Selective Orexin 2 Receptor Blockade Alleviates Cognitive Impairments and the Pathological Progression of Alzheimer's Disease in 3xTg-AD Mice.

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid ß (Aß) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aß deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aß pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.

Develop prediction model to help forecast advanced prostate cancer patients' prognosis after surgery using neural network.

Background: The effect of surgery on advanced prostate cancer (PC) is unclear and predictive model for postoperative survival is lacking yet. Methods: We investigate the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, to collect clinical features of advanced PC patients. According to clinical experience, age, race, grade, pathology, T, N, M, stage, size, regional nodes positive, regional nodes examined, surgery, radiotherapy, chemotherapy, history of malignancy, clinical Gleason score (composed of needle core biopsy or transurethral resection of the prostate specimens), pathological Gleason score (composed of prostatectomy specimens) and prostate-specific antigen (PSA) are the potential predictive variables. All samples are divided into train cohort (70% of total, for model training) and test cohort (30% of total, for model validation) by random sampling. We then develop neural network to predict advanced PC patients' overall. Area under receiver operating characteristic curve (AUC) is used to evaluate model's performance. Results: 6380 patients, diagnosed with advanced (stage III-IV) prostate cancer and receiving surgery, have been included. The model using all collected clinical features as predictors and based on neural network algorithm performs best, which scores 0.7058 AUC (95% CIs, 0.7021-0.7068) in train cohort and 0.6925 AUC (95% CIs, 0.6906-0.6956) in test cohort. We then package it into a Windows 64-bit software. Conclusion: Patients with advanced prostate cancer may benefit from surgery. In order to forecast their overall survival, we first build a clinical features-based prognostic model. This model is accuracy and may offer some reference on clinical decision making.

Case report: enzyme replacement therapy for Fabry disease presenting with proteinuria and ventricular septal thickening.

Fabry disease (FD) is an uncommon, X-linked, lysosomal storage disease that causes defects in the glycosphingolipid metabolic pathway due to deficient or absent lysosomal α-galactosidase (α-Gal A) activity. This leads to the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including endothelial, cardiac, renal, and corneal cells, and consequently, the progressive appearance of clinical symptoms in target organs. Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme and has been successfully administered for treating FD.Here, we report a case of a 37-year-old male with complaints of recurrent proteinuria and ventricular septal thickening. A renal biopsy revealed vacuolization and foamy changes in podocytes, and the presence of myelin-like bodies and zebra bodies. The white blood cell α-Gal A activity was very low, while the Lyso-GL-3 level was high. Additionally, genetic analysis revealed a gene variant c.902G > A p. Arg301Gln. The patient was diagnosed with FD, and subsequently received intravenous ERT with a dose of Agalsidase α (0.2 mg/kg, 17.5 mg every 2 weeks). Currently, the values of proteinuria and ventricular septum thickness remain stable during the 6-month follow-up. Initiating ERT at an early age can effectively decrease the deposition of GL-3, attenuate the progressive clinical manifestations of FD, and provide greater long-term benefits.

Fused Brain Functional Connectivity Network and Edge-attention Graph Convolution Network for Fibromyalgia Syndrome Diagnosis.

Fibromyalgia syndrome (FMS) is a type of rheumatology that seriously affects the normal life of patients. Due to the complex clinical manifestations of FMS, it is challenging to detect FMS. Therefore, an automatic FMS diagnosis model is urgently needed to assist physicians. Brain functional connectivity networks (BFCNs) constructed by resting-state functional magnetic resonance imaging (rs-fMRI) to describe brain functions have been widely used to identify individuals with relevant diseases from normal control (NC). Therefore, we propose a novel model based on BFCN and graph convolutional network (GCN) for automatic FMS diagnosis. Firstly, a novel fused BFCN method is proposed by fusing Pearson's correlation (PC) and low-rank (LR) BFCN, which retains information and reduces data redundancy to construct BFCN. Then we combine the feature of BFCN with non-image information of subjects to obtain nodes and adjacency matrices, which builds a graph with edge attention. Finally, the graph is sent to the GCN layer for FMS diagnosis. Our model is evaluated on the in-house FMS dataset to achieve 82.48% accuracy. The experimental results show that our method outperforms the state-of-the-art competing methods.

