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Zhao-Ting Gong,1 Yu-Yan Xiong,1,2 Yu Ning,1 Rui-Jie Tang,1 Jun-Yan Xu,3 Wen-Yang Jiang,1 Xiao-Song Li,1 Li-Li Zhang,1 Cheng Chen,1 Qi Pan,1 Meng-Jin Hu,1 Jing Xu,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Yue-Jin Yang, Email yangyjfw@126.comBackground: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI).Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism.Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway.Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation. Keywords: mesenchymal stem cell, exosomes, nicorandil, macrophage polarization, myocardial infarction

Qi Pan,1 Jing Xu,1 Cen-Jin Wen,2 Yu-Yan Xiong,1 Zhao-Ting Gong,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yue-Jin YangState Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaEmail yangyjfw@126.comAbstract: Despite several recent advances, current therapy and prevention strategies for myocardial infarction are far from satisfactory, owing to limitations in their applicability and treatment effects. Nanoparticles (NPs) enable the targeted and stable delivery of therapeutic compounds, enhance tissue engineering processes, and regulate the behaviour of transplants such as stem cells. Thus, NPs may be more effective than other mechanisms, and may minimize potential adverse effects. This review provides evidence for the view that function-oriented systems are more practical than traditional material-based systems; it also summarizes the latest advances in NP-based strategies for the treatment and prevention of myocardial infarction.Keywords: nanoparticles, myocardial infarction, treatment, prevention

Purpose: This study describes a nose prosthetic rehabilitation using computer-aided design and manufacturing (CAD-CAM) technology after facial disfigurement because of a total rhinectomy.Methods: A patient with a total rhinectomy was scheduled for a nasal prosthesis. Based on the 3-D model of the patient's face reconstructed with the CT data, a four-piece mould for the nasal prosthesis was prototyped using a CAD-CAM procedure. Conventional silicone was processed with this physical mould to fabricate the definitive nasal prosthesis.Results: A silicone nasal prosthesis was manufactured. The size, shape, and cosmetic look of the prosthesis were satisfactory and matched the nasal defect area well.Conclusions: The protocol presented herein illustrates favorable clinical treatment outcomes in the prosthetic rehabilitation after a total rhinectomy by means of CAD-CAM technology. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat kinase 2 (LRRK2, PARK8) gene has attracted considerable attention since the variants in this gene are recognized as the most common cause of Parkinson's disease (PD) so far. A number of association studies concerning variants of LRRK2 gene and PD susceptibility have been conducted in various populations. However, some results were inconclusive. To derive a more precise estimation of the relationship between LRRK2 and genetic risk of PD, we performed a comprehensive meta-analysis which included 27,363 cases and 29,741 controls from 61 published case-control studies. Totally, the effect of five LRRK2 variants all within the coding regions, i.e. G2019S, G2385R, R1628P, P755L and A419V, were evaluated in the meta-analysis using fixed effect model or random effects model if heterogeneity existed. There were genetic associations between four variants (G2019S, G2385R, R1628P and A419V) and increased PD risk, while there was no evidence of statistically significant association between P755L and PD. Publication bias and heterogeneity were absent in most analyses. Within its limitations, this meta-analysis demonstrated that the G2019S, G2385R, R1628P and A419V variations are risk factors associated with increased PD susceptibility. However, these associations vary in different ethnicities. [ABSTRACT FROM AUTHOR]

Glioblastoma stem cells (GSCs) have been implicated in the self-renewal and treatment resistance of glioblastoma (GBM). Our previous study found that 4,5-dimethoxycanthin-6-one has the potential to inhibit GBM cell proliferation. This current study aims to elucidate the molecular mechanism underlying the effects of 4,5-dimethoxycanthin-6-one in GBM development. The effect of 4,5-dimethoxycanthin-6-one on GSC formation and differentiation was explored in human GBM cell lines U251 and U87. Subsequently, 4,5-dimethoxycanthin-6-one binding to tetraspanin 1 (TSPAN1) / transmembrane 4 L six family member 1 (TM4SF1) was analyzed by molecular simulation docking. Co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were used to assess the interactions between TSPAN1 and TM4SF1 in GSCs. Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assay. To evaluate cell migration, invasion and apoptosis, we employed wound healing assay, transwell and flow cytometry, respectively. Furthermore, subcutaneous xenograft tumor models in nude mice were constructed to evaluate the impact of 4,5-dimethoxycanthin-6-one on GSCs in vivo by examining tumor growth and histological characteristics. 4,5-Dimethoxycanthin-6-one inhibited GSC formation and promoted stem cell differentiation in a concentration-dependent manner. Molecular docking models of 4,5-dimethoxycanthin-6-one with TM4SF1 and TSPAN1 were constructed. Then, the interaction between TSPAN1 and TM4SF1 in GSC was clarified. Moreover, 4,5-dimethoxycanthin-6-one significantly inhibited the expressions of TM4SF1 and TSPAN1 in vitro and in vivo. Overexpression of TSPAN1 partially reversed the inhibitory effects of 4,5-dimethoxycanthin-6-one on GSC formation, proliferation, migration and invasion. 4,5-Dimethoxycanthin-6-one inhibited GBM progression by inhibiting TSPAN1/TM4SF1 axis. 4,5-Dimethoxycanthin-6-one might be a novel and effective drug for the treatment of GBM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Glucose is a major energy substrate for cellular life activities, and its metabolic pathways include glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and the polyol pathway. Here, we review the glucose uptake pathways, metabolic characteristics, glucose transport, glucose metabolism-related enzymes, and biological importance in mammalian oocyte maturation, early embryo development, and embryonic stem cell proliferation and differentiation. Moreover, the interrelationships among glucose metabolism, female reproduction-related diseases and assisted reproductive technologies are focused. In addition, we review a number of analytical methodologies with the intention to integrate a multi-tiered strategy that encompasses cutting-edge metabolomics, artificial intelligence, epigenetics, and morphological assessments, setting the stage for a pivotal approach to cultivating high-caliber embryos in the future., Competing Interests: 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., (© 2024 The Authors.)

