Biological activities, Molecular mechanisms, and Clinical application of Naringin in Metabolic syndrome.

Metabolic syndrome has become major health problems in recent decades, and natural compounds receive considerable attention in the management of metabolic syndrome. Among them, naringin is abundant in citrus fruits and tomatoes. Many studies have investigated the therapeutic effects of naringin in metabolic syndrome. This review discusses in vitro and in vivo studies on naringin and implications for clinical trials on metabolic syndrome such as diabetes mellitus, obesity, nonalcoholic fatty liver disease, dyslipidemia, and hypertension over the past decades, overviews the molecular mechanisms by which naringin targets metabolic syndrome, and analyzes possible correlations between the different mechanisms. This review provides a theoretical basis for the further application of naringin in the treatment of metabolic syndrome.

Acupuncture Alters Brain's Dynamic Functional Network Connectivity in Stroke Patients with Motor Dysfunction: A Randomised Controlled Neuroimaging Trial.

Objectives: Neuroimaging studies have confirmed that acupuncture can promote static functional reorganization in poststroke patients with motor dysfunction. But its effect on dynamic brain networks remains unclear. This study is aimed at investigating how acupuncture affected the brain's dynamic functional network connectivity (dFNC) after ischemic stroke. Methods: We conducted a single-center, randomised controlled neuroimaging study in ischemic stroke patients. A total of 53 patients were randomly divided into the true acupoint treatment group (TATG) and the sham acupoint treatment group (SATG) at a ratio of 2 : 1. Clinical assessments and magnetic resonance imaging (MRI) scans were performed on subjects before and after treatment. We used dFNC analysis to estimate distinct dynamic connectivity states. Then, the temporal properties and strength of functional connectivity (FC) matrix were compared within and between the two groups. The correlation analysis between dynamic characteristics and clinical scales was also calculated. Results: All functional network connectivity (FNC) matrices were clustered into 3 connectivity states. After treatment, the TATG group showed a reduced mean dwell time and found attenuated FC between the sensorimotor network (SMN) and the frontoparietal network (FPN) in state 3, which was a sparsely connected state. The FC between the dorsal attention network (DAN) and the default mode network (DMN) was higher after treatment in the TATG group in state 1, which was a relative segregated state. The SATG group preferred to increase the mean dwell time and FC within FPN in state 2, which displayed a local tightly connected state. In addition, we found that the FC value increased between DAN and right frontoparietal network (RFPN) in state 1 in the TATG group after treatment compared to the SATG group. Correlation analyses before treatment showed that the Fugl-Meyer Assessment (FMA) lower score was negatively correlated with the mean dwell time in state 3. FMA score showed positive correlation with FC in RFPN-SMN in state 3. FMA-lower score was positively correlated with FC in DAN-DMN and DAN-RFPN in state 1. Conclusions: Acupuncture has the potential to modulate abnormal temporal properties and promote the balance of separation and integration of brain function. True acupoint stimulation may have a more positive effect on regulating the brain's dynamic function. Clinical Trial Registration. This trial is registered with Chinese Clinical Trials Registry (ChiCTR1800016263).

Annual risk of tuberculosis infection in rural China: a population-based prospective study.

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.

Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease.

MAFLD has become a major global health problem and is the leading cause of liver disease worldwide. The disease progresses from a simple fatty liver to gradual fibrosis, which progresses to cirrhosis and even hepatocellular liver cancer. However, the methods currently used for diagnosis are invasive and do not facilitate clinical assessment of the condition. As a result, research on markers for the diagnosis of MAFLD is increasing. In addition, there are no clinical medications for the treatment of MAFLD, and lifestyle interventions remain effective in the prevention and treatment of MAFLD. In this review, we attempt to make a summary of the emerging diagnostic indicators and effective lifestyle interventions for MAFLD and to provide new insights into the diagnosis and treatment of MAFLD.

Exploring the interactions between metabolic dysfunction-associated fatty liver disease and micronutrients: from molecular mechanisms to clinical applications.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition's progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD's pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.

Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial.

BACKGROUND: Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity. METHODS: IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation. RESULTS: 46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=-0.716, p=0.000) fitting the linear regression model (R2=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event. CONCLUSIONS: The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.

