Search

Background: Treatment of mild-moderate Alzheimer's disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores.Methods: For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline (N = 19 resveratrol-treated and N = 19 placebo-treated). We utilized multiplex Xmap technology to measure markers of neurodegenerative disease and metalloproteinases (MMPs) in parallel in CSF and plasma samples.Results: Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine (MDC), interleukin (IL)-4, and fibroblast growth factor (FGF)-2. Compared to baseline, resveratrol increased plasma MMP10 and decreased IL-12P40, IL12P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in mini-mental status examination (MMSE) scores, change in ADL (ADCS-ADL) scores, and CSF Aβ42 levels during the 52-week trial, but did not alter tau levels.Conclusions: Collectively, these data suggest that resveratrol decreases CSF MMP9, modulates neuro-inflammation, and induces adaptive immunity. SIRT1 activation may be a viable target for treatment or prevention of neurodegenerative disorders.Trial Registration: ClinicalTrials.gov NCT01504854. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a water-borne and widespread spirochetal zoonosis caused by pathogenic bacteria called leptospires. Human leptospirosis is an important zoonotic infectious disease with frequent outbreaks in recent years in China. Leptospirosis's emergence has been linked to many environmental and ecological drivers of disease transmission. In this paper, we identified the environmental and socioeconomic factors associated with leptospirosis in China, and predict potential risk area of leptospirosis using predictive models.Methods: Leptospirosis incidence data were derived from the database of China's web-based infectious disease reporting system, a national surveillance network maintained by Chinese Center for Disease Control and Prevention. We built statistical relationship between occurrence of leptospirosis and nine environmental and socioeconomic risk factors using logistic regression model and Maxent model.Results: Both logistic regression model and Maxent model have high performance in predicting the occurrence of leptospirosis, with AUC value of 0.95 and 0.96, respectively. Annual mean temperature (Bio1) and annual total precipitation (Bio12) are two most important variables governing the geographic distribution of leptospirosis in China. The geographic distributions of areas at risk of leptospirosis predicted from both models show high agreement. The risk areas are located mainly in seven provinces of China: Sichuan Province, Chongqing Municipality, Hunan Province, Jiangxi Province, Guangdong Province, Guangxi Province, and Hainan Province, where surveillance and control programs are urgently needed. Logistic regression model and Maxent model predicted that 403 and 464 counties are at very high risk of leptospirosis, respectively.Conclusions: Our results highlight the importance of socioeconomic and environmental variables and predictive models in identifying risk areas for leptospirosis in China. The values of Geographic Information System and predictive models were demonstrated for investigating the geographic distribution, estimating socioeconomic and environmental risk factors, and enhancing our understanding of leptospirosis in China. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China.Methods: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected.Results: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH2O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital.Conclusions: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China.Trial Registration: Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The emergence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) has become a significant problem worldwide and also being a major threat to children and newborns. Here we report an outbreak of NDM-1-producing K. pneumoniae in a neonatal unit. Results: Six CR-KP strains, isolated from neonates with symptoms of infection, were identified using a VITEK-2 compact system, and the clinical data were retrieved from the electronic case records. In vitro susceptibility testing with broth dilution method showed that all six K. pneumoniae isolates were resistant to carbapenems and susceptible to colistin, aminoglycosides, fluoroquinolones and tigecycline. Based on the polymerase chain reaction results, each isolate was found to be blaNDM-1 gene positive. Clonal relationships were analysed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and showed that two different PFGE patterns were formed, which belonged to sequence types ST234 and ST1412. Plasmids carrying blaNDM-1 were successfully transferred from four of the six isolates to an Escherichia coli recipient through conjugative assays. S1-PFGE and Southern blot hybridization showed that four NDM-1-producing K. pneumoniae were clonal and carried blaNDM-1 on the same plasmid. The outbreak was effectively controlled by reducing the potential infection sources. All the patients were successfully treated and recovered after receiving an increased dose of carbapenems. Although the source of this outbreak was not clear, comprehensive measures were carried out and the outbreak was effectively controlled. Conclusions: ST234 and ST1412 of NDM-1-producing Klebsiella pneumoniae are the resistant clone spread in the neonatal unit, comprehensive infection control measures and optimized carbapenem therapy played an important role in controlling this NDM-1-producing K. pneumoniae outbreak. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jiroveci pneumonia (PJP) in non-HIV patients is still a challenge for intensivists. The aim of our study was to evaluate mortality predictors of PJP patients requiring Intensive care unit (ICU) admission.Methods: Retrospectively review medical records of patients with diagnosis of PJP admitted to four ICUs of two academic medical centers from October 2012 to October 2015.Results: Eighty-two patients were enrolled in the study. Overall hospital mortality was 75.6 %. Compared with survivors, the non-survivors had older age (55 ± 16 vs. 45 ± 17, p = 0.014), higher APACHE II score (20 ± 5 vs. 17 ± 5, p = 0.01), lower white blood cell count (7.68 ± 3.44 vs. 10.48 ± 4.62, p = 0.005), less fever (80.6%vs. 100 %, p = 0.033), more hypotension (58.1 % vs. 20 %, p = 0.003), more pneumomediastinum (29 % vs. 5 %, p = 0.027). Logistic regression analysis demonstrated that age [odds ratio (OR)1.051; 95 % CI 1.007-1.097; p = 0.022], white blood cell count [OR 0.802; 95 % CI 0.670-0.960; p = 0.016], and pneumomediastinum [OR 16.514; 95 % CI 1.330-205.027; p = 0.029] were independently associated with hospital mortality.Conclusions: Mortality rate for non-HIV PJP patients requiring ICU admission was still high. Poor prognostic factors included age, white blood cell count and pneumomediastinum. [ABSTRACT FROM AUTHOR]