Validation of the 2011 and 2016 American college of rheumatology diagnostic criteria for fibromyalgia in a Chinese population.

PURPOSE: To provide a foundation for clinical diagnosis, epidemiological investigation and intervention trials, we examined the reliability and validity of the American College of Rheumatology (ACR) 2011 and 2016 survey diagnostic criteria among Chinese patients based on the fibromyalgia severity (FS) scale. METHODS: In this study, 200 fibromyalgia patients diagnosed according to the 1990 criteria (1990c) were matched with rheumatoid arthritis (RA) patients based on age and gender. The FS scale score and its subscales were examined to determine their correlations with the revised fibromyalgia impact questionnaire (FIQR). Receiver operator characteristic (ROC) analysis was performed, and test-retest reliability, internal consistency, and construct validity were examined. RESULTS: The area under the curve (AUC) for the ACR 2011c and 2016c was 0.870 and 0.845, respectively, and the sensitivity and specificity were 78.0% and 96.0% for the 2011c and 70.5% and 98.5% for the 2016c, respectively. The FS scale and its subscales were confirmed to exhibit good internal consistency, and they were significantly correlated with the FIQR, thereby indicating adequate construct validity. Using a lower cutoff value 11 points for the FS scale score based on the generalized pain requirement might be a more effective approach in the Chinese population; this approach yielded an AUC of 0.923 and a sensitivity of 87.0% and specificity of 97.5%. CONCLUSION: The 2011c and 2016c are reliable instruments for diagnosing fibromyalgia patients in China. The FS scale could be a valid tool to assist in fibromyalgia diagnosis, and a cutoff value 11 points is more suitable in Chinese patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03381131.

The Chinese version of the ACR 2011c and 2016c are valid tools for fibromyalgia diagnosis; and a cutoff value 11 points for FS might be more suitable to assist in fibromyalgia diagnosis in Chinese population. The Chinese 2011c and 2016c for fibromyalgia diagnosis can be found as an appendix to this article.

Exploration for the reference interval of C-reactive protein in the Chinese longevity people over 90 years of age.

BACKGROUND: Older individuals tend to develop chronic inflammation. As a commonly used nonspecific inflammatory marker, C-reactive protein (CRP) can predict metabolic syndrome, cardiovascular diseases, etc. However, little is known about CRP levels in longevity people. OBJECTIVES: Investigate the distribution and correlates of CRP and provide a reference for the establishment of normal interval values in Chinese longevity people over 90 years of age. METHODS: We performed a correlation analysis to evaluate the correlation between CRP levels and longevity based on the basic demographic characteristics, anthropometric measurements and blood data of 4,418 participants in the 2015 China Health and Retirement Longitudinal Study and 636 participants in an ongoing longitudinal study of natural longevity people in Guangxi. On this basis, the CRP reference interval for longevity was explored. RESULTS: The CRP concentration was significantly different among the three age groups, with a median of 3.80 mg/L for those older than 90 years, which was significantly higher than that for those aged 45-64 years (median 1.20 mg/L, p < 0.001) and 65-89 years (median 1.30 mg/L, p < 0.001). Body mass index, waist circumference, the waist-to-height ratio, systolic blood pressure, diastolic blood pressure, and fasting and postprandial blood glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol levels were positively correlated with CRP levels, while fasting high-density lipoprotein cholesterol was negatively correlated with CRP levels. The CRP reference interval (RI) value in longevity people was 0.25-9.22 mg/L. CONCLUSION: The concentrations of CRP increased with advancing age, and the CRP reference interval was different between older and younger adults.

Development of a model for the prediction of biological age.

