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Objectives. To identify relationships between US states' COVID-19 in-person activity limitation and economic support policies and drug overdose deaths among working-age adults in 2020. Methods. We used county-level data on 140 435 drug overdoses among adults aged 25 to 64 years during January 2019 to December 2020 from the National Vital Statistics System and data on states' COVID-19 policies from the Oxford COVID-19 Government Response Tracker to assess US trends in overdose deaths by sex in 3138 counties. Results. Policies limiting in-person activities significantly increased, whereas economic support policies significantly decreased, overdose rates. A 1-unit increase in policies restricting activities predicted a 15% average monthly increase in overdose rates for men (incident rate ratio [IRR] = 1.15; 95% confidence interval [CI] = 1.09, 1.20) and a 14% increase for women (IRR = 1.14; 95% CI = 1.09, 1.20). A 1-unit increase in economic support policies predicted a 3% average monthly decrease for men (IRR = 0.97; 95% CI = 0.95, 1.00) and a 4% decrease for women (IRR = 0.96; 95% CI = 0.93, 0.99). All states' policy combinations are predicted to have increased drug-poisoning mortality. Conclusions. The economic supports that states enacted were insufficient to fully mitigate the adverse relationship between activity limitations and drug overdoses. (Am J Public Health. 2024;114(7):714–722. https://doi.org/10.2105/AJPH.2024.307621) [ABSTRACT FROM AUTHOR]

Purpose: Oxidative stress has been reported to cause telomere attrition, which triggers cell apoptosis. Apoptosis of neurocytes may play an essential role in the pathogenesis of neurodegenerative diseases. This study hypothesized that folic acid (FA) supplementation decreased neurocyte apoptosis by alleviating oxidative stress-induced telomere attrition in 25-month-old Sprague Dawley (SD) rats. Methods: Three-month-old male SD rats were randomly divided into four diet groups by different concentrations of folic acid in equal numbers, with intervention for 22 months. Folate, homocysteine (Hcy), reactive oxygen species (ROS) levels, antioxidant activities, and telomere length in the brain tissues were tested at 11, 18, and 22 months of intervention, and 8-hydroxy-deoxyguanosine (8-OHdG) levels, neurocyte apoptosis and telomere length in the cerebral cortex and hippocampal regions were tested during the 22-month intervention. An automated chemiluminescence system, auto-chemistry analyzer, Q-FISH, qPCR, and TUNEL assay were used in this study. Results: The rats had lower folate concentrations and higher Hcy, ROS, and 8-OHdG concentrations in brain tissue with aging. However, FA supplementation increased folate concentrations and antioxidant activities while decreasing Hcy, ROS, and 8-OHdG levels in rat brain tissue after 11, 18, and 22 months of intervention. Furthermore, FA supplementation alleviated telomere length shortening and inhibited neurocyte apoptosis during the 22-month intervention. Conclusion: FA supplementation alleviated oxidative stress-induced telomere attrition and inhibited apoptosis of neurocytes in 25-month-old rats. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of Internet based intervention model on breastfeeding knowledge, attitude, self-confidence and breastfeeding rate. Methods: An electronic literature search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, Wanfang, CBM and VIP database was performed using combinations of the keywords "Breastfeeding," "Breastfeeding, Exclusive," "Internet," "Online," and "Website". The retrieval period was from their inception to March 31, 2023. Quality appraisal was performed using the Cochrane 5.1 for randomized controlled trials (RCTs). RevMan5.3 was used for data analysis. Results: Thirty-two studies were included in the review, with a total of 9514 samples. The results of Meta-analysis showed that, compared with routine nursing, the intervention model based on the Internet can effectively improve breastfeeding knowledge and attitude of pregnant women, improve breastfeeding self-confidence (P < 0.05), and improve the rate of exclusive breastfeeding in the short term (within 6 weeks) and the long-term postpartum (3–6 months) had a positive effect on the rate of exclusive breastfeeding (P < 0.05). Conclusions: The Internet breastfeeding intervention model may be an effective intervention to improve the effect of exclusive breastfeeding. In the future, more high-quality, large-sample randomized controlled trials can be carried out to further explore the effect of the Internet intervention model on breastfeeding. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole‐exome sequencing (WES). Methods: This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti–citrullinated protein antibody (ACPA−) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole‐exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA− PR and ACPA+ PR. Results: Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA−. We identified 8 novel loci (in the ACPA− PR group: ZNF503, RPS6KL1, HOMER3, HLA–DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA− PR group: HLA–DRB1*0803 and HLA–DQB1; in the ACPA+ PR group: HLA–DPA1*0401) that were associated with PR and that surpassed genome‐wide significance (P < 5 × 10−8). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R2 < 0.025), whereas ACPA+ PR and ACPA− PR showed a moderate genetic correlation (0.38 < R2 < 0.8). Conclusion: This study demonstrated the distinct genetic background between ACPA− and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar. [ABSTRACT FROM AUTHOR]

