[Micronutrient Powders Feeding Behaviors of Baby Caregivers in Remote Rural Areas of Sichuan Province: A Study Based on the Theory of Reasoned Action].

Objective: To explore the status quo and influencing factors of feeding behaviors of micronutrient powders (MNP), or yingyangbao in Pinyin, the Chinese Romanization system, of baby caregivers in remote rural areas of Sichuan Province. Methods: In 2019, caregivers of babies aged 6 to 24 months from 6 counties of Sichuan Province were selected as the respondents of the survey through a multistage cluster random sampling method. Data concerning the baby caregivers' attitude of behavior, subjective norms, behavioral intention, and feeding behaviors about MNP feeding were collected with a questionnaire through a structured interview. Based on the theory of reasoned action, a structural equation model was constructed to explore the influencing factors of feeding behaviors. Results: A total of 1002 valid samples were included in the study. The effective feeding rate of MNP among the baby caregivers was 55.49%. The results of model analysis suggested that attitude of behavior ( ß direct=0.212, 95% CI: 0.105-0.327), subjective norm ( ß direct=0.123, 95% CI: 0.016-0.228), and behavioral intention ( ß direct=0.162, 95% CI: 0.093-0.224) could have a significant direct impact on MNP feeding behaviors. Behavior attitude ( ß indirect=0.044, 95% CI: 0.023-0.073) and subjective norms ( ß indirect=0.018, 95% CI: 0.001-0.040) could have a significant indirect impact on MNP feeding behaviors through the intermediary of behavioral intention. Among the three theoretical elements, attitude of behavior had the largest total effect on the feeding behavior ( ß total=0.256, 95% CI: 0.148-0.366). Conclusion: The effective feeding rate of MNP among baby caregivers in remote rural areas of Sichuan Province is low. The attitude of behavior and subjective norms of caregivers may have a direct impact on their feeding behavior, and both attitude of behavior and subjective norms can have an indirect impact on the feeding behavior through the intermediary of behavioral intention. The influence of attitude of behavior attitude on feeding behavior is greater than that of subjective norms. Future intervention plans for promoting effective MNP feeding should incorporate health education for baby caregivers and their important social relations. Thus, baby caregivers' attitude and willingness for MNP feeding will be strengthened and the effective feeding rate of MNP will be improved accordingly.

[Evaluation of Accuracy and Influencing Factors for Diagnosis of Two Chronic Diseases by Primary Healthcare Providers in Sichuan Rural Areas Based on Standardized Patients].

Objective We used standardized patients to evaluate the accuracy and explore the influencing factors of the diagnosis of unstable angina pectoris and type 2 diabetes by primary healthcare providers in Sichuan rural areas,aiming to provide a scientific basis for improving the diagnosis accuracy of primary healthcare providers for the two chronic diseases. Methods A multi-stage stratified random cluster sampling method was adopted to select 100 villages from 50 townships in 5 districts/counties in Zigong city,Sichuan province. General and internal medicine practioners who were on duty on the survey day were enrolled in the survey.Two rounds of data collection were conducted.In the first round,the basic information of providers from township health centers and village clinics was collected.One month after the the first survey,standardized patients were used to collect the information related to the diagnosis of unstable angina pectoris and type 2 diabetes by rural primary providers.Logistic regression was carried out to analyze the factors influencing the diagnosis accuracy. Results A total of 172 rural primary healthcare providers were enrolled in the survey,who completed 186 standardized patient visits and showed the correct diagnosis rate of 48.39%.Specifically,the correct diagnosis rates of unstable angina pectoris and type 2 diabetes were 18.68%(17/91) and 76.84%(73/95),respectively.The providers with medical practitioner qualifications were more likely to make correct diagnosis(OR=4.857,95%CI=1.076-21.933, P=0.040).The providers who involved more necessary consultation and examination items in the diagnosis process had higher probability of correct diagnosis(OR=1.627,95%CI=1.065-2.485, P=0.024).Additionally,the providers were more likely to make a correct diagnosis for type 2 diabetes than for unstable angina pectoris(OR=6.306,95%CI=3.611-11.013, P<0.001). Conclusions The overall diagnosis accuracy of unstable angina pectoris and type 2 diabetes was relatively low among primary healthcare providers in Sichuan rural areas.The training of diagnosis process can be taken as a key for improving providers' practice ability so as to increase the diagnosis accuracy of chronic diseases.

