5% (rat), 8.2% (guinea pig), moreover part of them were lipidosis, according to Oil Red-O stain.the mainly problem of lung is congestion ,edema and Interstitial pneumonia ,the detectable rate of pulmonarydiseases is 15.5%(guinea pig).Conclusions The vast majority of laboratory rodents were pathologically diagnosed as healthy animals.The liver disease may be caused by improper feeding.And disease of lung may led by haze, unqualified bedding and low temperature.

Subcellular localization of ataxin-3 and its effect on the morphology of cytoplasmic organoids / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the subcellular localization of ataxin-3 and the effect of polyglutamine (polyQ) expansion mutation on the morphology of mitochondrion, golgi apparatus and endoplasmic reticulum.</p><p><b>METHODS</b>Transient transfection was employed to build cell models expressing wild-type or mutant ataxin-3 proteins. Indirect immunofluorescence was applied to identify markers of organelle membrane. The results were observed under a laser scanning confocal microscope.</p><p><b>RESULTS</b>No co-localization was observed for ataxin-3 protein and mitochondrial marker TOM20, but the percentage of cells with mitochondrial fragmentation has increased in cells expressing mutant ataxin-3 (P<0.05). No co-localization was observed for ataxin-3 protein and golgi marker GM130, and mutant ataxin-3 did not cause golgi fragmentation. Wide type and polyQ-expanded ataxin-3 both showed partial co-localization with ER marker calnexin. The latter showed more overlap with calnexin, and the overlapping signals were mostly located in the places where aggregates were situated.</p><p><b>CONCLUSION</b>PolyQ-expanded ataxin-3 protein may indirectly affect the integrity of mitochondria, but may cause no effect on the structure and functions of golgi apparatus. Endoplasmic reticulum may be another place where extended ataxin-3 protein can induce cytotoxicity in addition to the nucleus.</p>

Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

Objective:To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34 (GADD34). Methods: A total of 108 healthy male Sprague-Dawley rats were randomly divided into sham operation group, model group and edaravone group (36 cases for each group). Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawley rats. Then, GADD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats. Results: The GADD34 expression was detected in the peri-infarct regions of rats 1 h after reperfusion, which reached its peak 24 h after reperfusion. And edaravone could significantly down-regulate the GADD34 expression. Conclusions:Edaravon could down-regulate GADD34 expression, which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

Clinical effects of gastrodin injection combined with fluoxitine in the treatment of post-stroke depression / 中国综合临床

Objective To investigate the therapeutic effects and adverse reaction of Gastrodin Injection combined with Fluoxitine (Prozac) in the treatment of post-stroke depression (PSD).Methods One hundred and two patients with PSD were randomly allocated into two groups:51 cases in the Gastrodin Injection and Fluoxitine combination group (treatment group),51 cases in Fluoxitine Group (control group).The treatment group was treated by intravenous injection of 600 mg/d Gastrodin (14 days) plus oral administration of 20 mg/d Fluoxitine (30 days).The control group was only treated by oral administration of 20 mg/d Fluoxitine (30 days).The therapeutic effects were evaluated by the observations of the changes of symptoms and signs and Hamilton Depression Scale (HAMD) respectively in the two groups.Results The cured,effective,improved and invalid rates were 9.8％ (5/51),52.9％ (27/51),27.5％ (14/51) and 9.8％ (5/51) respectively in the treatment group and 2.0％ (2/51),11.7％ (6/51),66.7％ (34/51) and 19.6％ (10/51) in the control Group.The total effective rate in the treatment and the control groups were 90.2％ (46/51) and 80.4％ (41/51) respectively.The therapeutic effect was better in the treatment group than in the control group,and there was significant difference observed between the two groups (x2 =13.03,P ＜ 0.05).The rate of adverse reaction was significantly lower in the treatment group than in the control group (3.92％ (2/51) vs.25.5％ (13/51),x2 =9.64,P ＜ 0.01).Conclusion Gastrodin Injection in combination of Fluoxitine,with low adverse reation rate,is an effective therapeutic method for the treatment of PSD.

ENPP1/PC-1 gene K121Q polymorphism is associated with obesity in European adult populations: evidence from a meta-analysis involving 24,324 subjects / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Findings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP-1) or plasma cell membrane glycoprotein 1 (PC-1) gene single nucleotide polymorphism (K121Q, rs1044498) and genetic susceptibility to obesity. However, such relationship is not reproduced by some currently available studies. In this context, the present study is aimed to quantitatively analyze the association of K121Q variant with obesity in all published case-control studies in European adult populations.</p><p><b>METHODS</b>Published literature from PubMed, EMBASE, and ISI web of science databases were retrieved. The studies evaluating the association of ENPP1/PC1 gene K121Q polymorphism with obesity were included, in which sufficient data were presented to calculate the odds ratio (OR) with 95% confidence intervals (CIs).</p><p><b>RESULTS</b>Ten case-control studies meeting the inclusion criteria identified a total of 24,324 subjects including 11,372 obese and 12,952 control subjects. The meta-analysis results showed a statistically significant association of K121Q with obesity [OR (95%CI): 1.25 (1.04-1.52) P=0.021] under a recessive model of inheritance (QQ vs. KK+KQ) without heterogeneity or publication bias.</p><p><b>CONCLUSIONS</b>The results from the present study have indicated that ENPP1/PC1 Q121 variant may increase the risk of obesity and that more well-designed studies based on a larger population will be required to further evaluate the role of ENPP1/PC1 gene K121Q polymorphism in obesity and other related metabolic syndromes.</p>