Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective To investigate the role and mechanism of microRNA-21-5p(miR-21)in cisplatin(CDDP)resistance in non-small cell lung cancer.Methods The expression of miR-21 in cancer tissues and paracancerous tissues of non-small cell lung cancer patients was detected by real-time fluorescence quantitative PCR.Non-small cell lung cancer CDDP-resistant cells H1299/CR and H1975/CR were constructed using non-small cell lung cancer cell lines H1299 and H1975.CCK-8 was used to detect the cell activity of each group of cells under CDDP treatment,and apoptosis was analyzed by flow cytometry.Dual luciferase was used to detect the role of miR-21 in relation to PTEN in H1299 cells,RT-qPCR was used to detect the miR-21 level,and Western blotting was used to detect the protein expression level of PTEN and PTEN downstream Wnt/β-catenin signaling pathway.H1299 and H1299/CR were used to construct a hormonal nude mouse model to verify the effect of miR-21 on the sensitivity of CDDP treatment in non-small cell lung cancer.Results The expression of miR-21 was significantly higher in cancer tissues than in adjacent normal tissues(P＜0.001).The expression of miR-21 in drug-resistant cells H1299/CR and H1975/CR was significantly elevated compared to that in H1299 and H1975 cells(P＜0.05).After transfection with miR-21 inhibitor,cell viability in the inhibitor group was significantly lower than in the inhibitor NC group when treated with CDDP ≥12 pmol/L(P＜0.001).Flow cytometry analysis showed that while the apoptosis rate in the CDDP and miR-21 inhibitor groups did not significantly differ from that in the untreated group,the apoptosis rate in the CDDP+miR-21 inhibitor group was significantly higher(P＜0.001).In contrast,after transfection with miR-21 mimic,the cell viability of the mimic-NC group was significantly reduced compared to the miR-21 mimic group when treated with CDDP ≥12 pmol/L(P＜0.05).TargetScan predicted that miR-21 could bind to the 3-UTR region of PTEN.Dual-luciferase reporter assays confirmed that miR-21 directly targeted PTEN.Overexpression of PTEN(PTEN-OE)together with miR-21 mimic co-transfection in H1299 cells resulted in decreased PTEN expression and increased levels of p-β-catenin(Ser552,Ser675)and β-catenin,while the PTEN expression in the miR-21 mimic+PTEN-OE group was elevated,with a corresponding decrease in p-β-catenin andβ-catenin levels.Flow cytometry showed that apoptosis was significantly increased in the mimic-NC group after CDDP treatment(P＜0.05).In H1299 xenograft models,after treatment with miR-21 mimic and CDDP,tumor growth was slower in the control+CDDP group than in the control group;tumors were larger in the miR-21+CDDP group than in the control+CDDP group at all time points.TUNEL staining revealed that apoptosis in the tumor tissues of the control+CDDP group was higher than in the control group,while apoptosis was reduced in the miR-21+CDDP group compared to the control+CDDP group.In the H1299/CR xenograft model,after 5 days of treatment,the tumors were smaller in the H1299/CR+CDDP group than in the H1299/CR group,and those in the H1299/CR+CDDP+inhibitor group were smaller than in the H1299/CR+CDDP group.TUNEL staining showed that apoptosis was increased in the H1299/CR+CDDP group compared to the H1299/CR group,and further increased in the H1299/CR+CDDP+inhibitor group.Conclusion In non-small cell lung cancer,miR-21 overexpression inhibits PTEN level and activates the Wnt/β-catenin pathway involved in the development of CDDP resistance in non-small cell lung cancer.Inhibition of miR-21 expression in tumor cells will enhance the sensitivity of tumor cells to CDDP.

