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Shen-Zhong Qiu,1 Guan-Rong Zheng,1 Cai-Yan Ma,2 Bin Chen,1 Jian-Jun Huang,1 Ge Huang,1 Hai Hua1 1Department of Neurosurgery, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Fuyang District of Hangzhou City, Hangzhou, People’s Republic of ChinaCorrespondence: Hai Hua Tel +86 571 63349039Email huahai1760@163.comObjective: Intracerebral hemorrhage (ICH) triggers an inflammatory cascade that damages brain tissues and worsens functional outcome. S100A12 functions to promote brain inflammation. We aimed to investigate the relationship between serum S100A12 levels and functional outcome in ICH patients.Methods: Serum S100A12 levels were measured in 101 ICH patients hospitalized within 24 h after symptom onset. Poor functional outcome was defined as a modified Rankin scale of 3 or greater at 3 months after stroke. Early neurologic deterioration was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score or death at 24 hours from symptoms onset.Results: High serum S100A12 levels were independently correlated with NIHSS score (t = 5.384, P < 0.001), hematoma volume (t = 4.221, P < 0.001) and serum C-reactive protein levels (t = 5.068, P < 0.001). Serum S100A12 levels were substantially higher in patients with a poor outcome (median, 66.5 versus 37.7 ng/mL; P < 0.001) or early neurological deterioration (median, 76.5 versus 40.1 ng/mL; P < 0.001) than in the other remainders, independently predicted a poor outcome (odds ratio, 1.035; 95% confidence interval, 1.007– 1.064; P = 0.015) and early neurologic deterioration (odds ratio,1.032; 95% confidence interval, 1.003– 1.060; P = 0.027), and significantly discriminated a poor outcome (area under curve, 0.794; 95% confidence interval, 0.702– 0.868) and early neurologic deterioration (area under curve, 0.760; 95% confidence interval, 0.664– 0.839) under receiver operating characteristic curve.Conclusion: High serum S100A12 levels at admission are highly associated with the extent of inflammatory response, severity, a poor functional outcome and early neurologic deterioration in ICH patients, substantializing serum S100A12 as a promising prognostic biomarker for ICH.Keywords: biomarker, functional outcome, inflammation, intracerebral hemorrhage, early neurological deterioration, S100A12

Purpose: Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. Although micro-ribonucleic acid-210-3p (miR-210-3p) is correlated with hypoxia-induced tumor development, its role in the relationship between IH and tumor function remains poorly understood. The present work focused on elucidating the molecular mechanism through which miR-210-3p drives tumor progression under IH., Methods: MiR-210-3p levels were quantified within tumor samples from patients with lung adenocarcinoma who had or did not have OSA. Correlations between miR-210-3p and polysomnographic variables were analyzed. For in vitro experiments, miR-210-3p was inhibited or overexpressed via transfection under IH conditions. Cell viability, growth, invasion and migration assays were carried out. For in vivo modeling of IH using mouse xenografts, a miR-210-3p antagomir was intratumorally injected, tumor biological behaviors were evaluated, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry and western blot were carried out for detecting miR-210-3p and E2F transcription factor 3 (E2F3) expression., Results: For patients with lung adenocarcinoma and OSA, high miR-210-3p levels showed positive relation to polysomnographic variables, such as oxygen desaturation index, apnea-hypopnea index, and proportion of total sleep time with oxygen saturation in arterial blood < 90%. IH enhanced tumor viability, proliferation, migration, and invasion, downregulated E2F3 expression, and increased miR-210-3-p levels. miR-210-3p overexpression induced similar changes. These changes were reversed by miR-210-3p inhibition in vitro or miR-210-3p antagomir through intratumoral injection in vivo., Conclusions: IH-induced tumor development is driven through miR-210-3p by E2F3 suppression. MiR-210-3p represents a potential therapeutic target among patients with concomitant cancer and OSA., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chimeric antigen receptor (CAR)-T cells have shown great promise in cancer therapy. However, the anti-tumor efficiency is limited due to the CAR-induced T cell apoptosis or exhaustion. The intracellular domain of CAR comprised of various signaling modules orchestrates CAR-T cell behaviors. The modularity of CAR signaling domain functions as the "mainboard" to assemble diversified downstream signaling components. Here, we implemented the modular recombination strategy to construct a library of CARs with synthetic co-signaling modules adopted from immunoglobin-like superfamily (IgSF) and tumor necrosis factor receptor superfamily (TNFRSF). We quantitatively characterized the signaling behaviors of these recombinants by both NFAT and NF-κB reporter, and identified a set of new CARs with diverse signaling behaviors. Specifically, the 28(NM)-BB(MC) CAR-T cells exhibited improved cytotoxicity and T cell persistence. The synthetic approach can promote our understanding of the signaling principles of CAR molecule, and provide a powerful tool box for CAR-T cell engineering., Competing Interests: A patent application has been submitted based on results presented in this paper. P.W., W.S., YY.F., and HP.W. are listed as the inventors. The authors declare no competing interests., (© 2023 The Author(s).)