Background: Reduced expression of tripartite motif-containing 3 (TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma. In our previous research, we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma (HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients. However, the role of TRIM3 in liver cancer remains unknown. This study aimed to investigate the function of TRIM3 in liver cancer cells., Methods: The protein levels of TRIM3 in five liver cancer cell lines (SK-Hep1, Hep3B, Huh7, HepG2, Bel-7402) and one normal liver cell line (L02) were detected with Western blotting. HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3 (LV-TRIM3), whereas Huh7 and Hep3B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA (siTRIM3). The functions of TRIM3 in the proliferation, colony formation, cell cycle, migration, invasion, and apoptosis of the above cell lines were examined. The effect of TRIM3 on tumor growth and metastases in nude mice was also investigated., Results: TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection, which further reduced proliferation, colony formation, migration, and invasion of both cell lines. Cell cycle analysis showed that TRIM3 overexpression induced G 0 /G 1 phase arrest in HepG2 and Bel-7402 cells. Moreover, apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3. Contrarily, silencing TRIM3 expression in Huh7 and Hep3B cells by siTRIM3 led to significantly decreased percentages of both cells in the G 0 /G 1 phase and promoted cell proliferation, colony formation, migration, and invasion. In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis., Conclusions: TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G 0 /G 1 phase.

Background: Leptospirosis is a water-borne and widespread spirochetal zoonosis caused by pathogenic bacteria called leptospires. Human leptospirosis is an important zoonotic infectious disease with frequent outbreaks in recent years in China. Leptospirosis's emergence has been linked to many environmental and ecological drivers of disease transmission. In this paper, we identified the environmental and socioeconomic factors associated with leptospirosis in China, and predict potential risk area of leptospirosis using predictive models., Methods: Leptospirosis incidence data were derived from the database of China's web-based infectious disease reporting system, a national surveillance network maintained by Chinese Center for Disease Control and Prevention. We built statistical relationship between occurrence of leptospirosis and nine environmental and socioeconomic risk factors using logistic regression model and Maxent model., Results: Both logistic regression model and Maxent model have high performance in predicting the occurrence of leptospirosis, with AUC value of 0.95 and 0.96, respectively. Annual mean temperature (Bio1) and annual total precipitation (Bio12) are two most important variables governing the geographic distribution of leptospirosis in China. The geographic distributions of areas at risk of leptospirosis predicted from both models show high agreement. The risk areas are located mainly in seven provinces of China: Sichuan Province, Chongqing Municipality, Hunan Province, Jiangxi Province, Guangdong Province, Guangxi Province, and Hainan Province, where surveillance and control programs are urgently needed. Logistic regression model and Maxent model predicted that 403 and 464 counties are at very high risk of leptospirosis, respectively., Conclusions: Our results highlight the importance of socioeconomic and environmental variables and predictive models in identifying risk areas for leptospirosis in China. The values of Geographic Information System and predictive models were demonstrated for investigating the geographic distribution, estimating socioeconomic and environmental risk factors, and enhancing our understanding of leptospirosis in China.

