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Background Housework may provide a sustainable form of physical activity for older adults and improve health and survival outcomes. Longitudinal studies on associations between housework status over time and health outcomes are lacking. We aim to assess the longitudinal association of intensity and duration of housework with frailty and mortality outcomes. Methods Among 3270 community-dwelling prospective cohort study participants, aged ≥55 years, data on light housework (N=2996) and heavy housework (N=3022) were available at baseline (March 6, 2009, to June 11, 2013) and follow-up at 3 to 5 years later, (January 16, 2013 to August 24, 2018). Median time spent per week on light (≥420min/week) and heavy (>0min/week) household activities at baseline and follow-up were used to categorise individuals into three groups (i) consistent low levels of housework at both baseline and follow-up, (ii) inconsistent high levels of housework at either baseline or follow-up and (iii) consistent high levels of housework at both baseline and follow-up. Baseline and follow-up frailty index >0.10, and all-cause, cancer and cardiovascular mortality from mean 9.5 years follow-up to March 31, 2021. Effect estimates were adjusted for socio-demographics, nutritional risk, lifestyle and other physical activities. Results Overall, participants had mean [SD] age, 66.9 [7.8] years; 1916 [62.7%] were female. Participation in high levels of light and heavy housework consistently over time was associated with decreased odds of prefrailty/frailty at follow-up, [OR,0.61;95%CI,0.40–0.94] and [OR,0.56;95%CI,0.34–0.90] respectively, in the older group aged ≥65, compared to participants with consistent low levels of housework at baseline and follow-up. Sex-stratified analysis revealed an association between regular heavy housework participation and lower prevalence of prefrailty/frailty at follow-up in older men but not women [OR,0.31;95%CI,0.13–0.72]. Regular participation in high levels of light housework was associated with 41% lower risk of all-cause mortality [95%CI,0.36–0.96] in women but not in men, and 54% lower risk of cardiovascular mortality [95%CI,0.22–0.96]. Conclusions Regular participation in above average levels of light housework is associated with decreased odds of prefrailty/frailty in older adults aged ≥65 years, and all-cause mortality in older women. Heavy housework participation is associated with decreased odds of prefrailty/frailty, especially in older men aged ≥65. Housework may be a meaningful occupation for older adults and should be encouraged for health and wellbeing.

Experimental evidence suggest that tea polyphenols have anti-depressant effect and tea consumption may reduce the risk and severity of depression. We investigated whether tea consumption was associated with changes in depressive symptoms over time among Asian older adults. Population-based prospective cohort study with mean 4 years of follow up. Singapore Longitudinal Ageing Study (SLAS) of community-living older persons. 3177 participants overall (mean age 67 years) and 3004 participants who were depression-free at baseline. Baseline tea consumption which include Chinese (black, oolong or green) tea or Western (mixed with milk) tea and change in Geriatric Depression Scale (GDS) measure of depression. Incident depression was defined by GDS≥5, and GDS depression improvement or deterioration by GDS change of ≥4 points. Estimated odds ratio and 95% confidence intervals (OR, 95%CI) were adjusted for baseline age, sex, ethnicity, education, housing type, single/divorced/widowed, living alone, physical and social activity, smoking, alcohol, number of comorbidities, MMSE, and baseline GDS level. Compared to non-tea drinkers, participants who consumed ≥3 cups of tea of all kinds were significantly less likely to have worsened GDS symptoms: OR=0.32, 95% CI=0.12, 0.84. Among baseline depression-free participants, the risk of incident GDS (≥5) depression was significantly lower (OR=0.34, 95%CI=0.13, 0.90) for daily consumption of all types of tea, and Chinese (black, oolong or green) tea (OR=0.46, 95%CI=0.21,0.99). This study suggests that tea may prevent the worsening of existing depressive symptoms and the reduce the likelihood of developing threshold depression.