Objective. Evidence-based research methods were applied to assess the efficacy of faecal microbiota transplantation (FMT) for the treatment of autism in children. Methods. We searched the Chinese Biomedical Literature, CNKI, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library databases to collect randomised controlled trials on faecal microbiota transplantation for the treatment of autism in children. The search included studies published from the creation of the respective database to 5 April 2022. Literature screening, data extraction, and quality evaluation were implemented by three investigators according to the inclusion and exclusion criteria. The meta-analysis was performed using the RevMan 5.1 software. Results. Nine studies with population-based subjects and four studies with animal-based subjects were included. Five papers were screened for the meta-analysis. The results showed that FMT markedly reduced Autism Behaviour Checklist (ABC) scores in children with autism spectrum disorder (weighted mean difference (WMD) = −14.96; 95% confidence intervals (CI), −21.68 to −8.24; P < 0.001 ; I2 = 0%). FMT also reduced Childhood Autism Rating Scale (CARS) scores (WMD = −6.95; 95% CI, −8.76 to −5.14; P < 0.001 ; I2 = 28.1%). Conclusion. Our results indicate that FMT can benefit children with autism by reducing ABC and CARS scores, but more high-quality studies are needed to verify these results. [ABSTRACT FROM AUTHOR]

Objective To explore whether inactivated coronavirus disease 2019 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary APS patients. Methods We enrolled 39 primary APS patients who received two doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and 4 weeks after the second dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. Results There was no significant difference in the presence of all 11 autoantibodies detected before and 4 weeks after vaccination: for aCL, IgG (14 vs 16, P  = 0.64), IgM (13 vs 19, P  = 0.34), IgA (2 vs 3, P  = 0.64); anti-β2GP1, IgG (12 vs 12, P  = 1.00), IgM (5 vs 8, P  = 0.36), IgA (4 vs 3, P  = 0.69); anti-PS/PT IgG (13 vs 16, P  = 0.48), IgM (17 vs 22, P  = 0.26); LAC (22 vs 28, P  = 0.16); aPF4-heparin (0 vs 0, P  = 1.00) and ANA (23 vs 26, P  = 0.48). Notably, the distribution of the aPL profile in the pre- and post-vaccination cohorts was not affected by SARS-CoV-2 vaccination: for patients with a low-risk aPL profile (11 vs 10, P  = 0.799) and patients with a high-risk aPL profile (28 vs 29, P  = 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. Conclusion Inactivated SARS-CoV-2 vaccine does not influence the profile of anti-phospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients. [ABSTRACT FROM AUTHOR]

