Search

Xinkai Luo,1,* Ying Wang,2,* Yufei Mao,3,* Xiaowei Xu,1,4 Weifeng Gu,1 Wen Li,1 Chaoming Mao,1 Tingting Zheng,1 Liyang Dong1 1Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Department of Ultrasound Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 4Department of Laboratory Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyang Dong; Tingting Zheng, Email liyangdong@ujs.edu.cn; tingtingzheng@ujs.edu.cnBackground: Nebulization of hypoxic human umbilical cord mesenchymal stem cell-derived extracellular vesicles (Hypo-EVs) can suppress airway inflammation and remodeling in a chronic asthmatic mouse; however, the exact mechanism remains unclear. Recently, airway epithelial barrier defects have been regarded as crucial therapeutic targets in asthma. The aim of this study was to investigate whether and how Hypo-EVs protect against the disruption of the airway epithelial barrier under asthmatic conditions.Methods: The therapeutic effects of Hypo-EVs on airway epithelial barrier defects were evaluated in ovalbumin (OVA)-induced asthmatic mice and in IL-4 and IL-13-induced HBE135-E6E7 cell models by detecting cell monolayer leakage and junctional protein expression. The protein levels in Hypo-EVs were determined by Western blotting, and a gene knockdown approach was used to investigate the biofactors in Hypo-EVs.Results: Nebulization of Hypo-EVs directly alleviated airway epithelial barrier defects in asthmatic mice, as evidenced by colocalization with bronchial epithelial cells, decreased albumin concentration, and increased ZO-1 and E-cadherin expression. In vitro, Hypo-EV treatment dramatically rescued the increase in airway cell permeability, and upregulated the ZO-1 and E-cadherin protein expressions. Based on WB analysis, we found that caveolin-1 (CAV-1) was strongly enriched in Hypo-EVs. The knockdown of CAV-1 protein levels in Hypo-EVs significantly impaired Hypo-EV-mediated barrier protection in vitro and in vivo. Moreover, CAV-1 knockdown significantly abolished the beneficial effects of Hypo-EVs on airway inflammation and remodeling in asthmatic mice. In addition, we showed that IL-4/IL-13-induced airway epithelial barrier defects were mainly related to activation of STAT6 phosphorylation (p-STAT6), and overexpression of CAV-1 or Hypo-EV treatment inhibited the levels of p-STAT6 in IL-4/IL-13-induced HBE135-E6E7 cells.Conclusion: Nebulization of Hypo-EVs can attenuate airway epithelial barrier defects in asthma by delivering CAV-1 to inhibit p-STAT6 expression and may be used to treat other barrier defect diseases.Keywords: nebulization, Hypo-EVs, asthma, airway epithelial barrier, caveolin-1