[Psychological Status and Influencing Factors of Staff at Centers for Disease Control and Prevention in Sichuan Province during the Outbreak of Coronavirus Disease 2019].

Objective To assess the psychological status of staff at the centers for disease control and prevention(CDC) in Sichuan during the outbreak of coronavirus disease 2019(COVID-19) and explore the influencing factors. Methods The staff at Sichuan provincial,municipal,and county(district)-level CDC were selected by convenience sampling.Their basic information,work status,training status,work difficulties,and support from the work group were collected from the self-filled questionnaires online.The Generalized Anxiety Disorder Scale and the 9-question Patient Health Questionnaire were respectively employed to measure the anxiety and depression of the staff.The stepwise Logistic regression was carried out to analyze the influencing factors of anxiety and depression in CDC staff. Results Among the 653 staff,58.35% and 50.06% presented anxiety and depression,respectively.The regression results showed that age(OR=0.95,95%CI=0.92-0.97) and mental support from the work group(OR=0.61,95%CI=0.45-0.82) were the protective factors while physical fatigue(OR=1.82,95%CI=1.20-2.74),work pressure(OR=1.61,95%CI=1.21-2.12),and insufficient protective equipment(OR=1.92,95%CI=1.06-3.49) were the risk factors for depression of CDC staff.Age(OR=0.97,95%CI=0.94-0.99),length of sleep per day(OR=0.74,95%CI=0.56-0.96),and participation in technical training(OR=0.33,95%CI=0.12-0.95) were the protective factors while mental fatigue(OR=1.68,95%CI=1.18-2.41),work pressure(OR=2.94,95%CI=2.08-4.17),and unclear incentive system for overtime(OR=1.99,95%CI=1.23-3.23) were the risk factors for the anxiety of CDC staff. Conclusion The anxiety and depression status of CDC staff during the COVID-19 outbreak were worrying,which were mainly affected by age,sleep,supply of protective equipment,incentive system,fatigue,and work pressure.

[The Association Between Abdominal Obesity and Diabetes among Middle-aged and Older Adults with Normal BMI].

OBJECTIVE: To explore the relationship between abdominal obesity and diabetes among middle-aged and older adults with normal body mass index (BMI) and to provide reference information for formulating targeted diabetes prevention and control measures for this population. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study (CHARLS) done in 2015. Middle-aged and older adults who were aged 45 and older and had normal BMI were included in the study. According to their status of diabetes, the subjects were divided into two groups, non-diabetes and diabetes groups. χ 2 test was used to investigate the difference between two groups. Logistic regression was used to do the multivariate analysis of factors influencing diabetes. RESULTS: A total of 5 197 middle-aged and older adults with normal BMI ranging between 18.5 and 24 kg/m 2 were included. The prevalence of diabetes was 11.26% (585/5 197) and the prevalence of abdominal obesity was 41.56% (2 160/5 197). Univariate analysis showed that the difference in age, residence, the status of hypertension, dyslipidemia and abdominal obesity between non-diabetic group and the diabetic group were statistically significant ( P<0.01). The prevalence of diabetes among adults with abdominal obesity was 14.2% (307/2 160) and that among people with no abdominal obesity was 9.2% (278/3 037). Compared with people with no abdominal obesity, the prevalence of diabetes among people with abdominal obesity was higher and the difference were statistically significant ( P<0.01). Multivariate logistic regression analysis showed that, among middle-aged and older adults with normal BMI, those with abdominal obesity, aged 60 years and older, living in urban areas, having hypertension and having dyslipidemia had higher probability of developing diabetes. CONCLUSION: Abdominal obesity and diabetes are becoming a serious problem among middle-aged and older adults with normal BMI and abdominal obesity may be related to higher risks of diabetes. It is recommended that more attention is given to abdominal obesity in this population to reduce the possibilities of diabetes.

