期刊：
Molecular and Cellular Biochemistry,2023年478(6):1217-1229 ISSN：0300-8177
通讯作者：
Shan Liu
作者机构：
[Tang, Juan] Univ South China, Affiliated Hosp 2, Hengyang Med Sch,Dept Cardiovasc Med,Key Lab Hear, Clin Med Res Ctr Arteriosclerot Dis Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Tang, Qi-Xia] Grad Collabrat Training Base Second Affiliated Ho, Hengyang 421001, Hunan, Peoples R China.;[Liu, Shan] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Emergency, 35 Jiefang Ave, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Shan Liu] D;Department of Emergency, Hengyang Medical School, The Second Affiliated Hospital, University of South China, Hengyang, China
摘要：
Myocardial infarction (MI) is one of the important factors leading to death in today's society. Therefore, to study the related mechanism of MI and reduce myocardial ischemia-reperfusion injury is an important link to reduce MI injury. MI mice in vivo and cell model in vitro were constructed. The cardiac function and MI area of mice were detected, and myocardial tissue injury was detected by HE staining. ALAS2 expression in mice myocardial tissue was detected by IHC. The expressions of lncRNA-SNHG8, METTL3, PTBP1 and ALAS2 in myocardial tissue or cardiomyocytes were detected by qRT-PCR assay. MTT assay was used to measured viability of cardiomyocytes. The oxidative stress level in myocardial tissue or cardiomyocytes was detected by ELISA assay and ROS assay. RIP-qPCR and RNA pulldown assays determined the interaction between METTL3 and lncRNA-SNHG8, as well as PTBP1 and ALAS2. lncRNA-SNHG8 knockdown in MI mice was reduced myocardial infarction size, alleviated myocardial tissue injury and oxidative stress, and inhibited ALAS2 expression in myocardial tissue. RNA pulldown and RIP assays showed that lncRNA-SNHG8 binged with PTBP1 and PTBP1 interacted with ALAS2 mRNA. Knockdown of lncRNA-SNHG8, METTL3 or PTBP1 in MI cells enhanced viability of myocardial cells, attenuated ROS release and MDA level, increased SOD level, alleviated oxidative stress. ALAS overexpression attenuated the corresponding effect of knockdown of lncRNA-SNHG8 and/or PTBP1 on MI cells. In sum,our paper is demonstrated for the first time that METTL3 can promote lncRNA-SNHG8 through m6A modification, thereby regulating ALAS2 to induce oxidative stress and aggravate myocardial injury.
摘要：
In recent years, there have been multiple breakthroughs in cancer immunotherapy, with immune checkpoint inhibitors becoming the most promising treatment strategy. However, available drugs are not always effective. As an emerging immune checkpoint molecule, CD155 has become an important target for immunotherapy. This review describes the structure and function of CD155, its receptors TIGIT, CD96, and CD226, and summarizes that CD155 expressed by tumor cells can upregulate its expression through the DNA damage response pathway and Ras-Raf-MEK-ERK signaling pathway. This review also elaborates the mechanism of immune escape after binding CD155 to its receptors TIGIT, CD96, and CD226, and summarizes the current progress of immunotherapy research regarding CD155 and its receptors. Besides, it also discusses the future direction of checkpoint immunotherapy.
