Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. PURPOSE: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. METHODS: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. RESULTS: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome. CONCLUSIONS: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

The novel HLA-B*40:555 allele identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:555 differs from HLA-B*40:01:02:01 by one nucleotide in exon 3.

Predictors of dysphagia screening and pneumonia among patients with intracerebral haemorrhage in China: a cross-sectional hospital-based retrospective study.

OBJECTIVES: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH). DESIGN: Our study was a cross-sectional hospital-based retrospective study. STUDY DESIGN AND SETTINGS: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia. PARTICIPANTS: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were DS and pneumonia during acute hospitalisation. RESULTS: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95). CONCLUSION: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.

Associations between admission levels of multiple biomarkers and subsequent worse outcomes in acute ischemic stroke patients.

The modified Rankin Scale change score (ΔmRS) is useful for evaluating acute poststroke functional improvement or deterioration. We investigated the relationship between multiple biomarkers and ΔmRS by analyzing data on 6931 patients with acute ischemic stroke (average age 62.3 ± 11.3 years, 2174 (31.4%) female) enrolled from the Third China National Stroke Registry (CNSR-III) and 15 available biomarkers. Worse outcomes at 3 months were defined as ΔmRS3m-discharge ≥1 (ΔmRS3m-discharge = mRS3m-mRSdischarge). Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated from logistic regression models. At 3-months poststroke, 1026 (14.8%) patients experienced worse outcomes. The highest quartiles of white blood cells (WBCs) (aOR [95%CI],1.37 [1.12-1.66]), high-sensitivity C-reactive protein (hs-CRP) (1.37 [1.12-1.67]), interleukin-6 (IL-6) (1.43 [1.16-1.76]), interleukin-1 receptor antagonist (IL-1Ra) (1.46 [1.20-1.78]) and YKL-40 (1.31 [1.06-1.63]) were associated with an increased risk of worse outcomes at 3 months. Results remained stable except for YKL-40 when simultaneously adding multiple biomarkers to the basic traditional-risk-factor model. Similar results were observed at 6 and 12 months after stroke. This study indicated that WBCs, hs-CRP, IL-6, IL-1Ra, and YKL-40 were significantly associated with worse outcomes in acute ischemic stroke patients, and all inflammatory biomarkers except YKL-40 were independent predictors of worse outcomes at 3 months.

Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs.

Lymphatic vessels (LVs) interdigitated with blood vessels, travel and form an extensive transport network in the musculoskeletal system. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, by near infrared indocyanine green lymphatic imaging (NIR-ICG), we examined lymphatic draining function at the tibial fracture sites and found lymphatic drainage insufficiency (LDI) occurred as early as two weeks after fracture. Sufficient lymphatic drainage facilitates fracture healing. In addition, we identified that lymphatic platelet thrombosis (LPT) blocks the draining lymphoid sinus and LVs, caused LDI and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage decreased neutrophils and increased M2-like macrophages of hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). These findings demonstrate that LPT limits bone regeneration by blocking lymphatic drainage from transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone repair.

[Effect of preoperative carbohydrates intake on the gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures].

OBJECTIVE: To investigate the effect of 300 mL carbohydrates intake two hours before sur-gery on the gastric volume (GV) in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures by using gastric antrum sonography, and further assess the risk of reflux aspiration. METHODS: From June 2020 to February 2021, a total of 80 patients, aged 18-65 years, body mass index (BMI) 18-35 kg/m2, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for gynecological laparoscopic procedures positioning in trendelenburg were recruited and divided into two groups: the observation group (n =40) and the control group (n=40). In the observation group, solid food was restricted after 24:00, the patients were required to take 300 mL carbohydrates two hours before surgery. In the control group, solid food and liquid intake were restricted after 24:00 the night before surgery. The cross-sectional area (CSA) of gastric antrum was measured in supine position and right lateral decubitus position before anesthesia. Primary outcome was gastric volume (GV) in each group. Secondary outcome included Perlas A semi-quantitative grading and gastric volume/weight (GV/W). All the patients received assessment of preoperative feeling of thirsty and hunger with visual analogue scale (VAS). RESULTS: Complete data were available in eighty patients. GV was (58.8±23.6) mL in the intervention group vs. (56.3±22.1) mL in the control group, GV/W was (0.97±0.39) mL/kg vs. (0.95±0.35) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 24 patients (60%), 1 in 15 patients (37.5%), 2 in 1 patient (2.5%) in the intervention group and 0 in 25 (62.5%), 1 in 13 (32.5%), 2 in 2 (5%) in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). A total of 3 patients (1 in the intervention group and 2 in the control group) with Perlas A semi-quantitative grading 2 were treated with special intervention, no aspiration case was observed in this study. The observation group endured less thirst and hunger (P＜0.05). CONCLUSION: Three hundred mL carbohydrates intake two hours before surgery along with ultrasound guided gastric content monitoring does not increase gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic surgery, and is helpful in minimizing disturbance to the patient's physiological needs, therefore leading to better clinical outcome.