Background: Patients with tracheotomy are often monitored in the anesthesia recovery room after reoperation. During this period, oxygen therapy is necessary, and the existing tracheostomy oxygen supply device has many defects., Objective: To evaluate the efficacy of a self-made tracheostomy oxygen delivery device on oxygen therapy during postoperative anesthesia recovery., Methods: Patients were randomly divided into two groups, E and C, with 30 patients in each group, and admitted to the post-anesthesia care unit (PACU). Patients in group E received oxygen through a self-made tracheostomy oxygen delivery device, while patients in group C were supplied oxygen through a unilateral nasal cannula. Respiration (R), pulse oximetry (SpO2), and the number of patients on ventilators were recorded at the time of admission (T0) and one hour after admission (T1). Rapid dry blood gas analyses were performed on 0.6 ml samples of arterial blood collected at T0 and T1., Results: Compared to group C, patients in group E had significantly higher arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), total carbon dioxide (T-CO2), and actual bicarbonate (AB), while arterial partial pressure of carbon dioxide (PaCO2) was significantly reduced (P< 0.01 or < 0.05). Compared to T0, PaO2 decreased in both groups at T1, PaCO2 decreased in group E, while SaO2, T-CO2, and AB decreased in group C (P< 0.01 or < 0.05)., Conclusion: We found that using the self-made tracheostomy oxygen delivery device in postoperative anesthesia recovery had advantages such as a secure connection to the tracheostoma, adjustable oxygen concentration, air filtration, and the ability to switch oxygen supply between the ventilator and humidifier.

Objective: To analyze the risk factors of Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its impact on survival., Methods: The clinical data of 347 patients who underwent their first allo-HSCT in our hospital from January 2014 to June 2021 were retrospectively analyzed. Patients were divided into EBV ( n =114) and Non-EBV ( n =233) groups according to whether they were infected with EBV. The incidence of EBV infection after allo-HSCT was calculated, and the risk factors of EBV infection were analyzed., Results: A total of 114(32.8%) patients presented EBV infection (all peripheral blood EBV-DNA were positive). EBV infection occurred in 88 patients within 100 days after transplantation, which accounted for 77.2% of all patients with EBV infection. 5 cases (1.44%) were confirmed as post-transplant lymphoproliferative disorder (PTLD). The median onset time of patients was 57(7-486) days after transplantation. Multivariate analysis showed that the use of ATG/ATG-F, occurrence of CMV viremia, and grade III-IV aGVHD were risk factors for EBV infection. Furthermore, compared to BUCY, the use of intensified preconditioning regimens containing FA/CA was significantly increased the risk of EBV infection., Conclusion: EBV infection is a common complication after allo-HSCT. Intensified preconditioning regimens, use of ATG/ATG-F, CMV viremia and grade III to IV aGVHD increase the risk of EBV infection after allo-HSCT.

Purpose: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear., Methods: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF., Results: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels., Conclusion: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Various methods have been used for in vivo and in vitro skin regeneration, including stem cell therapy, tissue engineering, 3D printing, and platelet-rich plasma (PRP) injection therapy. However, these approaches are rooted in the existing knowledge of skin structures, which overlook the normal physiological processes of skin development and fall short of replicating the skin's regenerative processes outside the body. This comprehensive review primarily focuses on skin organoids derived from human pluripotent stem cells, which have the capacity to regenerate human skin tissue by restoring the embryonic skin structure, thus offering a novel avenue for producing in vitro skin substitutes. Furthermore, they contribute to the repair of damaged skin lesions in patients with systemic sclerosis or severe burns. Particular emphasis will be placed on the origins, generations, and applications of skin organoids, especially in dermatology, and the challenges that must be addressed before clinical implementation., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interest., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) ( n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS 2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS 2 model has excellent potential to be a dependable application for individualized clinical decision making., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT)., Methods: The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group ( n =62) and High-CONUT group ( n =17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve., Results: The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group ( P <0.01), but CR rate did not( P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective., Conclusion: The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival., Methods: The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed., Results: The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old ( P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine ( P =0.002), albumin≤30 g/L on d30 after transplantation ( P =0.007), CMV-DNA positive ( P =0.028), fungal infection before transplantation ( P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD ( P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation ( P =0.008) and albumin≤30 g/L on d30 after transplantation ( P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC ( P =0.041)., Conclusion: For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.