COVID-19 vaccination and the risk of autoimmune diseases: a Mendelian randomization study.

Background: In recent times, reports have emerged suggesting that a variety of autoimmune disorders may arise after the coronavirus disease 2019 (COVID-19) vaccination. However, causality and underlying mechanisms remain unclear. Methods: We collected summary statistics of COVID-19 vaccination and 31 autoimmune diseases from genome-wide association studies (GWAS) as exposure and outcome, respectively. Random-effects inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode were used as analytical methods through Mendelian randomization (MR), and heterogeneity and sensitivity analysis were performed. Results: We selected 72 instrumental variables for exposure (p < 5 × 10-6; r2 < 0.001, genetic distance = 10,000 kb), and MR analyses showed that COVID-19 vaccination was causally associated with an increased risk of multiple sclerosis (MS) (IVW, OR: 1.53, 95% CI: 1.065-2.197, p = 0.026) and ulcerative colitis (UC) (IVW, OR: 1.00, 95% CI: 1.000-1.003, p = 0.039). If exposure was refined (p < 5 × 10-8; r2 < 0.001, genetic distance = 10,000 kb), the associations became negative. No causality was found for the remaining outcomes. These results were robust to sensitivity and heterogeneity analyses. Conclusion: Our study provided potential evidence for the impact of COVID-19 vaccination on the risk of MS and UC occurrence, but it lacks sufficient robustness, which could provide a new idea for public health policy.

Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study.

BACKGROUND: The management of latent Mycobacterium tuberculosis infection is a new priority action for the WHO End Tuberculosis (TB) Strategy. However, national guidelines on latent tuberculosis infection testing and treatment have not yet been developed in China. Here, we present the results from the 2-year follow-up of a study that aimed to track the development of active disease in individuals with latent tuberculosis infection, identify priority populations for latent infection management, and explore the most suitable latent infection diagnostic approach. METHODS: A population-based multicentre prospective study was done in four sites in rural China, between 2013 and 2015. The baseline survey in 2013 measured the prevalence of latent tuberculosis infection using QuantiFERON-TB Gold In-Tube (QFT) and tuberculin skin test (TST) in eligible participants. During the follow-up phase between 2014-15, we assessed individuals who had tuberculosis infection at baseline (QFT-positivity or TST tuberculin reaction size [induration] of ≥10 mm) for the development of active disease through active case finding. Eligible participants included in follow-up survey had a birth date before June 1, 2008 (5 years or older in 2013), and continuous residence at the study site for 6 months or longer in the past year. Participants with current active tuberculosis at baseline survey were excluded. FINDINGS: Between Sept 1, 2013, and Aug 31, 2015, 7505 eligible participants (aged 5 years or older) were included in tuberculosis infection test positive cohorts (4455 were QFT positive, 6404 had TST induration ≥10 mm, and 3354 were positive for both tests) after baseline examination. During the 2-year follow-up period, 84 incident cases of active tuberculosis were diagnosed. Of participants who developed active tuberculosis, 75 were diagnosed with latent infection by QFT, 62 were diagnosed by TST, and 53 were diagnosed by both tests. An incidence rate of 0·87 (95% CI 0·68-1·07) per 100 person-years was observed for individuals who tested positive with QFT, 0·50 (0·38-0·63) per 100 person-years for those who tested positive with TST (p<0·0001), and 0·82 (0·60-1·04) per 100 person-years for those who tested positive with both tests. Male sex and a history of tuberculosis were significantly associated with increased risk of disease development with adjusted hazard ratios of 2·36 (95% CI 1·30-4·30) for male sex and 5·40 (3·34-8·71) for a history of tuberculosis. INTERPRETATION: Our results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-γ releasing assay rather than a TST. FUNDING: National Science and Technology Major Project of China, Program for Changjiang Scholars and Innovative Research Team in University of China, CAMS Innovation Fund for Medical Sciences, and Sanming Project of Medicine in Shenzhen.

Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study.

BACKGROUND: Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. METHODS: Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON [QFT]) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. FINDINGS: 21,022 (90%) of 23,483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. INTERPRETATION: On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. FUNDING: The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.