Chunying Zheng,1,* Hanliang Fan,1,* Peng Ye,1,* Xing Zhang,1 Xiaochun Zheng,1,2 Ting Zheng1 1Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, People’s Republic of China; 2Fujian Provincial Key Laboratory of Emergency Medicine, Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Co-Constructed Laboratory of “belt and Road”, Fujian Emergency Medical Center, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaochun Zheng; Ting Zheng, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, No. 134, Dongjie, 350001, Fuzhou, Fujian, People’s Republic of China, Tel +86 8821 7841, Email zhengxiaochun7766@163.com; zhengting1223@163.comPurpose: Previous research has demonstrated that real-time ultrasound-guided (UG) spinal anesthesia requires a higher minimum local anesthetic dose (MLAD) compared to traditional methods. However, the precise MLAD of ropivacaine for UG cesarean sections remains undetermined. In this study, we ascertained the MLAD of ropivacaine for cesarean section. We also investigated the mechanism underlying the diffusion of ropivacaine within the spinal canal using fluid simulation technology.Patients and Methods: We randomly placed 60 healthy parturients undergoing elective cesarean section with real-time UG spinal anesthesia into Groups I (26-gauge spinal needle) and II (24-gauge spinal needle). For the first parturient in both groups, 15 mg of ropivacaine was administered intrathecally. Based on the effective or ineffective response of the previous parturient, the dose for the subsequent parturient was increased or decreased by 1 mg. Spinal anesthesia characteristics and side effects were recorded. A computer-generated spinal canal model was developed. Leveraging fluid dynamics simulation technology, we documented the diffusion of ropivacaine in the spinal canal using 26-and 24-gauge spinal needles.Results: The MLADs in Groups I and II were 12.728 mg (12.339– 13.130 mg) and 9.795 mg (9.491– 10.110 mg), respectively. No significant difference was observed in the onset times and durations of sensory or motor blocks, incidence of complications, or neonatal Apgar scores between both groups. Fluid simulation modeling indicated that the 26-gauge spinal needle achieved a higher distribution level more quickly; however, its peak drug concentration was lower compared to the 24-gauge spinal needle.Conclusion: For cesarean section anesthetization, the required MLAD of ropivacaine when using a real-time UG 26-gauge spinal needle is significantly greater than that with a 24-gauge needle. The spinal needle diameter influences ropivacaine’s MLAD by markedly affecting its diffusion rate within the spinal canal.Keywords: anesthetic diffusion, spinal needle diameter, fluid dynamics simulation, cesarean anesthetization

Yanan Huang,1,* Yunfeng Wang,2,* Tianyu Zheng,1,* Shuang Nie,1 Yanli Wang,3 Hui Shen,1 Fengfeng Mo1 1Department of Naval Nutrition and Food Hygiene, Faculty of Navy Medicine, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Gastroenterology, Changhai Hospital, Shanghai, People’s Republic of China; 3International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanli Wang; Fengfeng Mo, Email hyyaoxueyuan2022@163.com; mofengfeng@smmu.edu.cnPurpose: Erythrocytes and fibroblasts in the pancreatic cancer tumor microenvironment promote tumor cell growth and invasion by providing nutrients and promoting immunosuppression. Additionally, they form a barrier against the penetration of chemotherapeutic drugs. Therefore, the search for diversified tumor-targeting materials plays an essential role in solving the above problems.Methods: Physicochemical characterization of Graphene fluorescent nanoparticles (GFNPs) and nanomedicines were analyzed by transmission electron microscopy (TEM), elemental analyzers and ultraviolet fluorescence (UV/FL) spectrophotometer. Localization of GFNPs in cell and tissue sections imaged with laser confocal microscope, fluorescence scanner and small animal in vivo imager. Qualitative detection and quantitative detection of GFNPs and GFNPs-GEM were performed using High performance liquid chromatography (HPLC).Results: Based on the 3 nm average dimensions, GFNPs penetrate vascular endothelial cells and smooth muscle cells, achieve up to label 30% tumor cells and 60% cancer-associated fibroblasts (CAFs) cells, and accurately label mature red blood cells in the tumor microenvironment. In orthotopic transplanted pancreatic cancer models, the fluorescence intensity of GFNPs in tumors showed a positive correlation with the cycle size of tumor development. The differential spatial distribution of GFNPs in three typical clinical pancreatic cancer samples demonstrated their diagnostic potential. To mediate the excellent targeting properties of GFNPs, we synthesized a series of nanomedicines using popular chemotherapeutic drugs, in which complex of GFNPs and gemcitabine (GFNPs-GEM) possessed stability in vivo and exhibited effective reduction of tumor volume and fewer side effects.Conclusion: GFNPs with multiple targeting tumor microenvironments in pancreatic cancer possess diagnostic efficiency and therapeutic potential. Keywords: graphene fluorescent nanoparticles, cancer-associated fibroblasts, pancreatic cancer cells, dual-targeting, chemo-target therapy

