OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule （黄芩清热除痹胶囊， HQC） on self-perception of patients （SPP） and immune inflammation in patients with rheumatoid arthritis （RA）， and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group （274 cases）， treated with conventional western medicine， and an observation group （178 cases）， treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching （PSM） was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey （SF-36）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， visual analog scale （VAS）， and Chinese patient-reported index for rheumatoid arthritis （CPRI-RA）， as well as immune inflammatory indicators， including erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （anti-CCP）， interleukin-6 （IL-6）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， complement C3， and complement C4， were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression， association rule analysis， and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA， followed by molecular docking verification. In cell experiments， cells were divided into normal group， model group， 20% medicated serum group， and 80 nmol/L control group. Human synovial fibroblasts （FLS） were cultured with complete medium in the normal group， while human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were cultured in the model group. In the 20% medicated serum group， RA-FLS were cultured with medium containing 20% HQC-medicated serum， and in the 80 nmol/L control group， RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture， cell viability was detected by cell counting kit-8 （CCK-8） assay. Levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and interleukin-10 （IL-10） in the cell supernatant were measured by enzyme-linked immunosorbent assay （ELISA）. Protein levels of matrix metalloproteinase 9 （MMP9）， transcription factor AP-1 subunit （JUN）， vascular endothelial growth factor A （VEGFA）， and C-X-C motif chemokine ligand 8 （CXCL8） were detected by Western Blot， and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM， 178 cases were included in each group. After treatment， SF-36 scores increased， while scores of SAS， SDS， VAS and CPRI-RA， levels of ESR， hs-CRP， IL-6， complement C3， and complement C4 levels decreased in both groups； IgG and IgM levels were also reduced in the observation group （P＜0.05）. Physical functioning （correlation coefficient -0.19， P＜0.05） and social functioning （correlation coefficient -0.18， P＜0.05） of SF-36 were negatively correlated with hs-CRP， while VAS score was positively correlated with hs-CRP （correlation coefficient 0.19， P＜0.05）. HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory， and acted as a protective factor for the improvement of several SPP； hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC （P＜0.05）. Network pharmacology analysis identified baicalein， quercetin， α1-sitosterol， β-sitosterol， stigmasterol， baicalin， and crocetin as the core active components， and JUN， IL-6， VEGFA， MMP9， IL-1β， and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA， JUN， MMP9， IL-6， and IL-1β， of baicalin with VEGFA and MMP9， and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration， reduced levels of IL-1β， IL-6， and IL-8， decreased protein levels of MMP9， JUN， VEGFA， and CXCL8， and increased IL-10 levels （P＜0.05）. ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

BACKGROUND/OBJECTIVES: Stroke represents the primary cause of death and persistent disability globally, leading to around 5.5 million annual patient fatalities. The objective was to explore the relationship of dietary fiber with all-cause and cardiovascular disease (CVD) mortality risk in patients with stroke. SUBJECTS/METHODS: We extracted stroke patients’ data from the National Health and Nutrition Examination Survey (NHANES) database. All-cause and CVD mortality were outcomes. Dietary fiber consists of non-digestible forms of carbohydrates, usually polysaccharides that originate from plant-based foods. Covariates including demographic data, vital signs, comorbidities, laboratory parameters, and medication use were screened using the weighted multivariate Cox regression models with backward elimination. Weighted univariate and multivariate Cox regression models were performed to explore the relationship between dietary fiber intake and all-cause/CVD mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). The association was further investigated in different subgroups. RESULTS: A total of 1,578 patients with stroke were included, of whom 688 (43.6%) died.Total fiber and vegetable fiber intake were analyzed as categorical variables, and the lowest intake was considered reference groups. High intake of total fiber (HR, 0.73; 95% CI, 0.57–0.94) and high intake of vegetable fiber (HR, 0.63; 95% CI, 0.48–0.82) were related to lower all-cause mortality risk in individuals with stroke. Similar findings were also observed between higher total fiber (HR, 0.56; 95% CI, 0.37–0.85) and vegetable fiber intake (HR, 0.57; 95% CI, 0.36–0.89) with decreased CVD mortality risk. The relationship between higher total fiber intake and lower all-cause mortality risk was discovered in individuals aged ≥ 60 yrs, smoking, non-CVD, and chronic kidney disease (CKD). High total fiber, or vegetable fiber consumption was linked to lower CVD mortality risk in stroke individuals aged ≥ 60 yrs, females, body mass index ≥ 30 kg/m 2 , non-smoking, and CKD. CONCLUSION Dietary fiber intake and vegetable fiber intake may benefit the prognosis of patients with stroke. Increasing dietary fiber consumption, especially vegetable fiber intake, potentially benefits the prognosis of stroke patients.

