Dietary Macronutrient Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

Inhibiting MiR-34α reduces retinal cell apoptosis and downstream NF-κB pathway in diabetic retinopathy rats through regulating HMGB1 expression.

BACKGROUND: This is a research aimed to study the effect of micro ribonucleic acid (miR)-34α on the retinal cell apoptosis in diabetic retinopathy (DR) rats and its key molecular mechanism. METHODS: Sprague-Dawley rats were randomly divided into healthy group (H group, N.=5), diabetes group (D group, N.=5), diabetes + negative control transfection group (N group, N.=5) and diabetes + miR-34α inhibitor transfection group (M group, N.=5). The rat model of diabetes was established via intraperitoneal injection of 2% streptozotocin solution (60 mg/kg). After 72 h, the urine glucose and blood glucose were detected, and the urine glucose above 3+ and the blood glucose concentration >16.7 mmol/L indicated the successful modeling. After the rats were normally fed for 4 months, the changes in expression of miR-34α in retinal tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR), the pathological changes in retinal tissues were observed via hematoxylin-eosin (HE) staining, and the retinal cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the changes in the number of cells containing active caspase-3 in retinal tissues were determined through immunohistochemistry, and the changes in expressions of caspase-3, high mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) in retinal tissues were determined through Western blotting. RESULTS: Compared with those in H group, the cell density declined, and the cells were arranged disorderly with swelling in each retinal layer, the expression of miR-34α in retinal tissues was increased, the retinal cell apoptosis was enhanced, the number of cells containing active caspase-3 in retinal tissues rose, and the expressions of caspase-3, HMGB1 and NF-κB in retinal tissues were increased in D group, N group and M group (P<0.05). Compared with those in D group and N group, the cell density rose, and the cells were arranged less disorderly with milder swelling in each retinal layer, the expression of miR-34α in retinal tissues declined, the retinal cell apoptosis was weakened, the number of cells containing active caspase-3 in retinal tissues was decreased, and the expressions of caspase-3, HMGB1 and NF-κB in retinal tissues were reduced in M group (P<0.05). CONCLUSIONS: Inhibiting miR-34α reduces the retinal cell apoptosis in DR rats through regulating the HMGB1 expression and downstream NF-κB pathway.

Application and mechanism of anti-VEGF drugs in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. The incidence rate increases with age in people over 50 years of age. With the advent of China's aging society, the number of patients is increasing year by year. Although researchers have done a lot of basic research and clinical research on the pathogenesis and treatment of AMD in recent years, the pathogenesis of AMD is still controversialdue to the complexity of the disease itself. AMD is the primary cause of blindness in the elderly over 50 years old. It is characterized by the formation of choroidal neovascularization (CNV) and the over secretion of vascular endothelial growth factor (VEGF) as its main mechanism, which can eventually lead to vision loss or blindness. The occurrence and development of AMD is an extremely complex process, in which a large number of regulatory factors and cytokines are involved. Most of the existing treatments are for its concomitant CNV. Targeted VEGF drugs for neovascularization, such as Lucentis and Aflibercept, are the first-line drugs for AMD. Their application has greatly reduced the blinding rate of patients. However, there are still some patients who have no response to treatment or cannot maintain their vision after long-term treatment. Frequent injection also increases the risk of complications and economic burden. In order to further improve the quality of life and long-term prognosis of AMD patients, a variety of new treatmentshave been or will be applied in clinic, including combined treatment with the same or different targets to improve the curative effect, change or simplify the mode of medication, inhibit VEGF receptor tyrosine protein kinase and so on. This article provides a brief review of the research progress of anti-VEGF drugs and their mechanisms for the treatment of AMD, it is expected to provide a better treatment plan for AMD treatment.

USP22 promotes pro­inflammatory responses in Pseudomonas aeruginosa­induced keratitis by targeting TRAF6.