Introduction: The identification of modifiable health span-promoting factors is a public health priority. Objective: To explore the socio-environmental, lifestyle, behavioural, and psychological determinants of a clinical phenotypic measure of biological ageing in the Singapore Longitudinal Ageing Study (SLAS) cohort. Methods: Using cross-sectional data on 2,844 SLAS-2 adults with a chronological age (CA) ≥55 years, we estimated biological age (BA) using a validated panel of clinical, biochemical, physiological, and functional indicators (8 in men and 10 in women) and calculated the difference between BA and CA (BA – CA in years). Potential determinants included education, housing status, loss of a spouse, living alone, lifestyle and health activity, smoking, alcohol consumption, nutritional risks, consumption of milk, soy, fruit, vegetables, coffee and tea, sleep parameters, and life satisfaction. Results: The mean CA was 67.0 (standard deviation [SD] 7.9; range 55–94) years. The estimated BA varied more widely (SD 8.9 years; range 47.5–119.9 years), and BA – CA ranged from –11.3 to 30.0 years. In stepwise selection regression analyses, multiple significant independent determinants in a final model were larger for private housing, being single/divorced/widowed, productivity, cognitive and leisure time activity scores, 10 h/week of moderate-to-vigorous physical activity, unintended loss of weight, life satisfaction, and daily consumption of fruits 1–2 or ≥3 servings and Chinese tea 1–2 or ≥3 cups daily, together explaining 16% of BA – CA variance in men and 14% in women. Associated BA – CA estimates were highest in men with high-end housing status (–1.8 years, effect size 0.015) and unintended weight loss (1.5 years, effect size 0.017). Conclusion: We identified determinants of biological ageing which can promote health span.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis and the destruction of small joints. Emerging evidence shows that immunoglobulin D (IgD) stimulation induces T-cell activation, which may contribute to diseases pathogenesis in RA. In this study, we investigated the downstream signaling pathways by which IgD activated T cells as well as the possible role of IgD in the T–B interaction. Peripheral blood mononuclear cells were isolated from peripheral blood of healthy controls and RA patients. We demonstrated that IgD activated T cells through IgD receptor (IgDR)-lymphocyte-specific protein tyrosine kinase (Lck)-zeta-associated protein 70 (ZAP70)/phosphatidylinositol 3-kinase (PI3K)/nuclear factor kappa-B (NF-κB) signaling pathways; IgD-induced CD4(+) T cells promoted the proliferation of CD19(+) B cells in RA patients. A novel fusion protein IgD-Fc-Ig (composed of human IgD-Fc domain and IgG(1) Fc domain, which specifically blocked the IgD–IgDR binding) inhibited the coexpression of IgDR and phosphorylated Lck (p-Lck) and the expression levels of p-Lck, p-ZAP70, p-PI3K on CD4(+) T cells, and decreased NF-κB nuclear translocation in Jurkat cells. Meanwhile, IgD-Fc-Ig downregulated the expression levels of CD40L on CD4(+) T cells as well as CD40, CD86 on CD19(+) B cells in RA patients and healthy controls. It also decreased the expression levels of CD40L on CD4(+) T cells and CD40 on CD19(+) B cells from spleens of collagen-induced arthritis (CIA) mice and reduced IL-17A level in mouse serum. Moreover, administration of IgD-Fc-Ig (1.625–13 mg/kg, iv, twice a week for 4 weeks) in CIA mice dose-dependently decreased the protein expression levels of CD40, CD40L, and IgD in spleens. IgD-Fc-Ig restrains T-cell activation through inhibiting IgD-IgDR-Lck-ZAP70-PI3K-NF-κB signaling, thus inhibiting B-cell activation. Our data provide experimental evidences for application of IgD-Fc-Ig as a highly selective T cell-targeting treatment for RA.

Background: Basic fibroblast growth factor (bFGF) plays an important role in the pathogenesis of acute myeloid leukemia (AML). Whether the levels of circulating bFGF are increased or not in untreat...