Background: Scavenger receptor A (SRA) can regulate immune response and is involved in pathophysiological processes of acute brain injury. We analyzed the prognostic role of serum soluble SRA in intracerebral hemorrhage (ICH)., Methods: In this prospective cohort study of 110 healthy controls and 110 patients with acute basal ganglia hemorrhage, serum soluble SRA concentrations were detected. Univariate analyses, followed by multivariate logistic regression analyses, were utilized to explore the relationship between serum soluble SRA concentrations and early neurologic deterioration (END) plus post-stroke 3-month poor prognosis (modified Rankin Scale scores of 3-6)., Results: Serum soluble SRA concentrations of patients were significantly higher than those of controls (median, 3.6 vs 0.9 ng/ml; P < 0.001). Serum soluble SRA concentrations of patients were independently correlated with hematoma volume (β, 0.201; 95 % confidence interval (CI), 0.093-0.309; P = 0.001), National Institutes of Health Stroke Scale (NIHSS) scores (β, 0.118; 95 % CI, 0.024-0.213; P = 0.024), and 3-month modified Rankin Scale scores (β, 0.148; 95 % CI, 0.063-0.232; P = 0.001). Serum soluble SRA concentrations independently predicted END and poor 3-month prognosis with odds ratio values of 1.394 (95 % CI, 1.024-1.899; P = 0.035) and 1.441 (95 % CI, 1.016-2.044; P = 0.040) respectively. Serum soluble SRA concentrations were efficiently predictive of the development of END (ROC AUC 0.746; 95 % CI, 0.631-0.861) and poor 3-month prognosis (AUC, 0.773; 95 % CI, 0.685-0.861). Serum soluble SRA concentrations significantly improved AUCs of NIHSS score and hematoma volume to 0.889 (95 % CI, 0.829-0.948; P = 0.035) and 0.873 (95 % CI, 0.811-0.936; P = 0.036) for prognostic prediction. The END predictive ability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.900; 95 % CI, 0.835-0.965) was significantly superior to those of NIHSS score (P = 0.020) and hematoma volume (P = 0.022). The prognostic predictive capability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.907; 95 % CI, 0.852-0.962) substantially exceeded those of NIHSS score (P = 0.009) and hematoma volume (P = 0.005)., Conclusions: Serum soluble SRA concentrations may reflect illness severity and neurologic function after ICH, indicating serum soluble SRA may serve as a promising prognostic biochemical marker of ICH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rationale: Subglottic tracheal stenosis is stenosis of the trachea between the vocal cords and the lower margin of the cricoid cartilage. The Montgomery T-tube is used as a tracheostomy tube and a combined tracheal stent to avoid postoperative tracheal stenosis., Patient Concerns: Because the stenosis is close to the glottis, surgical treatment is complex, and many complications may arise., Diagnoses: Subglottic tracheal stenosis., Interventions: The patients underwent endotracheal intubation or tracheotomy because of acute pancreatitis, laryngeal malignancy, or cerebral hemorrhage after endotracheal intubation or tracheotomy and presented with varying degrees of tracheal stenosis and dyspnea. We relieved airway stenosis and improved dyspnea in these 3 patients by placing a Montgomery T-tube., Outcomes: None of the 3 patients had intraoperative complications. In 2 of the cases, airway secretions were stored after surgery., Lessons: Montgomery T-tube placement is safe and effective for patients with complex subglottic tracheal stenosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Serum glucose-phosphate ratio has been revealed to be associated with severity and prognosis of aneurysmal subarachnoid hemorrhage. Objective of this study was to investigate the relationship between serum glucose-phosphate ratio and severe traumatic brain injury outcome., Methods: Patients with severe traumatic brain injury were stratified in quartiles according to their serum glucose-phosphate ratio. Outcome parameters included mortality, overall survival and poor outcome defined as Glasgow outcome scale score of 1-3 at post-traumatic 6 months. Multiple logistic regression analysis was performed to evaluate the association between quartiles of serum glucose-phosphate ratio and outcome., Results: Data from 105 patients were retrospectively reviewed. Glasgow coma scale score declined, Glasgow outcome scale score decreased, Rotterdam computed tomography classification were raised, mortality increased, overall survival probability reduced and percentage of poor outcome rose significantly with each quartile of serum glucose-phosphate ratio. After adjusting for other confounding factors, serum glucose-phosphate ratio according to quartiles was substantially related to 6-month mortality, overall survival and poor outcome. Under receiver operating characteristic curve, serum glucose-phosphate ratio showed a significantly high prognostic predictive capability., Conclusions: Serum glucose-phosphate ratio might be a potential variable that can reflect trauma severity and prognosis in patients with severe traumatic brain