Purpose: COVID‐19 mortality rates are higher in rural versus urban areas in the United States, threatening to exacerbate the existing rural mortality penalty. To save lives and facilitate economic recovery, we must achieve widespread vaccination coverage. This study compared adult COVID‐19 vaccination rates across the US rural‐urban continuum and across different types of rural counties. Methods: We retrieved vaccination rates as of August 11, 2021, for adults aged 18+ for the 2,869 counties for which data were available from the CDC. We merged these with county‐level data on demographic and socioeconomic composition, health care infrastructure, 2020 Trump vote share, and USDA labor market type. We then used regression models to examine predictors of COVID‐19 vaccination rates across the USDA's 9‐category rural‐urban continuum codes and separately within rural counties by labor market type. Findings: As of August 11, 45.8% of adults in rural counties had been fully vaccinated, compared to 59.8% in urban counties. In unadjusted regression models, average rates declined monotonically with increasing rurality. Lower rural rates are explained by a combination of lower educational attainment and higher Trump vote share. Within rural counties, rates are lowest in farming and mining‐dependent counties and highest in recreation‐dependent counties, with differences explained by a combination of educational attainment, health care infrastructure, and Trump vote share. Conclusion: Lower vaccination rates in rural areas is concerning given higher rural COVID‐19 mortality rates and recent surges in cases. At this point, mandates may be the most effective strategy for increasing vaccination rates. [ABSTRACT FROM AUTHOR]

Background. With a high incidence and limited treatments, gastric cancer (GC) seriously threatens human health worldwide. Weikang Keli (WK) is a compound prescription summed up from clinical experience. In our previous studies, WK has been proved to exert antitumor effects. However, there are no research studies to discuss and verify its mechanism as a compound. Objective. The aim of the study is to explore the potential molecular mechanism of WK in the treatment of GC with the aid of network pharmacology and verify it through experiments. Methods. Related databases were used to obtain genes and targets of WK and gastric cancer. A protein-protein interaction (PPI) network is constructed and visualized by Cytoscape 3.7.2. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze core targets. The cell viability of MFC and BGC-823 cells was determined by CCK8. Immunofluorescence was used to determine autophagy of GC cells. Moreover, the effect of WK on the MAPK signaling pathway in GC cells and tumor tissues of ICR mice was detected by Western blot. Results. A total of 106 cross targets of WK and GC were obtained. According to the enrichment analysis of GO and KEGG, we target the MAPK signaling pathway to discuss the mechanism of WK on GC. Cell experiments proved that WK inhibited the viability of gastric cancer cells in a dose-dependent and time-dependent manner. Autophagosome aggregation and an increase in the expression of an autophagy marker protein LC3-II can also be observed in WK groups. Further animal experiments showed that the tumor inhibition rate of WK showed a dose-effect relationship. Moreover, the expressions of p-JNK, p-p38, and p-ERR1/2 proteins in the MAPK signaling pathway in WK Group were downregulated both in the cell and animal experiments, compared with the blank control group. Conclusion. WK showed an explicit antitumor effect on gastric cancer through the MAPK signaling pathway, and the curative effect varies in different concentrations. Besides, in model mice, the antitumor effect of high-dose WK group is close to that of platinum. This study provided a theoretical basis for the application of WK in the clinical treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Objectives Thrombosis occurring in the central nervous system is common in APS patients, leading to neuropsychiatric symptoms. We investigated the prevalence of silent brain abnormalities on MRI in primary APS (PAPS) patients and aPL carriers and assessed the association between the vascular risk factors, aPL profile, clinical manifestations and MRI abnormalities. Methods We consecutively included 44 PAPS patients, 24 aPL carriers and 23 healthy controls with comparable age and gender in a single-centre, observational, cross-sectional study. None of the patients had a history of stroke, transient ischaemic attack, migraine, dementia, epilepsy or bipolar disorders. On cerebral MRI, we assessed the imaging features and location of abnormality. Multivariate analysis was performed to identify the risk factors contributing to the MRI abnormalities. Results A total of 38 (55.88%) patients had abnormal MRI findings, while only one healthy control showed some abnormalities. Lacunes were the most frequent MRI abnormality in the aPL-positive group [31/68 (45.59%)], which were followed by white matter hyperintensities [20/68 (29.41%)]. In the study population, age [odds ratio (OR) 1.086, P  = 0.016] and LA positivity (OR 5.191, P  = 0.002) were independent associated factors with brain MRI abnormalities. When analysed in only the aPL-positive group, age (OR 1.116, P  = 0.007), female gender (OR 7.519, P  = 0.025) and thrombocytopenia (OR 8.336, P  = 0.047) were the significant independent risk factors with abnormal MRI. Conclusions PAPS patients and aPL carriers showed a high prevalence of brain MRI abnormalities, indicating an increased cerebrovascular risk, which emphasized attention to silent cerebral lesions in persistently aPL-positive patients. [ABSTRACT FROM AUTHOR]