Tianli Zheng,1,2 Weiwei Fu,1,2 Shuang Jiang,3 Xiaodong Yang1,2 1School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, Jiangsu, People’s Republic of China; 3The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of ChinaCorrespondence: Xiaodong Yang, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, No. 88, Keling Road, Suzhou, Jiangsu Province, 215000, People’s Republic of China, Email xiaodong.yang@sibet.ac.cnPurpose: The prevalence of obesity and myopia in young people is increasing worldwide; however, the association between body mass index (BMI) and myopia remains controversial. This study aimed to assess the association between BMI and myopia in Chinese schoolchildren.Patients and Methods: In this study, the open data for analysis were obtained from DATADRYAD website (www.datadryad.org). A total of 3658 children were enrolled in this study. Logistic regression model was used to analyze the relationship between BMI and myopia.Results: Compared with individuals with lower BMI Q1 (less than 25 kg/m2), the adjusted odds ratios (ORs) for BMI and myopia were 2.15 (95% confidence interval [CI]: 1.62– 2.86) in Q2 (25.0– 29.9 kg/m2) and 2.39 (95% CI: 1.37– 4.18) in Q3 (30.0 kg/m2 or more). Moreover, the association between BMI and myopia exhibited an inverted L-shaped curve (nonlinear; p < 0.001). When the BMI was < 25 kg/m2, an increased BMI was significantly associated with a higher risk of myopia (OR = 1.244 [95% CI: 1.211– 1.277], p < 0.001). However, when the BMI was ≥ 25 kg/m2, the association lost its significance (OR = 1.063 [95% Cl: 0.964– 1.171], p = 0.219).Conclusion: This study found an inverted L-shaped association between BMI and myopia in Chinese schoolchildren. A higher BMI was associated with a higher risk of myopia reaching 25 kg/m2, after which an increase in BMI was no longer associated with an increased risk of myopia.Keywords: myopia, body mass index, cross-sectional, schoolchildren, logistic regression

Guangyi Xu,1 Ting Liu,1 Yunxia Jiang,1 Yanhong Xu,2 Taohua Zheng,2 Xiaona Li3 1Author affiliations School of Nursing, Qingdao University, Shandong, People’s Republic of China; 2Author affiliations Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Shandong, People’s Republic of China; 3Author Affiliations Endoscopic Diagnosis and Treatment Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, People’s Republic of ChinaCorrespondence: Ting Liu, School of Nursing, Qingdao University, 1 Ningde Road, Qingdao, Shandong, 266073, People’s Republic of China, Tel +86 15066237573, Email liuting201516@163.comPurpose: To identify the distinct profiles of psychosocial adaptation of Chinese inflammatory bowel disease (IBD) patients and the predictive factors.Patients and Methods: A cross-sectional survey method was used to recruit 263 IBD patients who were treated in a tertiary hospital in Shandong Province from July 2022 to April 2023. The general information questionnaire, Inflammatory Bowel Disease Psychosocial Adaptation Questionnaire, Resilience Scale for Inflammatory Bowel Disease, Chinese Benefit Finding Scale, and Stigma Scale for Chronic Illnesses, Medical Coping Modes Questionnaire and Inflammatory Bowel Disease-Disk were used as the instruments for investigation. Latent profile analysis was conducted with the six dimensions of the IBD Psychosocial Adaptation Questionnaire as the explicit indicators. The predictors of profile membership were analyzed by multinomial logistic regressions.Results: Four profiles of psychosocial adaptation in IBD patients were identified: Low level psychosocial adaptation (14.1%), Medium level psychosocial adaptation – High body image distress (25.5%), Medium level psychosocial adaptation – Low body image distress (30.0%) and High level psychosocial adaptation (30.4%). Compared with Low level psychosocial adaptation group, High level psychosocial adaptation group had a higher level of positive cognition (OR=2.930, 95%IC 0.017– 0.305, p< 0.001) and overall psychological resilience (OR=1.832, 95%IC 0.000– 0.016, p < 0.001), more health behaviors (OR= 2.520, 95%IC 0.191– 1.358, p=0.001), a lower level of internal stigma (OR=0.135, 95%IC 0.043– 0.420, p < 0.001) and overall stigma (OR=0.010, 95%IC 0.003– 0.118, p=0.001), less acceptance-resignation coping style (OR=0.055, 95%IC 0.209– 3.200, p < 0.001) and lower disease burden (OR=0.407, 95%IC 0.298– 0.698, p=0.006).Conclusion: About a half of IBD patients had a medium level of psychosocial adaptation. Psychological resilience, benefit finding, stigma, medical coping styles and disease burden predicted psychosocial adaptation profiles. Healthcare providers need to focus on the heterogeneity of psychosocial adaptation of IBD patients and formulate personalized intervention programs for patients with different profiles to improve their psychosocial adaptation.Keywords: inflammatory bowel disease, latent profile analysis, psychosocial adaptation, benefit finding, resilience, coping, stigma

