IL-17a promotes hepatocellular carcinoma by increasing FAP expression in hepatic stellate cells via activation of the STAT3 signaling pathway.

Studies have shown that hepatic stellate cells (HSCs) and interleukin-17a (IL-17a) play important roles in liver tumorigenesis. In addition, fibroblast activation protein-α (FAP) has been shown to be a key regulator of hepatic stellate cell activation. In this study, in vivo and in vitro experiments were performed to verify the promoting effects of IL-17a administration, IL-17a overexpression, and FAP upregulation in HSCs on liver fibrosis and liver tumorigenesis. The cleavage under targets & release using nuclease (CUT&RUN) technique was used to verify the binding status of STAT3 to the FAP promoter. The in vitro studies showed that IL-17a activated HSCs and promoted HCC development and progression. FAP and IL-17a overexpression also activated HSCs, promoted HCC cell proliferation and migration, and inhibited HCC cell apoptosis. The in vivo studies suggested that IL-17a and FAP overexpression in HSCs facilitated liver tumor development and progression. The CUT&RUN results indicated that FAP expression was regulated by STAT3, which could bind to the FAP promoter region and regulate its transcription status. We concluded that IL-17a promoted HCC by increasing FAP expression in HSCs via activation of the STAT3 signaling pathway.

Recurrence Characteristics on Optical Coherence Tomography and Treatments of Reis-Bücklers Corneal Dystrophy after Phototherapeutic Keratectomy or Penetrating Keratoplasty: Recurrence characteristics and treatments of RBCD.

PURPOSE: To evaluate the recurrence characteristics on optical coherence tomography and clinical outcomes after phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PKP) in patients with Reis-Bücklers corneal dystrophy (RBCD). DESIGN: Retrospective interventional case series. METHODS: Seventeen patients with RBCD (31 eyes, including six surgery-naïve eyes and 25 surgical eyes) received 44 surgical interventions from 1996 through 2022. PTK or PKP was performed as the initial surgical procedure. Significant recurrence was determined when best spectacle-corrected visual acuity decreased at least two lines with increased opacity in the superficial cornea. Repeated PTK or PTK on the corneal graft (CG-PTK) was considered if patients could not endure poor vision due to significant recurrence. Recurrence depth and annual increase in thickness of the central cornea and subepithelial deposits were assessed by anterior segment optical coherence tomography. RESULTS: The mean follow-up time was 12.8±8.5 years (range, 2.0-25.5 years). The mean logMAR best spectacle-corrected visual acuity improved from 1.24±0.48 preoperatively to 0.27±0.09 postoperatively in the initial PTK group (13 eyes, P<0.001), from 1.84±0.69 to 0.40±0.13 in the PKP group (12 eyes, P<0.001), from 1.04±0.46 to 0.30±0.07 in the repeated PTK group (12 times in 7 eyes, P<0.001), and from 1.29±0.43 to 0.39±0.11 in the CG-PTK group (7 times in 5 eyes, P=0.001). The median significant recurrence time was 27 months (95% confidence interval 23.9-30.1), 96 months (84.1-107.9), 31 months (28.8-33.1), and 24 months (19.8-28.2), respectively (P<0.001). The depth of superficial deposits located between the epithelium and the anterior stroma was approximately 115µm (85-159µm). The annual thickening of subepithelial deposits was 14±2µm after initial PTK, 7±3µm after PKP, 14±3µm after repeated PTK, and 30±11µm after CG-PTK, compared to 4±2µm in surgery-naïve eyes (P=0.002, 0.515, 0.002, <0.001). The thickness of the central cornea increased by 15±2µm, 7±2µm, 15±3µm, and 31±10µm per year in the four surgery groups, respectively, compared to 5±2µm in surgery-naïve eyes (P=0.001, 0.469, 0.001, <0.001). CONCLUSIONS: Better visual acuity can be achieved after PTK than PKP for treatment of RBCD. The annual thickening of subepithelial deposits may approximate an increase in central corneal thickness. The superficial distribution of subepithelial deposits makes it feasible to perform repeated PTK, even on the corneal allograft, for recurrent RBCD.