Clinical characteristics, in-hospital management, and outcomes of patients with in-hospital vs. community-onset ischaemic stroke: a hospital-based cohort study.

Background: Lack of high-quality national-level data on in-hospital ischaemic stroke hinders the development of tailored strategies for this subgroup's identification, treatment, and management. Methods: We analyzed and compared clinical characteristics, in-hospital management measures, and outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), disability at discharge, and in-hospital complications between in-hospital and community-onset ischaemic stroke enrolled in the Chinese Stroke Center Association registry from August 2015 to December 2022. Findings: The cohort comprised 14,948 in-hospital and 1,366,898 community-onset ischaemic stroke patients. In-hospital ischaemic stroke exhibited greater stroke severity, higher prevalence of comorbidities, more pre-admission medications, and had suboptimal management measures, for example, the onset-to-needle time within 4.5 h (83.3% vs. 93.1%; difference, -9.8% [-11.4% to -8.3%]), and antithrombotics at discharge (78.6% vs. 90.0%; difference, -11.4% [95% CI, -12.1% to -10.7%]). After adjusting for covariates, in-hospital ischaemic stroke remains associated with higher risks of unfavorable outcomes, including in-hospital death/DAMA (13.9% vs. 8.6%; adjusted risk difference [aRD], 2.2% [95% CI, 1.8%-2.7%]; adjusted odds ratio [aOR], 1.35 [95% CI, 1.25-1.45]), MACE (12.6% vs. 6.5%; aRD, 4.1% [95% CI, 3.5%-4.7%]; aOR, 1.68 [95% CI, 1.52-1.85]), and complications (23.7% vs. 12.1%; aRD, 6.5% [95% CI, 5.1%-7.9%]; aOR, 1.72 [95% CI, 1.64-1.80]), except for disability at discharge (41.1% vs. 33.1%; aRD, 0.4% [95% CI, -1.7% to 2.5%]; aOR, 0.99 [95% CI, 0.88-1.11]). Interpretation: In-hospital ischaemic stroke demonstrated more severe strokes, worse vascular risk profiles, suboptimal management measures, and worse outcomes compared to community-onset ischaemic stroke. This emphasizes the urgent need for improved hospital systems of care and targeted quality improvement initiatives for better outcomes in in-hospital ischaemic stroke. Funding: National Key R&D Programme of China and Beijing Hospitals Authority.

A comprehensive and systematic review of the potential neuroprotective effect of quercetin in rat models of spinal cord injury.

CONTEXT: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. OBJECTIVE: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. DATA SOURCES: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. STUDY SELECTION: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. RESULTS: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. CONCLUSIONS: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

Assessment of rehabilitation following subarachnoid haemorrhage in China: findings from the Chinese Stroke Center Alliance.

BACKGROUND: Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. METHODS: To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. RESULTS: Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.04 to 1.05) and care such as dysphagia screening (OR, 1.88; 95% CI, 1.73 to 2.04), DVT prophylaxis (OR, 1.56; 95% CI, 1.41 to 1.72) and vessel evaluation (OR, 1.80; 95% CI, 1.63 to 1.98). For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay (OR, 1.96; 95% CI, 1.81 to 2.12), a higher modified Rankin Scale (mRS) score at discharge (OR, 1.49; 95% CI, 1.36 to 1.64), and higher rates of discharge to a rehabilitation center (OR, 3.23; 95% CI, 1.81-5.75). CONCLUSION: More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients.