Jie Liu,1,&ast; Ke Zhao,2,&ast; Wei Kang,1,&ast; Siyu Tong,1 Yao Xu,1 Wei Jin,1 Mengxuan Qiao,1 Yuan Li,1 Lan Hong,3 Keqing Yao,4,5 Tiansheng Zheng6 1School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, People’s Republic of China; 3The Third Hospital of Quzhou, Quzhou, People’s Republic of China; 4Shenzhen Mental Health Center, Shenzhen, Guangdong, People’s Republic of China; 5Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China; 6The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Yao, Shenzhen Mental Health Center, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-82927264, Email KQKangning@gmail.com Tiansheng Zheng, The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, People’s Republic of China, Email sky.tsh@163.comIntroduction: Non-suicidal self-injury (NSSI) is becoming an increasingly prevalent phenomenon among adolescents, endangering their health. The aims of this study were to 1) explore the associations between borderline personality features, alexithymia and NSSI and 2) examine if alexithymia mediates the relationships between borderline personality features and both the severity of NSSI and the various functions that maintain NSSI in adolescents.Methods: This cross-sectional study recruited 1779 outpatient and inpatient aged 12– 18 years from psychiatric hospitals. All adolescents completed a structured four-part questionnaire including demographic items, the Chinese version of the Functional Assessment of Self-Mutilation, the Borderline Personality Features Scale for Children and the Toronto Alexithymia Scale.Results: The structural equation modelling results indicated that alexithymia partially mediated the associations between borderline personality features and both the severity of NSSI and the emotion regulation function of NSSI (B = 0.058 and 0.099, both p < 0.001), after controlling for age and sex.Discussion: These findings suggest that alexithymia may play a role in the mechanism and treatment of NSSI among adolescents with borderline personality features. Further longitudinal studies are essential to validate these findings.Keywords: self-harm, health, emotion regulation, structural equation modelling

Tingting Zheng,1,&ast; Wenjuan Hu,1,&ast; Hao Wang,1 Xiaoli Xie,2 Lang Tang,3 Weiyan Liu,4 Pu-Yeh Wu,5 Jingjing Xu,1,&ast; Bin Song1,&ast; 1Department of Radiology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Song; Jingjing Xu, Department of Radiology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, 201199, People’s Republic of China, Email songbin@fudan.edu.cn; sb72778@189.cnPurpose: BRAF V600E mutation can compensate for the low detection rate by fine-needle aspiration (FNA) and is related to aggressiveness and lymph node metastasis. This study aimed to investigate the relationship between texture analysis features based on magnetic resonance imaging (MRI) and mutations.Methods: Retrospective analysis was performed on patients with postoperative pathology confirmed papillary thyroid carcinoma (PTC) from 2017 to 2021. One thousand one hundred and thirty-two texture features were extracted from T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) separately by outlining the tumor volume of interest (VOI). Univariate, minimum redundancy maximum relevance (mRMR), and multivariate analyses were used for feature selection to construct 3 models (T2WI, CE-T1WI, and combined model) to predict mutation. The reproducibility between observers was evaluated by intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) analysis was used to assess the performance of models. The diagnostic performance of the optimal cut-off value of models were calculated and validated by 10-fold cross-validation.Results: A total of 80 PTCs (22 BRAF V600E wild-type and 58 BRAF V600E mutant) were included in our study. Good interobserver agreement was found on texture features we selected (all ICCs > 0.75). The area under the ROC curves (AUCs) for the T2WI model, CE-T1WI model, and combined model were 0.83 (95% CI: 0.75– 0.91), 0.83 (95% CI: 0.73– 0.90), and 0.88 (95% CI: 0.81– 0.94), respectively. The accuracy, sensitivity, specificity, PPV, and NPV were 0.776, 0.679, 0.905, 0.905, and 0.679 for the T2WI model at a cut-off value of 0.674; 0.755, 0.750, 0.762, 0.808, and 0.696 for the CE-T1WI model at a cut-off value of 0.573; 0.816, 0.893, 0.714, 0.806, and 0.833 for the combined model at a cut-off value of 0.420.Conclusion: MRI-based texture analysis could be a potential method for predicting BRAF V600E mutation in PTC preoperatively.Keywords: magnetic resonance imaging, texture analysis, radiomics, papillary thyroid carcinoma, BRAF V600E