A Rare Waterborne Outbreak of Bacillus paranthracis in Shandong Province, China, 2020: Epidemiologic Survey, Genomic Insights, and Virulence Characteristics.

ABSTRACTBacillus paranthracis, a Gram-positive conditional pathogen of Bacillus cereus group species, is capable of causing foodborne and waterborne illnesses, leading to intestinal diseases in humans characterized by diarrhea and vomiting. However, documented cases of B. paranthracis infection outbreaks are rare in the world, and the genomic background of outbreak strains is seldom characterized. This study retrospectively analyzed strains obtained from a outbreak in schools, as well as from water systems in peri-urban areas, China, in 2020.In total, 28 B. cereus group isolates were retrieved, comprising 6 from stool samples and 22 from water samples. Epidemiological and phylogenetic investigations indicated that the B. paranthracis isolate from drinking water as the causative agent of the outbreak. Genomic comparison revealed a high degree of consistency among 8 outbreak-related strains in terms of antimicrobial resistance gene profiles, virulence gene profiles, genomic content, and multilocus sequence typing (MLST). The strains related to the outbreak show highly similar genomic ring diagrams and close phylogenetic relationships. Additionally, this study shed light on the pathogenic potential and complexity of B. cereus group through its diversity in virulence genes and mice infection model. The findings highlight the usefulness of B. paranthracis genomes in understanding genetic diversity within specific environments and in tracing the source of pathogens during outbreak situations, thereby enabling targeted infection control interventions.

Unsuccessful Recanalization versus Medical Management of Patients with Large Ischemic Core : Analysis of the ANGEL-ASPECT Randomized Trial.

PURPOSE: The outcomes of patients with large ischemic core who fail to recanalize with endovascular therapy (EVT) compared to medical management (MM) are uncertain. The objective was to evaluate the clinical and safety outcomes of patients who underwent EVT in patients with large ischemic core and unsuccessful recanalization. METHODS: This was a post hoc analysis of the ANGEL-ASPECT randomized trial. Unsuccessful recanalization was defined as patients who underwent EVT with eTICI 0-2a. The primary endpoint was 90-day very poor outcome (mRS 5-6). Multivariable logistic regression was conducted controlling for ASPECTS, occlusion location, intravenous thrombolysis, and time to treatment. RESULTS: Of 455 patients 225 were treated with MM. Of 230 treated with EVT, 43 (19%) patients had unsuccessful recanalization. There was no difference in 90-day very poor outcomes (39.5% vs. 40%, aOR 0.93, 95% confidence interval, CI 0.47-1.85, p = 0.95), sICH (7.0% vs. 2.7%, aOR 2.81, 95% CI 0.6-13.29, p = 0.19), or mortality (30% vs. 20%, aOR 1.65, 95% CI 0.89-3.06, p = 0.11) between the unsuccessful EVT and MM groups, respectively. There were higher rates of ICH (55.8% vs. 17.3%, p < 0.001), infarct core volume growth (142.7 ml vs. 90.5 ml, ß = 47.77, 95% CI 20.97-74.57 ml, p < 0.001), and decompressive craniectomy (18.6% vs. 3.6%, p < 0.001) in the unsuccessful EVT versus MM groups. CONCLUSION: In a randomized trial of patients with large ischemic core undergoing EVT with unsuccessful recanalization, there was no difference in very poor outcomes, sICH or death versus medically managed patients. In the unsuccessful EVT group, there were higher rates of any ICH, volume of infarct core growth, and decompressive craniectomy.

Outcomes of antiplatelet therapy before endovascular treatment of acute large vessel occlusion: Data from the ANGEL-ACT registry.