INTRODUCTION: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. METHODS: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. RESULTS: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. CONCLUSION These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.
Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/administration & dosage* ; Rheumatic Diseases/immunology* ; Singapore ; SARS-CoV-2 ; Vaccination/methods* ; Delphi Technique ; Immunization, Secondary

Intravenous thrombolysis and mechanical thrombectomy are well-established reperfusion therapies for acute ischemic stroke,which can significantly improve clinical outcomes compared to conventional treatments.However,both strategies face the following challenges:although it is the first-line treatment,intravenous thrombolysis suffers from low recanalization rates and a narrow therapeutic time window(3-4.5 h),which limits its clinical benefit.Mechanical thrombectomy,while achieving over 80％recanalization,still results in disability or death in more than 50％of patients.Future efforts should focus on optimizing thrombolytic drugs by developing novel agents with higher fibrin specificity and safety profiles,thus expanding the population benefiting from thrombolysis.Moreover,reperfusion therapy based on the"tissue window"could be achieved with utilizing advanced imaging techniques to break the traditional time window limitation.The promotion of mobile stroke units could facilitate ultra-early reperfusion treatment.Additionally,optimization of post-thrombolysis antithrombotic strategies is essential to prevent neurological deterioration.For mechanical thrombectomy,it is crucial to enhance perioperative management and actively explore neuroprotective strategies for further improvement of outcomes.

Objective To analyze the cerebral angiographic characteristics of patients with central retinal artery occlusion(CRAO)and to study their prognosis.Methods A retrospective study was conducted,with 182 CRAO patients enrolled,who were treated at Xuanwu Hospital,Capital Medical University,the First Affiliated Hospital of Anhui Medical University,the Affiliated Suzhou Hospital of Anhui Medical University,and the People's Hospital of Shihezi City from January 1,2014,to June 1,2024.All patients underwent cerebral angiography within one month of onset.The baseline characteristics,treatment details,and follow-up data were collected.The Spearman rank correlation coefficient was used to evaluate the correlation between the characteristics of the ophthalmic artery and the ipsilateral carotid artery angiography,and Logistic regression analysis was performed to explore factors related to patient prognosis.Results Cerebral angiography results showed that 81.3％of patients had ocular blood supply from the ipsilateral internal carotid artery,12.1％from the ipsilateral external carotid artery,and 6.6％from the ipsilateral middle cerebral artery.Among the patients,80(44.0％)had varying degrees of stenosis or occlusion of the affected ophthalmic artery,with 69 patients(86.3％)showing stenosis at the origin of the ophthalmic artery.Additionally,135 patients(74.2％)had varying degrees of stenosis or occlusion of the ipsilateral carotid artery,with 110 patients(60.4％)showing stenosis at the carotid bulb,88 patients(48.3％)having unilateral carotid lesions,and 41 patients(22.5％)having multiple lesions.Correlation analysis indicated a significant correlation between the degree of stenosis in the ophthalmic artery and the carotid artery(r=0.76,P=0.006).Univariate and multivariate Logistic regression analyses revealed that the time from symptom onset to hospital admission(OR=0.93,95％CI:0.85-0.98,P=0.018),the grading of oxygenation-based hypoperfusion maculopathy(OHM)(OR=3.12,95％CI:1.09-6.34,P=0.005),intravenous thrombolysis(IVT)(OR=2.75,95％CI:1.08-5.35,P=0.031),and the absence of stenosis in the ophthalmic artery(OR=1.33,95％CI:1.02-3.41,P=0.026)were independent predictors of prognosis for CRAO patients.Conclusions The degree of stenosis in the ophthalmic artery is significantly correlated with the degree of stenosis in the carotid artery in CRAO patients.Time from symptom onset to hospital admission,OHM grading,IVT,and the absence of stenosis in the ophthalmic artery are independent factors influencing the prognosis of CRAO patients.

Intravenous thrombolysis and mechanical thrombectomy are well-established reperfusion therapies for acute ischemic stroke,which can significantly improve clinical outcomes compared to conventional treatments.However,both strategies face the following challenges:although it is the first-line treatment,intravenous thrombolysis suffers from low recanalization rates and a narrow therapeutic time window(3-4.5 h),which limits its clinical benefit.Mechanical thrombectomy,while achieving over 80％recanalization,still results in disability or death in more than 50％of patients.Future efforts should focus on optimizing thrombolytic drugs by developing novel agents with higher fibrin specificity and safety profiles,thus expanding the population benefiting from thrombolysis.Moreover,reperfusion therapy based on the"tissue window"could be achieved with utilizing advanced imaging techniques to break the traditional time window limitation.The promotion of mobile stroke units could facilitate ultra-early reperfusion treatment.Additionally,optimization of post-thrombolysis antithrombotic strategies is essential to prevent neurological deterioration.For mechanical thrombectomy,it is crucial to enhance perioperative management and actively explore neuroprotective strategies for further improvement of outcomes.