[Study on the Relationship between First-Time Complementary Feeding Practice and the Nutritional Status of Infants and Young Children in the Multi-Ethnic Rural Areas of Sichuan Province].

OBJECTIVE: To evaluate the current status of first food supplement and the nutrition of infants and young children in rural areas inhabited by people of Han, Tibetan, and Yi ethnicities in Sichuan Province, and to explore the relationship between the first ever feeding of food supplement and the nutritional status. METHODS: Using a multi-stage randomized cluster sampling method, we selected 2 Han counties, 2 Tibetan counties and 2 Yi counties in rural areas of Sichuan Province. These counties were previously defined as economically poor counties, but had since been lifted out of poverty. They were selected for this study before they came out of poverty. Infants and young children of 12-24 months old and their main caregivers from these counties were the subjects of the study. Structured questionnaires were used to collect information concerning the sociodemographic characteristics of infants and young children and their caregivers, and the first complementary feeding for infants and young children. Infant and young children weight scales and length/height tapes were used to collect the weight and length/height data of infants and young children. Unconditional logistic regression was used to analyze the correlation between the behavior of giving supplementary food for the first time to infants and young children and their nutritional status. RESULTS: A total of 1117 pairs of infants and children and their caregivers were investigated. Regarding the time of first supplementary food addition, nearly half of the caregivers in Han areas started adding supplementary food when the infants were 6 months old, accounting for 43.07% (171/397). Most of the caregivers in Yi and Tibetan areas started giving infants and young children supplementary food when they were less than 6 months old, accounting for 77.18% (301/390) and 47.58% (157/330), respectively. In terms of the types of supplementary food added for the first time, caregivers in Han areas mainly used homemade rice cereal, accounting for 41.56% (165/397), caregivers in Tibetan areas mainly used meat, vegetables or fruits and other complementary foods, accounting for 42.12% (139/330), and caregivers in Yi areas mainly used homemade rice cereal, accounting for 46.41% (181/390). The overall malnutrition rate of infants and young children was 28.83% (322/1117) and the malnutrition rate of infants and young children in Han, Tibetan, and Yi areas were 10.58% (42/397), 24.85 (82/330), and 50.77 (198/390), respectively. The regression analysis results show that after controlling for confounding factors, compared with Han areas, it is more likely for infants and young children in Yi areas to be malnourished ( OR=9.49, 95% CI 6.00-15.00). Compared with adding other types of complementary foods for the first time, infants and young children given iron-fortified rice cereal had a lower risk of malnutrition ( OR=0.54, 95% CI0.29-0.99). CONCLUSION: The multi-ethnic rural areas of Sichuan Province had problems that supplementary foods are added too early, and that the types of supplementary foods added for the first time were not appropriate. In addition, the nutritional status of local infants and young children in these areas was causing concerns. The malnutrition problem of infants and young children was especially prominent in the Yi ethnic areas. Adding iron-fortified rice cereal for the first time could reduce the possibility of malnutrition in infants and young children to a certain extent. It is recommended that attention should be given to the health education intervention of the first supplementary food for infants and young children to effectively improve the nutritional status of infants and young children in these areas.

CDK5-mediated phosphorylation of Sirt2 contributes to depressive-like behavior induced by social defeat stress.