Pseudomonas aeruginosa (PA)­induced keratitis is characterized by inflammatory epithelial edema, stromal infiltration, corneal ulceration and can lead to vision loss. The present study aimed to study the effect of ubiquitin­specific protease 22 (USP22) on PA­induced keratitis. Using RT­qPCR and western blotting, significantly increased expression of USP22 was identified in mouse corneas and cultured RAW264.7 cells following PA stimulation. In addition, the results of in vivo experiments, western blot assay and ELISA suggested that the silencing of USP22 attenuated disease progression, downregulated the NF­κB pathway and suppressed the expression of pro­inflammatory cytokines following PA stimulation. Notably, it was identified that the expression of tumor necrosis factor receptor­associated factor 6 (TRAF6) was decreased by silencing of USP22 and USP22 was found to remove lysine 48­linked poly­ubiquitination chains from TRAF6 to stabilize TRAF6 expression and these effects were clearly aggravated following PA infection.

Alcohol consumption and incidence of sleep disorder: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: To investigate the association between alcohol consumption and incidence of sleep disorder. METHODS: PubMed, EMBASE and OVID were searched systematically until March 2020 for cohort studies quantitatively investigating the effect of alcohol on incident sleep disorder. We conducted a random-effects meta-analysis to calculate the summary ORs (odds ratios) and 95 %CIs (confidence intervals) on the incidence of sleep disorder in relation to alcohol consumption. RESULTS: The pooled analysis of eleven included cohort studies demonstrated that general drinking was significantly associated with incidence of sleep disorder (OR:1.37, 95 %CI:1.22,1.54,I²â€¯= 0.0 %) while heavy drinking was not (OR:1.22, 95 %CI:0.94,1.60, I²â€¯= 81.1 %). (general drinking (women <24 g/day; men <48 g/day; < 4 times/week), heavy drinking (women ≥24 g/day; men ≥48 g/day; ≥ 4times/week)). CONCLUSIONS: Findings from the present systematic review and meta-analyses showed that there was no evidence that alcohol consumption diminished sleep problems, and some evidence that general drinking might increase the sleep problems, but further study is necessary.

Moxibustion at 'Danzhong' (RN17) and 'Guanyuan' (RN4) for fatigue symptom in patients with depression: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Fatigue is one of the most prevalent and debilitating symptoms of major depressive disorder (MDD). The effective management of depression-related fatigue has an important impact on the patient's abilities, functioning, and quality of life (QOL). Moxibustion has been widely used in Traditional Chinese Medicine to manage fatigue. Recent studies have also demonstrated that moxibustion is effective for treating cancer-related fatigue and chronic fatigue syndrome. However, there is not sufficient data supporting the effect of moxibustion for depression-related fatigue. Therefore, this randomized, assessor-blinded, wait-list controlled trial is designed to evaluate the effectiveness, safety, and feasibility of moxibustion treatment for depression-related fatigue. METHODS: One hundred and seventy-six participants who meet the diagnostic criteria for depression in the International Classification of Diseases, tenth revision (ICD-10), and who also have a score of ≥1 on the 13 item of the Hamilton Depression Rating Scale-17 (HAMD-17), will be enrolled. At study entry, participants will undergo anti-depressant treatment for at least 1 month. Then those who still have a score of ≥1 on the 13 item of the HAMD-17 will be randomly allocated to either a moxibustion group or wait-list control group in a ratio of 1:1. Anti-depressants will be provided for both groups during the whole process of the study period. Participants in the moxibustion group will undergo 14 sessions of moxibustion (over 2 weeks) with anti-depressant treatment, and participants in the wait-list control group will receive only anti-depressant treatment. Subsequently, participants in the moxibustion group will be followed-up for 4 weeks. The primary outcome measure will be the Fatigue Severity Scale (FSS). The secondary outcome measure will be the HAMD-17. Safety will be assessed by monitoring adverse events during the study. Trial feasibility will also be assessed in this study. DISCUSSION: The results of this study may provide evidence for the efficacy of moxibustion as an adjunct to antidepressants for depression-related fatigue, and promote a more widespread foundation for the selection of moxibustion in the clinical setting as well as for future research in moxibustion therapy. TRIAL REGISTRATION: This study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800016905).

What is the optimal neuropsychological test battery for schizophrenia in China?