作者机构：
[Xiong, Tianqing; Liang, Jingyan; Guo, Dongming; Zhang, Jingwen] Yangzhou Univ, Inst Translat Med, Yangzhou 225009, Jiangsu, Peoples R China.;[Xu, Xiaofan; Liu, Zhenghai; Cao, Wenyu; Guo, Dongming; Li, Suyun] Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Xu, Yang] Univ South China, Inst Neurosci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Wang, Yingge] Affiliated Hosp Yangzhou Univ, Dept Neurol, Yangzhou 225009, Jiangsu, Peoples R China.;[Zhong, Xiaolin] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Liang, J.] T;[Cao, W.] H;Institute of Translational Medicine, Medical, Yangzhou University, 225009 Yangzhou, Jiangsu, China<&wdkj&>Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, Jiangsu 225009, China
摘要：
Pyroptosis, a newly discovered proinflammatory programmed cell death, is involved in the regulation of cognitive dysfunction, such as Alzheimer's disease. Exploring potential drug targets that prevent pyroptotic procedures might benefit the development of a cure for these diseases. In the present study, we explored whether the transient receptor potential vanilloid 4 (TRPV4) blocker HC067047 and knockdown of TRPV4 in the hip-pocampus could improve cognitive behavior through the inhibition of pyroptosis in a mouse model developed using systemic administration of lipopolysaccharide (LPS). We found that systemic administration of HC067047 or knockdown of hippocampal TRPV4 prevented the activation of canonical and noncanonical pyroptosis in the hippocampus of LPS-treated mice. Consistent with the inhibition of the hippocampal pyroptosis pathway, a knockdown of hippocampal TRPV4 lowered expression of TNF-alpha, IL-1 beta, IL-18, and IL-6. Furthermore, we verified that the main pyroptosis cell type might be a neuron, indicated by reduced neuronal marker expression. Me-chanically, we also found that knockdown of hippocampal TRPV4 might inhibit phosphorylation of CamkII alpha which results in NF kappa b mediated inflammasome reduction in the hippocampus of LPS-treated mice. More inter-estingly, mice intraperitoneally injected with HC067047 or the hippocampus injected with TRPV4 shRNA showed improved cognitive behavior, as indicated by the enhanced discrimination ratio in the NORT, NOPT, and SNPT. Collectively, we consider that HC067047 might be a small molecular drug that prevents pyroptosis, and TRPV4 could be an effective therapeutic target for preventing pyroptosis-induced cognitive dysfunction.
期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2023年238(8):1891-1908 ISSN：0021-9541
通讯作者：
Xie, W;Li, L
作者机构：
[Chen, Xi; Li, Pin; Zhi, Chenxi; Xie, Zhongcheng; Yu, Jiang; You, Jia; Ma, Wentao; Ouyang, Siyu; Tan, Xiaoqian; Xie, Wei; Xie, Nan; Peng, Tianhong; Lin, Xiaoyan; Liu, Zhiyang; Hou, Qin] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Li, Liang] Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang, Hunan, Peoples R China.;[Xie, Wei] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Li, Liang] Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xie, W ; Li, L ] U;Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
关键词：
atherosclerosis;ferroptosis;p53/SLC7A11/GPX4
摘要：
Ferroptosis as a novel programmed cell death that involves metabolic dysfunction due to iron-dependent excessive lipid peroxidation has been implicated in atherosclerosis (AS) development characterized by disrupted lipid metabolism, but the atherogenic role of ferroptosis in vascular smooth muscle cells (VSMCs), which are principal components of atherosclerotic plaque fibrous cap, remains unclear. The aim of this study was to determine the effects of ferroptosis on AS induced by lipid overload, and the effects of that on VSMCs ferroptosis. We found intraperitoneal injection of Fer-1, a ferroptosis inhibitor, ameliorated obviously high-fat diet-induced high plasma levels of triglycerides, total cholesterol, low-density lipoprotein, glucose and atherosclerotic lesions in ApoE(-/-) mice. Moreover, in vivo and in vitro, Fer-1 reduced the iron accumulation of atherosclerotic lesions through affecting the expression of TFR1, FTH, and FTL in VSMCs. Interestingly, Fer-1 did augment nuclear factor E2-related factor 2/ferroptosis suppressor protein 1 to enhance endogenous resistance to lipid peroxidation, but not classic p53/SCL7A11/GPX4. Those observations indicated inhibition of VSMCs ferroptosis can improve AS lesions independent of p53/SLC7A11/GPX4, which preliminarily revealed the potential mechanism of ferroptosis in aortic VSMCs on AS and provided new therapeutic strategies and targets for AS.
