作者机构：
[Xie, Qinling; Wang, Wei; Luo, Jiangyi; Liang, Ling; Jiang, Sai; Chen, Shenghuang; Fu, Yangfen; Yuan, Hanwen] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha, Peoples R China.
通讯机构：
[Luo, Jiangyi] T;TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Material Medical Research Institute, School of Pharmacy, Hunan University of Chinese Medicine Changsha China wangwei402@hotmail.com +86-731-8845-8227 +86-136-5743-8606
摘要：
Gentianae Macrophyllae Radix, the dried root of Gentiana macrophylla Pall., Gentiana crassicaulis Duthie ex Burk., Gentiana straminea Maxim., or Gentiana dahurica Fisch., is a traditional Chinese medicine with multi-origins and some adulterants. Liquid chromatography coupled to electrostatic orbitrap high-resolution mass spectrometry (LC-Orbitrap-MS) was used to search the different components of Gentianae Macrophyllae Radix of the four species. High-performance liquid chromatography (HPLC) combined with fingerprint analysis, principal components analysis (PCA), and partial least-squares discrimination analysis (PLS-DA) was also utilized to distinguish them and their adulterants based on the critical components identified by LC-MS. A single standard to determine the multi-components (SSDMC) method was established for the determination of the critical markers. A total of 93 compounds were identified from Gentianae Macrophyllae Radix, including 58 common ones. Their HPLC fingerprints show a significant difference with the adulterants. In addition, PCA and PLS-DA could make a distinction among the four species. Loganic acid, 6'-O-β-d-glucosylgentiopicroside, swertiamarine, gentiopicroside, and sweroside were identified as the critical markers and then quantified by the SSDMC method. The developed strategy is powerful for the quality control and authentication of Gentianae Macrophyllae Radix.
作者机构：
[Liu, Yu; Yue, ZH; Wang, Shaohua; Pan, Sian; Yuan, Hanyu; Yue, Zenghui; Li, Juan; Xue, Xiao] Hunan Univ Chinese Med, Coll Acupuncture Massage & Rehabil, Changsha, Peoples R China.;[Liu, Xin; Xue, Xiao] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Chinese Med, Heng Yang, Hunan, Peoples R China.
通讯机构：
[Liu, Y; Yue, ZH ] H;Hunan Univ Chinese Med, Coll Acupuncture Massage & Rehabil, Changsha, Peoples R China.
摘要：
BACKGROUND: Primary dysmenorrhea in women is a common and serious public health problem with psychological and physical effects. Painkillers have adverse effects, such as tolerance, addiction, irritation of the digestive tract, and liver and kidney damage. Electroacupuncture has been used as alternative therapy, although with no (non-anecdotal) evidence of effectiveness. OBJECTIVE: This study aims to provide evidence for the feasibility and efficacy of electroacupuncture in the treatment of primary dysmenorrhea. Moreover, by observing changes in serum and urine metabolites, we will evaluate the putative mechanisms mediating electroacupuncture effects in primary dysmenorrhea. METHODS: This multicenter, randomized, participant-blinded, sham-controlled clinical trial including 336 women with primary dysmenorrhea is being conducted at three hospital centers in China and consists of a 12-week treatment and a 3-month follow-up. Women will undergo electroacupuncture (n = 168) or sham acupuncture (n = 168), beginning 7 days before their menstruation, once per day, until menstruation. Each menstrual cycle equals one course of treatment, and we will evaluate a total of three courses of treatment. The primary outcome of interest is the change in visual analogue scale scores before and after treatment. The secondary outcomes include changes in the numeric rating scale, Cox Menstrual Symptom Scale, traditional Chinese medicine symptoms, the Self-Rating Anxiety Scale, Self-Rating Depression Scale, and 36-Item Short Form questionnaire scores, and a safety evaluation. Moreover, we will preliminarily investigate the metabolomics mechanism as a potential mediator of the association between electroacupuncture and primary dysmenorrhea symptomology. DISCUSSION: We aim to find a suitable non-medicinal alternative for primary dysmenorrhea treatment to reduce reliance on non-steroidal anti-inflammatory drugs. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100054234; http://www.chictr.org.cn/.
