作者：
Li, Qi-Mei;Zhu, HongBo;Zhu, Hong;Xiao, Lu-shan;Liu, Li
期刊：
Frontiers in Pharmacology,2024年15:1281095 ISSN：1663-9812
作者机构：
Guangdong Provincial Key Laboratory of Hepatic Diseases, Southern Medical University, Guangzhou, China;Department of Medical Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan Province, China;Nanfang Hospital, Southern Medical University, Guangzhou, China
摘要：
Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17–1.28, P<0.001; quartile 3: OR 1.44; 95% CI 1.38–1.51, P<0.001; quartile 4: OR 1.66, 95% CI 1.59–1.74, P<0.001). The results of prospective analyses were similar. Conclusions: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.
摘要：
Two de novo and two biallelic CCDC88C variants were identified in four cases with focal epilepsy without neurodevelopmental disorders. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy‐associated variants were mainly missense, the proportion of which was significantly higher than that of patients with congenital hydrocephalus. Abstract CCDC88C gene, which encodes coiled‐coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole‐exome sequencing (trio‐based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult‐onset epilepsy, whereas patients with biallelic variants displayed infant‐onset epilepsy. They all responded well to anti‐seizure medications and were seizure‐free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non‐classical splicing and a variant located at crucial domain, suggesting a sub‐molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy‐associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus‐associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.
作者机构：
[Zhang, Liang; Zheng, Jing; Zhang, Bo; Liu, Shi-Yan] Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541199, China;[Zhang, Liang] Department of Anesthesiology, National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China;[Hou, Li-Li; Zhang, Liang] Department of Anesthesiology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China;[Tian, Shao-Wen] Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541199, China. Electronic address: tiansw@glmc.edu.cn
通讯机构：
[Tian, Shao-Wen] G;Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541199, China. Electronic address:
摘要：
Lactate acts as an important metabolic substrate and signalling molecule modulating neural activities in the brain, and recent preclinical and clinical studies have revealed its antidepressant effect after acute or chronic peripheral administration. However, the neural mechanism underlying the antidepressant effect of lactate, in particular when lactate is acutely administered remains largely unknown. In the current study, we focused on forced swimming test (FST) to elucidate the neural mechanisms through which acute intracerebroventricular (ICV) infusion of lactate exerts antidepressant-like effect. A total of 238 male Sprague Dawley rats were used as experimental subjects. Results showed lactate produced antidepressant-like effect, as indicated by reduced immobility, in a dose- and time-dependent manner. Moreover, the antidepressant-like effect of lactate was dependent of new protein synthesis but not new gene expression, lactate's metabolic effect or hydroxy-carboxylic acid receptor 1 (HCAR1) activation. Furthermore, lactate rapidly promoted dephosphorylation of eukaryotic elongation factor 2 (eEF2) and increased brain-derived neurotrophic factor (BDNF) protein synthesis in the hippocampus in a cyclic adenosine monophosphate (cAMP)-dependent manner. Finally, inhibition of cAMP production blocked the antidepressant-like effect of lactate. These findings suggest that acute administration of lactate exerts antidepressant-like effect through cAMP-dependent protein synthesis.
作者机构：
[Zeng, Qun] Department of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China;[Jiang, Tingting] Department of Clinical Laboratory, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: 554860529@qq.com
通讯机构：
[Jiang, Tingting] D;Department of Clinical Laboratory, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address:
摘要：
Hypochlorous acid (HClO) is used in food preservation. However, excessive HClO can deteriorate nutritional composition of food, compromise its quality, and potentially induce various diseases. Consequently, the development of multifunctional fluorescent probes for the sensitive and selective detection of HClO is highly anticipated for food safety. In this work, we designed a nanoprobe using N-aminomorpholine (AM)-functionalized bromine-doped carbon dots (Br-CDs-AM) for sensing HClO. This nanoprobe exhibits pH stability, strong resistance to photobleaching, superior long-term photostability (12weeks), high sensitivity (19.3nM), and an ultrarapid response (8s) for detecting HClO residues in food matrices with percentage recovery (96.5%-108%) and RSDs less than 5.34%. In addition, extremely low cytotoxicity and outstanding biocompatibility enable the nanoprobe to be used primarily for lysosome tracking and rapidly visualizing HClO in live cells. Thus, this study provides a new pathway to design unconventional nanoprobes for food safety assessment and subcellular organelle-specific imaging HClO.
