Neurotransmitter accumulation and Parkinson's disease-like phenotype caused by anion channelrhodopsin opto-controlled astrocytic mitochondrial depolarization in substantia nigra pars compacta.

Parkinson's disease (PD) is a mitochondria-related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial-targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α-synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD.

[Research progress on induced hepatic stellate cell ferroptosis in prevention and treatment of liver fibrosis].

Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

Multicenter registry study of cerebral venous thrombosis in china (RETAIN-CH): Rationale and design.

BACKGROUND AND RATIONALE: Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder that mainly affects young and middle-aged adults. Epidemiological data on the incidence, risk factors, diagnosis, treatment, and prognosis of CVT are lacking in China. In addition, there is a lack of evidence from large, multicenter, real-world studies on the efficacy and safety of endovascular. AIM: To understand the incidence, diagnosis and treatment status of CVT in China and to estimate the effectiveness and safety of endovascular treatment in the real-world. METHODS: A multicenter, retrospective observational cohort study will be conducted on CVT patient records from 104 hospitals, between January 1, 2018 and June 30, 2022, identified using a 2-stage cluster sampling design based on per capita gross domestic product. Each enrolled participant is required to complete a further follow-up, which includes the current situation and the assessment at 3 and 12 months after discharge. STUDY OUTCOMES: The outcomes of this study will include the current status of the incidence, pathogenesis, etiology, clinical symptoms, diagnosis, and treatment of CVT in China, as well as the effectiveness and safety of endovascular treatment in the real-world. DISCUSSION: Results from this study will provide evidence on the incidence, specific risk factors, symptomatic and imaging features, and clinical outcomes of CVT in China as well as indicate whether endovascular treatment is superior to medical management alone for patients with acute CVT in the real-world. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. IDENTIFIER: NCT05448248.

Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model.

BACKGROUND: Neuroinflammation, mediated by the activation of microglia, contributes to central sensitization, which is associated with the development of chronic migraine (CM). TREM1 receptors amplify the inflammatory response. However, their relationship to CM is unclear. Thus, this study endeavoured to elucidate the exact role of TREM1 in CM. METHODS: Nitroglycerin (NTG) was repeatedly administered intraperitoneally to establish the CM model. Mechanical and thermal sensitivities were assessed using von Frey filaments and hot plate assays. Using Western blotting, TREM1, NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were all detected. Immunofluorescence was used to examine the cellular distribution of TREM1 and NLRP3, the number of microglia, immunoreactivity, and morphological changes. We examined the effects of TREM1 antagonists (LR12) and NF-κB inhibitors (PDTC) on pain behaviour, as well as the production of c-fos and CGRP. Additionally, we investigated whether LR12 and PDTC affect the activation of microglia and the NLRP3 inflammasome. We synthesized siRNA and TREM1-overexpressing plasmids to transfect BV2 cells treated with LPS and normal BV2 cells and treated TREM1-overexpressing BV2 cells with PDTC. The NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were quantified using Western blotting. RESULTS: Following NTG administration, the expression of TREM1 was significantly upregulated and exclusively localized in microglia in the TNC, and was well co-localized with NLRP3. Furthermore, activation of the classical NF-κB pathway was observed. Pre-treatment with LR12 and PDTC effectively attenuated mechanical hypersensitivity, suppressed the expression of c-fos and CGRP, and inhibited NF-κB activity in CM mice. Additionally, inhibition of TREM1 and NF-κB activity mitigated NTG-induced microglia and NLRP3 activation, as well as proinflammatory cytokines production. In vitro, knockdown of TREM1 resulted in attenuated activation of the NF-κB pathway following lipopolysaccharide (LPS) treatment and reduced expression of NLRP3 inflammasome components as well as proinflammatory cytokines. After TREM1 overexpression, the NF-κB pathway was activated, NLRP3 inflammasome components and proinflammatory cytokines were upregulated, and PDTC reversed this phenomenon. CONCLUSIONS: Our findings suggest that TREM1 regulates microglia and NLRP3 activation via the NF-κB pathway, thereby contributing to central sensitization and implicating its involvement in chronic migraine pathogenesis.

TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model.