Effectiveness of a Quality Improvement Intervention on Reperfusion Treatment for Patients With Acute Ischemic Stroke: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China. Objective: To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China. Design, Setting, and Participants: In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020. Interventions: Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team. Main Outcomes and Measures: The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2. Results: All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals. Trial Registration: ClinicalTrials.gov Identifier: NCT03578107.

Analysis of gene expression profiles and experimental validations of a rat chronic cervical cord compression model.

Cervical spondylotic myelopathy (CSM) is a severe non-traumatic spinal cord injury (SCI) wherein the spinal canal and cervical cord are compressed due to the degeneration of cervical tissues. To explore the mechanism of CSM, the ideal model of chronic cervical cord compression in rats was constructed by embedding a polyvinyl alcohol-polyacrylamide hydrogel in lamina space. Then, the RNA sequencing technology was used to screen the differentially expressed genes (DEGs) and enriched pathways among intact and compressed spinal cords. A total of 444 DEGs were filtered out based on the value of log2(Compression/Sham); these were associated with IL-17, PI3K-AKT, TGF-ß, and Hippo signaling pathways according to the GSEA, KEGG, and GO analyses. Transmission electron microscopy indicated the changes in mitochondrial morphology. Western blot and immunofluorescence staining revealed neuronal apoptosis, astrogliosis and microglial neuroinflammation in the lesion area. Specifically, the expression of apoptotic indicators, such as Bax and cleaved caspase-3, and inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, were upregulated. The activation of IL-17 signaling pathway was observed in microglia instead of neurons or astrocytes, the activation of TGF-ß and inhibition of Hippo signaling pathways were detected in astrocytes instead of neurons or microglia, and the inhibition of PI3K-AKT signaling pathway was discovered in neurons rather than microglia of astrocytes in the lesion area. In conclusion, this study indicated that neuronal apoptosis was accompanied by inhibiting of the PI3K-AKT pathway. Then, the activation of microglia IL-17 pathway and NLRP3 inflammasome effectuated the neuroinflammation, and astrogliosis was ascribed to the activation of TGF-ß and the inhibition of the Hippo pathway in the chronic cervical cord of compression. Therefore, therapeutic methods targeting these pathways in nerve cells could be promising CSM treatments.

Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability.

AIM: Post-stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow-up stroke event indirectly. We aimed to use post-stroke proinflammatory cytokine interleukin-6 (IL-6) as a marker of inflammatory burden and quantify post-stroke inflammation's direct and indirect effect on functional disability. METHODS: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome. RESULTS: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence. CONCLUSIONS: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly.

U-shaped association between low-density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke.

During the acute stage of ischemic stroke, it remains unclear how to interpret the low low-density lipoprotein cholesterol (LDL-C) level. We aimed to evaluate the association between LDL-C levels, post-stroke infection, and all-cause mortality. 804,855 ischemic stroke patients were included. Associations between LDL-C levels, infection, and mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection. The association between LDL-C and mortality risk was U-shaped. The nadir in LDL-C level with the lowest mortality risk was 2.67 mmol/L. Compared with the group with LDL-C = 2.50-2.99 mmol/L, the multivariable-adjusted odds ratio for mortality was 2.22 (95% confidence intervals (CI): 1.77-2.79) for LDL-C <1.0 mmol/L and 1.22 (95% CI: 0.98-1.50) for LDL-C ≥5.0 mmol/L. The association between LDL-C and all-cause mortality was 38.20% (95% CI: 5.96-70.45, P = 0.020) mediated by infection. After stepwise excluding patients with increasing numbers of cardiovascular risk factors, the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis, but the LDL-C interval with the lowest mortality risk increased progressively. The mediation effects of infection were largely consistent with the primary analysis in subgroups of age ≥65 years, female, body mass index <25 kg/m2, and National Institutes of Health Stroke Scale ≥16. During the acute stage of ischemic stroke, there is a U-shaped association between LDL-C level and all-cause mortality, where post-stroke infection is an important mediating mechanism.

Epidemiological study of calcified aortic valve stenosis in a Chinese community population.