Objective Injured tubular reabsorption is highlighted as one of the causes of increased albuminuria in the early stage of diabetic nephropathy; however, the underlying mechanism has not been fully elucidated. In this study, we aimed to explore whether reducing inflammation and remodeling the insulin signaling pathway could improve albumin uptake of renal tubules. Methods 8-week-old male db/db mice (

Background/Aim: Studies of the associations of the metabolic syndrome (MetS) with cognitive function and decline are inconclusive. We investigated the associations of the MetS with cognitive functions in 823 Chinese >55-year-olds followed up over 4.5 years. Methods: The relationships between the MetS and baseline and follow-up z-scores of cognitive domain functions were examined using mixed model analysis. Results: There were specific inverse cross-sectional associations of single cardiometabolic risk factors with cognition, such as hyperglycemia with processing speed (p = 0.045). The MetS was negatively associated with 3 out of 4 cognitive domains (p = 0.018 to p = 0.003), and the count of cardiometabolic risk factors with all cognitive domains (p = 0.025 to p = 0.002). Longitudinally, dyslipidemia was associated with worse decline in memory and learning (p = 0.022). The count of cardiometabolic risk factors was associated with worse declines in cognition (p = 0.032 for global cognition). Conclusion: Among middle-aged and older Asians, an increased number of component cardiometabolic risk factors of the MetS was associated with a worse decline in cognitive function over time.

Background The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. Methods From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. Results Eighty nine TACE procedures (1.35 ± 0.67; 1–4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), “typical tumor enhancement” (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. Conclusions The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

Aim Neuropathic pain responds poorly to drug treatments. Partial relief is achieved in only about half of the patients. Danggui Sini decoction (DSD), an aqueous extract of Angelica sinensis, Ramulus Cinnamomi, and Radix Puerariae, has been used extensively in China to treat inflammatory and ischemic diseases. The current study examined the putative effects of DSD on neuropathic pain. Method We used two commonly-used animal models: chronic constriction injury (CCI) and diabetic neuropathy for the study. And we examined effects of DSD on pain response, activation of microglia and astroglia in spinal dorsal horn, and expression of proinflammatory cytokines in the spinal cord. Results Consecutive intragastric administration of DSD (25 - 100 mg/kg) for 10 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models, DSD inhibited the over-expression of specific markers for microglia (Iba-1) and astroglia (GFAP) activation in the spinal dorsal horn. DSD also reduced the elevated nuclear NF-κB level and inhibited the up-regulation of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. Conclusion DSD can alleviate CCI and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of DSD may be related to the suppression of spinal NF-κB activation and/or cytokines expression. .

An impaired gut―liver axis is a potential factor that contributes to alcoholic liver disease. Specifically, ethanol decreases intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is negatively altered following acute ethanol exposure. This study aimed to determine whether kaempferol could protect against alcoholic liver injury (AALI) in mice by regulating tight junction (TJ) proteins and butyrate receptors and transporters in intestines. Male Institute of Cancer Research (ICR) mice were randomly divided into five treatment groups: control, ethanol administered (5 g/kg), and the low-, medium- and high-dosage kaempferol (25, 50, 100 mg/kg) treatments. Intestinal expression was evaluated for the TJ proteins ZO-1 and occludin and the butyrate receptor GPR109A and butyrate transporter SLC58A proteins, in addition to plasma ALT and AST levels and pathomorphological changes in liver and intestinal tissues. The expression of the TJ proteins ZO-1 and occludin, butyrate receptors, and butyrate transporters in the ileum and proximal colon decreased in AALI mice, while plasma ALT and AST levels markedly increased. Kaempferol supplementation reversed these effects. These results suggest that kaempferol could serve as a prophylactic treatment against AALI in mice by increasing the expression of butyrate receptors, transporters, and TJ proteins in the intestinal mucosa.

Objective To investigate diet adherence, medication adherence and self-care behaviour among patients with chronic heart failure (CHF) in a multi-ethnic society and identify the significant factors associated with their diet and medication adherence. Methods A cross-sectional descriptive correlational study was conducted with a convenience sample of 107 patients with CHF recruited from two cardiology wards of a public tertiary hospital in Singapore. Study variables were measured using the Dietary Sodium Restriction Questionnaire, the Medication Adherence Rating Scale-5 items and the European Heart Failure Self-care Behaviour Scale-12 items. Results Our sample reported positive attitudes towards diet adherence, poor self-care behaviour, and good medication adherence. The multiple linear regression results indicated that lower income, Chinese ethnicity, diabetic complications, current smoking, lower New York Heart Association classification I and II, and poorer self-care behaviour predicted poorer diet adherence. In addition, absence of hypertension, having non-myocardial infarction as a cause of CHF, and moderately diminished ejection fraction were identified as significant predictors of poorer medication adherence. Conclusion The findings from this study have established the need to improve current education and rehabilitation programmes for patients with CHF by addressing those factors significantly influencing their adherence to diet and medication.