OBJECTIVES: To investigate whether single or dual antiplatelet therapy (SAPT or DAPT) within 24 hours before endovascular treatment (EVT) could improve the clinical outcomes of patients with large vessel occlusion (LVO). METHODS: Patients from the ANGEL-ACT registry were divided into antiplatelet therapy (APT) and non-APT groups. The APT group was divided into SAPT and DAPT groups. Outcome measurement included 90-day modified Rankin Scale (mRS) distribution, change in the NIHSS at 7 days or discharge, number of passes, modified first pass effect (mFPE), symptomatic intracranial hemorrhage (SICH), and mortality within 90 days. To compare the outcomes, we performed multivariable analyses by adjusting for the propensity score calculated by the logistic regression model. RESULTS: Of 1611 patients, 1349 were in the non-APT group, while 262 (16.3 %) were in the APT group (122 [46.6 %] received SAPT, 140 [53.4 %] received DAPT). APT, SAPT or DAPT were not associated with a shift to better outcomes (non-APT vs. APT, 3[0-5] vs. 3[0-5], common odds ratio [OR], 1.04, 95 %confidence interval [CI]:0.82-1.34, P = 0.734). DAPT was associated with mFPE (OR,2.05, 95 %CI:1.39-3.01, P<0.001), more NIHSS reduction at 7 days or discharge (ß, -2.13, 95 %CI: -4.02--0.24, P = 0.028), lower number of passes (ß, -0.40, 95 %CI: -0.68--0.12, P=0.006), and shorter procedure duration (ß, -12.4, 95 %CI: -23.74--1.05, P = 0.032) without increasing odds of successful recanalization, PH within 24 hours and mortality with 90 days . CONCLUSIONS: APT before MT for AIS due to LVO does not affect clinical outcome in 90 days despite a tendency to reduce MT procedure time and number of passes. APT before MT in LVO does not increase SICH or mortality rates.

The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion.

Background and purpose: Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Methods: Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0-1, 0-2, and 0-3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. Results: A total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0-5) vs. 1(0-4) vs. 1(0-4) vs. 3(0-5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45-1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78-2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64-1.64, P = 0.912). The adjusted OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27-0.98, P = 0.042) and 0.50 (95% CI, 0.26-0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18-0.94, P = 0.036), and the OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11-0.74, P = 0.011) and 0.25 (95% CI, 0.09-0.67, P = 0.006). Conclusions: Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO. Clinical trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT03370939.

Modification effects of long-term air pollution levels on the relationship between short-term exposure to meteorological factors and hand, foot, and mouth disease: A distributed lag non-linear model-based study in Shandong Province, China.

The occurrence of hand, foot, and mouth disease (HFMD) is closely related to meteorological factors. However, location-specific characteristics, such as persistent air pollution, may increase the complexity of the impact of meteorological factors on HFMD, and studies across different areas and populations are largely lacking. In this study, a two-stage multisite time-series analysis was conducted using data from 16 cities in Shandong Province from 2015 to 2019. In the first stage, we obtained the cumulative exposure-response curves of meteorological factors and the number of HFMD cases for each city. In the second stage, we merged the estimations from the first stage and included city-specific air pollution variables to identify significant effect modifiers and how they modified the short-term relationship between HFMD and meteorological factors. High concentrations of air pollutants may reduce the risk effects of high average temperature on HFMD and lead to a distinct peak in the cumulative exposure-response curve, while lower concentrations may increase the risk effects of high relative humidity. Furthermore, the effects of average wind speed on HFMD were different at different levels of air pollution. The differences in modification effects between subgroups were mainly manifested in the diversity and quantity of significant modifiers. The modification effects of long-term air pollution levels on the relationship between sunshine hours and HFMD may vary significantly depending on geographical location. The people in age＜3 and male groups were more susceptible to long-term air pollution. These findings contribute to a deepening understanding of the relationship between meteorological factors and HFMD and provide evidence for relevant public health decision-making.

Simultaneous detection of dual microRNAs related to EV71 using ICP-MS based on metal nanoparticle labeling with hybridization chain reaction.