Ying Ning,&ast; Yanju Gong,&ast; Tianyan Zheng, Ya Xie, Shiqing Yuan, Weijun Ding School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weijun Ding; Shiqing Yuan, Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Road, Chengdu, 611137, People’s Republic of China, Tel + 86-28-61800219, Fax + 86-28-61800225, Email Dingweijun@cdutcm.edu.cn; yuanshiqing@cdutcm.edu.cnBackground: The increasing incidence of obesity and its complications has become a global public health problem. Lingguizhugan decoction (LGZGD) is a representative compound of traditional Chinese medicine (TCM) for metabolic diseases, such as nonalcoholic fatty liver disease, but its role in insulin resistance (IR) treatment is still less known. This study aims to evaluate the therapeutic properties of LGZGD on obesity-induced IR and explore the potential mechanism of LGZGD on gut microbiota and its metabolites in the treatment of IR.Methods: In this study, we induced an IR model in the form of high-fat diet (HFD) rats gavaged with LGZGD (1.64 g/kg BW) for three weeks. The IR status was measured by biochemical assays and oral glucose tolerance tests. The degrees of damage to liver function and the intestinal barrier were observed by hematoxylin and eosin (H&E) staining and immunohistochemistry. Alterations in intestinal microbiota and metabolites were assessed by 16S rRNA and an untargeted metabolomics platform.Results: Our results showed that after LGZGD treatment, the body weight, plasma insulin concentration and blood lipids were significantly decreased, and glucose tolerance and hepatic steatosis were ameliorated. In addition, small intestinal villi were restored, and the expression of Occludin was upregulated. The relative abundance of Akkermansia, Faecalibacterium and Phascolarctobacterium in the HFD-LGZG group was upregulated. Obesity-related metabolic pathways, such as bile secretion, biosynthesis of amino acids, phenylalanine metabolism, serotonergic synapse, protein digestion and absorption, taurine and hypotaurine metabolism, and primary bile acid biosynthesis, were changed. After LGZGD intervention, metabolites developed toward the healthy control group. In addition, the expression of bile acid metabolism related genes was also regulated in IR rats.Conclusion: We showed that LGZGD relieved IR, possibly by regulating the composition of the fecal microbiota and its metabolites. The above studies provide a basis for further study of LGZGD in the treatment of IR and its clinical application.Keywords: insulin resistance, IR, lingguizhugan decoction, LGZGD, intestinal microbiota, nontargeted metabolomics, high-fat diet, HFD