Objective Anti-β-2 glycoprotein I (anti-β2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-β2GP1 IgG with clinical features of APS. Methods We purify anti-β2GPI IgG and total IgG from 82 APS patients including nine catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyse all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry. Results Both purified anti-β2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with healthy control (HC) IgG. Anti-β2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aβ2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aβ2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-β2GPI IgG subclasses, increased bisection and core fucosylation of anti-β2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs). Conclusion We comprehensively characterize the N-Glycans landscape of both anti-β2GP1 and total IgG in APS. Altered N-glycan profiles of anti-β2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-β2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments. [ABSTRACT FROM AUTHOR]

Background: The current study was to evaluate the effects of canagliflozin and metformin on insulin resistance and visceral adipose tissue in people with newly-diagnosed type 2 diabetes. Methods: This is an open-label, parallel and controlled study. Participants were divided into canagliflozin (100 mg/qd) or metformin (1000 mg/bid) groups. At baseline and after 12 weeks' therapy, insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], subcutaneous and visceral adipose tissue, fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), C-reactive protein (CRP) and nitric oxide (NO) were evaluated and compared. Results: There was no significant between-group difference in baseline characteristics. After 12 weeks' therapy, in canagliflozin group (n = 67), compared to baseline, FBG, HbA1c and HOMA-IR were decreased, accompanying with reduction of visceral adipose tissue. Compared to metformin group (n = 73), FBG, HbA1c and HOMA-IR were lower in canagliflozin group, accompanying with less visceral adipose tissue and lower serum CRP level and higher NO level. After multivariable regression analysis, age, visceral adipose tissue and CRP remained associated with increased insulin resistance, while canagliflozin treatment and higher NO level were associated with reduced insulin resistance. Body mass index, waist/hip ratio, CRP and HOMA-IR remained associated with increased visceral adipose tissue, while canagliflozin treatment and higher NO level were associated with reduced visceral adipose tissue. There was no difference in adverse event between these two groups. Conclusion: Canagliflozin reduces visceral adipose tissue and improves blood glucose, insulin resistance and systemic inflammation in people with newly-diagnosed type 2 diabetes. [ABSTRACT FROM AUTHOR]

Urban vegetation can deposit dust to reduce pollution, and dust retention capacity of vegetation has become an important indicator for urban ecological construction. We selected five representative vegetation in Shanghai to explore the regularity of dust deposition on vegetation leaves. Due to the influence of leaf area and surface characteristics, the amount of dust deposition was significantly different to each vegetation; Vegetation shows different dust retention capacity under different pollution intensity, before this capacity reaches its limit, and it will increase with the increase of dust content in the environment; Furthermore, water content of leaves was an important factor affecting dust retention capacity by vegetation. There was a linear positive correlation between the two variables. Our work suggests that the dust retention capacity of vegetation leaves was affected by various factors, but it showed certain regularity, which can provide a scientific basis for the configuration of urban green plant species. [ABSTRACT FROM AUTHOR]

Objectives To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). Methods We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan–Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. Results A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. Conclusion Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up. [ABSTRACT FROM AUTHOR]