Central sensitization is an important pathophysiological mechanism underlying chronic migraine (CM). Previous studies have shown that microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to central sensitization. Toll-like receptor 2 (TLR2) is a receptor expressed on the membrane of microglia and participates in central sensitization in inflammatory and chronic pain; however, its role in CM is unclear. Therefore, this study investigated TLR2 involvement in CM in detail. Mice treated with recurrent nitroglycerin (NTG) were used as a CM model. Hyperalgesia was assessed using a 50% paw mechanical threshold and a 50% periorbital threshold on a Von Frey filament pain meter. Western blotting and immunofluorescence analyses were used to detect the expression of TLR2, microglia, c-fos and CGRP in TNC. The expression of inflammatory factors (IL-6, IL-1ß、 IL-10、TNF-α and IFN-ß1) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). A selective TLR2 antagonist (C29) was systematically administered to observe its effect on hyperalgesia, microglia activation and the expression of c-fos, CGRP and inflammatory factors. Recurrent administration of NTG resulted in acute and chronic hypersensitivity, accompanied by upregulation of TLR2 expression and microglial activation in TNC. C29 partially inhibited pain hypersensitivity. C29 suppressed microglial activation induced by NTG administration. Inhibition of TLR2 reduced the expression of c-fos and CGRP in TNC after NTG treatment. C29 inhibited the expression of inflammatory mediators in TNC. These data showed that microglial TLR2 plays a critical role in the pathogenesis of CM by regulating microglial activation in TNC.

Short-term surgical outcomes of spontaneous intracerebral hemorrhage in China from 2019 to 2021: a retrospective cohort study.

Background: China has the highest prevalence of spontaneous intracerebral hemorrhage (sICH) worldwide. To date, no national-level report has revealed sICH surgical performance. We aimed to investigate the current status and short-term outcomes of patients who underwent surgical treatment for sICH between 2019 and 2021. Methods: Data from 7451 patients undergoing sICH surgical treatment in China between 2019 and 2021, including demographic information, disease severity, surgical treatments for sICH, complications, and follow-up information, were retrieved from the Bigdata Observatory Platform for Stroke of China. Propensity score matching (PSM) was applied to balance the baseline characteristics. The surgical treatment performance on 3-month mortality and functional outcome were then explored by regression analysis. The influence of stroke center level and region on surgical performance was then explored. Findings: The numbers of sICH patients undergoing open craniotomy (OC), cranial puncture (CP), decompressive craniectomy (DC) and endoscopic evacuation (EE) were 2404 (32.3%), 3030 (40.7%), 1700 (22.8%) and 317 (4.3%), respectively. The 3-month mortality rate was 20.2%. Among the surviving patients, the 3-month poor functional prognosis (mRS 3-5) rate was 46.5%. After PSM, regression analysis showed that DC was associated with a higher mortality risk (OR = 1.31, 95% CI 1.06-1.61) than OC. CP was associated with a lower risk of poor mRS scores than OC (OR = 0.84, 95% CI 0.70-1.01), especially in stroke prevention centers and specific regions. Interpretation: Outcome improvements in Chinese sICH patients undergoing surgical treatment are worth expecting. Inconsistent surgical performance, especially functional outcome, affected by inhomogeneity of the hospital should be addressed. Funding: This work was supported by the Beijing Hospitals Authority Youth Programme (QML20230804), the National Natural Science Foundation of China (81701796, 82030037, 81871009), Capital Health Research and Development of Special Fund (2020-2Z-2019), Science and Technology Innovation 2030-Major Project (2021ZD0201801), and the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders (11000022T000000444685).

China stroke surveillance report 2021.