摘要：
The permeability of the blood-brain barrier (BBB) is increased in Alzheimer's disease (AD). This plays a key role in the instigation and maintenance of chronic inflammation during AD. Experiments using AD models showed that the increased permeability of the BBB was mainly caused by the decreased expression of tight junction-related proteins occludin and claudin-5. In this study, we found that ZNF787 and HDAC1 were upregulated in β-amyloid (Aβ)(1-42)-incubated endothelial cells, resulting in increased BBB permeability. Conversely, the silencing of ZNF787 and HDAC1 by RNAi led to reduced BBB permeability. The silencing of ZNF787 and HDAC1 enhanced the expression of occludin and claudin-5. Mechanistically, ZNF787 binds to promoter regions for occludin and claudin-5 and functions as a transcriptional regulator. Furthermore, we demonstrate that ZNF787 interacts with HDAC1, and this resulted in the downregulation of the expression of genes encoding tight junction-related proteins to increase in BBB permeability. Taken together, our study identifies critical roles for the interaction between ZNF787 and HDAC1 in regulating BBB permeability and the pathogenesis of AD.
期刊：
Current Problems in Cardiology,2024年49(1):102096 ISSN：0146-2806
通讯作者：
Tang, CK
作者机构：
[Tang, Chao-Ke; Jiang, Wan-Li; Zhou, Jing; Nie, Gui-Ying; Li, Jing; Yu, Jiang; Zhang, Shi-Qian; Zeng, Guang-Gui] Univ South China, Hengyang Med Sch, Hunan Int Sci & Technol Cooperat Base Arterioscler, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Guang-Gui] Univ South China, Grade Excellent Doctor Class Hengyang Med Coll 202, Hengyang 421001, Hunan, Peoples R China.;[Zhou, Jing] Univ South China, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Wan-Li; Li, Jing; Yu, Jiang; Zhang, Shi-Qian] Univ South China, Hengyang Med Coll, Dept Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Nie, Gui-Ying] Univ South China, Grade Excellent Doctor Class Hengyang Med Coll 201, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, CK ] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
Nuclear factor interleukin-3 (NFIL3), a proline- and acidic-residue-rich (PAR) bZIP transcription factor, is called the E4 binding protein 4 (E4BP4) as well, which is relevant to regulate the circadian rhythms and the viability of cells. More and more evidence has shown that NFIL3 is associated with different cardiovascular diseases. In recent years, it has been found that NFIL3 has significant functions in the progression of atherosclerosis (AS) via the regulation of inflammatory response, macrophage polarization, some immune cells and lipid metabolism. In this overview, we sum up the function of NFIL3 during the development of AS and offer meaningful views how to treat cardiovascular disease related to AS.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease among old adults. As a traditional Chinese medicine, the herbal decoction Tian-Si-Yin consists of Morinda officinalis How. and Cuscuta chinensis Lam., which has been widely used to nourish kidney. Interestingly, Tian-Si-Yin has also been used to treat dementia, depression and other neurological conditions. However, its therapeutic potential for neurodegenerative diseases such as AD and the underlying mechanisms remain unclear. AIM OF THE STUDY: To evaluate the therapeutic effect of the herbal formula Tian-Si-Yin against AD and to explore the underlying mechanisms. MATERIALS AND METHODS: The N2a cells treated with amyloid β (Aβ) peptide or overexpressing amyloid precursor protein (APP) were used to establish cellular models of AD. The in vivo anti-AD effects were evaluated by using Caenorhabditis elegans and 3×Tg-AD mouse models. Tian-Si-Yin was orally administered to the mice for 8 weeks at a dose of 10, 