Background: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy., Patients and Methods: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled., Conclusions: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients., Clinical Trial Registration: NCT05457049 (CTONG 2201)., Competing Interests: Disclosure W.-Z. Zhong declares honoraria from AstraZeneca, BMS, MSD, Roche, and Innovent outside the submitted work. Y.-L. Wu declares advisory services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; speaker fees from AstraZeneca, Beigene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi; and grants from AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, and Roche outside the submitted work. The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH., Methods: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed., Results: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH., Conclusion: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future.

Objective: This study investigates the effect of pre-operative cluster care nursing on patient compliance during preoperative isolation of pediatric patients from their family members before cochlear implant surgery., Study Methods: A total of 350 pediatric patients who underwent cochlear implant surgery at Sichuan Rehabilitation Hospital from January 2021 to December 2022 were enrolled. The children were divided into two groups:Experimental group (group E) consisted of 182 children who received pre-operative cluster care nursing, and control group (group C) consisted of 168 children who received pre-operative routine nursing. The compliance scores of the two groups of patients when separated from their families before entering the operating room and the number of patients requiring intravenous injection of midazolam were recorded., Results: The compliance scores of group E were significantly lower than those of group C (t = 4.141, P < 0.001). The percentage of patients requiring intravenous injection of midazolam was recorded: it was 21.98% (40/182) in group E and 42.26% (71/168) in group C. Notably, the injection rate of midazolam in group E was significantly lower than that in group C (χ 2  = 16.597, P < 0.001)., Conclusion: Pre-operative cluster care nursing can improve patient compliance and reduce the use of sedative drugs during preoperative isolation of pediatric patients from their family members for cochlear implant surgery., 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 © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Ferroptosis has excellent potential in glioblastoma (GBM) therapy. In this study, we attempted to explore the effect of miR 491-5p on ferroptosis in GBM., Methods: In this study, publicly available ferroptosis-related genome maps were used to screen genes upregulated in GBM and their target genes. The Spearman correlation coefficient was applied to analyze the correlation between the tumor protein p53 gene (TP53) and miR-491-5p. The expressions of miR-491-5p and TP53 were determined. The protein abundances of the TP53-encoded factors p53 and p21 were measured. Cell proliferation, migration and invasion were assessed. We pretreated U251MG cells and GBM mice with a ferroptosis inducer (erastin). The mitochondrial state was observed. The contents of reactive oxygen species (ROS), total Fe and Fe 2+ were calculated., Results: The level of TP53 was significantly increased in GBM and negatively correlated with miR-491-5p. miR-491-5p overexpression promoted U251MG cell proliferation, migration and invasion and interfered with the p53/p21 pathway. TP53 supplement reversed the effects of miR-491-5p. U251MG cells and GBM mice exhibited significant accumulations of ROS and iron. Erastin promoted the expression of TP53. Inhibition of TP53 reversed erastin-induced physiological phenotypes. Moreover, miR-491-5p overexpression caused a decrease in the number of damaged mitochondria and the contents of ROS, total Fe and Fe 2+ . TP53 supplement disrupted miR-491-5p-repressed ferroptosis. Erastin could inhibit GBM growth, and miR-491-5p overexpression impeded the therapeutic effect of erastin., Conclusions: Our findings reveal the functional diversity of miR-491-5p in GBM and suggest that miR-491-5p/TP53 signaling hinders the sensitivity of GBM to ferroptosis through the p53/p21 pathway., 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 © 2023 Elsevier Inc. All rights reserved.)

Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear., Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors., Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice., Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Peng, Li, Ding, Wang, Wang, Xiong, Xiong, Li and Song.)

Background: Platelet distribution width (PDW) is a predictor for all-cause mortality in patients with cardiovascular diseases (CVD). This study aimed to evaluate the prognostic implication of PDW in predicting cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis (PD)., Methods: In total, 762 PD patients from a single center were recruited retrospectively from 2005 to 2017 and followed up until 2021. The primary and secondary outcomes were cardiovascular and all-cause mortality, respectively. Survival analysis was conducted using Kaplan-Meier estimates and Cox regression analysis., Results: During a median of 52.2 months of follow-up, 135 (17.7%) cases of CVD and 253 (33.2%) cases of all-cause mortality were reported. After multivariate adjustment, high levels of PDW were associated with an increased risk of death from CVD (HR: 1.583; 95% CI: 1.109-2.258; P = 0.011) and all-cause mortality (HR: 1.313; 95% CI: 1.006-1.758; P = 0.045). Subgroup analysis indicated a stronger association between PDW and all-cause mortality among female participants (P-value for interaction = 0.033). Higher levels of PDW predicted an increased risk of all-cause mortality in female patients (HR: 1.986; 95% CI,1.261-3.127)., Conclusion: High levels of PDW are independently associated with cardiovascular and all-cause mortality in the PD population, and differences by sex exist in the association of PDW with all-cause mortality.