BACKGROUND: Hand, foot, and mouth (HMFD) disease caused by enterovirus 71 (EV 71), is closely associated with severe clinical manifestations and can be deadly. Early detection of EV 71 can be achieved by detecting the increment in miR296 and miR16 in the serum. Using HCR to amplify signals and convert biological signals into metal nanoparticle signals detectable by ICP-MS is a detection method that can collect more accurate and reliable information, compared with traditional methods, in the detection of biological samples. RESULTS: We described a strategy for the simultaneous detection of miR296 and miR16 by ICP-MS based on metal nanoparticles (NPs) labeling with HCR. Briefly, single-stranded DNA (ssDNA) and magnetic beads (MBs), as well as NPs and signal probes for miRNA (Sp-miR) were firstly conjugated via the streptavidin-biotin recognition system, constituting ssDNA-MBs and NPs-Sp-miR complex, respectively. The latter complex then hybridized with the former through HCR, generating the nanosensors for targets. Then, the targets were added and hybridized with ssDNA, and the HCR complex with NPs was released into the solution. Finally, the corresponding signals of the NPs were measured by ICP-MS. Results demonstrated that the developed method had good sensitivity and satisfactory selectivity and precision. Furthermore, when applied to biological samples with a complex matrix, the developed method also showed good recovery (88 % - 92 %) and reproducibility (RSD<10 %). SIGNIFICANCE: This method contributes to the early diagnosis of HFMD and opens up ideas for the further development of high-throughput biomarker detection. The strategy has practical potential for miR296 and miR16 detection in biological samples and provides a promising tool for multiple miRNA detection.

Immune Cell Infiltration Types as Biomarkers for the Recurrence Diagnosis and Prognosis of Bladder Cancer.

This study aimed to investigate the role of infiltrating immune cell types in diagnosing and predicting bladder cancer recurrence. This study mainly applied some algorithms, including Estimate the Proportion of Immune and Cancer Cells (EPIC), support vector machine-recursive feature elimination (SVM-RFE), random forest out-of-bag (RF-OOB) and least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. We found six immune infiltrating cell types significantly associated with recurrence prognosis and two independent clinical prognostic factors. Infiltrating immune cell types (IICTs) based on the prognostic immune risk score (pIRS) models may provide significant biomarkers for the diagnosis and prognostic prediction of bladder cancer recurrence.

Recent progress in plasma modification of 2D metal chalcogenides for electronic devices and optoelectronic devices.

Two-dimensional metal chalcogenides (2D MCs) present a great opportunity for overcoming the size limitation of traditional silicon-based complementary metal-oxide-semiconductor (CMOS) devices. Controllable modulation compatible with CMOS processes is essential for the improvement of performance and the large-scale applications of 2D MCs. In this review, we summarize the recent progress in plasma modification of 2D MCs, including substitutional doping, defect engineering, surface charge transfer, interlayer coupling modulation, thickness control, and nano-array pattern etching in the fields of electronic devices and optoelectronic devices. Finally, challenges and outlooks for plasma modulation of 2D MCs are presented to offer valuable references for future studies.

Sex differences in outcomes of endovascular therapy for acute vertebrobasilar occlusion: data from ANGEL-ACT Registry.