BACKGROUND AND OBJECTIVE: Rates of aging vary markedly among individuals, and biological age serves as a more reliable predictor of current health status than does chronological age. As such, the ability to predict biological age can support appropriate and timely active interventions aimed at improving coping with the aging process. However, the aging process is highly complex and multifactorial. Therefore, it is more scientific to construct a prediction model for biological age from multiple dimensions systematically. METHODS: Physiological and biochemical parameters were evaluated to gage individual health status. Then, age-related indices were screened for inclusion in a model capable of predicting biological age. For subsequent modeling analyses, samples were divided into training and validation sets for subsequent deep learning model-based analyses (e.g. linear regression, lasso model, ridge regression, bayesian ridge regression, elasticity network, k-nearest neighbor, linear support vector machine, support vector machine, and decision tree models, and so on), with the model exhibiting the best ability to predict biological age thereby being identified. RESULTS: First, we defined the individual biological age according to the individual health status. Then, after 22 candidate indices (DNA methylation, leukocyte telomere length, and specific physiological and biochemical indicators) were screened for inclusion in a model capable of predicting biological age, 14 age-related indices and gender were used to construct a model via the Bagged Trees method, which was found to be the most reliable qualitative prediction model for biological age (accuracy=75.6%, AUC=0.84) by comparing 30 different classification algorithm models. The most reliable quantitative predictive model for biological age was found to be the model developed using the Rational Quadratic method (R2=0.85, RMSE=8.731 years) by comparing 24 regression algorithm models. CONCLUSIONS: Both qualitative model and quantitative model of biological age were successfully constructed from a multi-dimensional and systematic perspective. The predictive performance of our models was similar in both smaller and larger datasets, making it well-suited to predicting a given individual's biological age.

Amorphous Co-Mo-S nanospheres fabricated via room-temperature vulcanization for asymmetric supercapacitors.

Ternary metal sulfides employed in supercapacitors exhibit better electrochemical performances than their counterpart oxides due to their superior conductivity. However, the insertion/extraction of electrolyte ions can lead to a significant volume change in electrode materials, which can result in poor cycling stability. Herein, novel amorphous Co-Mo-S nanospheres were fabricated through a facile room-temperature vulcanization method. It involves the conversion of crystalline CoMoO4 by reacting it with Na2S at room temperature. In addition to the conversion of the crystalline state into an amorphous structure with more grain boundaries, which is beneficial for the transport of electron/ion and can accommodate the volume change generated by the insertion/extraction of electrolyte ions, the production of more pores led to an increased specific surface area. The electrochemical results indicate that the as-prepared amorphous Co-Mo-S nanospheres had a specific capacitance of up to 2049.7F/g@1 A/g together with good rate capability. The amorphous Co-Mo-S nanospheres can be used as the cathode of supercapacitors and assembled with an activated carbon anode into an asymmetric supercapacitor possessing a satisfactory energy density of 47.6 Wh kg-1@1012.9 W kg-1. One of the prominent features exhibited by this asymmetric device is its remarkable cyclic stability, with a capacitance retention of 107% after 10,000 cycles.

Fibromyalgia in China: sleep quality is related to symptoms, quality of life and especially mental health.

OBJECTIVES: To investigate sleep quality in patients with fibromyalgia (FM) and to analyse the effect of sleep on FM symptoms and quality of life. METHODS: Patients with FM and healthy subjects were recruited to assess their sleep quality, and patients were further assessed for pain, fatigue, depression, psychological stress and quality of life. The patients were divided into a sleep disorder group as measured by the Pittsburgh Sleep Quality Index (PSQI score >7 points) and a group without sleep disorders (PSQI score ≤7 points). Linear regression analysis was used to explore the effect of sleep quality on FM pain controlling for sex and age, and the effect of sleep quality on FM fatigue, depression, psychological stress and quality of life controlling for sex, age and pain. RESULTS: A total of 450 patients and 50 healthy subjects participated in the study. The number of FM patients with sleep disorders was significantly higher than that of healthy subjects (90% vs. 14%, p≤0.001). In addition to the number of pain sites, the levels of pain, fatigue, depression, stress symptoms and quality of life were significantly impaired in FM patients with sleep disorders (p<0.05). In terms of the effects on quality of life assessed with the 36-item short-form health survey, the decrease in mental health was more substantial than the decrease in physical health (B=-12.10 vs. B=-5.40). CONCLUSIONS: Similar to FM patients in other countries and regions, a decrease in sleep quality is also the core symptom of FM patients in China and is significantly correlated with the severity of pain, fatigue, depression and stress symptoms and reduced quality of life, especially with regard to mental health, suggesting that the treatment of this disease should include sleep disorder interventions.