Background: It has been widely accepted that oral health status is related to oral health literacy. The need to measure oral health literacy has led to the development of measurement instruments. This study aimed to develop a comprehensive instrument for adults and to examine its reliability and validity in China. Methods: A three-step design process was used. First, a literature review and expert panel discussion were used to draw up a 37-item pool covering oral health knowledge, belief, practice, skill, and functional oral health literacy. The Delphi method was used to delete and modify questions in the item pool. The draft instrument was evaluated by nine experts and the consensus among them was calculated using the content validity index. The scale was then used to conduct a psychometric study among 370 participants from community health centers in Beijing. Construct validity, discriminant validity and concurrent validity were examined. The Cronbach's alpha coefficient, and test–retest methods were used to assess reliability. Results: The final scale included 30 items across four dimensions. The item–level content validity index was 0.90. Exploratory factor analysis extracted four fixed factors, and the result of the Kaiser–Meyer–Olkin and Bartlett's tests was 0.752, with the model explaining 35.21% of the total variance. The four dimensions were associated with oral health knowledge, perceptions of oral health issues, oral health practice and skills, and functional oral health literacy. The mean score of the lowest 27% was significantly lower than the highest 27% (P < 0.01), suggesting adequate discriminant validity. The associations between comprehensive oral health literacy scores and educational level, income and self-reported literacy level were significant (P < 0.001), showing adequate overall concurrent validity. Internal consistency and test–retest reliability were acceptable, with a Cronbach's alpha of 0.72 and a total test–retest reliability coefficient of 0.979. Conclusions: Initial testing of the comprehensive oral health literacy instrument suggested that it is a valid and reliable instrument to evaluate individuals' oral health literacy, with four dimensions for evaluating knowledge, belief, skills, and functional oral health literacy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and effectiveness of Qishe Pill (芪麝丸) on neck pain in real-world clinical practice. Methods: A multi-center, prospective, observational surveillance in 8 hospitals across Shanghai was conducted. During patients receiving 4-week Qishe Pill medication, Visual Analogue Scale (VAS) and Neck Disability Index (NDI) assessments have been used to assess their pain and function, while safety monitoring have been observed after 2 and 4 weeks. Results: Results from 2,023 patients (mean age 54.5 years) suggest that the drug exposure per unit of body mass was estimated at 3.41 ± 0.62 g/kg. About 8.5% (172/2,023) of all participants experienced adverse events (AEs), while 3.8% (78/2,023) of all participants experienced adverse reaction. The most common AEs were gastrointestinal events and respiratory events. The VAS score (pain) and NDI score (function) significantly decreased after 4-week treatment. An effect-quantitative analysis was also conducted to show that the normal clinical dosage may be consider as 3–4 g/kg, at which dosage the satisfactory pain-relief effect may achieve by 40-mm reduction in VAS. Conclusion: These findings showed that patients with cervical radiculopathy who received Qishe Pill experienced significant improvement on pain and function. (Registration No. NCT01875562) [ABSTRACT FROM AUTHOR]

Objective: Adult‐onset Still's disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin‐like receptor A3 (LIR‐A3; gene name LILRA3) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD. Methods: The LILRA3 deletion polymorphism and its tagging single‐nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR‐A3 were detected using enzyme‐linked immunosorbent assay (ELISA), and the correlation between LIR‐A3 plasma levels and disease activity and levels of circulating NET‐DNA was investigated. LIR‐A3–induced NETs were determined using PicoGreen double‐stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil‐like differentiated NB4 cell line transfected with LIR‐B2 small interfering RNA. Results: The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030–4.291], P = 0.034), and associated with leukocytosis (P = 0.039) and increased levels of circulating neutrophils (P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells (P < 0.0001) and neutrophils (P < 0.001) of LILRA3+/+ patients. Plasma levels of LIR‐A3 were elevated in patients with AOSD (P < 0.0001) and correlated with disease activity indicators and levels of circulating NET–DNA complexes. Finally, enhanced NET formation was identified in neutrophils from healthy controls and patients with inactive AOSD after stimulation of the neutrophils with LIR‐A3. Moreover, NET formation was impaired in NB4 cells after knockdown of LILRB2 gene expression. Conclusion: Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR‐A3 may play a pathogenic role by inducing formation of NETs. [ABSTRACT FROM AUTHOR]