injury., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The solid wastes of Chinese materia dedica industrialization represented by Salvia miltiorrhiza residues have a strong small-molecule bio-recalcitrance in the process of high-value utilization of biotransformation. Highly tolerant strains were bred to break bio-recalcitrance of Salvia miltiorrhiza residues and produce high-value added cellulose, which has a significant significance for recycling and industrial utilization of solid waste. In this study, a strain of fungus, Penicillium expansum SZ13, was found with small-molecule antibacterial substance tanshinone contained in Salvia miltiorrhiza residues by a biological method. The optimal enzyme production process and peak period of SZ13 were determined. It was found that SZ13 could maintain peak enzyme production for 5 days by degrading residues under the conditions of temperature 35 ℃, rotation speed 180 r·min~(-1), 5% of residues addition, and 5% seed solution addition. Meanwhile, the ability of SZ13 to degrade the enzyme production of multiple types of residues was explored. The results showed a high enzyme activity and stable enzyme production of SZ13 in the process of degrading residues. SZ13 could efficiently utilize various types of Chinese medicine residues, such as Salvia miltiorrhiza residues, to realize the high-value utilization of cellulose in multiple types of residues.

Background: Tissue kallikrein (TK) plays an important role in the kallikrein-kinin system. Its protective role has been demonstrated in traumatic brain injury (TBI). We attempted to determine relationship between serum TK levels and trauma severity in addition to clinical outcome in TBI., Methods: We recruited 112 patients with severe TBI (Glasgow coma scale score < 9) and 112 controls. We configured 2 multivariate models to assess the relationship between serum TK levels and 30-day death. Its prognostic predictive ability was analyzed under receiver operating characteristic curve., Results: TK levels were significantly lower in patients than in controls (median 0.148 mg/l, the upper - lower quartiles 0.121-0.185 vs. median 0.258 mg/l, the upper - lower quartiles 0.207-0.342, P < 0.001). TK levels were closely and positively correlated with Glasgow coma scale score (r = 0.550). TK levels <0.148 mg/l independently predicted 30-day mortality with odds ratio value of 4.752 (95% confidence interval (CI), 1.166-19.367) and 30-day overall survival with hazard ratio value of 3.698 (95% CI, 1.026-13.333). TK levels significantly discriminated 30-day mortality with area under curve of 0.822 (95% CI, 0.738-0.887)., Conclusions: Serum TK can represent a potential predictor of clinical outcome in TBI patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Oxidative stress is related to brain injury after spontaneous intracerebral hemorrhage (ICH). Myeloperoxidase (MPO) is a potent oxidizing enzyme. We tested the hypothesis that serum MPO concentrations are increased after ICH and they correlate with stroke severity and outcome., Methods: Serum MPO concentrations were measured in 128 ICH patients and 128 controls. Odds ratios of dependent variables, including early neurological deterioration, hematoma growth, 1-week mortality, 6-month mortality, 6-month unfavorable outcome (modified Rankin Scale score > 2) and 6-month overall survival, were calculated and adjusted for age, sex, hematoma volume, National Institutes of Health Stroke Scale (NIHSS) score and vascular risk factors., Results: As compared to the controls, the patients had significantly increased serum MPO concentrations. MPO concentrations of the ICH patients were strongly correlated with hematoma volume and NIHSS scores. Serum MPO were independently associated with the above-mentioned study points. Its area under receiver operating characteristic curve was equivalent to those of hematoma volume and NIHSS score. Moreover, serum MPO significantly improved the discriminatory ability of hematoma and NIHSS in predicting 6-month mortality and unfavorable outcome., Conclusions: Serum MPO concentrations rise in ICH patients and there is a correlation between MPO concentrations and severity or prognosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cyclophilin A is involved in brain injury. We investigated the relationship between serum cyclophilin A concentrations, hemorrhagic severity and clinical outcome in intracerebral hemorrhage (ICH)., Methods: We enrolled 105 ICH patients and 105 healthy individuals. Admission serum cyclophilin A concentrations were detected in ICH patients. Hemorrhagic severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Modified Rankin Scale score > 2 was defined as a poor outcome., Results: Serum cyclophilin A concentrations were significantly higher in patients than in controls. There was a close correlation of serum cyclophilin A concentrations with NIHSS scores and hematoma volume. Serum cyclophilin A emerged as an independent predictor for 6-month mortality, overall survival and poor outcome. Moreover, it had a strong discriminatory ability