BACKGROUND: Understanding sex disparities in stroke can identify gaps in clinical care. The objective of this study was to investigate whether sex differences could influence clinical outcomes of patients with acute vertebrobasilar artery occlusion (VBAO) who underwent endovascular therapy (EVT). METHODS: Patients were selected from the ANGEL-ACT Registry. The primary outcome was favorable functional outcome (90-day modified Rankin Scale [mRS] 0-3). Secondary outcomes included 90-day mRS distribution, excellent outcome (mRS 0-1), functional independence (mRS 0-2), early neurological improvement, recanalization, intracranial hemorrhage, and mortality within 90 days. The above outcomes were compared by two adjustment models, including (1) multivariable logistics analysis adjusting for all baseline and procedural variables with a P < 0.05; (2) adjusting for the propensity score. RESULTS: There were 347 acute VBAO patients treated with EVT included, of whom 72 (20.7%) were women and 275 (79.3%) were men. Women were older (72[63-76] vs. 62[53-69], P < 0.001) and had a higher rate of atrial fibrillation (31.9% vs. 8.7%, P < 0.001), lower rates of underlying intracranial atherosclerotic disease (30.6% vs. 51.3%, P = 0.007), and tandem occlusion (8.3% vs. 21.8%, P = 0.009) than men. The rate of favorable outcome (mRS 0-3) was similar between women and men (41.7% vs. 51.3%, adjusted odds ratio 1.56, 95%CI: 0.83-2.95, P = 0.171). There were no sex differences in other clinical outcomes (all P > 0.05). CONCLUSIONS: In the ANGEL-ACT registry, the percentage of men with acute VBAO undergoing EVT was approximately fourfold higher than that of women with acute VBAO undergoing EVT. Sex differences did not modify the outcomes of acute VBAO after EVT.

Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial.

BACKGROUND: The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs). AIM: To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS. DESIGN: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35-80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%-99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years. STUDY OUTCOMES: Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome. DISCUSSION: BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS. TRIAL REGISTRATION NUMBER: NCT03703635; https://www. CLINICALTRIALS: gov.

Alberta Stroke Program Early Computed Tomography Score, Infarct Core Volume, and Endovascular Therapy Outcomes in Patients With Large Infarct: A Secondary Analysis of the ANGEL-ASPECT Trial.

Importance: Endovascular therapy (EVT) demonstrated better outcomes compared with medical management in recent randomized clinical trials (RCTs) of patients with large infarct. Objective: To compare outcomes of EVT vs medical management across different strata of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and infarct core volume in patients with large infarct. Design, Setting, and Participants: This prespecified secondary analysis of subgroups of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) RCT included patients from 46 stroke centers across China between October 2, 2020, and May 18, 2022. Participants were enrolled within 24 hours of symptom onset and had ASPECTS of 3 to 5 or 0 to 2 and infarct core volume of 70 to 100 mL. Patients were divided into 3 groups: ASPECTS of 3 to 5 with infarct core volume less than 70 mL, ASPECTS of 3 to 5 with infarct core volume of 70 mL or greater, and ASPECTS of 0 to 2. Interventions: Endovascular therapy or medical management. Main Outcomes and Measures: The primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Results: There were 455 patients in the trial; median age was 68 years (IQR, 60-73 years), and 279 (61.3%) were male. The treatment effect did not vary significantly across the 3 baseline imaging subgroups (P = .95 for interaction). The generalized odds ratio for the shift in the 90-day mRS distribution toward better outcomes with EVT vs medical management was 1.40 (95% CI, 1.06-1.85; P = .01) in patients with ASPECTS of 3 to 5 and infarct core volume less than 70 mL, 1.22 (95% CI, 0.81-1.83; P = .23) in patients with ASPECTS of 3 to 5 and infarct core volume of 70 mL or greater, and 1.59 (95% CI, 0.89-2.86; P = .09) in patients with ASPECTS of 0 to 2. Conclusions and Relevance: In this study, no significant interaction was found between baseline imaging status and the benefit of EVT compared with medical management in patients with large infarct core volume. However, estimates within subgroups were underpowered. A pooled analysis of large core trials stratified by ASPECTS and infarct core volume strata is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04551664.

Spatial multimodal analysis revealed tertiary lymphoid structures as a risk stratification indicator in combined hepatocellular-cholangiocarcinoma.