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6-18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3-3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2-2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4-12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95% CI 2.1-2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age ± standard error (SE) was (65.700 ± 0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean ± SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6 ± 16.3), ranging from (13,310.1 ± 12.8) in IS to (81,369.8 ± 260.7) in SAH, and out-of-pocket expenses were (5788.9 ± 8.6), ranging from (4449.0 ± 6.6) in IS to (30,778.2 ± 156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95% CI 9.2-9.2%), ranging from 6.4% (95% CI 6.4-6.5%) for IS to 21.8% for ICH (95% CI 21.8-21.9%). From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT + MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95% CI 3.2-3.3%), 7.7% (95% CI 7.5-8.0%), and 12.9% (95% CI 12.3-13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95% CI 8.8-9.0%), 16.5% (95% CI 16.2-16.9%), and 16.8% (95% CI 16.2-17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [% (95% CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95% CI 14.6-15.0%) and 14.0% (95% CI 13.8-14.2%), respectively. The mortality rate [% (95% CI)] of stroke at 3-month and 12-month was 4.2% (95% CI 4.1-4.3%) and 8.5% (95% CI 8.4-8.6%), respectively. The recurrence rate [% (95% CI)] of stroke at 3-month and 12-month was 3.6% (95% CI 3.5-3.7%) and 5.6% (95% CI 5.4-5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis.

Non-cardioembolic ischemic stroke (IS) is the predominant subtype of IS. This study aimed to construct a nomogram for recurrence risks in patients with non-cardioembolic IS in order to maximize clinical benefits. From April 2015 to December 2019, data from consecutive patients who were diagnosed with non-cardioembolic IS were collected from Lanzhou University Second Hospital. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. Multivariable Cox regression analyses were used to identify the independent risk factors. A nomogram model was constructed using the "rms" package in R software via multifactor Cox regression. The accuracy of the model was evaluated using the receiver operating characteristic (ROC), calibration curve, and decision curve analyses (DCA). A total of 729 non-cardioembolic IS patients were enrolled, including 498 (68.3%) male patients and 231 (31.7%) female patients. Among them, there were 137 patients (18.8%) with recurrence. The patients were randomly divided into training and testing sets. The Kaplan-Meier survival analysis of the training and testing sets consistently revealed that the recurrence rates in the high-risk group were significantly higher than those in the low-risk group (p < 0.01). Moreover, the receiver operating characteristic curve analysis of the risk score demonstrated that the area under the curve was 0.778 and 0.760 in the training and testing sets, respectively. The nomogram comprised independent risk factors, including age, diabetes, platelet-lymphocyte ratio, leukoencephalopathy, neutrophil, monocytes, total protein, platelet, albumin, indirect bilirubin, and high-density lipoprotein. The C-index of the nomogram was 0.752 (95% CI: 0.705~0.799) in the training set and 0.749 (95% CI: 0.663~0.835) in the testing set. The nomogram model can be used as an effective tool for carrying out individualized recurrence predictions for non-cardioembolic IS.

Clinical and humoral immune response characterization of SARS-CoV-2 Omicron BA.2.38 infection in pediatric patients.

Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a health concern for both unvaccinated and vaccinated individuals against coronavirus disease 2019 (COVID-19). To date, the humoral immune response following vaccination and natural infection remains uncharacterized in children ages 17 years and younger. To address this concern, we performed clinical and immunological analyses of IgM and IgG antibody responses to SARS-CoV-2 Omicron BA.2.38 infection in 64 pediatric patients. COVID-19 symptom severity decreased with age in pediatric patients, from 70.8% (17/24) in patients 0-2 years of age to 50% (6/12) and 50% (14/28) in patients 3-5 years and 6-17 years of age, respectively. Furthermore, fewer patients experienced symptoms when vaccinated with the CoronaVac or BBIBP-CorV vaccine (50%, 13/26) than unvaccinated patients (71%, 22/31). Using a protein array, we found that the Omicron BA.2.38 infection induced antibody responses to other Omicron variants (Omicron BA.1-BA.5), which increased with vaccination. Notably, non-Omicron and Omicron variants showed distinct serotypes. Altogether, our results provide insight into the clinical and immunological characteristics of pediatric patients with COVID-19 Omicron BA.2.38 who have and have not been vaccinated against COVID-19. These data may help develop more effective diagnostic tests and vaccines in the future.

Age and geographic disparities in acute ischaemic stroke prehospital delays in China: a cross-sectional study using national stroke registry data.