Objective Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. Methods Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. Results LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. Conclusion Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation. [ABSTRACT FROM AUTHOR]

Introduction: To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme‐linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS). Methods: The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA. Results: Total agreement between the two methods ranged from 83.50% for anti‐β2GPI IgG antibodies to 92.76% for anti‐β2GPI IgM antibodies in all the groups. Anti‐β2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti‐β2GPI IgG = 0.742, aCL IgG = 0.715). Anti‐β2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti‐β2GPI IgG ELISA (52.08%). For diagnosis of APS, anti‐β2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant. Conclusion: CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti‐β2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS. [ABSTRACT FROM AUTHOR]

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions. [ABSTRACT FROM AUTHOR]

To examine the association between B vitamins status and the risk of dementia in older adults through a systematic review and meta-analysis of cohort studies. Systematic review and meta-analysis. Older adults aged ≥60 years from community, nursing home, institution, or hospital. PubMed, Cochrane Library, EMBASE, Web of Science, CINAHL, ClinicalTrials, WHO-ICTRP, NHS Trusts, and ACTR were searched from the date of their inception up to November 28, 2021. We included cohort studies that assessed the association between serum B vitamins or B vitamins intake and the risk of dementia among older adults aged ≥60 years. The quality of all studies was assessed by the modified Newcastle-Ottawa Scale (NOS). The hazard ratios (HRs) and 95% CIs were calculated by the random effects model. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence. Eleven cohort studies with sample sizes ranging from 233 to 3634 were included in the meta-analysis. Levels of serum folate showed statistically significant association with the risk of dementia (≥10 nmol/L: HR 1.57, 95% CI 1.01-2.46, low certainty; <10 nmol/L: HR 0.93, 95% CI 0.88-0.99, very low certainty). However, levels of vitamin B 6 intake showed no statistically significant effects on risk of dementia; levels of serum vitamin B 12 and vitamin B 12 intake also showed no statistically significant effects on risk of dementia in older adults. The results from our meta-analysis suggest that vitamin B 6 , B 12 , and folate may not be modifiable risk factors for dementia among older adults. Current evidence on the relationship between vitamin B status and dementia is not sufficient for development of vitamin B recommendations. More high-quality cohort studies are needed to confirm the relationship between the two in the future. [ABSTRACT FROM AUTHOR]

We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers. Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism. [ABSTRACT FROM AUTHOR]

To compare and rank the effectiveness of group cognitive stimulation therapy (group CST), maintenance cognitive stimulation therapy (MCST), and individual cognitive stimulation therapy (iCST) on cognition and quality of life (QoL) in people with dementia. Systematic review and network meta-analysis (NMA). All published randomized controlled trials (RCTs) that compared the differences among 3 different settings of CST or a control group in treating people with dementia. Relevant electronic databases, including PubMed, Embase, Cochrane Library for clinical trials, Web of Science, CINAHL, PsycINFO, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data were systematically searched from inception to March 2021. RCTs that compared the differences among 3 different settings of CST or a control group in treating people with dementia were included. Then, a pairwise and network meta-analysis was conducted to evaluate the relative effects and rank probability of different CST settings. PRISMA guidelines were used for abstracting data, and the Cochrane Risk of Bias tool was used to assess data quality. In total, 17 studies were included, which enrolled 1680 participants. Compared with the control group, MSCT [standardized mean difference (SMD) = 1.39, 95% CI 0.86, 1.91; low-quality evidence] and group CST (SMD 0.62, 95% CI 0.39, 0.84; very low-quality evidence) could significantly improve cognitive function. MCST (SMD 1.00, 95% CI 0.16, 1.85; low-quality evidence) and group CST (SMD 0.53, 95% CI 0.13, 0.92; low-quality evidence) demonstrated a statistically significant effect in improving the QoL, whereas iCST was not significantly inferior to the control condition. None of the treatments were significantly different from each other with respect to acceptability. For people with dementia, group CST and MCST seems to promote more consistent benefits in terms of cognition and QoL than the iCST, and MCST was likely to be the most effective CST setting. Further RCTs with respect to the MCST and iCST efficacy are needed. [ABSTRACT FROM AUTHOR]