The microenvironment created by tertiary lymphoid structures (TLSs) can support and regulate immune responses, affecting the prognosis and immune treatment of patients. Nevertheless, the actual importance of TLSs for predicting the prognosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients remains unclear. Herein, using spatial transcriptomic analysis, we revealed that a gene signature of TLSs specific to cHCC-CCA was associated with high-intensity immune infiltration. Then, a novel scoring system was developed to evaluate the distribution and frequency of TLSs in intra-tumoral and extra-tumoral regions (iTLS and eTLS scores) in 146 cHCC-CCA patients. iTLS score was positively associated with promising prognosis, likely due to the decreased frequency of suppressive immune cell like Tregs, and the ratio of CD163+ macrophages to macrophages in intra-tumoral TLSs via imaging mass cytometry, while improved prognosis is not necessarily indicated by a higher eTLS score. Overall, this study highlights the potential of TLSs as a prognostic factor and an indicator of immune therapy in cHCC-CCA.

Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update.

BACKGROUND: China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases. METHODS: We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee. RESULTS: This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management. CONCLUSIONS: This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

Endovascular Therapy for Acute Stroke: New Evidence and Indications.

Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke. In the past few years, endovascular treatment indications have expanded to include patients being treated in the extended window, with large ischemic core infarction, basilar artery occlusion (BAO) thrombectomy, as demonstrated by several randomized clinical trials. Intravenous thrombolysis (IVT) bridging to mechanical thrombectomy has also been studied via several randomized clinical trials, with the overall results indicating that IVT should not be skipped in patients who are candidates for both IVT and EVT. Simplification of neuroimaging protocols in the extended window to permit non-contrast CT, CTA collaterals have also expanded access to mechanical thrombectomy, particularly in regions across the world where access to advanced imaging may not be available. Ongoing study of areas to develop include rescue stenting in patients with failed thrombectomy, medium vessel occlusion thrombectomy, and carotid tandem occlusions. In this narrative review, we summarize recent trials and key data in the treatment of patients with large ischemic core infarct, simplification of neuroimaging protocols for the treatment of patients presenting in the late window, bridging thrombolysis, and BAO EVT evidence. We also summarize areas of ongoing study including medium and distal vessel occlusion.

Endovascular treatment for young patients with acute large vessel occlusion stroke in China: analysis of the ANGEL-ACT registry.

Background: The incidence of acute ischemic stroke caused by large vessel occlusion is relatively infrequent in the young adult population. We sought to evaluate their clinical outcomes after endovascular treatment (EVT) and stroke etiology compared with older patients. Methods: We examined data from the ANGEL-ACT registry, a nationwide study in China focusing on EVT for acute ischemic stroke. We compared two age groups: <50 years old and ≥50 years old. Our analysis focused on outcome measures such as the 90-day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage (sICH). We adjusted for confounding variables. Results: We included 1,691 patients, and 216 patients (13%) were <50 years old. Young patients had lower median National Institutes of Health Stroke Scale (NIHSS) scores (14 vs. 17, P < 0.001) and fewer cardiovascular comorbidities than older patients. Underlying intracranial atherosclerosis disease (ICAD) was higher in young patients (39.4 vs. 28.7%, P = 0.001). Clinical outcome was less favorable in older compared to younger patients (mRS shift: 0.76 [95% confidence interval (CI), 0.58-0.99]); functional independence [mRS score 0-2] 61% vs. 39% (adjusted odds ratio (OR), 0.7 [95% CI, 0.51-0.97]). Mortality and sICH did not differ between groups. Onset to puncture time (OTP) was longer in young patients (357 min vs. 294 min, P = 0.001). Conclusion: An estimated 13% of patients who underwent endovascular thrombectomy for acute ischemic stroke were <50 years old. Symptomatic underlying ICAD was more prevalent in the younger patient population. Despite a prehospital delay, younger patients exhibited more favorable outcomes than their older counterparts.

Circular RNA cFAM210A, degradable by HBx, inhibits HCC tumorigenesis by suppressing YBX1 transactivation.