摘要：
The protection of the blood-brain barrier (BBB) is the key direction to improving subarachnoid hemorrhage (SAH). Therefore, developing appropriate targeted drugs and therapies has become an urgent task for SAH patients. In this study, we investigated the role of dendritic cells (DCs) exosomal miR-3064-5p in repairing the BBB, providing a new basis for treating SAH. We detected the expression of miR-3064-5p in exosomes secreted by DCs (DCs-exo). AnSAH rat model was constructed by intravascular perforation and characterized by HE and TUNEL-IF staining. We found that overexpression of miR-3064-5p in SAH rats suppressed iNOS expression and promoted the accumulation of tight junction proteins (Occludin, Claudin-3, ZO-1), whereas knockdown of miR-3064-5p exerted the opposite effect. Dual-LUC assay confirmed that miR-3064-5p could target and inhibit SIRT6. Knockdown of SIRT6 inhibited inflammatory cytokine (IL-6, IL-1β, IFN-γ, and TGF-β1) levels and apoptosis. The results of the co-IP assay showed that SIRT6 interacted with PCSK9, and knockdown of SIRT6 suppressed the expression of PCSK9. Moreover, DCs-exo reduced brain edema, upregulated miR-3064-5p and downregulated SIRT6 and PCSK9 in SAH rats. DCs-exo reduced inflammatory factors and increased tight junction proteins in SAH rats. Overexpression of miR-3064-5p enhanced the protective effect of DCs-exo, while overexpression of SIRT6 partially counteracted the effect. This study confirmed that DCs could secrete miR-3064-5p to ameliorate BBB damage after SAH. Mechanistically, miR-3064-5p alleviated BBB damage by targeting and inhibiting SIRT6/PCSk9 signaling pathway.
期刊：
Journal of Drug Targeting,2023年31(4):421-432 ISSN：1061-186X
通讯作者：
Xuefeng Yang<&wdkj&>Duo Li
作者机构：
[Wang, Lijun] Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Dept Stomatol, Hengyang, Hunan, Peoples R China.;[Zhu, Lingping; Yang, Xuefeng; Zhou, Kebing; Hu, Yang; Wu, Qing; Li, Duo] Univ South China, Nanhua Affiliated Hosp, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Zhu, Lingping; Yang, Xuefeng; Zhou, Kebing; Wu, Qing; Li, Duo] Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Dept Gen Med, Hengyang, Hunan, Peoples R China.;[Yang, Xuefeng; Zhou, Kebing; Hu, Yang] Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Dept Gastroenterol, Hengyang, Hunan, Peoples R China.
通讯机构：
[Xuefeng Yang; Duo Li] H;Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, The Nanhua Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China<&wdkj&>The Nanhua Affiliated Hospital, Department of General Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China<&wdkj&>The Nanhua Affiliated Hospital, Department of Gastroenterology, Hengyang Medical School, University of South China, Hengyang, Hunan, China<&wdkj&>Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, The Nanhua Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China<&wdkj&>The Nanhua Affiliated Hospital, Department of General Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
摘要：
BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver disease worldwide and comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to identify and treat patients at risk. However, the aetiology and mechanisms remain largely unknown, warranting further analysis. METHODS: We first identified differential genes in NASH by single-cell analysis of the GSE129516 dataset and conducted expression profiling data analysis of the GSE184019 dataset from the Gene Expression Omnibus (GEO) database. Then single-cell trajectory reconstruction and analysis, immune gene score, cellular communication, key gene screening, functional enrichment analysis, and immune microenvironment analysis were carried out. Finally, cell experiments were performed to verify the role of key genes in NASH. RESULTS: We conducted transcriptome profiling of 30,038 single cells, including hepatocytes and non-hepatocytes from normal and steatosis adult mouse livers. Comparative analysis of hepatocytes and non-hepatocytes revealed pronounced heterogeneity as non-hepatocytes acted as major cell-communication hubs. The results showed that Hspa1b, Tfrc, Hmox1 and Map4k4 could effectively distinguish NASH tissues from normal samples. The results of scRNA-seq and qPCR indicated that the expression levels of hub genes in NASH were significantly higher than in normal cells or tissues. Further immune infiltration analysis showed significant differences in M2 macrophage distribution between healthy and metabolic-associated fatty liver samples. CONCLUSIONS: Our results suggest that Hspa1b, Tfrc, Hmox1 and Map4k4 have huge prospects as diagnostic and prognostic biomarkers for NASH and may be potential therapeutic targets for NASH.