Background: Stroke has been the leading cause of death in China for decades. The extremely low intravenous thrombolysis rate is largely due to the prehospital delays that make patients ineligible for the time-sensitive therapy. Limited studies evaluated prehospital delays across China. We investigated prehospital delays in the stroke population across China and the associated age, rurality, and geographic disparities. Methods: A cross-sectional study design was employed using the Bigdata Observatory platform for Stroke of China in 2020, the nationwide, prospective, multicentre registry of patients with acute ischaemic stroke (AIS). Mixed-effect regression models were used to account for the clustered data. Findings: The sample contained 78,389 AIS patients. The median onset-to-door (OTD) time was 24 h, with only 11.79% (95% confidence interval [CI]: 11.56-12.02%) patients arriving at hospitals within 3 h. About 12.43% (95% CI: 12.11-12.74%) of patients 65 years or older arrived at hospitals within 3 h, which was significantly higher than the young and middle-aged patients (11.03%; 95% CI: 10.71-11.36%). After controlling for potential confounders, young and middle-aged patients were less likely to present to hospitals within 3 h (adjusted odds ratio: 0.95; 95% CI: 0.90-0.99) compared to patients 65 years or older. The 3-h hospital arrival rate was the highest in Beijing (18.40%, 95% CI: 16.01-20.79%), which was almost 5 times higher than that in Gansu (3.45%, 95% CI: 2.69-4.20%). The arrival rate in urban areas was almost 2 times higher than that in rural areas (13.35% versus. 7.66%). Interpretation: We found that the low rates of timely arrival at hospitals after a stroke is more salient in the younger population, rural settings, or those residing in less developed geographic regions. This study calls for more tailored interventions focusing on younger people, rural areas, and less developed geographic regions. Funding: The National Natural Science Foundation of China; CIHR, Grant/Award Number: 81973157, PI: JZ. Natural Science Foundation of Shanghai; CIHR, Grant/Award Number: 17dz2308400, PI: JZ. Funding from the University of Pennsylvania; Grant/Award Number: CREF-030, PI: RL.

Inpatient rehabilitation therapy in stroke patients with reperfusion therapy: a national prospective registry study.

BACKGROUND: Little is known about the rate of real-world inpatient rehabilitation therapy (IRT) after stroke. We aimed to determine the rate of inpatient rehabilitation therapy and its associated factors in patients who undergo reperfusion therapy in China. METHODS: This national prospective registry study included hospitalized ischemic stroke patients aged 14-99 years with reperfusion therapy between January 1, 2019, and June 30, 2020, collecting hospital-level and patient-level demographic and clinical data. IRT included acupuncture or massage, physical therapy, occupational therapy, speech therapy, and others. The primary outcome was the rate of patients receiving IRT. RESULTS: We included 209,189 eligible patients from 2191 hospitals. The median age was 66 years, and 64.2% were men. Four in five patients received only thrombolysis, and the rest 19.2% underwent endovascular therapy. The overall rate of IRT was 58.2% (95% CI, 58.0-58.5%). Differences in demographic and clinical variables existed between patients with and without IRT. The rates of acupuncture or massage, physical therapy, occupational therapy, speech therapy, and other rehabilitation interventions were 38.0%, 28.8%, 11.8%, 14.4%, and 22.9%, respectively. The rates of single and multimodal interventions were 28.3% and 30.0%, respectively. A lower likelihood of receiving IRT was associated with being 14-50 or 76-99 years old, female, from Northeast China, from Class-C hospitals, receiving only thrombolysis, having severe stroke or severe deterioration, a short length of stay, Covid-19 pandemic and having intracranial or gastrointestinal hemorrhage. CONCLUSION: Among our patient population, the IRT rate was low with limited use of physical therapy, multimodal interventions, and rehabilitation centers and varied by demographic and clinical features. The implementation of IRT remains a challenge for stroke care, warranting urgent and effective national programs to enhance post-stroke rehabilitation and the adherence to guidelines.

Estimated Burden of Stroke in China in 2020.

Importance: Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. Objective: To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. Design, Setting, and Participants: This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Main Outcomes and Measures: Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. Results: The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%]; P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years; P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years; P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32]). Conclusions and Relevance: In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

A review of edible plant-derived natural compounds for the therapy of liver fibrosis.