Background: Heavy episodic drinking (HED) can have health and social consequences. This study assesses the associations between HED and demographic, socioeconomic, motivation and effects indicators for people aged 18&ndash, 34 years old living in four cities in different regions of the world. Method: Multistage random sampling was consistent across the four cities (Ilorin (Nigeria), Wuhan (China), Montevideo (Uruguay) and Moscow (Russia)). The questionnaire was forward/back translated and face-to-face interviewing was undertaken. A total of 6235 interviews were undertaken in 2014. Separate univariable and multivariable modelling was undertaken to determine the best predictors of HED. Results: HED prevalence was 9.0%. The best predictors differed for each city. The higher probability of HED in the final models included beliefs that they have reached adulthood, feeling relaxed as an effect of drinking alcohol, and forgetting problems as an effect of drinking alcohol. Lower probability of HED was associated with not being interested in alcohol as a reason for limiting alcohol, and the belief that drinking alcohol is too expensive or a waste of money. Conclusion: Although some indicators were common across the four cities, the variables included in the final models predominantly differed from city to city. The need for country-specific prevention and early intervention programs are warranted.

Background The objective of this study is to analyze the treatment outcome and secondary reactions in 98 patients with stage I–III cervical carcinoma who underwent postoperative radiotherapy. Methods From 2006 to 2014, 98 patients with stage I–III cervical carcinoma were treated with postoperative radiotherapy. The major histological type, found in 92.86% of the patients (91 cases), was squamous cell carcinoma. Patients were staged according to the 2002 TNM guidelines. The postoperative radiotherapy methods included two-field irradiation (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates were represented using Kaplan-Meier curves, and prognosis analyses were performed using Cox multivariate analyses. Results The 5-year overall survival and progression-free survival rates were 82.0 and 76.0%, respectively. Only one patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and 4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%), respectively. Multivariate analyses showed that anemia before radiotherapy and tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. Conclusions Postoperative radiotherapy for patients with risk factors of cervical cancer procured good efficacy levels with mild side effects. Anemia and tumor size were important OS predictors.

Diabetic neuropathy is characterized by progressive degeneration of nerve fibers associated with diabetes mellitus. Antidepressants and anticonvulsants are the mainstay of pharmacological treatment, but are often limited in effectiveness against the core clinical feature of pain. In the current study, we examined the potential effects of koumine, a Gelsemium elegans Benth alkaloid, using a rat model of diabetic neuropathy. Rats were administered intraperitoneally a single dose of streptozocin (60 mg/kg) to induce type 1 diabetes. Koumine was given at a dose range of 0.056-7 mg/kg subcutaneously for one week starting 3 weeks after streptozocin adminstration. Behavioral responses to mechanical stimuli were evaluated every day after streptozocin injection. At 4 weeks after streptozocin injection, sensory nerve conduction velocity (SNCV) and morphological alternation of sciatic nerves were assessed by electron microscopy. Diabetic rats developed mechanical hyperalgesia within 3 weeks after streptozocin injection and exhibited reduced SNCV and impaired myelin/axonal structure. Koumine treatment of diabetic rats decreased neuropathic pain behavior as early as after the first administration. At a dose of 7 mg/kg, koumine was more effective than gabapentin (100 mg/kg), and decreased mechanical sensitivity threshold to a level comparable to healthy control. Repeated treatment of koumine significantly reduced the damage to axon and myelin sheath of the sciatic nerve and increased SNCV, without affecting body weight and blood glucose. These findings encourage the use of koumine in the treatment of diabetic neuropathy.

Aim: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. Methods: Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. Results: A total of five separate case–control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/−polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/−polymorphism with PCa (p0.05). Conclusion: These analyses suggest that XPC gene PAT+/−polymorphism, but not rs2228001, likely contributes to susceptibility to PCa.