作者机构：
[史子毕; 阮倩倩; 胡月; 范明; 朱玲玲] Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China;[赵名] Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China. zhaoming1981@hotmail.com;[朱玲玲] School of Life Sciences, Anhui Medical University, Hefei 230032, China;[朱玲玲] Hengyang Medical School, University of South China, Hengyang 421001, China;[朱玲玲] Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. linglingzhuamms@126.com
作者机构：
[杨丽] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang 421001, China;[袁中华] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang 421001, China. yzh5555@163.com
摘要：
Precise quantification of low-dose ionizing radiation is of great significance in protecting people from damage caused by clinical radiotherapy or environmental radiation. Traditional techniques for detecting radiation, however, remain extreme challenges to achieve high sensitivity and speed in quantifying radiation dosage. In this work, we report a Cas13a-Microdroplet platform that enables sensitive detection of ultra-low doses of radiation (0.5 Gy vs. 1 Gy traditional) within 1 h. The micro-platform adopts an ideal, specific radiation-sensitive marker, m6A on NCOA4 gene (NCOA4-m6A) that was first reported in our recent work. Microfluidics of the platform generate uniform microdroplets that encapsulate a CRISPR/Cas13a detection system and NCOA4-m6A target from the whole RNA extraction, achieving 10-fold enhancement in sensitivity and significantly reduced limit of detection (LOD). Systematic mouse models and clinical patient samples demonstrated its superior sensitivity and LOD (0.5 Gy) than traditional qPCR, which show wide potentials in radiation tracking and damage protection.
作者机构：
[Sun, Hong; Li, Enmin; Xu, Liyan; Zhang, Yimeng] Shantou Univ, Med Coll, Key Lab Mol Biol High Canc Incidence Coastal Chao, Shantou 515041, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Fang, Qiaoli; Li, Chunquan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Fang, Qiaoli; Li, Chunquan] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Li, Chunquan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Inte, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Li, Chunquan] Univ South China, Hunan Prov Base Sci & Technol Innovat Cooperat, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Enmin Li; Chunquan Li] T;The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>School of Computer, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College , Shantou 515041, China<&wdkj&>Department of Biochemistry and Molecular Biology, Shantou University Medical College , Shantou 515041, China
摘要：
Chromatin regulators (CRs) regulate epigenetic patterns on a partial or global scale, playing a critical role in affecting multi-target gene expression. As chromatin immunoprecipitation sequencing (ChIP-seq) data associated with CRs are rapidly accumulating, a comprehensive resource of CRs needs to be built urgently for collecting, integrating, and processing these data, which can provide abundant annotated information on CR upstream and downstream regulatory analyses as well as CR-related analysis functions. This study established an integrative CR resource, named CRdb (http://cr.liclab.net/crdb/), with the aim of curating a large number of available resources for CRs and providing extensive annotations and analyses of CRs to help biological researchers clarify the regulation mechanism and function of CRs. The CRdb database comprised a total of 647 CRs and 2,591 ChIP-seq samples from more than 300 human tissues and cell types. These samples have been manually curated from NCBI GEO/SRA and ENCODE. Importantly, CRdb provided the abundant and detailed genetic annotations in CR-binding regions based on ChIP-seq. Furthermore, CRdb supported various functional annotations and upstream regulatory information on CRs. In particular, it embedded four types of CR regulatory analyses: CR gene set enrichment, CR-binding genomic region annotation, CR-TF co-occupancy analysis, and CR regulatory axis analysis. CRdb is a useful and powerful resource that can help in exploring the potential functions of CRs and their regulatory mechanism in diseases and biological processes.