BACKGROUND/OBJECTIVES: Stroke represents the primary cause of death and persistent disability globally, leading to around 5.5 million annual patient fatalities. The objective was to explore the relationship of dietary fiber with all-cause and cardiovascular disease (CVD) mortality risk in patients with stroke. SUBJECTS/METHODS: We extracted stroke patients’ data from the National Health and Nutrition Examination Survey (NHANES) database. All-cause and CVD mortality were outcomes. Dietary fiber consists of non-digestible forms of carbohydrates, usually polysaccharides that originate from plant-based foods. Covariates including demographic data, vital signs, comorbidities, laboratory parameters, and medication use were screened using the weighted multivariate Cox regression models with backward elimination. Weighted univariate and multivariate Cox regression models were performed to explore the relationship between dietary fiber intake and all-cause/CVD mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). The association was further investigated in different subgroups. RESULTS: A total of 1,578 patients with stroke were included, of whom 688 (43.6%) died.Total fiber and vegetable fiber intake were analyzed as categorical variables, and the lowest intake was considered reference groups. High intake of total fiber (HR, 0.73; 95% CI, 0.57–0.94) and high intake of vegetable fiber (HR, 0.63; 95% CI, 0.48–0.82) were related to lower all-cause mortality risk in individuals with stroke. Similar findings were also observed between higher total fiber (HR, 0.56; 95% CI, 0.37–0.85) and vegetable fiber intake (HR, 0.57; 95% CI, 0.36–0.89) with decreased CVD mortality risk. The relationship between higher total fiber intake and lower all-cause mortality risk was discovered in individuals aged ≥ 60 yrs, smoking, non-CVD, and chronic kidney disease (CKD). High total fiber, or vegetable fiber consumption was linked to lower CVD mortality risk in stroke individuals aged ≥ 60 yrs, females, body mass index ≥ 30 kg/m 2 , non-smoking, and CKD. CONCLUSION Dietary fiber intake and vegetable fiber intake may benefit the prognosis of patients with stroke. Increasing dietary fiber consumption, especially vegetable fiber intake, potentially benefits the prognosis of stroke patients.

BACKGROUND/OBJECTIVES: Stroke represents the primary cause of death and persistent disability globally, leading to around 5.5 million annual patient fatalities. The objective was to explore the relationship of dietary fiber with all-cause and cardiovascular disease (CVD) mortality risk in patients with stroke. SUBJECTS/METHODS: We extracted stroke patients’ data from the National Health and Nutrition Examination Survey (NHANES) database. All-cause and CVD mortality were outcomes. Dietary fiber consists of non-digestible forms of carbohydrates, usually polysaccharides that originate from plant-based foods. Covariates including demographic data, vital signs, comorbidities, laboratory parameters, and medication use were screened using the weighted multivariate Cox regression models with backward elimination. Weighted univariate and multivariate Cox regression models were performed to explore the relationship between dietary fiber intake and all-cause/CVD mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). The association was further investigated in different subgroups. RESULTS: A total of 1,578 patients with stroke were included, of whom 688 (43.6%) died.Total fiber and vegetable fiber intake were analyzed as categorical variables, and the lowest intake was considered reference groups. High intake of total fiber (HR, 0.73; 95% CI, 0.57–0.94) and high intake of vegetable fiber (HR, 0.63; 95% CI, 0.48–0.82) were related to lower all-cause mortality risk in individuals with stroke. Similar findings were also observed between higher total fiber (HR, 0.56; 95% CI, 0.37–0.85) and vegetable fiber intake (HR, 0.57; 95% CI, 0.36–0.89) with decreased CVD mortality risk. The relationship between higher total fiber intake and lower all-cause mortality risk was discovered in individuals aged ≥ 60 yrs, smoking, non-CVD, and chronic kidney disease (CKD). High total fiber, or vegetable fiber consumption was linked to lower CVD mortality risk in stroke individuals aged ≥ 60 yrs, females, body mass index ≥ 30 kg/m 2 , non-smoking, and CKD. CONCLUSION Dietary fiber intake and vegetable fiber intake may benefit the prognosis of patients with stroke. Increasing dietary fiber consumption, especially vegetable fiber intake, potentially benefits the prognosis of stroke patients.