Systemic lupus erythematosus (SLE) is a severe complex rheumatic disease, but good estimate of its prevalence and risk factors is lacking in China. The aim of the study was to explore the prevalence of SLE and risk factors in rural areas of Anhui Province of China. Eleven counties were randomly selected in Anhui Province, and then, 15% of the villages in selected counties were randomly sampled as study sites. Patients with SLE were identified through two phases. Based on the cases identified, a population-based case-control study was designed to examine risk factors associated with SLE. A total of 1,253,832 individuals and identified 471 SLE cases were surveyed. Crude and age-standardized prevalence were estimated at 37.56 and 36.03 per 100,000 persons, respectively. Gender difference in the prevalence of SLE was significant (P = 4.62 × 10(-76)), and the age-standardized prevalence was 6.17 for males and 67.78 for females per 100,000 persons. The distribution of SLE prevalence was significant by age group (P = 1.78 × 10(-53)), and the peak prevalence was observed at 40-50 years. Multiple environmental factors were associated with SLE, including birth conditions, sweet food, cooking oil, taste, fruit consumption, sunlight exposure, quality of sleep, physical activities, drinking water, residence, negative life events, hepatitis B vaccine, age of menarche, and age at birth of first child (P0.05). Our large population-based epidemiological survey estimated the prevalence of SLE at 37.56 per 100,000 persons. Multiple environmental factors were associated with the development of SLE.

Although glucocorticoids (GCs) are effective in inducing remission in systemic lupus erythematosus (SLE) patients, there is a significant variation in response to therapeutic GCs, and some patients do not achieve full remission. The aim of this study was to explore the impact of environmental factors on the efficacy of GCs in a Chinese population with SLE. This was a prospective cohort study, and a total of 260 SLE patients treated with GCs (prednisone) were followed up for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index. Environmental factors were collected using a questionnaire. Single-variable analysis and multivariate logistic regression analysis were used to discriminate the impact of environmental factors on the efficacy of GCs. Two hundred forty-seven patients (95.00 %) completed the 12-week follow-up. Among these patients, 131 (53.04 %) were classified into sensitive group and 116 (46.96 %) were classified into insensitive group. Results from logistic analysis showed that the following environmental factors were significantly associated with decreased efficacy of GCs: high salt intake (OR = 3.464, 95%CI = 1.481–8.102, P = 0.004), introverted personality (OR = 3.550, 95%CI = 1.901–6.628, P

Benzene is an important industrial chemical and an environmental contaminant, but the pathogenesis of hematotoxicity induced by chronic occupational benzene exposure (HCOBE) remains to be elucidated. To gain an insight into the molecular mechanisms and developmental biomarkers for HCOBE, isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) were utilized. Identification and quantitation of differentially expressed proteins between HCOBE cases and healthy control were thus made. Expressions of selected proteins were confirmed by western blot and further validated by ELISA. A total of 159 unique proteins were identified (≥95% confidence), and relative expression data were obtained for 141 of these in 3 iTRAQ experiments, with fifty proteins found to be in common among 3 iTRAQ experiments. Plasminogen (PLG) was found to be significantly up-regulated, whereas platelet basic protein (PBP) and apolipoprotein B100 (APOB100) were significantly down-regulated in the serum of HCOBE cases. Additionally, the altered proteins were associated with the molecular functions of binding, catalytic activity, enzyme regulator activity and transporter activity, and involved in biological processes of apoptosis, developmental and immune system process, as well as response to stimulus. Furthermore, differential expressions of PLG, PBP and APOB100 were confirmed by western blot, and the clinical relevance of PBP and APOB100 with HCOBE was validated by ELISA. Overall, our results showed that lowered expression of PBP and APOB100 proteins served as potential biomarkers of HCOBE, and may play roles in the benzene-induced immunosuppressive effects and disorders in lipid metabolism.

Background Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. Objectives To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. Search methods We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. Selection criteria Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. Data collection and analysis Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. Main results We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. Authors' conclusions There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.