15 or 20mg/kg/day, respectively. Its protective role on memory deficits of mice was examined using the Morris water maze and fear conditioning tests. Network pharmacology, proteomic analysis and ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS) were used to explore the underlying molecular mechanisms, which were further investigated by Western blotting and immunohistochemistry. RESULTS: Tian-Si-Yin was shown to improve cell viability of Aβ-treated N2a cells and APP-expressing N2a-APP cells. Tian-Si-Yin was also found to reduce ROS level and extend lifespan of transgenic AD-like C. elegans model. Oral administration of Tian-Si-Yin at medium dose was able to effectively rescue memory impairment in 3×Tg mice. Tian-Si-Yin was further shown to suppress neuroinflammation by inhibition of glia cell activation and downregulation of inflammatory cytokines, diminishing tau phosphoralytion and Aβ deposition in the mice. Using UHPLC-MS/MS and network pharmacology technologies, 17 phytochemicals from 68 components of Tian-Si-Yin were identified as potential anti-AD components. MAPK1, BRAF, TTR and Fyn were identified as anti-AD targets of Tian-Si-Yin from network pharmacology and mass spectrum. CONCLUSIONS: This study has established the protective effect of Tian-Si-Yin against AD and demonstrates that Tian-Si-Yin is capable of improving Aβ level, tau pathology and synaptic disorder by regulating inflammatory response.
期刊：
Journal of Affective Disorders,2024年349:342-348 ISSN：0165-0327
通讯作者：
Zhao, JF
作者机构：
[Cao, Xueer; Li, Qingqi; Zhao, Jianfeng] Univ South China, Inst Neurosci, Hengyang Med Sch, Hengyang, Peoples R China.;[Wu, Hongrong; Tang, Shuangyang] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang, Peoples R China.;[Zhao, Jianfeng] Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang, Peoples R China.;[Zhao, Jianfeng] Univ South China, Inst Neurosci, Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhao, JF ] U;Univ South China, Inst Neurosci, Med Sch, Hengyang 421001, Hunan, Peoples R China.
关键词：
Depression;Diabetes;Statin
摘要：
Background: Depression is a common mental disorder. Some studies have demonstrated that people with diabetes are more likely to suffer from depression. Statins are an everyday use for diabetes. Trials of statin therapy have had conflicting findings on the potential risk of depression. Methods: The National Health and Nutrition Examination Survey (NHANES) 2005-2018 was used to collect a representative sample. Weighted multivariate logistic regression models were used to evaluate odds ratios (ORs) and 95 % CIs for having depression symptoms. We performed stratified analyses to compare the effects of statins in subsamples with and without diabetes on depression symptoms. Results: Statin use showed a significant and strong decreasing effect on having depression symptoms in participants with diabetes (aOR (adjusted OR) 0.59, p = 0.014) compared with that in non -diabetics (aOR 0.78, p = 0.128). Diabetic individuals with statin use for >5 years had a lower risk of having depression symptoms (aOR 0.42, p = 0.002) than those with shorter -term statin use (1-5 years, aOR 0.69, p = 0.111; <1 year: aOR 0.83, p = 0.646). Atorvastatin was more effective in decreasing depression symptoms either in diabetes (aOR 0.49, p = 0.018) or in non -diabetes (aOR 0.58, p = 0.033). Limitations: First, the dosage of statins cannot be obtained from NHANES datasets. Second, after being stratified, the number of participants for several statins was insufficient. Third, recall bias may exist in the survey. Conclusions: Diabetics with depression symptoms may benefit from long-term statin therapy. Atorvastatin and pravastatin should be recommended for diabetic patients with depression.