Integrated analysis of the lncRNA-associated ceRNA network in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that worsens with age. Long non-coding RNAs (lncRNAs) dysregulation and its associated competing endogenous RNA (ceRNA) network have a potential connection with the occurrence and development of AD. A total of 358 differentially expressed genes (DEGs) were screened via RNA sequencing, including 302 differentially expressed mRNAs (DEmRNAs) and 56 differential expressed lncRNAs (DElncRNAs). Anti-sense lncRNA is the main type of DElncRNA, which plays a major role in the cis and trans regulation. The constructed ceRNA network consisted of 4 lncRNAs (NEAT1, LINC00365, FBXL19-AS1, RAI1-AS1719) and 4 microRNAs (miRNAs) (HSA-Mir-27a-3p, HSA-Mir-20b-5p, HSA-Mir-17-5p, HSA-Mir-125b-5p), and 2 mRNAs (MKNK2, F3). Functional enrichment analysis revealed that DEmRNAs are involved in related biological functions of AD. The co-expressed DEmRNAs (DNAH11, HGFAC, TJP3, TAC1, SPTSSB, SOWAHB, RGS4, ADCYAP1) of humans and mice were screened and verified by real-time quantitative polymerase chain reaction (qRT-PCR). In this study, we analyzed the expression profile of human AD-related lncRNA genes, constructed a ceRNA network, and performed functional enrichment analysis of DEmRNAs between human and mice. The obtained gene regulatory networks and target genes can be used to further analyze AD-related pathological mechanisms to optimize AD diagnosis and treatment.

A Chinese version of the revised Fibromyalgia Impact Questionnaire: A validation study.

OBJECTIVE: The revised Fibromyalgia Impact Questionnaire (FIQR) was developed to measure the quality of life of patients with fibromyalgia in randomized controlled trials and routine care. The purpose of this study was to translate and adapt the FIQR from English to Chinese, and to examine the validity and reliability of the Chinese version of the FIQR (CFIQR). METHODS: Following the translation of the FIQR, fibromyalgia patients from 6 centers were recruited and completed the CFIQR, the validated Chinese version of the Medical Outcome Study Short Form 36 Health Survey (SF-36) and the Beck Depression Inventory (BDI). In this study, Cronbach's alpha coefficient, test-retest reliability and item total correlation were used for evaluating external and internal reliability; and criterion and structural validity were evaluated. RESULTS: A total of 200 fibromyalgia patients completed the study. The internal consistency was excellent (Cronbach's alpha .90, .88, .88 and .93 for function, overall impact, symptoms scales and total score, respectively; item-total correlations from .25 to .83.) Test-retest reliability levels of the CFIQR total and subscale scores were strong correlation (intraclass correlation coefficient >0.75). Furthermore, there were significant correlations between the 3 subscale and the total score of the CFIQR and the SF-36, as well as the CFIQR and the BDI, by criterion validity (P < .01). Confirmatory factor analysis gave an acceptable value for structural validity according to the 3-factor structures of function, overall impact and symptoms. CONCLUSIONS: The CFIQR is a valid and reliable instrument for both clinical practice and research purposes with Chinese speakers globally. [ClinicalTrials.gov: NCT03381131].

The general law of plasma proteome alterations occurring in the lifetime of Chinese individuals reveals the importance of immunity.

BACKGROUND: Aging is characterized by a continuous loss of protein homeostasis. A closer examination of peripheral blood, which houses proteins from nearly all tissues and cells, helped identify several biomarkers and other aspects of aging biology. To further explore the general law of aging and identify key time nodes and associated aging biology, we collected 97 plasma samples from 253 healthy individuals aged 0-100 years without adverse outcomes to conduct nano-Ultra High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (nano-UHPLC-MS/MS) and weighted gene co-expression network analysis (WGCNA). RESULTS: Through biological processes and key biological pathways identified in discrete age group modules, our analyses highlighted a strong correlation between alterations in the immune system and aging process. We also identified hub genes associated with distinct age groups that revealed alterations not only in protein expression but also in signaling cascade. Among them, hub genes from age groups of 0-20 years old and 71-100 years old are mostly involved in infectious diseases and the immune system. In addition, CDC5L and HMGB2 were the key transcription factors (TFs) regulating genes expression in people aged between 51-60 and 71-100 years of age. They were shown to not only be independent but also mutually regulate certain hub gene expressions. CONCLUSIONS: This study reveals that the plasma proteome undergoes a complex alteration over the lifetime of a human. In this process, the immune system is crucial throughout the lifespan of a human being. However, the underlying mechanism(s) regulating differential protein expressions at distinct ages remains to be elucidated.