Major depressive disorder (MDD) is a common, severe and recurrent psychiatric disorder worldwide; however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases (HDACs) appear to play an essential role in depression. As the class III HDACs, Sirt1 and Sirt2 have attracted the most interest in the nervous system. Indeed, chronic stress decreased Sirt1 activity and down-regulated Sirt1 gene expression in MDD. Nevertheless, there is a paucity of literature on the role of Sirt2. To study the role of Sirt2 we established a MDD mouse model in wild type and Sirt2 knockout C57BL/6 mice using social defeat stress (SDS). We found that a lack of Sirt2 blocked the development of SDS-induced depressive-like behavior. Moreover, SDS led to Sirt2 phosphorylation in the amygdala without changing total Sirt2 levels, and blocking the phosphorylation of Sirt2 by CDK5 at serine residues 368 and 372 prevented SDS-induced depressive-like behavior and Sirt2 nuclear import. We also discovered that SDS-induced Sirt2 phosphorylation was involved in VTA-amygdala modulation using TetTag-pharmacogenetic method. These results suggest that CDK5 mediates phosphorylation of Sirt2 in the amygdala and contributes to the depressive-like behavior induced by SDS. This study highlights that inhibiting CDK5-dependent phosphorylation of Sirt2 at serine residues 368 and 372 by myristoylated membrane-permeabilising peptide (Sirt2-p), rather than using non-specific sirtuin inhibitors, may be a novel strategy for treating depression.

[A Social Network Perspective on the Transmission of Cysticercuscellulose Infections in Tibetan School Children in Sichuan].

OBJECTIVE: To determine the transmission characteristics of Cysticercuscellulose infections from a social network perspective in Tibetan school children in Sichuan. METHODS: A cluster sampling strategy was adopted to select two primary schools with high level of Cysticercuscellulose infections in the Tibetan agriculture areas of Liangshan prefecture, Sichuan province. All of the students from the selected schools were enrolled in the study. Their social network data, including classroom seating, dormitory roommates, best playmates, and those who shared meals and snacks etc, were collected by trained investigators. Stool and blood samples of the students were collected for parasite detection. The transmission network of Cysticercuscellulose infections and the overall social network of school children were analysed. RESULTS: A total of 644 children participated in the study. Taenia solium were found in 6.11% of the stool samples and 13.25% blood samples returned with seropositive. The transmission was centered around the sources of infections: dormitory-clustering in the boarding school and playmate-clustering in the day school. The overall social network analysis revealed "core people" (more relationships), "information disseminators" (closer to other nodes) and "information hubs" (between two nodes) in both schools. CONCLUSION: Close contacts in dormitories and playgrounds are the main sources of transmission of cysticercosis in the Tibetan schools. The "core people" "information disseminators" and "information hubs" are critical for the prevention and control of cysticercosis in the future.

Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.

Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms.

Expression of FLK1 and CD146 at day 7 following reperfused acute myocardial infarction.

OBJECTIVES: To investigate the expression of FLK1, CD146 and microvessel density of angiogenesis at the first week of reperfused acute myocardial infarction (AMI). METHODS: 16 of mini-swines (20 to 30 Kg) were randomly assigned to the sham-operated group and the AMI group. Pathologic myocardial tissue was collected at day 7 following reperfusion and detected by dual immunochemistry, real-time quantitative polymerase chain reaction and western blot. RESULTS: The infarcted area had higher FLK1 mRNA expression than the sham-operated area and the normal area (all P < 0.05), and the infarcted and marginal areas showed higher CD146 protein expression than the sham-operated area (all P < 0.05), but the microvessel density (CD31 positive expression of microvessels/HP) was not significantly different between the infarcted area and the sham-operated area (8.92 ± 3.05 vs 6.43 ± 1.54)(P > 0.05). CONCLUSION: FLK1 and CD146 expression significantly increase in the infarcted and marginal areas, and the microvessel density of angiogenesis in the infarcted area is similar to normal microvessel density of healthy heart tissue, suggesting that FLK1 and CD146 are possible associated with angiogenesis at day 7 following reperfused acute myocardial infarction.

[Clinical implication of microvasculopathy in patients post heart transplantation].