In our previous study, we found that glucocorticoid receptor (GR) gene genetic polymorphisms may play a major role in the efficacy of glucocorticoids (GCs) in Chinese systemic lupus erythematosus (SLE) patients. The aim of this study is to explore the association of GR gene genetic polymorphisms and improvement of health-related quality of life (HRQOL) in Chinese SLE patients treated with GCs. A total of 195 Chinese SLE patients were treated with GCs for 12 weeks. The HRQOL of patients was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and 12 weeks. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. One hundred eighty-four patients (94.36 %) completed the 12-week follow-up. Twenty-three single-nucleotide polymorphisms of GR gene were genotyped. There was a significant association between rs10482672 polymorphism and improvement in physical function (P = 0.043), general health (P = 0.024), and social function (P = 0.013). The rs12656106 polymorphism was associated with improvement in the total score of SF-36 (P = 0.014), physical function (P = 0.013), general health (P = 0.010), vitality (P = 0.015), social function (P = 0.004), physical component summary (P = 0.016), and mental component summary (P = 0.014). The rs4912905 polymorphism was associated with improvement in bodily pain (P = 0.040) and general health (P = 0.038). The rs4912911 polymorphism was associated with improvement in general health (P = 0.026) and vitality (P = 0.027). The rs4986593 polymorphism was associated with improvement in bodily pain (P = 0.034). The rs7719514 polymorphism was associated with improvement in vitality (P = 0.002) and mental component summary (P = 0.041). We also found a significant association between rs9324924 polymorphism and improvement in physical function (P = 0.040), bodily pain (P = 0.007), and general health (P = 0.019). These results indicate that there may be an association of GR gene rs10482672, rs12656106, rs4912905, rs4912911, rs4986593, rs7719514, and rs9324924 polymorphisms with improvement of HRQOL in Chinese SLE patients treated with GCs.

Inflammatory pain and neuropathic pain are major health issues that represent considerable social and economic burden worldwide. In this study we investigated the potential of obtusifolin and gluco-obtusifolin, two anthraquinones found in the seeds of the widely used traditional Chinese medical botanical Cassia obtusifolia, to reduce neuropathic and inflammatory pain. The potential analgesic effects of obtusifolin and gluco-obtusifolin were evaluated by mice formalin test and complete Freund's adjuvant (CFA)-induced nociceptive behaviors in rats. Chronic constriction injury (CCI), L5 spinal nerve ligation (L5 SNL), diabetes, and chemotherapeutics inducing allodynia were used to test whether repeated treatment with obtusifolin and gluco-obtusifolin ameliorated neuropathic pain. Finally, we explored whether obtusifolin and gluco-obtusifolin altered the degree of neuroinflammation in rat spinal cord after CFA administration and CCI induction. Obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reduced licking/biting time in dose-dependent manner in phase 2 of formalin-induced behavior in mice. Furthermore, repeated administration of obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed mechanical allodynia induced by CFA, CCI, L5 SNL, diabetes, and oxaliplatin in a dose-dependent manner in rats. Levels of activated nuclear factor-kappa B (NF-κB) and proinflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α)) in lumbar spinal cord were elevated in rats following CFA treatment and CCI induction, and obtusifolin and gluco-obtusifolin significantly inhibited these effects. Our results demonstrate that obtusifolin and gluco-obtusifolin produce significant antinociceptive action in rodent behavioral models of inflammatory/neuropathic pain, and that this activity is associated with modulation of neuroinflammation in spinal cord.

Hypoxia-inducible factor 1 (HIF-1) introduced the immune imbalance between Th17 and Treg cells, which may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of the present study was to determine whether the HIF1A gene influences the susceptibility to SLE. A study on this relationship has not been conducted to date. A total of 3,793 subjects (1,497 SLE patients and 2,296 controls) were included in this study. The genotyping of five single-nucleotide polymorphisms (SNPs) (rs11549465, rs12434438, rs1957757, rs1951795, rs7143164) was determined by Sequenom MassARRAY technology. The statistical analysis was conducted using chi-square test. Odds ratio (OR) with 95 % confidence interval (CI) was calculated using unconditional logistic regression with adjustment of age and sex. The allele frequencies were not associated with the disease. No significant differences in genotype frequencies existed between the patients with SLE and the controls in all five SNPs. It is worth mentioning that the allele T at rs11549465, located at the exon sequence, revealed a trend but no significant difference towards the more frequent allele T in SLE than in controls (C versus T: OR = 1.206, 95 % CI = 0.972–1.495, p = 0.088). The genotype effects of recessive, dominant, and codominant models were observed; however, no significant evidence for association was detected. Our findings suggest that the gene polymorphisms of HIF1A might not contribute to SLE susceptibility in the Chinese population. However, further studies are needed on an independent cohort from different genetic backgrounds to confirm HIF1A as an SLE genetic factor.