A structural basis for the functional differences between the cytosolic and plastid phosphoglucose isomerase isozymes.

Phosphoglucose isomerase (PGI) catalyzes the interconversion between glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P), thereby regulating sucrose synthesis in plant cells. In general, plants contain a pair of PGI isozymes located in two distinct compartments of the cell (cytosol and plastid) with differences in both the primary structure and the higher-order structure. Previously, we showed that the activity of cytosolic PGI (PGIc) is more robust (activity, thermal stability, substrate turnover rate, etc.) than that of the plastid counterpart (PGIp) in multiple organisms, including wheat, rice, and Arabidopsis. The crystal structures of apoTaPGIc (an isotype cytosol PGIc in Triticum aestivum), TaPGIc-G6P complex, and apoTaPGIp (an isotype plastid PGIp in Triticum aestivum) were first solved in higher plants, especially in crops. In this study, we detailed the structural characteristics related to the biochemical properties and functions of TaPGIs in different plant organelles. We found that the C-terminal domains (CTDs) of TaPGIc and TaPGIp are very different, which affects the stability of the dimerized enzyme, and that Lys213TaPGIc/Lys193TaPGIp and its surrounding residues at the binding pocket gateway may participate in the entrance and exit of substrates. Our findings provide a good example illuminating the evolution of proteins from primary to higher structures as a result of physical barriers and adaptation to the biochemical environment.

Life among Chinese fibromyalgia patients: a cross-sectional study.

OBJECTIVE: This study is to examine the impact of age on the clinical characteristics, fibromyalgia-related symptom severity and quality of life (QOL) among Chinese fibromyalgia patients. METHODS: A packet of questionnaires on demographics, medical history, and severity of six major symptoms of fibromyalgia (i.e., pain, fatigue, sleep quality, depression, stress, and QOL) was completed by 124 Chinese patients. The patients were stratified into three groups by age (32 (25.8%) "young" patients, ≤ 39 years; 73 (58.9%) "middle-age" patients, 40-59 years; and 19 (15.3%) "older" patients, ≥ 60 years). Analysis of covariance was conducted and adjusted for body mass index and symptom fibromyalgia duration. RESULTS: The majority of patients in this study were women (107, 86.3%), and the mean age was 49.4 years (SD 10.8 years). Pairwise comparisons among the three age groups found that the young and middle-aged patients were significantly more troubled than the older patients by their symptoms in several categories: morning tiredness (P ≤ 0.012), depression (P ≤ 0.002), anxiety (P ≤ 0.004), mental health index (P ≤ 0.002), and mental component summary score (P ≤ 0.017). The middle-aged patients reported more trouble than the older patients with regard to social functioning (P = 0.008), emotional roles (P = 0.012), depression (P = 0.012), and sleep quality (P = 0.017). The young patients exhibited the highest levels of current experienced stress (young vs. old, P = 0.013). CONCLUSION: This study has identified that middle-aged Chinese fibromyalgia patients exhibited less compromise of their QOL than did their older peers. This discrepancy begs a logical explanation and deserves further study. Key Points • This is the first clinical study to show the potential effect of age on fibromyalgia patients in China. • Characteristics, symptom severity, and QOL differ in different age groups. • The younger patients are, the worse their quality of life.

The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory microenvironment.

Type 2 diabetes mellitus (T2DM) is a classic metaflammatory disease, and the inflammatory states of the pancreatic islet and insulin target organs have been well confirmed. However, abundant evidence demonstrates that there are countless connections between these organs in the presence of a low degree of inflammation. In this review, we focus on cell-cell crosstalk among local cells in the islet and organ-organ crosstalk among insulin-related organs. In contrast to that in acute inflammation, macrophages are the dominant immune cells causing inflammation in the islets and insulin target organs in T2DM. In the inflammatory microenvironment (IME) of the islet, cell-cell crosstalk involving local macrophage polarization and proinflammatory cytokine production impair insulin secretion by ß-cells. Furthermore, organ-organ crosstalk, including the gut-brain-pancreas axis and interactions among insulin-related organs during inflammation, reduces insulin sensitivity and induces endocrine dysfunction. Therefore, this crosstalk ultimately results in a cascade leading to ß-cell dysfunction. These findings could have broad implications for therapies aimed at treating T2DM.