作者机构：
[Zhang, Yuexin; Wang, Qiuyu; Zhang, Guorui; Song, Chao; Wang, Yuezhu; Zhou, Liwei; Zhao, Jun; Li, Chunquan; Qian, Fengcui] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Xilong; Feng, Chenchen; Wang, Qiuyu; Bai, Xuefeng; Zhang, Jian; Wang, Yuezhu; Ai, Bo; Liu, Xinyu; Zhou, Liwei; Zhao, Jun; Li, Chunquan; Zhu, Jiang; Wang, Fan] Harbin Med Univ, Sch Med Informat, Daqing Campus, Daqing 163319, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Zhang, Guorui; Song, Chao; Li, Chunquan; Qian, Fengcui] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Li, Chunquan; Qian, Fengcui] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Inte, Hengyang 421001, Hunan, Peoples R China.;[Wang, Qiuyu; Li, Chunquan] Univ South China, Hunan Prov Base Sci & Technol Innovat Cooperat, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Chunquan Li] T;The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>School of Medical Informatics, Daqing Campus, Harbin Medical University , Daqing 163319, China<&wdkj&>School of Computer, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang , Hunan 421001, China<&wdkj&>Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang , Hunan 421001, China
摘要：
Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including ‘Search SE by TF-based’, ‘Differential-Overlapping-SE analysis’ and ‘SE-based TF–Gene analysis’. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.
作者：
Yi, Xianhao;Zhang, Xuan;Li, Qingchun;Ouyang, Jun
期刊：
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES,2023年37(12):9228-9243 ISSN：0930-2794
通讯作者：
Ouyang, J
作者机构：
[Yi, Xianhao; Ouyang, Jun] Univ South China, Affiliated Hosp 1, Dept Gastrointestinal Surg, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Xuan] Univ South China, Affiliated Hosp 1, Dept Stomatol, Hengyang 421001, Hunan, Peoples R China.;[Li, Qingchun] Univ South China, Affiliated Hosp 1, Dept Radiol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Ouyang, J ] U;Univ South China, Affiliated Hosp 1, Dept Gastrointestinal Surg, Hengyang 421001, Hunan, Peoples R China.
关键词：
Perioperative outcomes;Oncological outcomes;Transanal total mesorectal excision;Laparoscopic total mesorectal excision;Meta-analysis
摘要：
INTRODUCTION: Meta-analysis of the results of transanal total mesorectal excision (taTME) and laparoscopic TME (laTME) regarding perioperative and oncological outcomes have been conducted. Due to the lack of high-quality randomized controlled trials (RCTs) and prospective studies in the included literature, the conclusions are unreliable. This study included RCTs and prospective studies for analysis to obtain more reliable conclusions. MATERIALS AND METHODS: Systematic searches of the PubMed, Embase, and Cochrane Library databases were conducted up to June 2023. To assess the quality, the Cochrane quality assessment tool and the Newcastle-Ottawa Scale were employed. The perioperative and oncological outcomes were then analyzed. The I(2) statistic was used to evaluate statistical heterogeneity and sensitivity analyses was conducted. RESULTS: A total of 22 studies, comprising 5056 patients, were included in the analysis, of which 6 were RCTs and 16 were prospective studies. The conversion rate in the taTME group was significantly lower than that in the laTME group (OR 0.14, 95% CI 0.09 to 0.22, P < 0.01), and the circumferential resection margin (CRM) was longer (MD 0.99mm, 95% CI 0.66 to 1.32mm, P < 0.01), with a lower rate of positive CRM involvement (OR 0.68, 95% CI 0.47 to 0.97, P = 0.03). No statistically significant differences were found in terms of the operation time, intraoperative blood loss, complications, anastomotic leakage, uroschesis, obstruction, secondary operation, hospital stay, urethral injury, readmission, mortality rate within 30days, mesorectal resection quality, number of harvested lymph nodes, distal resection margin (DRM), positive DRM, local recurrence, and distance recurrence (P > 0.05). CONCLUSION: According to the findings of this meta-analysis, which is based on RCTs and prospective studies, taTME appears to have an advantage over laTME in terms of conversion rate and CRM involvement.