作者机构：
[Zhang, Shaoqi; Deng, Zhongliang; He, Jun; He, J; Zhen, Deshuai] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Clin Lab, Hengyang 421001, Hunan, Peoples R China.;[Fang, Jing; Zhang, Shaoqi; Deng, Zhongliang; Zhen, Deshuai; Yang, Aofeng; Ma, Qian] Univ South China, Coll Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;[Cai, Qingyun; Zhen, Deshuai] Hunan Univ, Sch Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.
通讯机构：
[He, J ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Clin Lab, Hengyang 421001, Hunan, Peoples R China.
关键词：
CRISPR/Cas9;Rolling circle amplification;S. aureus;Silver chain
摘要：
With the rising emphasis on food safety, technology to rapidly identify Staphylococcus aureus (S. aureus) is of great significance. Herein, we developed a novel electrochemical biosensor based on the CRISPR/Cas9 system and rolling circle amplification (RCA)-assisted "silver chain"-linked gold interdigital electrodes (Au-IDE). This sensor utilizes RCA to create DNA long chains that span the Au-IDE, and CRISPR/Cas9 as a recognition component to recognize capture/target dsDNA. Additionally, we used silver staining technology to improve detection sensitivity. Then, we detected S. aureus through impedance changes that occurred when the silver chain between the Au-IDE was connected or broke, with a limit of detection (LOD) of 7CFU/mL and a detection time of 1.5h. Lastly, we successfully employed this sensor to detect S. aureus in real food samples, making it a promising tool for food monitoring.
作者机构：
[Zhang, Yuexin; Mu, Xinxin; Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Song, Chao; Tang, Huifang; Yin, Mingxue; Zhang, Hang] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Mu, Xinxin; Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Song, Chao; Tang, Huifang; Yin, Mingxue; Zhang, Hang] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Yin, Mingxue] Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Yin, Mingxue] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, CQ ; Tang, HF ; Tang, HF] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
gated blood-pool imaging;chromatin;genetics;mice;enhancer of transcription;candidate disease gene;single nucleotide polymorphism;crispr;genes;rna;genome;methylation
摘要：
Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs. Graphical Abstract
通讯机构：
[Tan, XF; Yang, QL ] U;[Jiao, L ] Q;Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang Med Sch,Hunan Prov Key Lab Tumor Cellular, Hengyang 421001, Hunan, Peoples R China.;Qingdao Univ, Inst Mol Metrol, Coll Chem & Chem Engn, Qingdao 266071, Peoples R China.
摘要：
Although antibacterial platforms involving nanozymes have been extensively investigated, there are still problems of poor reactive oxygen species generation efficiency and obstinate bacterial biofilms. Developing a nanozyme-photothermal therapy nanoplatform with superior sterilization effects and minimal side effects would be a good alternative for completely eliminating bacteria and biofilms. Herein, an ultrathin PdMo bimetallene nanozyme with a planar topology and boosted metal utilization, exhibiting excellent photothermal and peroxidase-like activity, is designed for synergistic nanozyme-photothermal sterilization applications and accelerated wound healing. The superior catalytic activity of PdMo bimetallene nanozymes could convert a biosafe concentration of hydrogen peroxide (H2O2) into large quantities of toxic hydroxyl radicals (center dot OH) under laser irradiation, enhancing bacterial membrane permeability and thermal sensitivity for efficient removal of bacteria and biofilms. In addition, PdMo bimetallene presents a good wound-healing ability according to the results of fibroblast proliferation and collagen deposition with minor side effects. This work would provide an innovative avenue for developing metallene-based nanozymes for biomedical applications. An ultrathin PdMo bimetallene nanozyme with excellent photothermal and peroxidase-like activity is designed for synergistic nanozyme-photothermal sterilization applications and accelerated wound healing.