Objective To analyze the cerebral angiographic characteristics of patients with central retinal artery occlusion(CRAO)and to study their prognosis.Methods A retrospective study was conducted,with 182 CRAO patients enrolled,who were treated at Xuanwu Hospital,Capital Medical University,the First Affiliated Hospital of Anhui Medical University,the Affiliated Suzhou Hospital of Anhui Medical University,and the People's Hospital of Shihezi City from January 1,2014,to June 1,2024.All patients underwent cerebral angiography within one month of onset.The baseline characteristics,treatment details,and follow-up data were collected.The Spearman rank correlation coefficient was used to evaluate the correlation between the characteristics of the ophthalmic artery and the ipsilateral carotid artery angiography,and Logistic regression analysis was performed to explore factors related to patient prognosis.Results Cerebral angiography results showed that 81.3％of patients had ocular blood supply from the ipsilateral internal carotid artery,12.1％from the ipsilateral external carotid artery,and 6.6％from the ipsilateral middle cerebral artery.Among the patients,80(44.0％)had varying degrees of stenosis or occlusion of the affected ophthalmic artery,with 69 patients(86.3％)showing stenosis at the origin of the ophthalmic artery.Additionally,135 patients(74.2％)had varying degrees of stenosis or occlusion of the ipsilateral carotid artery,with 110 patients(60.4％)showing stenosis at the carotid bulb,88 patients(48.3％)having unilateral carotid lesions,and 41 patients(22.5％)having multiple lesions.Correlation analysis indicated a significant correlation between the degree of stenosis in the ophthalmic artery and the carotid artery(r=0.76,P=0.006).Univariate and multivariate Logistic regression analyses revealed that the time from symptom onset to hospital admission(OR=0.93,95％CI:0.85-0.98,P=0.018),the grading of oxygenation-based hypoperfusion maculopathy(OHM)(OR=3.12,95％CI:1.09-6.34,P=0.005),intravenous thrombolysis(IVT)(OR=2.75,95％CI:1.08-5.35,P=0.031),and the absence of stenosis in the ophthalmic artery(OR=1.33,95％CI:1.02-3.41,P=0.026)were independent predictors of prognosis for CRAO patients.Conclusions The degree of stenosis in the ophthalmic artery is significantly correlated with the degree of stenosis in the carotid artery in CRAO patients.Time from symptom onset to hospital admission,OHM grading,IVT,and the absence of stenosis in the ophthalmic artery are independent factors influencing the prognosis of CRAO patients.