Liver fibrosis has a high incidence worldwide and is the common pathological basis of many chronic liver diseases. Liver fibrosis is caused by the excessive deposition of extracellular matrix and concomitant collagen accumulation in livers and can lead to the development of liver cirrhosis and even liver cancer. A large number of studies have provided evidence that liver fibrosis can be blocked or even reversed by appropriate medical interventions. However, the antifibrosis drugs with ideal clinical efficacy are still insufficient. The edible plant-derived natural compounds have been reported to exert effective antifibrotic effects with few side-effects, representing a kind of promising source for the treatment of liver fibrosis. In this article, we reviewed the current progress of the natural compounds derived from dietary plants in the treatment of liver fibrosis, including phenolic compounds (capsaicin, chlorogenic acid, curcumin, ellagic acid, epigallocatechin-3-gallate, resveratrol, sinapic acid, syringic acid, vanillic acid and vitamin E), flavonoid compounds (genistein, hesperidin, hesperetin, naringenin, naringin and quercetin), sulfur-containing compounds (S-allylcysteine, ergothioneine, lipoic acid and sulforaphane) and other compounds (betaine, caffeine, cucurbitacin B, lycopene, α-mangostin, γ-mangostin, ursolic acid, vitamin C and yangonin). The pharmacological effects and related mechanisms of these compounds in in-vivo and in-vitro models of liver fibrosis are focused.

Prevalence of stroke in China, 2013-2019: A population-based study.

Background: The stroke burden in China has increased during the past 40 years. The present study aimed to determine the recent trends in the prevalence of stroke from 2013 to 2019 stratified by sociodemographic characteristics, including sex, age, residence, ethnicity, and province within a population-based screening project in China. Methods: We made use of data generated from 2013 to 2019 in the China Stroke High-risk Population Screening Program. All living subjects with confirmed stroke at interview were considered to have prevalent stroke. All analyses of prevalence of stroke were weighted and results were presented as percentage and 95% confidence interval (CI). Findings: A total of 4229,616 Chinese adults aged ≥40 years from 227 cities in the 31 provinces were finally included. The enrollment rate ranged from 58.8% (2017) to 67.8% (2013). The weighted prevalence of stroke increased annually from 2013 to 2019, being 2.28% (95% CI: 2.28-2.28%) in 2013, 2.34% (2.34-2.35%) in 2014, 2.43% (2.43-2.43%) in 2015, 2.48% (2.48-2.48%) in 2016, 2.52% (2.52-2.52%) in 2017, 2.55% (2.55-2.55%) in 2018, and 2.58% (2.58-2.58%) in 2019 (p for trend <0.001). The weighted prevalence of stroke was higher for male sex, older age, and residence in rural and northeast areas. Interpretation: The prevalence of stroke in China and most provinces has continued to increase in the past 7 years (2013-2019). These findings, especially in provinces with high stroke prevalence, can help public health officials to increase province capacity for stroke and related risk factors prevention. Fundings: This study was supported by grants from the National Major Public Health Service Projects.

Distribution of risk factors differs from coronary heart disease and stroke in China: a national population survey.

OBJECTIVES: This study aimed to explore the distribution differences of common risk factors between coronary heart disease (CHD) and stroke in China. SETTING: The China National Stroke Screening Survey is a cluster sampling survey based on a nationwide general community population, adopting multistage stratified sampling method and covering all 31 provinces in China mainland. PARTICIPANTS: A total number of 725 707 people aged 40 years and above were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The basic demographic information, lifestyle behaviour, physical examination, traditional risk factors, family history of cardiovascular disease (CVD) and CVD events were collected. Risk factors of CHD and stroke were explored and analysed in the whole investigated population to identify the common risk factors. Multivariate logistic regression analysis was used to analyse the distribution difference of risk factors between CHD and stroke. RESULTS: There were 13 variables associated with CHD and stroke, in which 11 variables revealed differences in the distribution between CHD and stroke. Family history of stroke (OR: 2.30; 95% CI 2.15 to 2.45), men (OR: 1.92; 95% CI 1.80 to 2.05), rural areas (OR: 1.70; 95% CI 1.60 to 1.80), transient ischaemic attack (OR: 1.41; 95% CI 1.30 to 1.54) and hypertension (OR: 1.28; 95% CI 1.19 to 1.38) indicated significantly stronger association with stroke, while family history of CHD (OR: 0.25; 95% CI 0.23 to 0.27), atrial fibrillation (OR: 0.60; 95% CI 0.51 to 0.71), diabetes (OR: 0.76; 95% CI 0.71 to 0.81), dyslipidaemia (OR: 0.76; 95% CI 0.72 to 0.81), smoking (OR: 0.79; 95% CI 0.73 to 0.85) and overweight/obesity (OR: 0.90; 95% CI 0.86 to 0.93) had closer relationship with CHD. CONCLUSIONS: The distribution of risk factors for CHD and stroke were substantial differences. More specific prevention and control measures should be formulated according to the distribution differences of risk factors related to CVD.