Microbial biotransformation of acetyl-11-keto-boswellic acid byCunninghamella elegansAS 3.1207 was carried out, and totally four transformed products were isolated. On the basis of the extensive spectral data, their structures were characterized as 7β-hydroxy-11-keto-boswellic acid (1), 7β,30-dihydroxy-11-keto-boswellic acid (2), 7β,16α-dihydroxy-3-acetyl-11-keto-boswellic acid (3), and 7β,15α,21β-trihydroxy-3-acetyl-11-keto-boswellic acid (4), respectively. Among them, products1and2are the new compounds. [ABSTRACT FROM PUBLISHER]

Objective: The aim of the study is to systematically review the effects of leg-driven treadmill-based exoskeleton robot training on balance and walking ability in poststroke patients. Design: The PubMed, Cochrane Library, Embase, Web of Science, Medline, CNKI, VIP, and Wanfang databases were searched from inception to August 2021. The literature quality was evaluated using Cochrane Handbook. Primary outcomes include the Functional Ambulation Category Scale and Berg Balance Scale, and secondary outcomes include the 10 meter walk test, 6 minute walk test, and gait assessment cadence were analyzed. Results: Seventeen randomized controlled trials were included in the systematic review, 15 studies in meta-analysis. Primary outcomes showed no significant difference in the Functional Ambulation Category Scale score; subgroup with the exoskeleton robot + conventional therapy of the Berg Balance Scale score was significantly increased; secondary outcomes showed no significance in 6 minute walk test or 10 meter walk test. The cadence score increased for the subgroup with an onset of more than 6 mos in the treatment group. The control group performed better than the subgroup with an onset of less than 6 mos. Conclusions: Leg-driven treadmill-based exoskeleton robot training can improve balance function in poststroke patients and is beneficial for patients with an onset of greater than 6 mos. However, there is no evidence to support the efficacy of walking ability. [ABSTRACT FROM AUTHOR]