Objective: To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival., Methods: A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed., Results: For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×10 4 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×10 9 /L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×10 4 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005)., Conclusion: The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×10 4 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

Background: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia., Methods: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities., Results: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF ( n  = 15,430), hypertension ( n  = 138,220), diabetes ( n  = 43,737), or hyperlipidemia ( n  = 16,855) were assessed separately. A 10 µg/m 3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively., Conclusion: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

Fish suffer from starvation due to environmental risks such as extreme weather in the wild and due to insufficient feedings in farms. Nutrient problems from short-term or long-term starvation conditions can result in stress-related health problems for fish. Yellowfin seabream (Acanthopagrus latus) is an important marine economic fish in China. Understanding the molecular responses to starvation stress is vital for propagation and culturing yellowfin seabream. In this study, the transcriptome and genome-wide DNA methylation levels in the livers of yellowfin seabream under 14-days starvation stress were analyzed. One hundred sixty differentially expressed genes (DEGs) by RNA-Seq analysis and 737 differentially methylated-related genes by whole genome bisulfite sequencing analysis were identified. GO and KEGG pathway enrichment analysis found that energy metabolism-related pathways such as glucose metabolism and lipid metabolism were in response to starvation. Using bisulfite sequencing PCR, we confirmed the presence of CpG methylation differences within the regulatory region of a DEG ppargc1a in response to 14-days starvation stress. This study revealed the molecular responses of livers in response to starvation stress at the transcriptomic and whole genome DNA methylation levels in yellowfin seabream., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continuation remain largely unknown. Here, we reveal a key brainstem region of GABAergic neurons in the control of both physiological REM sleep and cataplexy. Using fiber photometry and optic tetrode recording, we characterized the dorsal part of the deep mesencephalic nucleus (dDpMe) GABAergic neurons as REM relatively inactive and two different firing patterns under spontaneous sleep-wake cycles. Next, we investigated the roles of dDpMe GABAergic neuronal circuits in brain state regulation using optogenetics, RNA interference technology, and celltype-specific lesion. Physiologically, dDpMe GABAergic neurons causally suppressed REM sleep and promoted NREM sleep through the sublaterodorsal nucleus and lateral hypothalamus. In-depth studies of neural circuits revealed that sublaterodorsal nucleus glutamatergic neurons were essential for REM sleep termination by dDpMe GABAergic neurons. In addition, dDpMe GABAergic neurons efficiently suppressed cataplexy in a rodent model. Our results demonstrated that dDpMe GABAergic neurons controlled REM sleep termination along with REM/NREM transitions and represented a novel potential target to treat narcolepsy., (© 2022. The Author(s).)

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia., Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated., Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83)., Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-723/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Autologous stem cell transplantation (ASCT) is an important treatment for peripheral T-cell lymphoma (PTCL) patients both during front and salvage therapy. In order to explore the appropriate conditioning regiments and seek ways to improve the efficacy and safety of PTCL, we retrospectively compared the outcomes of 52 PTCL patients treated with CEAC (lomustine, etoposide, cytarabine and cyclophosphamide; n = 28), BEAM (carmustine, etoposide, cytarabine and melphalan; n = 14) and IEAC (idarubicin, etoposide, cytarabine and cyclophosphamide; n = 10) regimens followed by ASCT at our center between 2012 and 2021. Although the time of neutrophil engraftment in CEAC group was earlier than that in IEAC group (P = 0.042) and platelet infusion in BEAM group was significantly more than CEAC group (P = 0.042), there were no significant difference in platelet engraftment, hematopoietic engraftment and red blood cells infusion among the 3 groups. The transplantation related mortality rate (TRM) and the early overall response rate (ORR) was 3.8% and 85.7% respectively. The 5-year OS and PFS was 62.8% (95% CI: 54.8-70.8%) and 61.0% (95% CI: 53.1-68.9%) respectively. There was no significant difference in TRM, ORR and survival among the 3 groups. Univariate and multivariate analysis showed that high PIT score (the T cell lymphoma prognostic index, > 1) and failure to reach complete response (non-CR) at 3 months after ASCT were common risk factors for OS (P = 0.036 and 0.007) and PFS (P = 0.021 and 0.012). In conclusion, CEAC and IEAC regimen can be used as alternative conditioning regiments for ASCT in PTCL patients, and their efficacy and safety are comparable to BEAM regiment. Patients with high PIT score and non-CR early after ASCT had worse outcomes., (© 2022. The Author(s).)

Aims: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms., Methods and Results: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and CD127+ cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation., Conclusion: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

A nitro-decorated microporous covalent organic framework, TpPa-NO 2 , has been synthesized in a gram scale with a one-pot reaction. It can effectively selectively separate C 2 H 4 from a C 2 H 2 /C 2 H 4 /CO 2 mixture and capture CO 2 from CO 2 /N 2 based on ideal adsorption solution theory calculations and transient breakthrough experiments. Theoretical calculations illustrated that the hydrogen atoms of imine bonds, carbonyl oxygen, and nitro group show high affinity toward C 2 H 2 and CO 2 , playing vital roles in efficient separation.