Motivated by applications in text mining and discrete distribution inference, we test for equality of probability mass functions of K groups of high-dimensional multinomial distributions. Special cases of this problem include global testing for topic models, two-sample testing in authorship attribution, and closeness testing for discrete distributions. A test statistic, which is shown to have an asymptotic standard normal distribution under the null hypothesis, is proposed. This parameter-free limiting null distribution holds true without requiring identical multinomial parameters within each group or equal group sizes. The optimal detection boundary for this testing problem is established, and the proposed test is shown to achieve this optimal detection boundary across the entire parameter space of interest. The proposed method is demonstrated in simulation studies and applied to analyse two real-world datasets to examine, respectively, variation among customer reviews of Amazon movies and the diversity of statistical paper abstracts. [ABSTRACT FROM AUTHOR]

Zhengjun Lin,1,2 Yiting Xu,2 Xianghong Zhang,1 Jia Wan,1 Tao Zheng,1 Hongxuan Chen,1 Shijie Chen,3 Tang Liu1 1Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, People’s Republic of China; 3Department of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, People’s Republic of ChinaCorrespondence: Shijie ChenDepartment of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, 410006, Hunan, People’s Republic of ChinaTel +86-73185292111Email shijiechencsu@163.comTang LiuDepartment of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaTel +86-73185292111Email liutang1204@csu.edu.cnBackground: Pyroptosis is critically associated with cancer initiation and progression, which can be modulated by diverse long noncoding RNAs (lncRNAs). However, the roles of pyroptosis-related lncRNAs in soft tissue sarcomas (STS) are still largely unknown.Methods: Our study included a total of 259 STS patients extracted from The Cancer Genome Atlas Sarcoma (TCGA-SARC) dataset. Gene expression data fragments per kilobase of transcript per million mapped reads (FPKM) values were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) for the investigation of the expression pattern of pyroptosis-related lncRNAs. Unsupervised clustering based on pyroptosis-related lncRNAs was performed, and the associations of pyroptosis-related lncRNAs with clinical outcomes and immune microenvironment were investigated. Two risk signatures for overall survival (OS) and disease-free survival (DFS) were constructed and validated in independent cohorts.Results: A total of 166 pyroptosis-related lncRNAs were identified in STS. Patients were clustered into two subgroups by unsupervised clustering, and cluster 2 had better prognoses, higher immune scores, higher abundance of immune cells, and higher expression of some immune checkpoints. OS- and DFS-risk signatures based on 10 and 13 pyroptosis-related lncRNAs, respectively, with favorable discrimination were constructed and validated. High-risk patients had favorable prognoses, and receiver operating characteristic (ROC) curves showed that both risk signatures could function as excellent predictors for prognoses of STS patients. Besides, the OS-risk signature could also excellently predict the immune landscape of STS.Conclusion: In conclusion, our study revealed the clinical significance and critical roles of pyroptosis-related lncRNAs in STS, and constructed novel risk signatures based on pyroptosis-related lncRNAs that could effectively predict clinical outcomes and immune microenvironment in STS.Keywords: pyroptosis, immune microenvironment, prognostic signature, soft tissue sarcomas