OBJECTIVE: Assess the clinical implication of microvasculopathy detected by endomyocardial biopsy samples in patients post heart transplantation. METHODS: Light microscopic evaluations were performed in 278 endomyocardial biopsies harvested from 64 patients post heart transplantation for more than one year, microvasculopathy was defined as stenotic endothelial and/or medial disease. RESULTS: The patients with stenotic microvasculopathy were younger than those without microvasculopathy (40.7 ± 15.9 vs. 49.4 ± 8.7, P < 0.05). The mean score of acute cellular rejection (0.83 ± 0.39 vs. 0.37 ± 0.32, P < 0.01) and the numbers of ≥ grade II acute rejection (0.84 ± 0.16 vs. 0.23 ± 0.10, P < 0.01) were significantly greater in stenotic microvasculopathy group compared to those of non-stenotic group. Multivariate regression analysis confirmed that stenotic microvasculopathy is the independent risk factor for the mean acute rejection score (OR = 3.40, 95%CI, 4.62 - 193.07, P < 0.01), but not for the Quilty lesion, coronary heart disease of donor, diabetes mellitus. Angiographically confirmed coronary vasculopathy and cardiac dysfunction (χ(2) = 0.94, P > 0.05 and χ(2) = 2.90, P > 0.05) were similar between microvasculopathy group and non-microvasculopathy group. CONCLUSION: Post heart transplantation microvasculopathy is an immune-mediated phenomenon and associated with higher mean score of acute cellular rejection and higher numbers of ≥ grade II acute rejection but was not the prognostic risk factor for coronary vasculopathy and function reduction after heart transplantation.

Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review.

BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O'Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors' affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus' origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term.

Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

INTRODUCTION: Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. MATERIALS AND METHODS: Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. RESULTS: Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. CONCLUSIONS: Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

2-(4-Amino-phen-yl)-1,3-benzothia-zole.

The title compound, C(13)H(10)N(2)S, contains two independent mol-ecules in its asymmetric unit, with slightly different conformations. In one mol-ecule, the dihedral angle between the benzothia-zole unit and the benzene ring is 6.73 (1)°, while the corresponding angle in the other mol-ecule is 1.8 (1)°. In the crystal structure, the mol-ecules are linked into layers by N-H⋯N hydrogen bonds.

4-(1,3-Benzothia-zol-2-yl)-N-(2-pyridylmeth-yl)aniline monohydrate.

In the title compound, C(19)H(15)N(3)S·H(2)O, the benzothia-zole ring system forms a dihedral angle of 7.22 (1)° with the benzene ring and the benzene ring forms a dihedral angle of 80.89 (1)° with the pyridine ring. An intra-molecular N-H⋯O inter-action is present. The crystal structure is stablized by inter-molecular O-H⋯N hydrogen bonds, π-π [centroid-centroid distances = 3.782 (1), 3.946 (1) and 3.913 (1) Å] and C-H⋯π inter-actions, forming a three dimensional-network.

[Clinicopathologic analysis of dilated heart in cardiac transplant recipients].

OBJECTIVE: To study the pathologic features of dilated heart in cardiac transplant recipients, with clinicoradiologic correlation. METHODS: Sixty recipient hearts from cardiac transplantation performed in Fuwai Hospital were analyzed by gross examination, histologic observation and electron microscopy. Clinicoradiologic correlation was available in 40 cases. RESULTS: Amongst the 40 cases of dilated heart, 52.5% (21/40) were due to dilated cardiomyopathy, 22.5% (9/40) due to arrhythmogenic right ventricular cardiomyopathy, 15.0% (6/40) due to ischemic cardiomyopathy, and the remaining 10.0% (4/40) due to miscellaneous causes, including local noncompaction of ventricular myocardium, giant cell myocarditis, alcoholic cardiomyopathy and hypertensive cardiomyopathy. The discrepancy rate between clinical and pathologic diagnosis was 37.5% (15/40). The erroneous categories included arrhythmogenic right ventricular cardiomyopathy (7 cases), ischemic cardiomyopathy (5 cases), and giant cell myocarditis (1 case), which were all mistaken clinically as dilated cardiomyopathy. While ischemic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, noncompaction of ventricular myocardium and giant cell myocarditis have distinctive pathologic features, the diagnosis of alcoholic and hypertensive cardiomyopathies required clinicopathologic correlation. Dilated cardiomyopathy due to viral myocarditis was not identified in the cases studied. CONCLUSION: Pathologic examination is essential in analysis of transplant recipient heart and helps to rectify clinical diagnostic discrepancy.

CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson's disease model.

Parkinson's disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP+-treated neurons. Furthermore, XBP1s was identified as a substrate of CDK5 and that the phosphorylation of XBP1s at the Ser61 residue enhances its nuclear migration, whereas mutation of the residue to alanine substantially reduces its nuclear translocation and activity. Importantly, phosphorylated XBP1s acts as a nuclear transcription factor for multiple target genes, including metabolic-related genes, FosB, and non-coding RNAs. Our findings confirm that the IRE1α/XBP1 pathway is activated in PD, and reveal a novel role of XBP1s in the pathogenesis of PD. This pathway may be a new therapeutic strategy for PD.

[Beneficial effects of carvedilol on cardiomyocyte apoptosis and bcl-2/bax expression after acute myocardial infarction an experiment with rats].

OBJECTIVE: To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction (AMI). METHODS: Eighty-three female SD rats underwent ligation of left anterior descending coronary artery, and were randomly assigned to 2 groups 24 hours later: carvedilol (n = 40, 10 mg.kg(-1).d(-1)was administered via direct gastric gavage 24 hs after the ligation, Group C) and AMI control group (n = 43, normal saline of the same volume was given by gastric gavage, Group MI). Another 27 rats were used as sham operation group (Group S, administered with normal saline too). The rats of each group were killed and their hearts were taken out 48 hours and 4 weeks after observation respectively (MI-48 h, MI-4 week, C-48 h, C-4 week, S-48 h, and S-4 week subgroups). TUNEL and DNA gel electrophoresis were used to detect the cardiomyocyte apoptosis. Immunohistochemistry and Western blotting were used to detect the expression of bcl-2 and bax. RESULTS: The apoptotic indices of the infracted/scar, border and non-infarcted areas at any time-point of Group MI were all significantly higher than those of Group S (all P < 0.05). Only the apoptotic indices of the infracted/scar and border areas of the C-4 week subgroup were significantly lower than those of the MI-4 week subgroup (both P < 0.05), and were close to those of the non-infarcted area. DNA gel electrophoresis showed that the positive rate of Group S at any time-point were both 0, the positive rate of MI-48 h subgroup and C-48 h subgroup were both significantly higher than that of Group S (both P < 0.05) without significant difference between these 2 groups, and the positive rates of the MI-4 week subgroup and C-4 week subgroup were both 0. Immunohistochemistry showed that the bax gene expression was slightly to significantly increased in the infarcted/scar, border, and non-infarcted areas of the MI-48 h and MI-4 week subgroups. The bcl-2 expression was significantly increased only in the infracted area of the MI-48 h subgroup. The bcl-2 expression was slightly increased in the infracted and border areas of the C-48 h subgroup and the bax expression was significantly decreased in the infracted/scar area of the C-4 week subgroup. Western blotting showed that (1) the bcl-2 expression of the S-4 week subgroup was significantly higher than that of the S-48 h subgroup (P < 0.05), (2) the bcl-2 expression and bax expression of the MI-48 h subgroup were significantly higher than that of the S-48 h subgroup (P < 0.05 - 0.01), the bcl-2/bax ratio of the MI-48 h subgroup was significantly lower that that of the S-48 h subgroup, however, there were no significant differences in the bcl-2 and bax expression and bcl-2/bax ratio between the MI-4 week subgroup and S-48 h subgroup (all P > 0.05), and (3) There were no significant difference in the bcl-2 and bax expression between Group A and Group S (all P > 0.05), however, the bcl-2/bax ratios at the 2 time-points of Group C were both significantly higher than those of Group MI. CONCLUSION: Cardiomyocyte apoptosis occurs in the infarction/scar, border and non-infarcted areas after AMI. Prolonged treatment with carvedilol reduces cardiomyocyte apoptosis in the scar and border areas and increases the expression ratio of bcl-2/bax.