BACKGROUND/OBJECTIVES: Stroke represents the primary cause of death and persistent disability globally, leading to around 5.5 million annual patient fatalities. The objective was to explore the relationship of dietary fiber with all-cause and cardiovascular disease (CVD) mortality risk in patients with stroke. SUBJECTS/METHODS: We extracted stroke patients’ data from the National Health and Nutrition Examination Survey (NHANES) database. All-cause and CVD mortality were outcomes. Dietary fiber consists of non-digestible forms of carbohydrates, usually polysaccharides that originate from plant-based foods. Covariates including demographic data, vital signs, comorbidities, laboratory parameters, and medication use were screened using the weighted multivariate Cox regression models with backward elimination. Weighted univariate and multivariate Cox regression models were performed to explore the relationship between dietary fiber intake and all-cause/CVD mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). The association was further investigated in different subgroups. RESULTS: A total of 1,578 patients with stroke were included, of whom 688 (43.6%) died.Total fiber and vegetable fiber intake were analyzed as categorical variables, and the lowest intake was considered reference groups. High intake of total fiber (HR, 0.73; 95% CI, 0.57–0.94) and high intake of vegetable fiber (HR, 0.63; 95% CI, 0.48–0.82) were related to lower all-cause mortality risk in individuals with stroke. Similar findings were also observed between higher total fiber (HR, 0.56; 95% CI, 0.37–0.85) and vegetable fiber intake (HR, 0.57; 95% CI, 0.36–0.89) with decreased CVD mortality risk. The relationship between higher total fiber intake and lower all-cause mortality risk was discovered in individuals aged ≥ 60 yrs, smoking, non-CVD, and chronic kidney disease (CKD). High total fiber, or vegetable fiber consumption was linked to lower CVD mortality risk in stroke individuals aged ≥ 60 yrs, females, body mass index ≥ 30 kg/m 2 , non-smoking, and CKD. CONCLUSION Dietary fiber intake and vegetable fiber intake may benefit the prognosis of patients with stroke. Increasing dietary fiber consumption, especially vegetable fiber intake, potentially benefits the prognosis of stroke patients.

Objective:To investigate the difference in brain activity intensity between methamphetamine (MA) dependent patients (MA group) and healthy controls (control group) using fractional amplitude of low-frequency fluctuation (fALFF), and to establish a classification model between these two groups using support vector machine (SVM).Methods:From February 2014 to October 2019, a total of 46 male MA-dependent patients and 46 male healthy controls were recruited from the Affiliated Kangning Hospital of Ningbo University. The study collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the differences in brain functional activity between the two groups. This analysis was conducted using both static and dynamic fractional amplitude of low-frequency fluctuations (d-fALFF). Additionally, the study examined the correlation between fALFF/d-fALFF values in specific brain regions and the total scores, as well as each factor score, of the Brief Psychiatric Rating Scale (BPRS). Furthermore, the relationship between fALFF/d-fALFF values and the age of first use and total dose of MA in the MA group was investigated. Finally, the fALFF map and d-fALFF map of brain regions with significant differences between groups were used as features for constructing classification.Results:Compared to the healthy control group, those dependent on MA showed significantly increased fALFF mainly in the nucleus accumbens, caudate nucleus, thalamus, and amygdala nucleus( t=-5.21--2.72, all P<0.05). The MA group exhibited decreased fALFF in the superior frontal gyrus, middle frontal gyrus, orbital gyrus, and cingulate gyrus( t=3.59-5.00, all P<0.05). Most of the brain regions with decreased d-fALFF overlapped with those exhibiting decreased fALFF( t=3.33-4.87, all P<0.05). The results of the correlation analysis showed that the fALFF value of the right nucleus accumbens was positively correlated with the age of first use of MA ( r=0.537, P<0.001). There is no significant relationship between the abnormal fALFF and d-fALFF values in the MA group and the total scores and each factor scores of BPRS, as well as the total dose of MA taken (after removing outliers). Based on fALFF and d-fALFF values, the SVM classifier achieved accuracies of 90.33%±6.89% and 71.56%±7.80%, respectively. Conclusions:There are significant abnormalities in the low-frequency fluctuation of the resting brain in patients dependent on MA. These abnormalities reflect the rigidity of prefrontal cortex activity, functional impairment, and dysfunction of the anti-reward system. These factors may be one of the causes for MA dependent behavior and repeated episodes. In addition, the fALFF values may be helpful for distinguishing MA dependent individuals from the control group.