Background: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study., Methods: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups., Results: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P <0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment., Conclusions: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Background and Purpose: Dysphagia is common and is associated with aspiration pneumonia. However, little is known about the prevalence of and factors influencing dysphagia screening (DS) and pneumonia after subarachnoid hemorrhage (SAH)., Methods: We used data on SAH patients admitted to 1476 hospitals from the China Stroke Center Alliance (CSCA) from August 2015 to July 2019 to analyze the rates of DS and pneumonia. We then conducted univariate and multivariable analyses to examine the relationship between DS and pneumonia., Results: Among 4877 SAH patients who were eligible for DS and had complete data on pneumonia status, 3527 (72.3%) underwent DS, and 1006 (20.6%) developed pneumonia. Compared with patients without pneumonia, patients with pneumonia were older (mean: 63.4 vs. 57.8 years of age), had lower Glasgow Coma Scale (GCS) scores at admission (mean: 13.5 vs. 14.3), were more likely to have dysphagia (15.2% vs. 3.3%), and were more likely to have undergone aneurysm isolation (19.1% vs. 10.0%). In multivariable analyses, factors independently associated with a higher risk of pneumonia were dysphagia [odds ratio (OR), 3.77; 95% confidence interval (CI), 2.85-4.98], age (OR, 1.50 per 10-year increase; 95% CI, 1.40-1.60), male sex (OR, 1.23; 95% CI, 1.02-1.49), arrival at the hospital by emergency medical services (OR, 1.36; 95% CI, 1.16-1.58), nimodipine treatment (OR, 1.42; 95% CI, 1.11-1.81), endovascular embolization of aneurysms (OR, 1.23; 95% CI, 1.03-1.47), cerebral ventricular shunt placement (OR, 2.24; 95% CI, 1.41-3.54), and treatment at a higher grade hospital (OR, 1.44; 95% CI, 1.21-1.71)., Conclusion: More than a quarter of patients with SAH did not have documented DS, while one-fifth developed pneumonia. DS performance was associated with a lower risk of pneumonia. Randomized controlled trials may be needed to determine the effectiveness of DS., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Acute respiratory distress syndrome (ARDS) is a major cause of death in patients with severe acute pancreatitis (SAP). Although a series of prediction models have been developed for early identification of such patients, the majority are complicated or lack validation. A simpler and more credible model is required for clinical practice., Aim: To develop and validate a predictive model for SAP related ARDS., Methods: Patients diagnosed with AP from four hospitals located at different regions of China were retrospectively grouped into derivation and validation cohorts. Statistically significant variables were identified using the least absolute shrinkage and selection operator regression method. Predictive models with nomograms were further built using multiple logistic regression analysis with these picked predictors. The discriminatory power of new models was compared with some common models. The performance of calibration ability and clinical utility of the predictive models were evaluated., Results: Out of 597 patients with AP, 139 were diagnosed with SAP (80 in derivation cohort and 59 in validation cohort) and 99 with ARDS (62 in derivation cohort and 37 in validation cohort). Four identical variables were identified as independent risk factors for both SAP and ARDS: heart rate [odds ratio (OR) = 1.05; 95%CI: 1.04-1.07; P < 0.001; OR = 1.05, 95%CI: 1.03-1.07, P < 0.001], respiratory rate (OR = 1.08, 95%CI: 1.0-1.17, P = 0.047; OR = 1.10, 95%CI: 1.02-1.19, P = 0.014), serum calcium concentration (OR = 0.26, 95%CI: 0.09-0.73, P = 0.011; OR = 0.17, 95%CI: 0.06-0.48, P = 0.001) and blood urea nitrogen (OR = 1.15, 95%CI: 1.09-1.23, P < 0.001; OR = 1.12, 95%CI: 1.05-1.19, P < 0.001). The area under receiver operating characteristic curve was 0.879 (95%CI: 0.830-0.928) and 0.898 (95%CI: 0.848-0.949) for SAP prediction in derivation and validation cohorts, respectively. This value was 0.892 (95%CI: 0.843-0.941) and 0.833 (95%CI: 0.754-0.912) for ARDS prediction, respectively. The discriminatory power of our models was improved compared with that of other widely used models and the calibration ability and clinical utility of the prediction models performed adequately., Conclusion: The present study constructed and validated a simple and accurate predictive model for SAP-related ARDS in patients with AP., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Red tilapia ( Oreochromis spp . ) is one of the most popular fish in China due to its bright red appearance, fast growth rate, and strong adaptability. Understanding the sex determination mechanisms is of vital importance for the selection of all-male lines to increase aquacultural production of red tilapia. In this research, the genetic architecture for sex from four mapping populations ( n =1 090) of red tilapia was analyzed by quantitative trait loci (QTL)-seq, linkage-based QTL mapping, and linkage disequilibrium (LD)-based genome-wide association studies. Two genome-wide significant QTL intervals associated with sex were identified on ChrLG1 (22.4-23.9 Mb) and ChrLG23 (32.0-35.9 Mb), respectively. The QTL on ChrLG1 was detected in family 1 (FAM1), FAM2, and FAM4, and the other QTL on ChrLG23 was detected in FAM3 and FAM4. Four microsatellite markers located within the QTL were successfully developed for marker-assisted selection. Interestingly, three ( lpp , sox14 , and amh ) of the 12 candidate genes located near or on the two QTL intervals were abundantly expressed in males, while the remaining genes were more highly expressed in females. Seven genes ( scly , ube3a , lpp , gpr17 , oca2 , cog4 , and atp10a ) were significantly differentially expressed between the male and female groups. Furthermore, LD block analysis suggested that a cluster of genes on ChrLG23 may participate in regulating sex development in red tilapia. Our study provides important information on the genetic architecture of sex in red tilapia and should facilitate further exploration of sex determination mechanisms in this species.