Association between rehabilitation after reperfusion treatment and in-hospital mortality: Results from a national registry study.

Background: There is no effective regimen to reduce the mortality of patients treated with intravenous thrombolysis or endovascular therapy (EVT). Therefore, we aimed to examine whether sequential therapy by rehabilitation could effectively reduce the in-hospital mortality of patients treated with reperfusion therapy. Methods: This prospective registry study included patients with ischemic stroke who were treated by intravenous thrombolysis or endovascular therapy at Stroke Center Work Plan in China between 1 October 2018 and 31 July 2020. The patients were divided into 2 groups: those with (IRT+) or without (IRT-) inpatient rehabilitation therapy (IRT). The primary outcome was all-cause in-hospital mortality. We used Cox proportional hazards models and conducted a propensity score matching analysis to calculate hazard ratios (HRs) for mortality in the thrombolysis-only and EVT groups. Results: Of the 189,519 patients in the thrombolysis-only group, 35.7% were women, and the median (interquartile range, IQR) age, onset-to-needle time, and follow-up time were 66 (57-74) years, 165 (119-220) min, and 9 (5-12) days, respectively. Among the 45,211 patients in the EVT group, 35.9% were women, and the median (interquartile range, IQR) age, onset-to-puncture time, and follow-up time were 66 (56-74) years, 297 (205-420) min, and 11 (6-16) days, respectively. In the thrombolysis-only group with a median (IQR) initial National Institutes of Health Stroke Scale (NIHSS) score of 6 (3-11), 105,244 patients (55.5%) treated with IRT had significantly lower all-cause in-hospital mortality [0.6 vs. 2.3%; adjusted HR 0.18 (95% confidence interval (CI) 0.16-0.2)] than those without IRT. In the EVT group with a median (IQR) initial NIHSS score of 15 (10-20), 31,098 patients (68.8%) treated with IRT also had significantly lower all-cause in-hospital mortality [2 vs. 12.1%; adjusted HR, 0.13 (95% CI 0.12-0.15)]. IRT remained significantly associated with reduced in-hospital mortality in sensitivity, subgroup, and propensity score matching analyses among both the thrombolysis-only and EVT groups. Conclusion: Among the patients with ischemic stroke treated with intravenous thrombolysis or endovascular therapy, sequential therapy by rehabilitation was associated with lower all-cause in-hospital mortality. These findings suggest the necessity of promoting inpatient rehabilitation therapy after reperfusion in patients with ischemic stroke.

Non-HDL-C/HDL-C ratio is associated with carotid plaque stability in general population: A cross-sectional study.