The aim to this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of interleukin (IL)-23 receptor gene and systemic lupus erythematosus (SLE) in a Chinese population. A case–control study was performed to investigate the associations of SNPs in IL-23R gene (rs10889677 and rs1884444) with susceptibility to SLE in 521 Chinese SLE patients and 527 normal controls. The chi-square test and unconditional Logistic regression were used to analysis by SPSS 10.1 software. No significant differences were detected for the distribution of allele and genotype frequencies of these two SNPs between patients and controls as well as SLE patients with nephritis (LN) and those without nephritis. The findings suggest that the polymorphisms of IL-23R gene might not contribute to the susceptibility of SLE in the Chinese population.

The P2X7 receptor is a ligand-gated cationic channel receptor that is actived by ATP and normally expressed by a variety of immune system cells, including macrophages and lymphocytes. Because it leads to release of IL-1β and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of autoimmune inflammatory diseases, such as systemic lupus erythematosus (SLE). The P2X7R gene is highly polymorphic, and many single-nucleotide polymorphisms (SNPs) have been detected. A case-control study was performed to investigate the associations of SNPs in the P2X7R gene (rs1718119, rs2230911 and rs3751143) with susceptibility to SLE in 535 Chinese SLE patients and 532 controls. Results showed that rs1718119 was associated with SLE; in particular carriers of the A allele and AA/AG/(AG+AA) genotypes were at lower risk of the disease [A versus G, P < 0.001, odds ratio (OR) = 0.543, 95% CI: 0.424-0.697; AG versus GG, P = 0.018, OR = 0.659, 95% CI: 0.466-0.931; AA versus GG, P = 0.011, OR = 0.176, 95% CI: 0.046-0.668; AG+AA versus GG, P = 0.004, OR = 0.607, 95% CI: 0.433-0.850], but no significant differences in rs2230911 and rs3751143 were observed between SLE patients and controls. Stratification of cases for the presence of nephritis showed that rs2230911 G allele and CG/(CG+GG) genotypes were at a lower risk of SLE with nephritis (LN) (G versus C, P = 0.011, OR = 0.640, 95% CI: 0.454-0.903; CG versus CC, P = 0.035, OR = 0.645, 95% CI: 0.429-0.970; GG versus CC, P = 0.101, OR = 0.349, 95% CI: 0.099-1.228; CG+GG versus CC, P = 0.015 OR = 0.612, 95% CI: 0.411-0.910), but rs1718119 and rs3751143 were not associated with LN. Analysis of the haplotypes revealed one haplotype (ACA) that appeared to be a significantly 'protective' haplotype (P = 0.009, OR = 0.708, 95% CI: 0.546-0.918) with SLE. The findings suggest that the P2X7R gene might contribute to SLE susceptibility in the Chinese population.