Mollugin has been proven to have anti-tumor activity. However, its potential anti-tumor mechanism remains to be fully elaborated. Herein, we investigated the growth inhibition of HepG2 cells, as well as the anti-tumor effect of mollugin and its molecular mechanism on H22-tumor bearing mice. In vitro, mollugin was shown to have a strong inhibitory effect on HepG2 cells in a concentration-dependent manner. Mollugin induced S-phase arrest of HepG2 cells, and increased intracellular reactive oxygen species (ROS) levels. Comet assay demonstrated that mollugin induced DNA damage in HepG2 cells, as well as an increase in the expression of p-H2AX. In addition, mollugin induced changes in cyclin A2 and CDK2. However, the addition of antioxidant glutathione (GSH) was able to reverse the effect of mollugin. In vivo, mollugin significantly inhibited tumor growth and reduced the tendency of tumor volume growth in mice. The tumor cell density was found to be decreased in the administration group, and the content of ROS in the tumor tissue significantly increased. The expression of p-H2AX, cyclin A2 and CDK2 were consistent with in vitro results. Mollugin demonstrated anti-hepatocellular carcinoma activity in vitro and in vivo, and its anti-hepatocellular carcinoma activity was found to be related to DNA damage and cell cycle arrest induced by excessive ROS production in cells., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The indoor air quality is of prime importance for human daily life and health, for which the adsorbents like zeolites and silica-gels are widely used for air dehumidification and harmful gases capture. Herein, we develop a pore-nanospace post-engineering strategy to optimize the hydrophilicity, water-uptake capacity and air-purifying ability of metal-organic frameworks (MOFs) with long-term stability, offering an ideal candidate with autonomous multi-functionality of moisture control and pollutants sequestration. Through variant tuning of organic-linkers carrying hydrophobic and hydrophilic groups in the pore-nanospaces of prototypical UiO-67, a moderately hydrophilic MOF (UiO-67-4Me-NH 2 -38 %) with high thermal, hydrolytic and acid-base stability is screened out, featuring S-shaped water sorption isotherms exactly located in the recommended comfortable and healthy ranges of relative humidity for indoor ventilation (45 %-65 % RH) and adverse health effects minimization (40-60 % RH). Its exceptional attributes of water-uptake working capacity/efficiency, contaminants removal, recyclability and regeneration promise a great potential in confined indoor environment application., (© 2021 Wiley-VCH GmbH.)

Background: Glioblastoma is one of the most common fatal intracranial malignancies. Lysine-specific demethylase 1 (LSD1) reportedly has therapeutic effects on a variety of tumors. This study explored the therapeutic effect of LSD1 inhibition on glioblastoma cell lines and the possible underlying mechanisms., Methods: The MTT assay was utilized to screen for the sensitivity of U87, U251 and T98G cells to 4, 5-dimethoxycarrageenin-6-one. qRT-PCR and western blot were used to measure the proliferation, apoptosis, and pyroptosis signaling pathway expression to observe the effect of LSD1 inhibition on U251 and T98G cells. Flow cytometry, immunofluorescence, immunohistochemistry, wound scratch, clone formation, and TUNEL assay were used to analyze the effects of 4, 5-dimethoxycanthin-6-one on glioblastoma cells. The effect of 4, 5-dimethoxycanthin-6-one was examined in vivo in BALB/c nude mice injected with U251 cells. HE staining was used to detect the histopathology of the tumor., Results: LSD1 specifically catalyzes the demethylation of monomethylated and demethylated histone H3 lysine at position 4 (h3k4me1, h3k4me2, h3k4me3) and lysine at position 9 (h3k9me1). This regulated the transcriptional activity of proliferation, apoptosis, and pyroptosis signaling pathway genes. In vitro, the proliferation of glioblastoma cells was decreased in the 4, 5-dimethoxycanthin-6-one group. The expression of Caspase1 in glioblastoma cells treated with 4, 5-dimethoxycanthin-6-one increased, and the number of apoptotic cells increased. The tumor volume of mice injected with 4, 5-dimethoxycanthin-6-one decreased significantly., Conclusion: 4, 5-Dimethoxycanthin-6-one could act as a novel inhibitor of LSD1 to regulate glioblastoma, which could inhibit the proliferation of U251 and T98G cells and induce their apoptosis and pyroptosis. It is a potential drug for the treatment of glioblastoma., (© 2022. The Author(s).)

Titanium metal-organic frameworks (Ti-MOFs), as an appealing type of artificial photocatalyst, have shown great potential in the field of solar energy conversion due to their well-studied photoredox activity (similar to TiO 2 ) and good optical responsiveness of linkers, which serve as the antenna to absorb visible-light. Although much effort has been dedicated to developing Ti-MOFs with high photocatalytic activity, their solar energy conversion performances are still poor. Herein, we have implemented a covalent-integration strategy to construct a series of multivariate Ti-MOF/COF hybrid materials PdTCPP⊂PCN-415(NH 2 )/TpPa (composites 1, 2, and 3), featuring excellent visible-light utilization, a suitable band gap, and high surface area for photocatalytic H 2 production. Notably, the resulting composites demonstrated remarkably enhanced visible-light-driven photocatalytic H 2 evolution performance, especially for the composite 2 with a maximum H 2 evolution rate of 13.98 mmol g -1  h -1 (turnover frequency (TOF)=227 h -1 ), which is much higher than that of PdTCPP⊂PCN-415(NH 2 ) (0.21 mmol g -1  h -1 ) and TpPa (6.51 mmol g -1  h -1 ). Our work thereby suggests a new approach to highly efficient photocatalysts for H 2 evolution and beyond., (© 2021 Wiley-VCH GmbH.)