Objective To investigate the role and mechanism of microRNA-21-5p(miR-21)in cisplatin(CDDP)resistance in non-small cell lung cancer.Methods The expression of miR-21 in cancer tissues and paracancerous tissues of non-small cell lung cancer patients was detected by real-time fluorescence quantitative PCR.Non-small cell lung cancer CDDP-resistant cells H1299/CR and H1975/CR were constructed using non-small cell lung cancer cell lines H1299 and H1975.CCK-8 was used to detect the cell activity of each group of cells under CDDP treatment,and apoptosis was analyzed by flow cytometry.Dual luciferase was used to detect the role of miR-21 in relation to PTEN in H1299 cells,RT-qPCR was used to detect the miR-21 level,and Western blotting was used to detect the protein expression level of PTEN and PTEN downstream Wnt/β-catenin signaling pathway.H1299 and H1299/CR were used to construct a hormonal nude mouse model to verify the effect of miR-21 on the sensitivity of CDDP treatment in non-small cell lung cancer.Results The expression of miR-21 was significantly higher in cancer tissues than in adjacent normal tissues(P＜0.001).The expression of miR-21 in drug-resistant cells H1299/CR and H1975/CR was significantly elevated compared to that in H1299 and H1975 cells(P＜0.05).After transfection with miR-21 inhibitor,cell viability in the inhibitor group was significantly lower than in the inhibitor NC group when treated with CDDP ≥12 pmol/L(P＜0.001).Flow cytometry analysis showed that while the apoptosis rate in the CDDP and miR-21 inhibitor groups did not significantly differ from that in the untreated group,the apoptosis rate in the CDDP+miR-21 inhibitor group was significantly higher(P＜0.001).In contrast,after transfection with miR-21 mimic,the cell viability of the mimic-NC group was significantly reduced compared to the miR-21 mimic group when treated with CDDP ≥12 pmol/L(P＜0.05).TargetScan predicted that miR-21 could bind to the 3-UTR region of PTEN.Dual-luciferase reporter assays confirmed that miR-21 directly targeted PTEN.Overexpression of PTEN(PTEN-OE)together with miR-21 mimic co-transfection in H1299 cells resulted in decreased PTEN expression and increased levels of p-β-catenin(Ser552,Ser675)and β-catenin,while the PTEN expression in the miR-21 mimic+PTEN-OE group was elevated,with a corresponding decrease in p-β-catenin andβ-catenin levels.Flow cytometry showed that apoptosis was significantly increased in the mimic-NC group after CDDP treatment(P＜0.05).In H1299 xenograft models,after treatment with miR-21 mimic and CDDP,tumor growth was slower in the control+CDDP group than in the control group;tumors were larger in the miR-21+CDDP group than in the control+CDDP group at all time points.TUNEL staining revealed that apoptosis in the tumor tissues of the control+CDDP group was higher than in the control group,while apoptosis was reduced in the miR-21+CDDP group compared to the control+CDDP group.In the H1299/CR xenograft model,after 5 days of treatment,the tumors were smaller in the H1299/CR+CDDP group than in the H1299/CR group,and those in the H1299/CR+CDDP+inhibitor group were smaller than in the H1299/CR+CDDP group.TUNEL staining showed that apoptosis was increased in the H1299/CR+CDDP group compared to the H1299/CR group,and further increased in the H1299/CR+CDDP+inhibitor group.Conclusion In non-small cell lung cancer,miR-21 overexpression inhibits PTEN level and activates the Wnt/β-catenin pathway involved in the development of CDDP resistance in non-small cell lung cancer.Inhibition of miR-21 expression in tumor cells will enhance the sensitivity of tumor cells to CDDP.

Myocardial infarction with non-obstructive coronary artery(MINOCA)is a common acute coronary syn-drome in clinical practice.Its diagnosis is more difficult than general acute coronary syndrome,and may be difficult to distinguish from other non ischemic diseases that can cause similar symptoms and myocardial damage.Delayed treatment timing can have a significant detrimental effect on patients.This article provides a review of the clinical diagnosis and treatment progress of MINOCA,with the aim of providing guidance for clinical practice.

Background: and Purpose The optimal management of patients with acute basilar artery occlusion (BAO) is uncertain. We aimed to evaluate the safety and efficacy of endovascular thrombectomy (EVT) compared to medical management (MM) for acute BAO through a meta-analysis of randomized controlled trials (RCTs). Methods: We performed a systematic review and meta-analysis of RCTs of patients with acute BAO. We analyzed the pooled effect of EVT compared to MM on the primary outcome (modified Rankin Scale [mRS] of 0–3 at 3 months), secondary outcome (mRS 0–2 at 3 months), symptomatic intracranial hemorrhage (sICH), and 3-month mortality rates. For each study, effect sizes were computed as odds ratios (ORs) with random effects and Mantel-Haenszel weighting. Results: Four RCTs met inclusion criteria including 988 patients. There were higher odds of mRS of 0-3 at 90 days in the EVT versus MM group (45.1% vs. 29.1%, OR 1.99, 95% confidence interval [CI] 1.04–3.80; P=0.04). Patients receiving EVT had a higher sICH compared to MM (5.4% vs. 0.8%, OR 7.89, 95% CI 4.10–15.19; P<0.01). Mortality was lower in the EVT group (35.5% vs. 45.1%, OR 0.64, 95% CI 0.42–0.99; P=0.05). In an analysis of two trials with BAO patients and National Institutes of Health Stroke Scale (NIHSS) <10, there was no difference in 90-day outcomes between EVT versus MM. Conclusion In this systematic review and meta-analysis, EVT was associated with favorable outcome and decreased mortality in patients with BAO up to 24 hours from stroke symptoms compared to MM. The treatment effect in BAO patients with NIHSS <10 was less certain. Further studies are of interest to evaluate the efficacy of EVT in basilar occlusion patients with milder symptoms.