Hui Chen,1,&ast; Na Li,1,2,&ast; Xiang Zhan,1,&ast; Ting Zheng,1 Xinzhou Huang,1 Qianglin Chen,1 Zihao Song,1 Fei Yang,1,3 Hao Nie,1,3 Yanxiang Zhang,3 Bing Zheng,1,3 Quan Gong1,3 1Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People’s Republic of China; 3Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Zheng; Quan GongDepartment of Immunology, School of Medicine, Yangtze University, Jingzhou, People’s Republic of ChinaEmail hxzheng@yangtzeu.edu.cn; gongquan1998@163.comPurpose: Capsaicin (8-methyl-N-geranyl-6-nonamide; CAP) is an alkaloid isolated from chili peppers, which has complex pharmacological properties, including beneficial effects against various diseases. The aim of this study was to investigate the role of CAP in lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the possible underlying mechanisms.Materials and Methods: ALI was induced by intranasal administration of LPS (0.5 mg/kg), and CAP (1 mg/kg) injected intraperitoneally 3 days before exposure to LPS. Then, the histopathological changes were evaluated by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay and qPCR were used to detect pro-inflammatory cytokines in serum and lung tissue. The expressions of HMGB1/NF-κB, PI3K/AKT/mTOR signaling pathways and apoptosis-associated molecules were determined by Western blot and/or qPCR. In addition, the lung cell apoptosis was analyzed by TUNEL staining, and the expression and location of cleaved caspase-3 were detected by immunofluorescence analysis.Results: CAP pretreatment significantly protected mice from LPS-induced ALI, with reduced lung wet/dry weight ratio, lung histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and pro-inflammatory cytokine levels, and significant increased superoxide dismutase (SOD) activity. In addition, CAP pretreatment significantly inhibited the high-mobility group protein B1 (HMGB1) expression, nuclear factor-kappa B (NF-κB) activation, and the PI3K/AKT/mTOR signaling pathway. Furthermore, mice pre-treated with CAP exhibited reduced apoptosis of lung tissues, with associated down-regulation of caspase-3, cleaved caspase-3, and BAX expression, and up-regulation of BCL-2.Conclusion: Our data demonstrate that CAP can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory responses and apoptosis through down-regulation of the HMGB1/NF-κB and PI3K/AKT/mTOR pathways.Keywords: capsaicin, acute lung injury, HMGB1/NF-κB, PI3K/AKT/mTOR, apoptosis, inflammation

Yi Ren, Tiehua Zheng, Lei Hua, Fuzhou Zhang, Yangwei Ma, Jianmin Zhang Department of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaCorrespondence: Jianmin ZhangDepartment of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56, South Lishi Road, Beijing, 100045, People’s Republic of ChinaTel +861059616415Fax +861059616429Email zjm_bch@163.comPurpose: The Nuss procedure is a recognized treatment for adolescent pectus excavatum that results in severe postoperative pain. Erector spinae plane block (ESPB) is a novel technique that provides postoperative analgesia and reduces opioid consumption. Our aim is to explore whether ESPB produces analgesia similar to thoracic epidural anaesthesia (TEA) in paediatric patients undergoing Nuss procedure.Study Design and Methods: This randomized, controlled, non-inferiority trial will enrol 300 paediatric patients undergoing Nuss surgery. Participants will be randomly assigned 1:1 to receive ESPB or TEA preoperatively. The primary, joint endpoint is the average numeric rating scale (NRS) score and cumulative sufentanil consumption. The secondary endpoints are pain scores and sufentanil consumption at different time points after surgery, analgesia-related side effects, and other postoperative complications. Data will be analysed by the intention-to-treat principle.Discussion: This study investigates the effect of ESPB on postoperative opioid consumption and pain scores and intend to provide a new strategy of analgesia management for Nuss procedure in paediatric patients.Keywords: postoperative pain, erector spinae plane block, pectus excavatum, Nuss procedure, opiates

Yongli Pan,1,&ast; Qingzheng Jiao,2,&ast; Wei Wei,3,&ast; Tianyang Zheng,4,&ast; Xinyu Yang,5 Wenqiang Xin5 1Department of Neurology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Second Department of Internal Medicine, Gucheng County Hospital, Gucheng, Hebei, People’s Republic of China; 3Department of Neurology, Mianyang Central Hospital, Mianyang, Sichuan, People’s Republic of China; 4Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 5Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenqiang XinDepartment of Neurosurgery, Tianjin Medical University General Hospital, Anshan Road No. 154, Tianjin, 300052, People’s Republic of ChinaTel +86– 185 26201182Fax +86– 22 60362062Email xinwenqiangdr@126.comAbstract: As a crucial kind of pervasive gene, long noncoding RNAs (lncRNAs) are abundant and key players in brain function as well as numerous neurological disorders, especially ischemic stroke. The mechanisms underlying ischemic stroke include angiogenesis, autophagy, apoptosis, cell death, and neuroinflammation. Inflammation plays a vital role in the pathological process of ischemic stroke, and systemic inflammation affects the patient’s prognosis. Although a great deal of research has illustrated that various lncRNAs are closely relevant to regulate neuroinflammation and microglial activation in ischemic stroke, the specific interactional relationships and mechanisms between lncRNAs and neuroinflammation have not been described clearly. This review aimed to summarize the therapeutic effects and action mechanisms of lncRNAs on ischemia by regulating inflammation and microglial activation. In addition, we emphasize that lncRNAs have the potential to modulate inflammation by inhibiting and activating various signaling pathways, such as microRNAs, NF‐κB and ERK.Keywords: ischemic stroke, long noncoding RNA, microglia, neuroinflammation