[Clinicopathologic studies of 11 cases of primary cardiac valve tumors].

OBJECTIVE: To study the clinicopathologic features of primary cardiac valve tumors. METHODS: Eleven cases of primary valve tumors collected from Fuwai Hospital during the period from 1983 to 2005 were enrolled into the study. The tumors were stained with hematoxylin and eosin and Weigert-Van Gieson stain. Immunohistochemistry was also carried out in selected examples. RESULTS: Primary cardiac valve tumors were uncommon and accounted for only 3% (11/426) of all primary cardiac tumors. Most of them (10/11) were benign and malignancy was rarely encountered (1/11). The tumor subtypes included papillary fibroelastoma (4/11), cavernous hemangioma (4/11), glomus tumor (1/11), angiosarcoma (1/11) and hamartoma (1/11). Of the 11 tumors studied, 4 involved the tricuspid valve, 4 involved the mitral valve, 2 involved the pulmonary valve and 1 involved the aortic valve. The diagnosis was established by preoperative echocardiography in 7 patients. The remaining 4 cases were either misdiagnosed or undiagnosed. CONCLUSIONS: Preoperative diagnosis of primary cardiac valve tumors can be difficult due to lack of detailed information related to this group of lesions. Although benign cardiac valve tumors carry a good prognosis, the clinical outcome may be disastrous as a result of hemodynamic disturbances. Intraoperative frozen section examination is advisable for guiding proper surgical management.

[Effects of atenolol and metoprolol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction in rats].

OBJECTIVE: To compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats. METHODS: AMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis. RESULTS: Compared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05). CONCLUSION: Both Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.

[Pathological changes of radial artery used for coronary artery bypass grafting and its related risk factors for intimal hyperplasia].

OBJECTIVE: To examine the degree of intimal hyperplasia and the prevalence of atherosclerosis in radial arteries taken from the patients undergoing coronary artery bypass grafting (CABG), and to analyze the risk factors to obtain some helpful information for choosing arterial conduits. METHODS: Forty-one radial arteries and 11 internal mammary arteries samples were collected. The average age of patients was 48.5 years, and they all were male. Intimal hyperplasia, atherosclerosis, medial calcification were evaluated by routine histological methods, and the severity of diseases was measured on the percentage of luminal narrowing and the intima-to-media ratio (the intima area/media area). The risk factors for coronary heart disease were also analyzed. RESULTS: Ninety-three percent (38 of 41) of radial arteries showed mild intimal hyperplasia, which was not regarded to influence blood flowing after CABG. As a part of them, 54% (22/41) of radial arteries had a lower than 25% of luminal narrowing, meanwhile 39% (16/41) of radial arteries had the percentage of luminal narrowing between 25% and 50%. Only 7% (3 of 41) of radial arteries were found to have occlusive lesions, which made arterial lumen decreased more than 75%. The 3 patients including 2 with severe atherosclerosis and another 1 aged 17 years was involved by fibromuscular dysplasia. The later vessel was discarded after harvesting. The percentage of luminal narrowing and the intima-to-media ratio were higher in radial artery than that in internal mammary artery (t = 3.00, 2.49, P < 0.05). The two parameters were positively correlated with age (r = 0.398, 0.310, P < 0.05), but this study failed to show any relationship between intimal hyperplasia of radial artery and coronary lesions and other risk factors. Medial calcification was not found by routine histological method in all cases. CONCLUSION: Only mild intimal hyperplasia and no medial calcification are found in radial arteries used for CABG in the patients. Because the risk factors could not yet predict the severity of radial arterial lesions, this study strongly suggests that the Doppler ultrasonography and pre-operation clinical consideration should be emphasized to screen out some arteries with occlusive lesions.