Role of psoriatic keratinocytes in the metabolic reprogramming of dermal mesenchymal stem cells.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease, featured by epidermal hyperproliferation. Psoriasis exhibits metabolic abnormalities, which can further aggravate the condition of psoriasis. The present study aimed to investigate the role of psoriatic keratinocytes (KCs) in the metabolic reprogramming of dermal mesenchymal stem cells (DMSCs). METHODS: Dermal mesenchymal stem cells were cocultured with primary KCs either from psoriatic lesions or from normal subjects using Transwell plate. Glycolysis and mitochondrial metabolism of DMSCs were detected by Seahorse Metabolic Analyzer. Expression levels of proteins were analyzed by Western blotting. DMSCs proliferation was assessed using 5-ethynyl-2'-deoxyuridine assay and Cell Counting Kit-8. RESULTS: In comparison with normal KCs, coculture of psoriatic KCs with DMSCs dramatically increased glycolytic and mitochondrial metabolism, and expression levels of stem cell factor, epidermal growth factor, glucose transporter 1, and c-Myc. Moreover, psoriatic KCs were more potent than normal KCs in the stimulation of DMSC proliferation. CONCLUSIONS: In conclusion, psoriatic KCs display a higher potency in metabolic reprogramming and stimulation of DMSC proliferation, possibly contributing to the pathogenesis of psoriasis. However, whether the intervention of metabolic reprogramming of DMSCs can alleviate psoriasis remains to be determined.

Association between IL-1B (-511)/IL-1RN (VNTR) polymorphisms and type 2 diabetes: a systematic review and meta-analysis.

Interleukin-1 (IL-1) plays an essential role in the immune pro-inflammatory process, which is regarded as one of many factors in the development of type 2 diabetes mellitus (T2DM). Several case-control studies have illustrated the association of the IL-1B (-511) (rs16944, Chr 2:112,837,290, C/T Intragenic, Transition Substitution) and IL-1RN (VNTR) (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2) polymorphisms with T2DM risk. However, the results were inconsistent and inconclusive. We performed a meta-analysis (registry number: CRD42021268494) to assess the association of the IL-1B (-511) and IL-1RN (VNTR) polymorphisms with T2DM risk. Random-effects models were applied to calculate the pooled ORs (odds ratios) and 95% CIs (confidence intervals) to test the strength of the association in the overall group and subgroups stratified by ethnicity, respectively. Between-study heterogeneity and publication bias were evaluated by the Q-test, I2 statistic, Harbord test, and Peters test accordingly. Sensitivity analyses were also performed. A total of 12 publications evaluating the association of IL-1B (-511) and IL-1RN (VNTR) polymorphisms with the risk of T2DM development were included. The meta-analysis showed that IL-1RN (VNTR) was related to the increasing development of T2DM risk in the recessive model (OR = 1.62, 95% CI [1.09-2.42], Phet = 0.377, Pz = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07-3.83], Phet = 0.085, Pz = 0.031), and the IL-1RN 2* allele was found a significant association with evaluated T2DM risk in all ethnicities (OR = 2.08, 95% CI [1.43-3.02], Phet < 0.001, Pz < 0.001) and in EA (OR = 2.01, 95% CI [1.53-2.66], Phet = 0.541, Pz < 0.001). Moreover, stratification by ethnicity revealed that IL-1B (-511) was associated with a decreased risk of T2DM in the dominant model (OR=0.76, 95% CI [0.59-0.97], Phet = 0.218, P z = 0.027) and codominant model (OR = 0.73, 95% CI [0.54-0.99], Phet = 0.141, Pz = 0.040) in the East Asian (EA) subgroup. Our results suggest that the IL-1RN 2* allele and 2*2* homozygous polymorphism are strongly associated with increasing T2DM risk and that the IL-1B (-511) T allele polymorphism is associated with decreasing T2DM risk in the EA subgroup.