作者机构：
[Zhong, Xiaolin; Chen, Ling] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Metab & Endocrinol, Hengyang 421001, Hunan, Peoples R China.;[Liu, WenJia; Huang, Yanmei; Liang, Yue; Wang, Yajuan; Liu, Dandan; Xie, Lihua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Lab Med, Hengyang 421001, Hunan, Peoples R China.;[Cao, Wenyu] Univ South China, Hengyang Med Sch, Dept Human Anat, Hengyang 421001, Hunan, Peoples R China.;[Xu, Yang] Univ South China, Inst Neurosci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yang Xu] I;[Ling Chen] D;Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001 Hunan, China<&wdkj&>Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
摘要：
Sepsis-associated encephalopathy (SAE) is a common neurological complication of sepsis and is char-acterized by hyperneuroinflammation. NLRP3 inflammasome-mediated pyroptosis can induce an inflammatory cascade response and plays a key role in SAE. TRPV4 is involved in the hyperinflammatory response associated with inflammation; however, whether TRPV4 inhibition might alleviate SAE-related brain damage is still unknown. Therefore, we aimed to investigate the role and mechanism of HC067047, a potent inhibitor of TRPV4, in hyper-neuroinflammation and blood-brain barrier (BBB) dysfunction in a lipopolysaccharide (LPS)-induced SAE mouse model. We found that HC067047 administration significantly inhibited the expression of TRPV4 and p-CamkIIa in the hippocampi of SAE mice. Furthermore, HC067047 treatment attenuated LPS-induced endoplasmic reticulum (ER) stress and oxidative stress (OS), thus remarkably preventing NLRP3 inflammasome-mediated pyroptosis, as well as the expression of proinflammatory factors (IL-1b and IL-18). Additionally, we found that HC067047 selec-tively prevented pyroptosis in hippocampal cells, mainly the neurons, oligodendrocytes and the resident micro-glia. The disruption of BBB integrity in SAE mice was also rescued by HC067047 intervention. Thus, we can conclude that the TRPV4 inhibitor HC067047 could protect against hippocampal cell pyroptosis, which might be due to the attenuation of the NLRP3 inflammasome-mediated pyroptosis pathway caused by ER stress and OS. Our findings suggest a potential preventive role for HC067047 in SAE.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.
作者机构：
[Zeng, Jiayu; Yuan, Lin; Zhong, Rongbin; He, Longwei; Yang, Xuefeng; Cheng, Dan; Jiang, Renfeng] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst,Hengyang Med Sch, Hunan Prov Clin Res Ctr Metab Assoc Fatty Liver Di, Hengyang 421002, Hunan, Peoples R China.;[Yuan, Lin; Gong, Xiangyang; Cheng, Dan] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemomet, Changsha 410082, Peoples R China.
通讯机构：
[Longwei He; Dan Cheng] H;Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002 Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, 410082 Changsha, P. R. China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421002 Hunan, China
期刊：
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES,2023年32(8):107205 ISSN：1052-3057
通讯作者：
Zhu, GH
作者机构：
[Xiao, Zijian; Xiang, Tao; Zhu, Guanghua; Liu, Kai; Ye, Qing; Liang, Shengjiao] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Neurol, Hengyang, Peoples R China.;[Zhu, Guanghua] Univ South China, Dept Neurol, Affiliated Hosp 1, 69th Chuanshan Rd, Hengyang, Peoples R China.
通讯机构：
[Zhu, GH ] U;Univ South China, Dept Neurol, Affiliated Hosp 1, 69th Chuanshan Rd, Hengyang, Peoples R China.