Background: Increasing evidence indicates that alterations to the function and subunit composition of the glutamatergic NMDA receptor are associated with the pathophysiology of schizophrenia. The GluN2B protein is a structural and functional subunit of the NMDA receptor, with a growing body of evidence indicating it plays a critical role in cognitive functions mediated by the NMDA receptor. The hippocampus plays a key role in cognitive function, with studies suggesting lateralised glutamatergic dysfunction in this region may contribute to the cognitive deficits observed in schizophrenia patients. The present study, for the first time, investigated GluN2B protein and binding density in the left and right hippocampus of 20 schizophrenia subjects compared to 20 matched controls., Methods: The dentate gyrus of 20 schizophrenia and 20 control subjects, matched for age, post-mortem interval, and pH, was obtained from the NSW Tissue Resource Centre, Australia. Each group consisted of dentate gyrus from the left hemisphere (n = 10) and right hemisphere (n = 10). GluN2B protein density was measured via immunoblotting. GluN2B binding density was measured using the GluN2B antagonist, [3H] Ifenprodil. Analyses of covariance, covarying for demographic variables that influenced the data, were used to test for statistical significance between schizophrenia and control groups. Pearson's correlations were used to determine the association of GluN2B protein and binding density with demographic and clinical variables, including lifetime antipsychotic drug exposure., Results: GluN2B protein levels were decreased by 43% in the left hemisphere of schizophrenia subjects compared to controls (p = 0.012). There was no difference in GluN2B protein levels in the right hemisphere of schizophrenia subjects compared to controls. There were no differences in [(3)H] Ifenprodil binding according to diagnosis or hemisphere. There were no associations between GluN2B measures and lifetime antipsychotic drug exposure., Conclusions: Our findings provide the first evidence of GluN2 protein abnormalities in the hippocampus in schizophrenia, highlighting the hippocampal lateralisation in this disorder. We suggest this deficit could contribute to the cognitive dysfunctions that arise in patients. These findings provide preliminary support for the development of therapeutics that target the GluN2B subunit, as a novel therapy for schizophrenia, especially the cognitive dysfunctions.

Background: In China, even though the prevalence of dyslipidemia among adults increased yearly and dyslipidemia being an important risk factor for cardiovascular diseases among the Chinese population, however, the awareness, treatment and control of dyslipidemia are at low levels, and only limited studies on the influence factors associated with the awareness, treatment and control dyslipidemia in China have been carried out., Methods: The analysis was based on a representative sample of 7138 adult subjects aged 18~79 years recruited from a cross-sectional study of chronic disease and risk factors among adults in the Jilin province in 2012. Chi-square test was used to compare the rates of dyslipidemia awareness, treatment and control between different characteristics of participants. Multiple logistic regression analyses were performed separately for each group to explore the associations between participants' characteristics and dyslipidemia awareness, treatment and control., Results: Among participants with dyslipidemia, 11.6% were aware of the diagnosis, 8.4% were receiving treatment, and 34.8% had dyslipidemia controlled. Increase in age and BMI ≥ 24 kg/m2 were by far the strongest risk factors associated with better awareness and treatment of dyslipidemia. Retirees were more likely to be aware of their dyslipidemia condition (OR=1.255; 95% CI: 1.046, 1.506) and to be receiving treatment (OR=1.367; 95% CI: 1.114, 1.676) than manual workers. A family history of dyslipidemia increased the likelihood of awareness (OR=3.620; 95% CI: 2.816, 4.653) and treatment (OR=3.298; 95% CI: 2.488, 4.371) of dyslipidemia. Alcohol drinking and physical activity were associated with a lower level of awareness and treatment.Cigarette smokers (OR=0.501; 95% CI: 0.349, 0.719) and those with BMI ≥ 24 kg/m2 (OR=0.480; 95% CI: 0.326, 0.706) who received treatment were also associated with poor dyslipidemia control., Conclusion: Our study highlights low levels of awareness, poor treatment and control of dyslipidemia among adults aged 18~79 in the Jilin province. Promotion of healthy lifestyles and establishment of a comprehensive strategy of screening, treatment and control of dyslipidemia is needed to reduce or prevent the risk of cardiovascular disease in the Jilin province.

Background: Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios., Results: We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors., Conclusions: We suggest that thienobenzodiazepines 8b and 8c with lower binding affinity for the H1 receptors, but similar 5HT2A/D2 receptor binding affinity ratios to those of olanzapine. These compounds may offer a better pharmacological profile than olanzapine for treating patients with schizophrenia.

Background: Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF) in breast cancer patients undergoing endocrine therapy in an urban area., Methods: Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371) in the study. The 315 women who responded to the questionnaire (84.9%), 54 (17.1%) had completed endocrine therapy and 261 (82.9%) were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months); the average age was 48 (range, 33 to 72) years. The 11-point scale and Visual Analog Scale (VAS) were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF., Results: Among the 315 patients, 189 (60%) had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index), clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF., Conclusions: The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF and lifestyle in the management of breast cancer patients.