The magnitude and variability of the terrestrial CO2 sink remain uncertain, partly due to limited global information on ecosystem nitrogen (N) and its cycle. Without N constraint in ecosystem models, the simulated benefits from CO2 fertilization and CO2-induced increases in water use efficiency (WUE) may be overestimated. In this study, satellite observations of a relative measure of chlorophyll content are used as a proxy for leaf photosynthetic N content globally for 2003–2011. Global gross primary productivity (GPP) and evapotranspiration are estimated under elevated CO2 and N-constrained model scenarios. Results suggest that the rate of global GPP increase is overestimated by 85% during 2000–2015 without N limitation. This limitation is found to occur in many tropical and boreal forests, where a negative leaf N trend indicates a reduction in photosynthetic capacity, thereby suppressing the positive vegetation response to enhanced CO2 fertilization. Based on our carbon-water coupled simulations, enhanced CO2 concentration decreased stomatal conductance and hence increased WUE by 10% globally over the 1982 to 2015 time frame. Due to increased anthropogenic N application, GPP in croplands continues to grow and offset the weak negative trend in forests due to N limitation. Our results also show that the improved WUE is unlikely to ease regional droughts in croplands because of increases in evapotranspiration, which are associated with the enhanced GPP. Although the N limitation on GPP increase is large, its associated confidence interval is still wide, suggesting an urgent need for better understanding and quantification of N limitation from satellite observations.

Polysulfide shuttling has been the primary cause of failure in lithium-sulfur (Li-S) battery cycling. Here, we demonstrate an nucleophilic substitution reaction between polysulfides and binder functional groups can unexpectedly immobilizes the polysulfides. The substitution reaction is verified by UV–visible spectra and X-ray photoelectron spectra. The immobilization of polysulfide is in situ monitored by synchrotron based sulfur K-edge X-ray absorption spectra. The resulting electrodes exhibit initial capacity up to 20.4 mAh/cm2, corresponding to 1199.1 mAh/g based on a micron-sulfur mass loading of 17.0 mg/cm2. The micron size sulfur transformed into nano layer coating on the cathode binder during cycling. Directly usage of nano-size sulfur promotes higher capacity of 33.7 mAh/cm2, which is the highest areal capacity reported in Li-S battery. This enhance performance is due to the reduced shuttle effect by covalently binding of the polysulfide with the polymer binder.

The doping mechanism of poly (1-pyrenemethyl methacrylate) (PPy) is investigated through electrochemical analytical and spectroscopic method. The performance of PPy as a Si materials binder is studied and compared with that of a commercial available lithium polyacrylate (PAALi) binder. The pyrene moiety consumes lithium ions according to the cyclic voltammogram (CV) measurement, as a doping to the PPy binder. Based on the lithium consumption, PPy based Si/graphite electrode doping is quantified at 1.1 electron/pyrene moiety. The PPy binder based electrodes surface are uniform and crack free during lithiation/delithiation, which is revealed through Scanning electron microscope (SEM) imaging.

Tingting Zheng,1 Wenjuan Hu,1 Hao Wang,1 Xiaoli Xie,2 Lang Tang,3 Weiyan Liu,4 Pu-Yeh Wu,5 Jingjing Xu,1 Bin Song1 1Department of Radiology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of ChinaCorrespondence: Bin Song; Jingjing Xu, Department of Radiology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, 201199, People’s Republic of China, Email songbin@fudan.edu.cn; sb72778@189.cn