Hepatitis B protein x (HBx) has been reported to promote tumorigenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but the mechanism awaits further investigation. In this study, we found that cFAM210A (a circular RNA derived from the third exon of transcript NM_001098801 of the FAM210A gene; CircBase ID: hsa_circ_0003979) can be silenced by HBx. cFAM210A expression was downregulated and negatively correlated with tumorigenesis in patients with HBV-related HCC. Furthermore, cFAM210A reduced the proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, HBx increased the N6-methyladenosine (m6A) level of cFAM210A by promoting the expression of RBM15 (an m6A methyltransferase), thus inducing the degradation of cFAM210A via the YTHDF2-HRSP12-RNase P/MRP pathway. cFAM210A bound to YBX1 and inhibited its phosphorylation, suppressing its transactivation function toward MET. These findings suggest the important role of circular RNAs in HBx-induced hepatocarcinogenesis and identify cFAM210A a potential target in the prevention and treatment of HBV-related HCC.

Impact of the introduction of high-speed rail on the income gap between urban and rural residents.

The unprecedented expansion and development of high-speed rail (HSR) in China provides a unique opportunity and a new way of thinking for addressing the problem of urban-rural wealth disparities. In this paper, I examine the impact of the introduction of HSRs on the income disparity between urban and rural residents in China. Using panel data from 285 prefecture-level cities from 2004 to 2018, in this paper I employ the double-difference method to assess the impact of HSR on the income gap between urban and rural populations and the mechanism of its action; furthermore, I explore the influence of HSR on urban residents' per capita disposable income and rural residents' per capita net income, as well as the impact of HSR on the flow of elements such as labor and capital. My research findings reveal that the introduction of HSR has greatly widened the income gap between urban and rural residents; however, there is heterogeneity between different East, Central, and West regions, as well as between different levels of cities. A further mechanism study finds that HSR lowers farmers' per capita net income, raises urban residents' per capita disposable income, and widens the urban/rural income gap via mechanisms such as facilitating the interregional mobility of labor and capital factors. Therefore, it is necessary to comprehensively assess the economic effects brought about by HSR, strengthen the construction of urban-rural transport networks, and improve support for rural areas, so as to promote the coordinated development of inter-regional and urban-rural areas.

Incidence and predictors of futile recanalisation after endovascular therapy in acute vertebrobasilar artery occlusion patients: insight from the ANGEL-ACT registry.

OBJECTIVES: To identify the occurrence rate and predictors of futile recanalisation after endovascular therapy (EVT) for acute vertebrobasilar artery occlusion (VBAO). METHODS: Participants of the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischaemic Stroke (ANGEL-ACT) registry were selected for the analysis. Futile recanalisation was defined as patients did not achieve a 90-day good outcome (modified Rankin Scale ≤3) despite successful recanalisation (modified Treatment in Cerebral Ischaemia Scale ≥2b) after the procedure. Multivariable logistic regression analysis was conducted to find independent predictors of futile recanalisation in VBAO patients undergoing EVT. RESULTS: Three hundred and fifteen patients with VBAO who achieved successful recanalisation after EVT were included in current analysis, of whom, 155 (49.2%) suffered futile recanalisation, and 160 achieved effective recanalisation. After the multivariable analysis, we found admission National Institutes of Health Stroke Scale (NIHSS) ≥19 (OR 4.81, 95% CI 2.76 to 8.39, p<0.001), platelet-lymphocyte ratio (PLR) ≥162.2 (OR 1.93, 95% CI 1.14 to 3.27, p=0.001), onset-to-puncture time (OTP) ≥334 min (OR 2.15, 95% CI 1.25 to 3.68, p=0.005) and use of general anesthesia (GA) (OR 1.87, 95% CI 1.09 to 3.22, p=0.024) were associated with futile recanalisation. CONCLUSIONS: Futile recanalisation after EVT occurred 49.2% of VBAO patients in the ANGEL-ACT registry. NIHSS≥19, PLR≥162.2, OTP≥334 min and use of GA were independent predictors of futile recanalisation.