BACKGROUND AND AIMS: Due to the ageing global population, calcified aortic valve disease is currently the most common cardiac valve disorder. This study aimed to investigate the prevalence and the risk factors for calcified aortic valve stenosis (CAVS), and develop a prediction model for predicting CAVS risk. METHODS AND RESULTS: This study was derived from the cross-sectional baseline survey of the PRECISE study (NCT03178448). The demographic, clinical and laboratory information of each participant was obtained. Univariable and multivariable logistic regression models were used to determine CAVS risk factors. A prediction model for predicting CAVS risk based on risk factors was developed and the result was performed by nomogram. The discrimination of the prediction model was assessed by receiver operating characteristic curve analysis. The degree of fitting for the prediction model was assessed by calibration curve analysis. A total of 3067 participants (1427 men and 1640 women) were included. The prevalence of CAVS among those aged below 60 years old, 60-70 years old and over 70 years old was 4.1%, 10.3% and 21.9%, respectively. Multivariable regression analysis revealed that age (OR: 1.099; 95% CI: 1.076 to 1.123, p<0.001), pulse pressure (OR: 1.020; 95% CI: 1.009 to 1.031, p<0.001), uric acid (OR: 1.003; 95% CI: 1.001 to 1.004, p<0.001), glycosylated haemoglobin (HbA1c) (OR: 1.152; 95% CI: 1.028 to 1.292, p=0.015) and lipoprotein(a) (OR: 1.002; 95% CI: 1.001 to 1.002, p<0.001) were independent risk factors for CAVS. High-density lipoprotein cholesterol (HDL-C) was a protective factor for CAVS (OR: 0.539; 95% CI: 0.349 to 0.831, p=0.005). The prediction model including the above risk factors showed a risk prediction of CAVS with good discrimination. The area under the curve value was found to be 0.743 (95% CI: 0.711 to 0.775). CONCLUSION: CAVS is currently prevalent in the elderly Chinese population. Age, pulse pressure, HbA1c, lower-level HDL-C, lipoprotein(a) and uric acid are the independent risk factors for CAVS.

Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos.

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system. However, the underlying mechanism has not been fully elucidated. In the present study, we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1 (gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury. gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation. gHSF1 overexpression in gecko primary neurons significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3, and facilitated neuronal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, gHSF1 efficiently inhibited the macrophage-mediated inflammatory response by inactivating IkappaB-alpha/NF-kappaB signaling. Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation, and provide new avenues of investigation for promoting spinal cord injury repair in mammals.

Lipid management in ischaemic stroke or transient ischaemic attack in China: result from China National Stroke Registry III.

OBJECTIVES: The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA). DESIGN: Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III). SETTING: We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China. PARTICIPANTS: 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmol/L and LDL-C<1.4mmol/L, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months. RESULTS: Among the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge; the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmol/L and 1.4mmol/L was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR=0.69, 95% CI: 0.48-0.99, p=0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmol/L had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months. CONCLUSIONS: The LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmol/L might be a safe standard for this population.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Autoimmune gastritis with a gastric hamartomatous inverted polyp and two hyperplastic polyps: a case report.

We report an unusual case of autoimmune gastritis (AIG) complicated with a submucosal tumor (SMT) and two pedunculated polyps in a 60-year-old man. The patient was admitted for epigastric distention, heartburn, and anorexia. Endoscopy showed an SMT in the fundus, two pedunculated polyps in the body, and markedly atrophic mucosa of the body and fundus. The SMT, measuring 20 mm in diameter, was resected by endoscopic submucosal dissection and histologically diagnosed as a gastric hamartomatous inverted polyp (GHIP), which is characterized by submucosal glandular proliferation, cystic dilatation, and calcification. The gland structures consisted of foveolar cells and pseudopyloric or mucous-neck cell types. The two pedunculated polyps that were resected by endoscopic mucosal resection were histologically diagnosed as hyperplastic polyps, which are characterized by hyperplastic foveolar glands with pseudopyloric or mucous-neck glands in the inflamed stroma in the mucosa, which consisted of almost the same types of lining cells as the GHIP in the fundus. Findings may indicate the relationship between GHIP, hyperplastic polyp, and AIG. We highlight considering GHIP as a differential diagnosis for an SMT in patients with AIG.