BACKGROUND: The MATRICS consensus cognitive battery (MCCB) has been widely used to evaluate cognitive deficits in schizophrenia (SCZ), however, no study has formally examined the validity of the MCCB in Chinese SCZ. This study compared Chinese SCZ patients with healthy Chinese controls on the MCCB and some additional neurocognitive tests to determine if the Chinese MCCB is an optimal battery to assess the cognitive deficits in Chinese SCZ patients. METHOD: The study enrolled and examined 230 patients met DSM-IV criteria for SCZ and 656 healthy controls matched for gender, age and education. Besides the MCCB, we also included some additional neurocognitive tests that have been widely used in patients with schizophrenia. We selected MCCB and non-MCCB tests with large effect size, to assemble a new "optimal battery" and compared its performance with that of the standard MCCB. RESULTS: Comparing the putative "optimal" battery with the original MCCB, more patients with SCZ were identified as cognitively impaired according to the criteria of GDS ≥ 0.50 for the optimal battery (166 vs 135, or 72.2% vs 58.7%). The rate of cognitive impairment according to MCCB GDS in patients with SCZ who were currently working, ever worked and never worked are 45.5%, 61.6% and 70.8% (p = 0.051), whereas the optimal battery GDS showed 56.4%, 74.8%, 91.7% (p = 0.003), respectively. CONCLUSIONS: Our study needs validation with independent samples but suggests that the current "optimal" cognitive battery could be more sensitive than the widely used MCCB in detecting SCZ related cognitive impairment in China.

Longitudinal informed consent competency in stable community patients with schizophrenia: A one-week training and one-year follow-up study.

OBJECTIVE: This study explores the efficacy of a one-week informed consent information training process for improving competence to provide consent in stable community patients with schizophrenia over a one-year follow-up period. METHOD: A one-week training session designed to enhance competence to provide informed consent for research was conducted. The training was guided by a research protocol that provided detailed explanations of each major conceptual unit. Participants were followed for one year, and comprised 50 stable community outpatients with schizophrenia who were randomly assigned to either an intervention group (IG, n=33) or a control group (CG, n=17) that did not receive any training. The Chinese Mandarin MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) was used to assess competence for informed consent pre-training (baseline), post-training (one week later), and at the end of one year. RESULTS: A repeated measures analysis comparing the IG and CG at pre-training, post-training and the one-year follow-up revealed significant improvements in the Understanding and Appreciation subscale following the one-week training. However, by the end of one year, scores returned to baseline levels, with the exception of the Appreciation subscale, which was below baseline. There were significant main effects across time on the Appreciation and Reasoning subscales, indicating considerable changes over time. The CG showed no significant changes from pre-training to one week later or at one-year follow-up for all subscales. CONCLUSIONS: The capacities of understanding and appreciation can be improved in stable community patients with schizophrenia after one week of training; however, this training effect is not sustained one year later. The results suggest that more intensive or periodic trainings may be needed to maintain long-term competence levels in patients with schizophrenia, particularly with regard to their capacity to appreciate the nature and consequences of study participation.

The MATRICS Consensus Cognitive Battery (MCCB): Co-norming and standardization in China.

MATRICS Consensus Cognitive Battery (MCCB), packaging 10 tests selected from more than 90 nominated tests, is a method developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) group to evaluate the efficacy of treatments targeting cognitive impairments in schizophrenia. MCCB had been translated into a number of languages, but only the US and Spain had normative data reported. Inconsistency in translation and cultural differences make direct application of MCCB in China problematic. In this study, we administered the battery to a representative community sample based on Chinese population census in 2005 and obtained normative data. The effects of age, gender, education level, and scale of residence area on test performance were examined. The sample included 656 healthy volunteers from six sites in China. At each site, sample was stratified according to age, gender, and educational level, and scale of the area one was born in, grew up in and currently living in was recorded. We found age, gender, and education had significant effects on the normative data for MCCB in China, which are comparable to those found for the original standardized English version in the U.S. and the Spanish version in Spain. Remarkably, the residence scale effects on neuropsychological performance were significant, which should be taking into account when calculating the standardized T score for each subject. The practice effects were minor and test-retest reliability of MCCB was good, which suggests MCCB as an appropriate measure for clinical and research usage in China.