for 6-month mortality and poor outcome. Furthermore, it could significantly improve the prognostic predictive ability of NIHSS scores or hematoma volume alone., Conclusions: Increasted serum cyclophilin A concentrations are highly associated with stroke severity and prognosis after hemorrhagic stroke., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: CXC chemokine ligand-12 (CXCL12), a member of the CXC chemokine subfamily, is involved in both focal angiogenesis and inflammatory reactions. We examined serum CXCL12 concentration in intracerebral hemorrhage (ICH) patients and its correlation to stroke severity and outcome., Methods: The study was carried out on 105 ICH patients on 105 healthy controls. Serum samples were at admission obtained to measure CXCL12 concentrations. The National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were recorded to assess stroke severity., Results: As compared to the controls, CXCL12 concentrations were significantly increased in the patients. Also, non-survivors within 6months and patients with an unfavorable outcome (modified Rankin Scale score>2) at 6months had higher CXCL12 concentrations than other remaining ones. CXCL12 concentrations had positive correlation with NIHSS scores and hematoma volume. Serum CXCL12 significantly discriminated patients at risk of 6-month mortality and 6-month unfavorable outcome under receiver operating characteristic curve. Moreover, serum CXCL12 was independently associated with the mortality, overall survival and unfavorable outcome., Conclusions: Serum CXCL12 concentrations are enhanced after ICH and CXCL12 in serum has the potential to reflect severity and prognosis following hemorrhagic stroke., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1) in peripheral blood, which is identified as a marker for coagulation, was reported to be an independent predictor of poor outcome in some illnesses. We investigated the clinical utility of serum SCUBE1 in the prognosis of intracerebral hemorrhage (ICH)., Methods: A total of 128 consecutive patients, admitted to emergency service due to acute ICH, and 128 healthy individuals were included in this prospective study. The patients were followed up until 6months or death. An unfavorable outcome was defined as modified Rankin Scale score>2., Results: Serum SCUBE1 concentration was markedly higher in patients than in controls and was associated with hematoma volume, National Institutes of Health Stroke Scale (NIHSS) score and blood platelet count. After adjustment for hematoma volume and NIHSS score, it was still related to early neurological deterioration, hematoma growth, 1-week mortality, 6-month mortality, 6-month unfavorable outcome and 6-month overall survival. Additionally, serum SCUBE1 significantly improved areas under receiver operating characteristic curve of hematoma volume and NIHSS score to predict 6-month unfavorable outcome., Conclusions: Increased serum SCUBE1 concentrations have close relation to increasing severity and poor prognosis of ICH., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To explore the relationship between the hepatobiliary pathological changes under B-ultrasound examinations and Clonorchis sinensis infection, so as to provide the evidence for further prevention and control., Methods: The stool test and ELISA were applied to test the pathogeny and antibody to C. sinensis of the suspicious patients who had the hepatobiliary pathological changes under B-ultrasound examinations in People's Hospital of Wuxuan County from Jan. 2010 to Dec. 2013., Results: Totally 113 suspicious patients of C. sinensis infection were investigated, and the positive rates of egg and serum antibody were 64.60% (73 cases) and 66.37% (75 cases) respectively. The positive rates of the male and those aged ≥ 50 years were significantly higher than those of the female and the cases younger than 50 years respectively (χ² = 3.554, 6.267, both P < 0.05). In the C. sinensis infected patients, the degree of pathological changes of hepatobiliary was positively correlated with the infectiosity of C. sinensis (χ² = 64.952, P < 0.01)., Conclusion: The hepatobiliary pathological changes under B-ultrasound examinations may be resulted from the infection of C. sinensis, and the patients with the changes should be further investigated for the pathogen and antibody to C. sinensis.

The title compound, [Co(C(12)H(8)N(2))(H(2)O)(4)](2)[Co(H(2)O)(6)](C(11)H(7)O(8))(2)·4H(2)O, was obtanied by the reaction of cobalt acetate with 3,5-bis-(carb-oxy-meth-oxy)benzoic acid and 1,10-phenanthroline. The asymmetric unit contains one tetra-aqua-(1,10-phenanthroline)cobalt(II) cation, one half of a hexa-aqua-cobalt(II) cation that is completed by inversion symmetry, one 3,5-bis-(carboxyl-atometh-oxy)benzoate trianion and two lattice water mol-ecules. The two Co(II) atoms each show a slightly distorted octa-hedral coordination (CoO(6) and CoO(4)N(2)). The cations, anions and lattice water mol-ecules are linked by an intricate network of O-H⋯O hydrogen bonds into a three-dimensional structure.