关键词：
Klotho-Ischemic;Klotho-Ischemic stroke-P38;stroke-P38 mitogen-activated protein kinase-;Aquaporin;4-Neuroprotection
摘要：
OBJECTIVES: This study was aimed at exploring whether klotho improved neurologic function in rats with cerebral infarction by inhibiting P38 mitogen-activated protein kinase (MAPK) activation and thus down-regulating aquaporin 4 (AQP4). METHODS: In this study, we induced intracerebral Klotho overexpression in 6-week-old Sprague Dawley rats by injecting lentivirus carrying full-length rat Klotho cDNA into the lateral ventricle of the brain, followed by middle cerebral artery occlusion (MCAO) surgery after three days. Neurologic function was evaluated by neurological deficit scores. Infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. The expressions of Klotho, AQP4, and P38 MAPK were detected by Western blot and Immunofluorescence. RESULTS: when rats were subjected to cerebral ischemia, their neurologic function was impaired, the protein expressions of klotho downregulated, the protein expressions of AQP4 and P38 MAPK increased, and the ratios of AQP4 and P-P38-positive area were significantly increased compared with the sham group rats. LV-KL-induced Klotho overexpression greatly improved neurobehavioral deficits and reduced infarct volume in MCAO rats. Klotho overexpression significantly reduced AQP4 and P38 MAPK pathway-related protein expression levels and the ratios of P-P38 and AQP4-positive area in MCAO rats. In addition, SB203580, a P38 MAPK signal pathway inhibitor, improved neurobehavioral deficits, reduced infarct volume, downregulated the expressions levels of AQP4 and P38 MAPK, and reduced the size of P-P38 and AQP4-positive area in MCAO rats. CONCLUSION: Klotho could alleviate the infraction volume and neurological dysfunction in MCAO rats, and its mechanism may involve AQP4 expression downregulation by suppressing P38-MAPK activation.
作者机构：
[Li, Chen; Zhao, Qiang; Zhang, Zhiwei; Liu, Lu] Univ South China, Dept Pathol, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Juan] Univ South China, Dept Otorhinolaryngol, Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.;[Wu, Shihua] Second Hosp Shaoyang Coll, Dept Pathol, Hunan, Shaoyang 422000, Hunan, Peoples R China.;[Zhang, Zhiwei; Zeng, Xuemei] Univ South China, Canc Res Inst, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Qiang] Univ South China, Dept Pathol, Affiliated Hosp 1, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Qiang Zhao; Zhiwei Zhang] D;Department of Pathology, The First Affiliated Hospital of University of South China, Hunan, Hengyang, 421001, Hunan Province, China<&wdkj&>Cancer Research Institute of Hengyang Medical College, University of South China, Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hunan, Hengyang, 421001, China<&wdkj&>Department of Pathology, The First Affiliated Hospital of University of South China, Hunan, Hengyang, 421001, Hunan Province, China
期刊：
JOURNAL OF HEADACHE AND PAIN,2023年24(1):1-16 ISSN：1129-2369
通讯作者：
Dong, Zhao;Yu, SY
作者机构：
[Wang, Rongfei; Hou, Lei; Dong, Zhao; Dong, Z; Wang, Xiaolin; Zhang, Mingjie; Zhang, Shuhua; Chen, Xiaoyan; Zhao, Dengfa; Yu, SY; Han, Xun; Jia, Zhihua; Yu, Shengyuan; Ran, Ye; Liu, Yinglu] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Neurol, Beijing 100853, Peoples R China.;[Wang, Rongfei; Hou, Lei; Dong, Zhao; Dong, Z; Wang, Xiaolin; Zhang, Mingjie; Zhang, Shuhua; Chen, Xiaoyan; Zhao, Dengfa; Yu, SY; Han, Xun; Jia, Zhihua; Yu, Shengyuan; Ran, Ye; Liu, Yinglu] Chinese Peoples Liberat Army Gen Hosp, Int Headache Ctr, Beijing 100853, Peoples R China.;[Wan, Dongjun] 940Th Hosp Joint Logist Support Force Chinese Peop, Dept Neurol, Lanzhou 730050, Gansu, Peoples R China.;[Yin, Ziming] Univ Shanghai Sci & Technol, Sch Hlth Sci & Engn, Shanghai 200093, Peoples R China.;[Huang, Siyang; Xie, Fengbo] AffaMed Therapeut, Suite 4501,Tower A, 1 Jianguomenwai Ave, Beijing 100004, Peoples R China.