Investigation of the Reference Interval Values of Fasting Plasma Glucose, Blood Pressure, and Blood Lipids in the Longevity People Aged 90 Years Old and Above.

PURPOSE: To our knowledge, the normal fasting plasma glucose (FPG), blood pressure (BP), and blood lipids (BL) interval values have not been well-established in the longevity population. This study aims to provide a reference for the establishment of normal BP, FPG, and BL interval values in the longevity people in China. PATIENTS AND METHODS: A total of 7417 people were selected from the natural longevity cohort in Guangxi, with an age range of 20-110 years old, including 7093 classified as the non-longevity (20-89 years old) (94.02%) and 324 classified as the longevity (≥90 years old) (5.98%); there were 4309 men (58.1%) and 3108 women (41.9%). FPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels were defined as desirable levels when they were below the 75th percentile (P75), borderline levels from the 75th to 90th percentile (P75-P90), and high levels above P90; triglyceride (TG) levels above P90 were defined as high; and high-density lipoprotein cholesterol (HDL-C) levels below the 5th percentile (P5) were defined as low levels. RESULTS: The reference interval values of FPG in the longevity were as follows: desirable levels <6.15 mmol/L, borderline levels 6.15-7.45 mmol/L, high levels ≥7.45 mmol/L. Reference interval values of systolic blood pressure (SBP) were as follows: desirable levels <160.00 mmHg, borderline levels 160.00-174.50 mmHg, high levels ≥175.00 mmHg. DBP reference interval values were as follows: desirable levels <88.00 mmHg, borderline levels 88.00-90.00 mmHg, high levels ≥90.00 mmHg. TC reference interval values were as follows: desirable levels <5.59 mmol/L, borderline levels 5.59-6.45 mmol/L, high levels ≥6.45 mmol/L. LDL-C reference interval values were as follows: desirable levels <3.30 mmol/L, borderline levels 3.30-3.85 mmol/L, high levels ≥3.85 mmol/L. TG reference interval values were as follows: desirable levels <2.82 mmol/L, high levels ≥2.82 mmol/L. HDL-C reference interval values were as follows: low levels <0.80 mmol/L, desirable levels ≥0.80 mmol/L. CONCLUSION: The reference interval values of BP, FPG, and BL are different between the longevity population and the non-longevity population, and the interval values change with increasing age.

Therapeutic Effects of Ba-Duan-Jin versus Pregabalin for Fibromyalgia Treatment: Protocol for a Randomized Controlled Trial.

INTRODUCTION: Fibromyalgia is characterized by multi-focal pain and is associated with fatigue, unrefreshing sleep and psychological impairment. Pregabalin is one of the most frequently used agents in fibromyalgia treatment. However, it has failed to demonstrate benefit over placebo for reducing fatigue and psychological impairment, and may cause adverse effects (e.g. somnolence, dizziness). "Ba-Duan-Jin" (BDJ) is a common form of "Qigong" exercise for health promotion in China. Growing evidence suggests that BDJ may achieve satisfactory control of fibromyalgia-related symptoms in Chinese patients. Therefore, we wish to ascertain if BDJ could overcome the disadvantages of pregabalin. METHODS: A single-blind randomized controlled trial has been designed which will recruit 104 patients with fibromyalgia (age 18-70 years) with a visual analog scale (VAS) pain score of ≥ 40 mm These patients will be randomly assigned to one of two groups: (1) BDJ group (to undertake guided BDJ exercise and take a placebo capsule) or (2) pregabalin group (to take a pregabalin capsule and receive wellness education and guided muscle-relaxation exercises). The primary endpoint will be changes in the VAS score for pain. The secondary endpoints will be changes in the score for the Revised Fibromyalgia Impact Questionnaire, Multidimensional Fatigue Inventory-20, Pittsburgh Sleep Quality Index, Beck II Depression Inventory, Perceived Stress Scale and Short Form-36 Health Survey Questionnaire. These parameters will be assessed at 0, 4, 8, 12 and 24 weeks of follow-up. PLANNED OUTCOMES: Our results are expected to provide more clinical evidence for the beneficial effects of BDJ in treating fibromyalgia. TRIAL REGISTRATION: NCT03797560.