Objective: To evaluate the efficacy and safety of combination therapy of eltrombopag, recombinant human thrombopoietin (rhTPO) , and standard immunosuppressive therapy (IST) for severe aplastic anemia (SAA) . Methods: A total of 16 cases with SAA treated with IST combined with eltrombopag and rhTPO were retrospectively analyzed. Results: At 3 months, the total response rate was 81.3%, and the complete hematological response rate was 37.5%. At 6 months, the total response rate was 87.5%, and the complete hematological response rate was 50.0%. The median time of platelet transfusion independence was 35 (16-78) days, the median time of red blood cell transfusion independence was 47.5 (15-105) days, the median platelet transfusion was 5.5 (3-20) U, and the median red blood cell transfusion was 6.5 (2-16) U. Conclusion: The combination of eltrombopag and rhTPO can improve the hematological response rate of IST for SAA and the quality of hematological remission with minimal toxic effects.

Importance: Adherence to oral anticoagulants (OACs) per guideline recommendations is crucial in reducing ischemic stroke and systemic thromboembolism in high-risk patients with ischemic stroke and atrial fibrillation. However, data on OAC use are underreported in China., Objective: To assess adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescription of OACs, the temporal improvement in adherence, and the risk factors associated with OAC prescriptions., Design, Setting, and Participants: This quality improvement study was conducted at 1430 participating hospitals in the Chinese Stroke Center Alliance (CSCA) among patients with ischemic stroke and atrial fibrillation enrolled in the CSCA between August 1, 2015, and July 31, 2019., Exposure: Calendar year., Main Outcomes and Measures: Adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescribing of OACs (warfarin and non-vitamin K OACs, including dabigatran, rivaroxaban, apixaban, and edoxaban) at discharge., Results: Among 35 767 patients (18 785 women [52.5%]; mean [SD] age, 75.5 [9.2] years) with previous atrial fibrillation at admission, the median CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score was 4.0 (interquartile range, 3.0-5.0); 6303 (17.6%) were taking OACs prior to hospitalization for stroke, a rate that increased from 14.3% (20 of 140) in the third quarter of 2015 to 21.1% (118 of 560) in the third quarter of 2019 (P < .001 for trend). Of 49 531 eligible patients (26 028 men [52.5%]; mean [SD] age, 73.4 [10.4] years), 20 390 (41.2%) had an OAC prescription at discharge, an increase from 23.2% (36 of 155) in the third quarter of 2015 to 47.1% (403 of 856) in the third quarter of 2019 (P < .001 for trend). Warfarin was the most commonly prescribed OAC (11 956 [24.2%]) and had the largest temporal increase (from 5.8% [9 of 155] to 20.7% [177 of 856]). Older age (adjusted odds ratio [aOR] per 5 year increase, 0.89;95% CI, 0.89-0.90), lower levels of education (aOR for below elementary school, 0.84; 95% CI, 0.74-0.95 ), lower income (aOR for ≤¥1000 [$154], 0.66; 95% CI, 0.59-0.73), having new rural cooperative medical scheme insurance (aOR, 0.92; 95% CI, 0.87-0.96), prior antiplatelet use (aOR, 0.70; 95% CI, 0.66-0.74), having several cardiovascular comorbid conditions (including stroke or transient ischemic attack [aOR, 0.78; 95% CI, 0.75-0.82], hypertension [aOR, 0.84; 95% CI, 0.80-0.89], diabetes [aOR, 0.91; 95% CI, 0.83-0.99], dyslipidemia [aOR, 0.87; 95% CI, 0.80-0.94], carotid stenosis [aOR, 0.83; 95% CI, 0.69-0.98], and peripheral vascular disease [aOR, 0.80; 95% CI, 0.71-0.90]), and admission to secondary hospitals (aOR, 0.71; 95% CI, 0.68-0.74) or hospitals located in the central region of China (aOR, 0.80; 95% CI, 0.75-0.84) were associated with not being prescribed an OAC at discharge., Conclusions and Relevance: This quality improvement study suggests that, despite significant improvement over time, OAC prescriptions remained low. Efforts to increase OAC prescriptions, especially non-vitamin K OACs, are needed for vulnerable subgroups by age, socioeconomic status, and presence of comorbid conditions.