Background: Carotid atherosclerosis, especially the rupture of unstable plaques, plays an important role in the development of stroke. A novel lipid ratio, the non-high-density lipoprotein cholesterol (non-HDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, contains both atherogenic and anti-atherogenic particle information, and has been shown to be associated with carotid atherosclerosis. However, there is no data on evaluating the association between non-HDL-C/HDL-C ratio and carotid plaque stability. Methods: This study was carried out on 27,436 urban workers aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017. Carotid plaque stability was assessed using ultrasonography. Multinomial logistic regression models were used to explore the relationship between the non-HDL-C/HDL-C ratio and carotid plaque stability by odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: Carotid plaque was detected in 7,161 (26.1%) participants, with stable and unstable plaque accounting for 3,277 (11.9%) and 3,884 (14.2%), respectively. The prevalence of stable carotid plaque substantially increased with increasing non-HDL-C/HDL-C ratio quartile levels (p for trend < 0.001) and with a similar association for unstable carotid plaque (p for trend < 0.001). The mean non-HDL-C/HDL-C ratios (mean ± SD) of non-carotid plaque (2.9 ± 1.1), stable carotid plaque (3.2 ± 1.2), and unstable carotid plaque (3.4 ± 1.4) gradually increased (p < 0.001). In multinomial logistic regression, ORs (95% CIs) for the highest vs. lowest quartile of the non-HDL-C/HDL-C ratio were 1.70 (1.48-1.95) between stable carotid plaques and no carotid plaque, 2.34 (2.06-2.67) between unstable carotid plaques and no carotid plaque, and 1.38 (1.18-1.61) between unstable carotid plaques and stable carotid plaque, after adjusting for common cardiovascular risk factors. The results of subgroup analysis and sensitivity analysis were similar. Conclusion: Our findings suggested that the non-HDL-C/HDL-C ratio was significantly associated with carotid plaque stability and might be a useful indicator for the early identification of high-risk carotid plaque.

Effectiveness of Inactivated COVID-19 Vaccines against COVID-19 Caused by the SARS-CoV-2 Delta and Omicron Variants: A Retrospective Cohort Study.

BACKGROUND: Real-world evidence on the effectiveness of inactivated vaccines against the Delta and Omicron (BA.2.38) variants remains scarce. METHODS: A retrospective cohort study was conducted to estimate the adjusted vaccine effectiveness (aVE) of one, two, and three doses of inactivated vaccines in attenuating pneumonia, severe COVID-19, and the duration of viral shedding in Delta and Omicron cases using modified Poisson and linear regression as appropriate. RESULTS: A total of 561 COVID-19 cases were included (59.2% Delta and 40.8% Omicron). In total, 56.4% (184) of Delta and 12.0% (27) of Omicron cases had COVID-19 pneumonia. In the two-dose vaccinated population, 1.4% of Delta and 89.1% of Omicron cases were vaccinated for more than 6 months. In Delta cases, the two-dose aVE was 52% (95% confidence interval, 39-63%) against pneumonia and 61% (15%, 82%) against severe disease. Two-dose vaccination reduced the duration of viral shedding in Delta cases, but not in booster-vaccinated Omicron cases. In Omicron cases, three-dose aVE was 68% (18%, 88%) effective against pneumonia, while two-dose vaccination was insufficient for Omicron. E-values were calculated, and the E-values confirmed the robustness of our findings. CONCLUSIONS: In Delta cases, two-dose vaccination within 6 months reduced pneumonia, disease severity, and the duration of viral shedding. Booster vaccination provided a high level of protection against pneumonia with Omicron and should be prioritized.

Toll-like receptors and their role in neuropathic pain and migraine.

Migraine is a complex neurological disease of unknown etiology involving both genetic and environmental factors. It has previously been reported that persistent pain may be mediated by the immune and inflammatory systems. Toll-like receptors (TLRs) play a significant role in immune and inflammatory responses and are expressed by microglia and astrocytes. One of the fundamental mechanisms of the innate immune system in coordinating inflammatory signal transduction is through TLRs, which protect the host organism by initiating inflammatory signaling cascades in response to tissue damage or stress. TLRs reside at the neuroimmune interface, and accumulating evidence has suggested that the inflammatory consequences of TLR activation on glia (mainly microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to pain. Several studies have shown that TLRs may play a key role in neuropathic pain and migraine etiology by activating the microglia. The pathogenesis of migraine may involve a TLR-mediated crosstalk between neurons and immune cells. Innate responses in the central nervous system (CNS) occur during neuroinflammatory phenomena, including migraine. Antigens found in the environment play a crucial role in the inflammatory response, causing a broad range of diseases, including migraines. These can be recognized by several innate immune cells, including macrophages, microglia, and dendritic cells, and can be activated through TLR signaling. Given the prevalence of migraine and the insufficient efficacy and safety of current treatment options, a deeper understanding of TLRs is expected to provide novel therapies for managing chronic migraine. This review aimed to justify the view that TLRs may be involved in migraine.