通讯机构：
[Yu, SY ; Dong, Z] C;Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Neurol, Beijing 100853, Peoples R China.;Chinese Peoples Liberat Army Gen Hosp, Int Headache Ctr, Beijing 100853, Peoples R China.
摘要：
Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use. In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human–computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China. Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to “red-flag” responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients. The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human–computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor–client interactions will be future areas of research for the development of CDSS for headaches.
摘要：
Group 2 innate lymphoid cells (ILC2s), characterized by a lack of antigen receptors, have been regarded as an important component of type 2 pulmonary immunity. Analogous to Th2 cells, ILC2s are capable of releasing type 2 cytokines and amphiregulin, thus playing an essential role in a variety of diseases, such as allergic diseases and virus-induced respiratory diseases. Interferons (IFNs), an important family of cytokines with potent antiviral effects, can be triggered by microbial products, microbial exposure, and pathogen infections. Interestingly, the past few years have witnessed encouraging progress in revealing the important role of IFNs and IFN-producing cells in modulating ILC2 responses in allergic lung inflammation and respiratory viral infections. This review underscores recent progress in understanding the role of IFNs and IFN-producing cells in shaping ILC2 responses and discusses disease phenotypes, mechanisms, and therapeutic targets in the context of allergic lung inflammation and infections with viruses, including influenza virus, rhinovirus (RV), respiratory syncytial virus (RSV), and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).
摘要：
Syphilis, a chronic systemic sexually transmitted disease, is caused by the bacterium Treponema pallidum (T. pallidum). Currently, syphilis remains a widespread infectious disease with significant disease burden in many countries. Despite the absence of identified penicillin-resistant strains, challenges in syphilis treatment persist due to penicillin allergies, supply issues, and the emergence of macrolide-resistant strains. Vaccines represent the most cost-effective strategy to prevent and control the syphilis epidemic. In light of the ongoing global coronavirus disease 2019 (COVID-19) pandemic, nucleic acid vaccines have gained prominence in the field of vaccine research and development, owing to their superior efficiency compared to traditional vaccines. This review summarizes the current state of the syphilis epidemic and the preliminary findings in T. pallidum nucleic acid vaccine research, discusses the challenges associated with the development of T. pallidum nucleic acid vaccines, and proposes strategies and measures for future T. pallidum vaccine development.
摘要：
Chemodynamic therapy (CDT) is a particular oncological therapeutic strategy by generates the highly toxic hydroxyl radical (center dot OH) from the dismutation of endogenous hydrogen peroxide (H2O2) via Fenton or Fenton-like reactions. However, single CDT therapies have been limited by unsatisfactory efficacy. Enhanced chemodynamic therapy (ECDT) triggered by near-infrared (NIR) is a novel therapeutic modality based on light energy to improve the efficiency of Fenton or Fenton-like reactions. However, the limited penetration and imaging capability of the visible (400-650 nm) and traditional NIR-I region (650-900 nm) light-amplified CDT restrict the prospects for its clinical application. Combined with the high penetration/high precision imaging characteristics of the second near-infrared (NIR-II,) nanoplatform, it is expected to kill deep tumors efficiently while imaging the treatment process in real-time, and more notably, the NIR-II region radiation with wavelengths above 1000 nm can minimize the irradiation damage to normal tissues. Such NIR-II ECDT nanoplatforms have greatly improved the effectiveness of CDT therapy and demonstrated extraordinary potential for clinical applications. Accordingly, various strategies have been explored in the past years to improve the efficiency of NIR-II Enhanced CDT. In this review, the mechanisms and strategies used to improve the performance of NIR-II-enhanced CDT are outlined. This review summarizes the current typical designs for NIR-II light-enhanced chemodynamic therapy (CDT). The significant advances in combination therapies made possible by NIR-II light-enhanced approaches are discussed in detail. Current challenges, limitations, and prospects for NIR-II light-enhanced CDT-based combination therapies are thoroughly reviewed for potential clinical applications.image