Acute myocardial infarction (AMI) is an event of ischemic myocardial necrosis caused by acute coronary artery occlusion, which ultimately leads to a large loss of cardiomyocytes. The prerequisite of salvaging ischemic myocardium and improving cardiac function of patients is to provide adequate blood perfusion in the infarcted area. Apart from reperfusion therapy, it is also urgent and imperative to promote angiogenesis. Recently, growing evidence based on promising preclinical data indicates that mesenchymal stem cells (MSCs) can provide therapeutic effects on AMI by promoting angiogenesis. Extracellular vesicles (EVs), membrane-encapsulated vesicles with complex cargoes, including proteins, nucleic acids, and lipids, can be derived from MSCs and represent part of their functions, so EVs also possess the ability to promote angiogenesis. However, poor control of the survival and localization of MSCs hindered clinical transformation and made scientists start looking for new approaches based on MSCs. Identifying the role of MSCs and their derived EVs in promoting angiogenesis can provide a theoretical basis for improved MSC-based methods, and ultimately promote the clinical treatment of AMI. This review highlights potential proangiogenic mechanisms of transplanted MSCs and the derived EVs after AMI and summarizes the latest literature concerning the novel methods based on MSCs to maximize the angiogenesis capability.

Objective: Extranodal NK/T-cell lymphoma (ENKL) is aggressive and resistant to chemotherapy and radiotherapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for high-risk lymphomas owing to its associated graft-versus-lymphoma (GVL) effect. However, its application to ENKL is limited. We aim to summarize the characteristics of allo-HSCT for ENKL and, more importantly, evaluate whether allo-HSCT could offer any benefits for ENKL., Materials and Methods: A systematic review and data analysis were performed to evaluate the performance of allo-HSCT in the treatment of ENKL using studies obtained from PubMed, Medline, and Embase from January 2000 to December 2019 in the English language., Results: A total of 136 cases from 17 eligible publications were included in this study. It was found that after allo-HSCT, with an average follow-up time of 34 months (range: 1-121 months), 37.5% (52) of 136 patients had acute graft-versus-host disease (GVHD) and 31.6% (43) had chronic GVHD. Furthermore, 35.3% (48) of the patients were reported to have relapsed, but 2 of those relapsed only locally and achieved complete remission (CR) again with additional irradiation, chemotherapy, and donor lymphocyte infusions for one and rapid tapering and discontinuation of cyclosporine for the other, earning more than one year of extra survival. Finally, of the 136 patients, 51.5% (70) died because of primary disease progression (42.9%), infection (20.0%), GVHD (11.4%), organ failure (7.1%), hemorrhage (4.3%), and other causes (not specified/unknown) (14.3%)., Conclusion: Allo-HSCT may be a treatment option for advanced or relapsed/refractory ENKL, but its role still requires more rigorous future studies.

Background: It is unknown about the influence of prestroke antiplatelet use on early outcomes in patients with and without the indication. We aimed to evaluate the in-hospital prognosis of first-ever noncardiogenic ischemic stroke patients with and without indications of antiplatelet use for primary prevention., Methods: This was a retrospective, observational study based on a prospective hospital-based registry (Chinese Stroke Center Alliance). Using the data with 436,660 first-ever noncardiogenic acute ischemic strokes recorded from Aug 1, 2015, to July 31, 2019, from 1,453 hospitals in China, we examined the associations between the indication for prestroke antiplatelet use and in-hospital clinical outcomes., Results: Among 436,660 first-ever noncardiogenic ischemic stroke patients, 42,409 patients (9.7%) had a documented previous vascular indication and 394,251 (90.3%) did not. Compared to those without, patients with the indication were associated with increased prevalence of in-hospital morbid conditions, including stroke severity (OR 2.71; 95% CI: 2.62-2.81; P<0.0001), length of stay >14 days (OR 1.16; 95% CI: 1.13-1.19; P<0.0001), mortality (OR 2.20; 95% CI: 1.96-2.46, P<0.0001), and recurrence of ischemic stroke and transient ischemic attack (TIA) (OR 1.5; 95% CI: 1.43-1.59, P<0.0001). Among patients without indication, prestroke antiplatelet use was associated with lower mortality (OR 0.73, 95% CI: 0.56-0.96; P=0.0221); while among patients with indication, those receiving prestroke antiplatelet had lower odds ratios in stroke severity (P<0.0001) and disability (P=0.0003) than those who not., Conclusions: Patients with indications of prestroke antiplatelet use were more likely to have unfavorable outcomes than those without. Prestroke antiplatelet might be associated with lower mortality, less disability, and less stroke severity in certain population groups. Future studies to improve risk prediction rules are needed to guide effective primary prevention for ischemic stroke., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7902). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Acute myocardial infarction (AMI) is one of the leading causes of mortality around the world, and the inflammatory response plays a pivotal role in the progress of myocardial necrosis and ventricular remodeling, dysfunction and heart failure after AMI. Therapies aimed at modulating immune response after AMI on a molecular and cellular basis are urgently needed. Exosomes are a type of extracellular vesicles which contain a large amount of biologically active substances, like lipids, nucleic acids, proteins and so on. Emerging evidence suggests key roles of exosomes in immune regulation post AMI. A variety of immune cells participate in the immunomodulation after AMI, working together to clean up necrotic tissue and repair damaged myocardium. Stem cell therapy for myocardial infarction has long been a research hotspot during the last two decades and exosomes secreted by stem cells are important active substances and have similar therapeutic effects of immunomodulation, anti-apoptosis, anti-fibrotic and angiogenesis to those of stem cells themselves. Therefore, in this review, we focus on the characteristics and roles of exosomes produced by both of endogenous immune cells and exogenous stem cells in myocardial repair through immunomodulation after AMI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)