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.

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.

Rapid and label-free screening of echinococcosis serum profiles through surface-enhanced Raman spectroscopy.

Echinococcosis is a serious zoonotic parasitic disease that could be fatal without diagnosis and treatment in a timely manner. Herein, we present a rapid and label-free method for screening of echinococcosis using surface-enhanced Raman spectroscopy (SERS). Three groups of serum SERS spectra based on porous silicon/silver composites are obtained: one group from healthy volunteers (normal, n = 163) and two other groups from patients with pathologically confirmed echinococcosis (cystic echinococcosis (CE), n = 69 and alveolar echinococcosis (AE), n = 38). The derived characteristic spectrum was analyzed to explain differences between echinococcosis and healthy volunteers and a principal component analysis (PCA) was applied for classification. Raman spectra revealed that high sensitivity and specificity for echinococcosis diagnosis were associated with the contents of phenylalanine and tyrosine. In addition, Raman spectroscopy analysis identified two metabolites including phenylalanine and carotenoids that could distinguish three types of serum. Orthogonal partial least squares discriminant analysis (OPLS-DA) was successfully used as a discriminative model to classify echinococcosis with the highest sensitivity and specificity of 100% and 98.6%, respectively. Combination of serum metabolomics with SERS enabled accurate screening of echinococcosis patients. The results indicate that SERS-based serum profile analysis has the potential to be a valuable tool for the early diagnosis and screening of echinococcosis.

Ba-Duan-Jin alleviates pain and fibromyalgia-related symptoms in patients with fibromyalgia: results of a randomised controlled trial.

OBJECTIVES: Fibromyalgia is a chronic debilitating pain syndrome. There has been growing interest in the development of non-pharmacological therapies. Ba-Duan-Jin is an ancient Chinese exercise for health promotion, yet easy to learn. The purpose of this study is to evaluate the effectiveness of Ba-Duan-Jin in managing fibromyalgia symptoms experienced by Chinese patients. METHODS: In this randomised, usual therapy-controlled study, patients with fibromyalgia practiced Ba-Duan-Jin for one hour, twice a week for 12 weeks. The primary outcome measure was change in the Visual Analogue Scale for pain (pain VAS). Secondary outcomes included the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Assessment of Fatigue (MAF), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Perceived Stress Scale (PSS), and the Tender Point Count (TPC). These measures were assessed at baseline and after 4, 8, and 12 weeks. The Patient Global Impression of Change (PGIC) was collected at week 12. The Mann-Whitney U-test was performed using the intention-to-treat population. RESULTS: A total of 62 fibromyalgia patients were randomised to the Ba-Duan-Jin or the control groups. For the Ba-Duan-Jin group, significant improvement in pain VAS, FIQ, MAF, PSQI, and TPC were documented at weeks 4 (p≤0.046) and continued at week 8 (p≤0.003). At week 12, all of the outcome measures including BDI and PSS exhibited significant improvement (p≤0.004), and PGIC ratings were significantly better (p<0.001). No significant changes in the control group were observed. CONCLUSIONS: This study suggests that Ba-Duan-Jin exercise has the potential to be a valuable non-pharmacological intervention among Chinese fibromyalgia patients.

Surface-Modified Biochar with Polydentate Binding Sites for the Removal of Cadmium.

In this study, a surface chemical-modified rice husk biochar with abundant amino groups and disulfide bonds for the removal of cadmium was prepared using cystamine dihydrochloride as a modification ligand and glutaraldehyde as a crosslinker. The biochars were characterized by Fourier transform infrared spectrometry (FTIR), elemental analysis, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetry analysis (TGA), and nitrogen sorption (BET) before and after modification. The adsorption properties of the modified biochars for Cd (II) were investigated in detail via adsorption isotherm models, adsorption kinetics models, and selective adsorption experiments. The surfaces of the cystamine-modified biochars with granular nanopolymers of sufficient functional groups of primary amine and disulfide linkage rendered the biochar surface more conducive to electrostatic attraction and surface complexation. The theoretical maximum adsorption capacity of the modified biochars (81.02 mg g-1) was almost 10-fold greater than that of the raw biochars (8.347 mg g-1) for Cd (II). Besides, the cystamine-modified biochars had a better affinity for Cd (II) compared to other heavy metals (Zn, As, Cd, Co, Ni, Cr), showing six-fold greater affinity for Cd (II) than Zn2+. The results of this study indicate that the modification of biochars derived from rice husks shows great potential in the removal of Cd (II) from contaminated water.