摘要：
Key steps of mycoplasma invasion into host cells: Upon adhesin binding to cell membrane receptors (a), host cells undergo morphological changes characterized by progressive membrane invagination (b). Subsequently, mycoplasma undergo internalization facilitated by protein‐coated vesicles (c) and endosome transport (d). Ultimately, the mycoplasma survives, proliferates within the cell, and localizes to the nucleus (e). Abstract Mycoplasma belong to the genus Mollicutes and are notable for their small genome sizes (500–1300 kb) and limited biosynthetic capabilities. They exhibit pathogenicity by invading various cell types to survive as intracellular pathogens. Adhesion is a crucial prerequisite for successful invasion and is orchestrated by the interplay between mycoplasma surface adhesins and specific receptors on the host cell membrane. Invasion relies heavily on clathrin‐ and caveolae‐mediated internalization, accompanied by multiple activated kinases, cytoskeletal rearrangement, and a myriad of morphological alterations, such as membrane invagination, nuclear hypertrophy and aggregation, cytoplasmic edema, and vacuolization. Once mycoplasma successfully invade host cells, they establish resilient sanctuaries in vesicles, cytoplasm, perinuclear regions, and the nucleus, wherein specific environmental conditions favor long‐term survival. Although lysosomal degradation and autophagy can eliminate most invading mycoplasmas, some viable bacteria can be released into the extracellular environment via exocytosis, a crucial factor in the prolonging infection persistence. This review explores the intricate mechanisms by which mycoplasma invades host cells and perpetuates their elusive survival, with the aim of highlighting the challenge of eradicating this enigmatic bacterium.
摘要：
During embryonic development, the cardiovascular system and the central nervous system exhibit a coordinated developmental process through intricate interactions. Congenital heart disease (CHD) refers to structural or functional abnormalities that occur during embryonic or prenatal heart development and is the most common congenital disorder. One of the most common complications in CHD patients is neurodevelopmental disorders (NDD). However, the specific mechanisms, connections, and precise ways in which CHD co-occurs with NDD remain unclear. According to relevant research, both genetic and non-genetic factors are significant contributors to the co-occurrence of sporadic CHD and NDD. Genetic variations, such as chromosomal abnormalities and gene mutations, play a role in the susceptibility to both CHD and NDD. Further research should aim to identify common molecular mechanisms that underlie the co-occurrence of CHD and NDD, possibly originating from shared genetic mutations or shared gene regulation. Therefore, this review article summarizes the current advances in the genetics of CHD co-occurring with NDD, elucidating the application of relevant gene detection techniques. This is done with the aim of exploring the genetic regulatory mechanisms of CHD co-occurring with NDD at the gene level and promoting research and treatment of developmental disorders related to the cardiovascular and central nervous systems.
作者：
Chen, Y Q;Zhang, Y D;Yan, H;Qin, H Y;Huang, Z;...
期刊：
中华医学杂志,2024年104(4):282-289 ISSN：0376-2491
作者机构：
[Zhang, Y D; Chen, Y Q; Yan, H; Huang, Z; Qin, H Y; Zhang, X] Department of Medical Oncology, Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China;[Xiang, S Q] Department of Biochemistry and Immunology, Medical Research Center, Institute of Medicine, Jishou University, Jishou 416000, China;[Hu, X Q] Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China;[Wu, F] Department of Pathology, Immuno-Oncology Laboratory, School of Basic Medicine, Central South University, Changsha 410017, China;[Zhang, Y C; Zeng, L; Yang, N] Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Changsha 410013, China
摘要：
Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.
期刊：
Current Problems in Cardiology,2024年49(1):102116 ISSN：0146-2806
通讯作者：
Wang, C;Zheng, K
作者机构：
[Zheng, Kang; Zeng, Guang-Gui] Hengyang Cent Hosp, Dept Clin Lab, Hengyang, Hunan, Peoples R China.;[Wang, Chuan; Zeng, Guang-Gui] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang, Hunan, Peoples R China.;[Jiang, Wan-Li; Nie, Gui-Ying; Yu, Jiang; Zeng, Guang-Gui] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.;[Lu, Yu-Ru] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Emergency Med, Wuhan, Hubei, Peoples R China.;[Lu, Yu-Ru] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Intens Care Med, Wuhan, Hubei, Peoples R China.