Morphine and its major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were given intracerebroventricularly (i.c.v.) to rats. The antinociceptive effects were assessed in the tail-flick and hot-plate tests as well as the writhing test. Ventilatory effects were studied in halothane-anaesthetized rats. Based on calculated ED50 values, morphine-6-glucuronide was approximately 200 times more potent that morphine itself in the tail-flick and hot-plate tests. In the writhing test the difference in ED50 was approximately 9-fold. Morphine and morphine-6-glucuronide administered i.c.v. induced dose-related decreases in minute ventilation in the dose range 2.7 × 10−9-1.3 × 10−7 mol. The dose-response curve for minute ventilation was steeper for morphine-6-glucuronide than for morphine. Morphine-6-glucuronide was approximately 10 times more potent than morphine in depressing minute ventilation. Morphine-6-glucuronide reduced both tidal volume and respiratory frequency, while morphine reduced only the tidal volume. Morphine-3-glucuronide, in contrast, increased both tidal volume and respiratory frequency, causing an increase in minute ventilation. Apnoea was elicited after the highest doses of morphine-6-glucuronide but not of morphine. The potency difference for depression of minute ventilation between morphine-6-glucuronide and morphine corresponded well to the difference in the writhing test but not to the potency difference in the tail-flick or hot-plate tests. The ventilatory depression induced by morphine and morphine-6-glucuronide was readily reversed by naloxone, while the hyperventilation caused by morphine-3-glucuronide was slightly potentiated by the opioid antagonist. Naloxone pretreatment completely blocked the ventilatory depression induced by morphine-6-glucuronide. These results show that the potent ventilatory depression induced by morphine-6-glucuronide is related to its antinociceptive effects in rats. Furthermore, the fact that morphine-3-glucuronide stimulated ventilation and that morphine had a more shallow ventilatory dose-response curve compared to morphine-6-glucuronide may indicate that morphine-3-glucuronide is a functional antagonist of the depressive effects of morphine and morphine-6-glucuronide on ventilation.

Caudal ventrolateral medulla (CVLM) plays an important role in the regulation of reflex cardiovascular activity. In the present study, the possible involvement of the CVLM in mediating the depressor response elicited by the greater splanchnic nerve (GSPL) afferent stimulation was explored in rats anesthetized with urethane and alpha-chloralose. Microinjection of lidocaine, and the glutamate receptor antagonists, kynurenic acid and 2-amino-7-phosphonolieptanoic acid, into the CVLM significantly blocked the depressor response induced by the GSPL afferent stimulation. Electrical stimulation of the GSPL inputs excited 48 of 75 CVLM neurons tested (64%). Sixteen out of 21 excited CVLM neurons tested received baroreceptor inputs. Coherence analysis revealed a strong cardiac-related rhythm in the discharges of 11 out of these 21 excited neurons. These results suggest the involvement of CVLM neurons and activation of glutamate receptors in the CVLM in mediating the depressor response induced by the GSPL afferent stimulation in rats.

The experiments were carried out on guinea pig isolated ventricular myocytes by using whole-cell patch clamp. The effects of angiotensin II (Ang II) on potassium ion channels of acute ischemic myocytes were observed. Whole-cell patch clamp recordings showed that physiological potassium current, including delayed rectifier potassium current and inward rectifier potassium current were inhibited under the condition of simulated ischemia, and then further inhibited by treatment with Ang II. ATP-sensitive potassium currents were increased under simulated ischemia and were further enhanced by Ang II treatment.

The effects of the major morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, on nociception were assessed by the tail-flick, hot-plate and writhing tests in the rat. Morphine-3-glucuronide (M3G) 1.1 x 10(-9) mol (0.5 micrograms) or saline was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.) followed by a second injection of 2.0 x 10(-10) mol (0.1 microgram) or 2.0 x 10(-11) mol (0.01 microgram) morphine-6-glucuronide (M6G) 10 min later. Administration of M3G (i.c.v.) significantly attenuated the antinociceptive effects of M6G in the hot-plate test. After i.t. administration, the antinociceptive effect of M6G in all three tests was significantly reduced in the M3G pretreated group compared to the group receiving saline. The ventilatory effects of 4.0 x 10(-9)-1.0 x 10(-8) mol (2-5 micrograms) M6G and 1.7-2.2 x 10(-8) mol (8-10 micrograms) M3G given i.c.v. were studied by a whole-body plethysmographic technique in halothane anaesthetized rats. Separate groups of rats received M3G followed by M6G injection or vice versa. In animals receiving M3G there was a prevention or attenuation of the M6G induced depression of respiratory frequency, tidal volume and minute ventilation compared to control groups receiving M6G in combination with saline. These results show that M3G may functionally antagonize the central antinociceptive effects as well as the ventilatory depression induced by M6G. Interestingly, M3G was more potent in antagonizing the M6G-induced analgesia after i.t. administration than that after i.c.v. administration, which may suggest that the spinal cord is more sensitive to the non-opioid excitatory effects of M3G than supraspinal structures.