[Regularity of prescription and medication of Jiang Quan in treating rheumatoid arthritis].

The data mining method was used to analyze and summarize the prescription and medicate regularities of chief physician Jiang Quan in the treatment of rheumatoid arthritis,in order to provide references for the clinical treatment of rheumatoid arthritis. Totally 121 prescriptions of rheumatoid arthritis treated by chief physician Jiang Quan from 2007 to 2017 were collected and input into the Chinese medicine inheritance auxiliary system. The " prescription statistics" function of the software " statistical report" system,and the " prescription analysis" function of the " data analysis" system,the data mining methods such as rule analysis,integration correlation,complex system entropy clustering,and unsupervised entropy hierarchical clustering,were used to analyze the prescription regularity of chief physician Jiang Quan. A total of 121 prescriptions were included,involving 144 herbs,in which 30 herbs had a higher frequency of more than 20 times,20 two-herb combinations had a frequency of more than 59 times; after evolution,14 core combinations and 7 new prescriptions were obtained. Among the prescriptions in the treatment of rheumatoid arthritis,those for clearing heat and dampness,promoting blood circulation and removing blood stasis had a higher frequency,and the core prescriptions were modified " Qingre Huoxue Decoction" and modified " Ermiao Pills". The newly evolved prescriptions not only reflected director Jiang Quan' s method of treating rheumatoid arthritis by clearing away heat and dampness and promoting blood circulation by the,but also included the treatment methods of removing wind and removing dampness,dredging collaterals and removing phlegm,nourishing Yin and clearing heat,nourishing Yin and nourishing kidney,nourishing blood and nourishing Qi. The method can be used to analyze the pathogenetic changes of the mutual knot of phlegm and blood stasis,injury of Qi and blood,long-term implication on liver and kidney. At the same time,it also reflects the treatment principles of treating phlegm and strengthening the evil.

A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease.

Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP-1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivo electrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long-term spatial memory of 3xTg-AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long-term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid-ß (Aß) and phosphorylated tau aggregates, and upregulated the expression levels of S133 p-CREB, T286 p-CAMKII and S9 p-GSK3ß in the hippocampus of the 3xTg-AD mice. These results demonstrate for the first time that the novel GLP-1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg-AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD.

Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial.

BACKGROUND: Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF). METHODS: This study will be an 8-week double-blinded, randomized, placebo-controlled clinical trial conducted at Guang'anmen Hospital in Beijing, China, and 168 patients with moderately active RA will be randomly assigned with a 1:1 ratio to apply a topical gel preparation containing TwHF or placebo. The primary outcome variable will be the proportion of subjects, by study group, to achieve a 20% improvement in the American College of Rheumatology criteria (ACR20) by week 8. Secondary outcome measures to be assessed at weeks 4 or 8 will include: measurement of ACR20 response rate at week 4, ACR50 response rate, the changes in DAS28 score, and joint synovitis classification assessment monitored by musculoskeletal ultrasound. Safety evaluations conducted at weeks 4, 8 and 12 will be based on spontaneous complaints by the study subjects, but special emphasis will be focused on cutaneous allergy and alterations of menstruation in premenopausal female participants. Statistical analyses will be performed using the intention to treat analysis data set. DISCUSSION: This proposed clinical trail is designed to evaluate the efficacy and safety of CET based on a single topically-applied agent in a relatively large patient population with RA. This study protocol gives a detailed description of the usage and dosage of the topical compound TwHF gel and the methodology of this study. In addition, it is hoped that the outcomes of this study will be viewed as supporting the generalizability of CET in the setting of inflammatory rheumatic diseases. The results of this study are expected to have important public health implications for Asian RA patients that currently utilize CET as a complimentary treatment. TRIAL REGISTRATION: Clinical trial gov Identifier: NCT02818361 . Registrated on Jun. 15, 2016.

[Real-time measurement of Ca2+ flux in hippocampal slice with non-invasive micro-test technique].