Zingiberis Rhizoma (ZR) and Zingiberis Rhizoma Carbonisata (ZRC), as two forms of ginger-based herbal drugs used in China for at least 2000 years, have been recorded in Chinese Pharmacopoeia and applied for specific indications in traditional Chinese medicine (TCM). The present study aimed to explore the underlying therapeutic and processing mechanism of the absorbed components of ZR and ZRC on deficiency-cold and hemorrhagic syndrome (DCHS) using network pharmacological technique combined with pharmacokinetics strategy. In this study, a rapid and sensitive approach was conceived to simultaneously determine the seven components (zingiberone, 6-gingerol, 8-gingerol, 6-shogaol, 6-paradol, diacetyl-6-gingerol and 10-gingerol) in rat serum by HPLC-DAD-MS. The network pharmacological technique was employed to evaluate the effect of the absorbed components of ZR and ZRC on DCHS. Also, the vitro experiments were carried out to validate the functions of the seven compounds on coagulation and other major haematological effects. The values of intra-assay and inter-assay precision were determined to be less than 7.44%, with an accuracy value ranging from 83.64% to 107.99%. Analysis of rat plasma revealed that the extraction recoveries and matrix effects of the seven analytes were >85.76%. The method for validation following oral administration of ZR and ZRC to rats was proved to be a success in the pharmacokinetic study of the seven ingredients. Pharmacokinetics showed that ZR processing could enhance the absorption and utilization of 6-shogaol, 6-paradol and diacetyl-6-gingerol, meanwhile reduce the absorption of 6-gingerol, 8-gingerol, and 10-gingerol. Through the pathway enrichment analysis, it was found that the significant biological process of ZR and ZRC on DCHS was primarily associated with complement, coagulation cascades and platelet activation pathways. The vitro experiments indicated that zingiberone, 6-paradol and diacetyl-6-gingerol had a hemostatic effect by upregulating the expression of one or more targets such as TNF-α, FⅩa, FⅫ, FⅧ, ICAM-1, vWF and ITGB3. While 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol played a critical role in promoting blood circulation by increasing the expression of TM and/or PORC, and/or reducing the expression of ITGB3. In brief, network pharmacological technique in combination with pharmacokinetics strategy provided an applicable method for pharmacological mechanism study of ZR and ZRC, which, also, could be used as reference for quality control of the two drugs. In a broader sense, this combined strategy might even be valuable in uncovering the therapeutic and processing mechanism of Chinese herbs on a systematic level. [Display omitted] • ZRC were recorded in Chinese Pharmacopoeia for specificing dications in TCM. • ZRC could enhance the absorption of 6-shogaol, 6-paradol and diacetyl-6-gingerol. • ZRC on DCHS was associated with complement, coagulation cascades pathways. • Zingiberone, 6-paradol and diacetyl-6-gingerol had a hemostatic effect by HUVECs test. • 6-Gingerol, 6-shogaol, 8-gingerol and 10-gingerol had blood circulation by HUVECs test.. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Tripterygium preparations (TPs), a traditional Chinese Medicines extracted from Tripterygium wilfordii Hook f., are widely used for treatment of rheumatoid arthritis (RA). However, TPs from different Pharmaceutical factory have different efficacy and side effects for RA treatment. Aim of the study The purpose of the current study is to evaluate the efficacy and safety of four TPs from different Pharmaceutical factory in china on the treatment of collagen-induced arthritis (CIA) rats and provide a theoretical and experimental basis for the individualized use of TPs. Materials and methods The model of wistar rats of CIA was made, and the rats were perfused a stomach with four TPs for 3 weeks continuously. Then arthritis severity was determined by visual examination of the paws and histopathologic changes of joint, liver, kidney and testis were determined by hematoxylin–eosin (H&E) staining. The expression of inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) in the joint was analyzed by real-time PCR, and the count and motion parameters (sperm motility and progressive sperm) of sperm in cauda epididymis were assessed with computer-assisted sperm analysis (CASA) system. Routine blood tests were conducted using automated hematology analyzer, and the aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, creatinine (Cr), and blood urea nitrogen (BUN) in serum of CIA rats were measured using a UniCel DxC 880i autoanalyzer. Results All of tested TPs could reduce inflammatory score, histopathological arthritis severity and joint׳s inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) expression in CIA rats, however, TP-D showed stronger inhibitory effect for inflammatory score compared with other three TPs in vivo . All of tested TPs did not show hepatotoxicity and nephrotoxicity and also had little effect for the concentration of hemoglobin (Hb) and the count of white blood cell (WBC). Analysis of red blood cell (RBC) number showed that TP-C and TP-D could reverse lower RBC number in untreated CIA rats to normal level. Interestingly, the results showed TPs named TP-C and TP-D could decrease platelet (PLT) number which significantly increases in untreated CIA rats. Reproductive toxicity, the main side effect of TPs, assay showed that the sperm quality (density, viability, and motility) in four of TPs-treated CIA rats were decreased significantly, consistently with spermatogenic cell density reduced. However parallel analysis showed that in four TPs-treated rats, the number of sperm, motile sperm and progressive sperm were highest in TP-D group, in contrast, were lowest in TP-C group. Conclusions These findings suggested that four TPs showed significantly therapeutic effect on ameliorating inflammation of CIA rats, with no obvious hepatotoxicity and nephrotoxicity in vivo . TP-D showed advantages with its higher efficacy and less reproductive toxicity as well as increasing RBC number, decreasing PLT number in CIA treatment. Thus, in the development of individualized treatment plan for RA patients, TP-D might be considered preferentially. [ABSTRACT FROM AUTHOR]