通讯机构：
[Wang, C ] U;[Zheng, K ] H;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;Hengyang Cent Hosp, Dept Clin Lab, Hengyang 421001, Hunan, Peoples R China.
摘要：
Mpox, a novel epidemic disease, has broken out the period of coronavirus disease 2019 since May 2022, which was caused by the mpox virus. Up to 12 September 2023, there are more than 90,439 confirmed mpox cases in over 115 countries all over the world. Moreover, the outbreak of mpox in 2022 was verified to be Clade II rather than Clade I. Highlighting the significance of this finding, a growing body of literature suggests that mpox may lead to a series of cardiovascular complications, including myocarditis and pericarditis. It is indeed crucial to acquire more knowledge about mpox from a perspective from the clinical cardiologist. In this review, we would discuss the epidemiological characteristics and primary treatments of mpox to attempt to provide a framework for cardiovascular physicians.
期刊：
Current Problems in Cardiology,2024年49(1):102088 ISSN：0146-2806
通讯作者：
Tang, CK
作者机构：
Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang Med Sch,Hunan Int Sci & Technol Cooperat, Hengyang, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Grade Excellent Doctor Class 2020, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 7, Hunan Vet Adm Hosp, Hengyang Med Sch, Changsha, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Dept Clin Med, Hengyang, Hunan, Peoples R China.;[Tang, Chao-Ke] Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, CK ] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
Vascular disease is a common problem with high mortality all over the world. Apelin-13, a key subtype of apelin, takes part in many physiological and pathological responses via regulating many target genes and target molecules or participating in many signaling pathways. More and more studies have demonstrated that apelin-13 is implicated in the onset and progression of vascular disease in recent years. It has been shown that apelin-13 could ameliorate vascular disease by inhibiting inflammation, restraining apoptosis, suppressing oxidative stress, and facilitating autophagy. In this article, we sum up the progress of apelin-13 in the occurrence and development of vascular disease and offer some insightful views about the treatment and prevention strategies of vascular disease.
摘要：
BACKGROUND: The cellular endoplasmic reticulum (ER) is responsible for various functions, including protein synthesis, folding, distribution, and calcium ion storage. Studies have linked ER stress with acute lung injury (ALI), which can result in oxidative stress and even cell death. Peroxynitrite (ONOO(-)) is a well-known reactive oxygen species (ROS) that contributes to various physiological and pathological processes in oxidative stress diseases. To understand the role of ER ONOO(-) in ALI, it is crucial to accurately measure its level in the ER. Unfortunately, there is currently no probe available to detect ER ONOO(-) in an ALI model. RESULTS: To address this, we developed three near-infrared (NIR) fluorescent probes (DCM-F-ONOO, DCM-Cl-ONOO, and DCM-Br-ONOO) for the detection of ONOO(-) using pentafluorobenzenesulfonate (PFBS) moieties as fluorescence quenchers. Through comprehensive testing, we selected DCM-Br-ONOO as the best NIR fluorescent probe due to its rapid response (within 3min), high selectivity, good sensitivity (LOD=2.3nM), and approximately 66-fold enhanced response to ONOO(-) in fluorescence intensity. The probe was successfully applied to detect changes in ONOO(-) levels induced by different drugs in the ER of living cells. Importantly, a significant increase in the level of ONOO(-) was observed in the ER of an ALI cell model (4.5-fold) and an ALI mouse model (2.5-fold) using the probe, which is essential for understanding the role of ONOO(-) in ER-associated diseases. SIGNIFICANCE: Using DCM-Br-ONOO as a probe, present work further validated that the elevated levels of ONOO(-) secretion were accompanied by the ALI progressed. These findings may provide valuable results for figuring out the biological roles that ONOO(-) played in ALI.