The deposition of amyloid-ß protein (Aß) in the brain is the most important pathological feature of Alzheimer's disease (AD). The mechanism of Aß neurotoxicity may be closely related to the disturbance of intracellular Ca2+ homeostasis. Non-invasive micro-test technique (NMT) is a novel technique developed in recent years, which can be used to directly record transmembrane ion influx and efflux in a non-contact way by detecting the diffusion potentials outside of the membrane. The present study examined the effects of Aß31-35 pretreatment on glutamate (Glu)-induced Ca2+ influx and low [Ca2+] solution-induced Ca2+ efflux in the hippocampal slices of C57BL/6 mice using NMT. The results showed that: (1) acute administration of Glu (2.5, 5, 10 mmol/L) evoked a persistent transmembrane Ca2+ influx in hippocampal CA1 neurons, with a rapid onset and subsequent decay; (2) pretreatment with Aß dose-dependently increased the average rate of Ca2+ influx induced by Glu during the initial 5 min, which was blocked by NMDA receptor antagonist D-APV; (3) perfusion with low [Ca2+] artificial cerebrospinal fluid (aCSF) induced a continuous Ca2+ efflux, which was mostly blocked by KB-R7943, a specific antagonist of Na+/Ca2+ exchanger; (4) Aß31-35 pretreatment partially inhibited the low [Ca2+] aCSF-induced Ca2+ efflux. These results indicate that Aß not only facilitates Ca2+ influx but also inhibits Ca2+ efflux, which jointly contribute to the Aß-induced intracellular Ca2+ overload; the potentiation of Aß on Glu excitotoxicity is mainly mediated by NMDA receptors, while the target for Aß to affect Ca2+ efflux was mainly Na+/Ca2+ exchanger. NMT showed multiple advantages in detecting transmembrane Ca2+ flux in brain slices, such as non-invasiveness to target cells, fast, convenient and real-time acquisition of Ca2+ flux. Therefore, this study provided new experimental evidence for Aß-induced Ca2+ overload, as well as a novel application for NMT in measuring transmembrane Ca2+ flux of neurons in the brain.

[GLP-1/GIP/Gcg receptor Triagonist improves the cognitive behaviors in triple-transgenic mice of Alzheimer's disease].

Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which seriously affects human health but is still irreversible up to now. Recent studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor for AD, and the drugs used for treatment of T2DM have shown some neuroprotective effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and incorporated with partial amino acids of GIP. Recently, the Triagonist has been reported to be effective in alleviating diabetic complications in rodent models of obesity. The present study observed for the first time the cognitive improvement effects of the Triagonist in the triple-transgenic AD mice (3xTg-AD) by using multiple behavioral techniques, and explored its probable molecular mechanisms using ELISA and Western blot. The results showed that the chronic treatment with the Triagonist (i.p.) significantly reversed the impairments in working memory of 3xTg-AD mice, with an obvious increase in the percentage of correct spontaneous alternation in the Y maze; the Triagonist treatment also improved long-term spatial memory and re-learning ability of 3xTg-AD mice in classical Morris water maze and reverse water maze tests, with decreased escape latency in under water platform tests and increased swimming time in probe tests. ELISA and Western blot experiments showed that the Triagonist up-regulated the levels of cAMP, PKA and p-CREB in the hippocampus of 3xTg-AD mice. These results indicate that GLP-1/GIP/Gcg receptor Triagonist can improve the cognitive behaviors in 3xTg-AD mice, and the up-regulation of hippocampal cAMP/PKA/CREB signal pathway may mediate the neuroprotection of the Triagonist, suggesting that the GLP-1/GIP/Gcg receptor Triagonist may be a novel therapeutic strategy for the treatment of AD.

[Effect of External Applying Compound Tripterygium wilfordii Hook F. on Joint Pain of Rheumatoid Arthritis Patients].

OBJECTIVE: To observe the effectiveness and safety of external applying Compound Tripterygium wilfordii Hook F. (TwHF) in relieving joint pain in rheumatoid arthritis (RA) patients. METHODS: In this double-blinded, randomized multicenter trial, a total of 174 moderately active RA patients were enrolled and randomly assigned to the treatment group (treated with Compound TwHF, 87 cases) and the placebo control group (87 cases). Compound TwHF or placebo was externally applied in painful joints, 20 g each time, once per day for 8 weeks. Self-reported joint pain relief was taken as a primary effective indicator. Visual analogue scale for pain (VAS), disease activity score of 28 joints (DAS28), VAS for general health (GH) were evaluated before treatment, at week 4 and after treatment. Erythrocyte sedimentation rate (ESR) and hypersensitive C reactive protein (hs-CRP) were tested before and after treatment. Menstrual changes in females were observed during treatment. Skin irritation occurred during the recording process was assessed using skin irritation strength. Intention to treat (ITT) was statistically analyzed. RESULTS: The joint pain relief rate in the treatment group was 90.8% (79/87 cases), higher than that in the placebo control group (69.0%, 60/87 cases; P = 0.001). VAS pain score, DAS28, VAS for GH score were significantly improved in the two groups at week 4 of treatment and after treatment, as compared with before treatment (P < 0.01). ESR and hs-CRP levels significantly decreased in the treatment group after treatment (P < 0.05, P < 0.01). No difference was found in post-treatment VAS pain score, DAS28, VAS for GH score, ESR, or hs-CRP between the two groups (P > 0.05). Eight adverse events occurred in the treatment group (5 skin allergy, 1 intolerance of medical odor, and 2 mild liver injury), while 3 adverse events occurred in the placebo control group (2 skin allergy, 1 mild liver injury). There was no statistical difference in adverse event between the two groups (P > 0.05). No menstrual change occurred in the treatment group. CONCLUSION: External applying Compound TwHF was an effective and safe way to relieve-joint pain of RA patients, which could be taken as an adjuvant therapy.

Association of abuse history with symptom severity and quality of life in patients with fibromyalgia.

A high prevalence of abuse has been reported in patients with fibromyalgia. We aimed to examine the association between self-reported abuse history and symptom severity and quality of life (QOL) in 962 patients with fibromyalgia. All patients completed the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form 36 health survey (SF-36). Multivariate regression analyses were performed. In total, 289 patients (30%) reported a history of abuse. Of those who specified abuse types, 161 patients (59%) reported more than 1 type of abuse (36% emotional, 32% physical, 25% sexual, and 7% verbal). Patients in the abuse group were younger and more likely to be female, unemployed, unmarried, and current smokers compared with patients who reported no abuse. After adjusting for these differences, abuse history was associated with worse symptoms, as indicated by a higher FIQ total score (P < .001) and higher FIQ subscale scores in physical function (P = .001), work missed (P < .001), job ability (P < .001), pain (P = .02), depression (P < .001), and anxiety (P < .001). Similarly, abuse history was associated with worse QOL, with lower SF-36 scores in all domains except the physical component summary. In conclusion, abuse history in patients with fibromyalgia was associated with worse symptoms and QOL compared with those patients without abuse history. Future studies are needed to assess whether additional tailored interventions as part of fibromyalgia treatment are helpful for patients with a history of abuse.

miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes.

By influencing the activity of the PI3K/AKT pathway, IL-6 acts as an important regulator of hepatic insulin resistance. miR-200s have been shown to control growth by regulating PI3K, but the role of miR-200s in the development of hepatic insulin resistance remains unclear. The present study showed that elevated serum concentration of IL-6 is associated with decreased levels of miR-200s, impaired activation of the AKT/glycogen synthase kinase (GSK) pathway, and reduced glycogenesis that occurred in the livers of db/db mice. As shown in the murine NCTC 1469 hepatocytes and the primary hepatocytes treated with 10 ng/ml IL-6 for 24 h and in 12-week-old male C57BL/6J mice injected with 16 µg/ml IL-6 by pumps for 7 days, IL-6 administration induced insulin resistance through down-regulation of miR-200s. Moreover, IL-6 treatment inhibited the phosphorylation of AKT and GSK and decreased the glycogenesis. The effects of IL-6 could be diminished by suppression of FOG2 expression. We concluded that IL-6 treatment may impair the activities of the PI3K/AKT/GSK pathway and inhibit the synthesis of glycogen, perhaps via down-regulating miR-200s while augmenting FOG2 expression.

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.

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.

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.

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].

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.

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.