作者机构：
[Shi, Zhi Min; Wei, Jia-ming] Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Peoples R China.;[Wang, Zi-yan; Yuan, Hui; Liu, Cheng-xin] Hunan Univ Chinese Med, Clin Coll Chinese Med 1, Changsha 410208, Peoples R China.;[Wang, Zi-yan; Shi, Zhi Min; Yuan, Hui; Wei, Jia-ming; Liu, Cheng-xin] Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent Tradit Chine, Changsha 410208, Peoples R China.;[Li, Y; Li, Ya] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Li, Y ; Shi, ZM ] H;Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent Tradit Chine, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
关键词：
ApoE(-/-) mice;Atherosclerosis;NOX/ROS/NF-κB signal pathway;Vascular smooth muscle cell;Xin-tong-tai
摘要：
Background: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. Purpose: This study aims to explore the potential mechanism of XTTG for treating AS. Methods: An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (oxLDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/ NF-.kappa B signaling pathway indicators were observed. Results: XTTG improved blood lipid levels and pathological aortic changes of ApoE / mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-alpha, IKK-ss, NF-.kappa B protein and mRNA expression and the phosphorylation of NF-.kappa B. Conclusion: XTTG can inhibit NOX/ROS/NF-.kappa B signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.
期刊：
Evidence-Based Complementary and Alternative Medicine,2023年2023 ISSN：1741-427X
作者机构：
[Wang, Peng; Yi, Qipeng; Yue, Kaifeng; Sun, Shulin] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Xie, Xianmin; Xie, Xinjun] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept External Hand Trauma, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
摘要：
This study aimed to explore the effect and mechanism of Dragon's Blood on wound healing in patients with a pressure hand injury. A total of 120 patients with pressure hand injury treated in our hospital were randomly divided into two groups. Sixty patients in the control group were dressed with sterile gauze, and 60 patients in the observation group were smeared with blood exhaustion. The clinical effects and serological indexes of the two groups were compared, and the mechanism of wound healing was analyzed. The results showed that the treatment effective rate of the control group was 80% and that of the observation group was 93.33%. The treatment effective rate of the observation group was dramatically higher (P < 0.05). The number of patients with good granulation tissue in the observation group was 53, which was dramatically greater than that in the control group. The number of patients with a small amount of wound exudation was 51, which was dramatically greater than that in the control group (P < 0.05). After treatment, the levels of matrix metalloproteinase (MMP-3), vascular endothelial growth factor (VEGF), and transforming growth factor B1 (TGF-B1) in the observation group increased more dramatically (P < 0.05). The level of tissue inhibitor of metalloproteinase-1 (TIMP-1) decreased to 617.23 ng/L in the observation group, and the degree of reduction was more obvious (P < 0.05). Notably, Dragon's Blood promoted wound healing at the injury site by increasing the levels of MMP-3, VEGF, and TGF-B1and decreasing TIMP-1. The area of wound reduction in the observation group was 0.27 cm(2), and the reduction was more obvious (P < 0.05). The healing time of pressure hand injury in the observation group was 15.27 days, which was dramatically shorter (P < 0.05). In summary, Dragon's Blood had a good effect on the healing of the injured site in patients with pressure hand injury, which is worthy of promotion.
期刊：
Journal of Clinical Nursing,2023年32(13-14):3504-3515 ISSN：0962-1067
通讯作者：
Zhang, YH
作者机构：
[Yu, Qian; Feng, Xiaolin; Zhang, Yinhua; Pu, Haixu; Yan, Lichun] Hunan Univ Chinese Med, Sch Nursing, 300,Xueshi Rd, Changsha 410208, Peoples R China.;[Zhang, Xiaoqin] Hunan Univ Chinese Med, Sch Marxism, Changsha, Peoples R China.;[Luo, Liangchu] Hunan Univ Chinese Med, Sch Clin Med, Changsha, Peoples R China.
通讯机构：
[Zhang, YH ] H;Hunan Univ Chinese Med, Sch Nursing, 300,Xueshi Rd, Changsha 410208, Peoples R China.
关键词：
aged care facilities;associated risk factors;physical restraints;prevalence
摘要：
Aims and Objectives To investigate the use of physical restraints in aged care facilities(ACFs)and analyse its associated risk factors. Background Physical restraints have been widely used in ACFs worldwide, but they can cause physical and mental harm to older people. It is important to regulate the use of physical restraint. Design A cross-sectional observational and correlational multicentre study. Methods By convenience sampling method, we selected eight ACFs in four representative regions of Hunan province, China, for this study. The ACF-related information was obtained by interviewing the managers and reviewing records. We conducted investigation and observation on the elderly in the ACFs to understand the use of physical restraints at three different times: 9:30-11:30, 16:00-18:00 and 19:30-21:30 on a working day. The STROBE checklist was followed for this cross-sectional study. Results This study found that the utilisation rate of physical restraints was 23.2%. The critical risk factors affecting the use of physical restrains include the following: (1) the ratio of nursing staff to the elderly residents; (2)whether there is a dementia care unit at the facility; (3) the number of elderly residents in each room; (4) the elderly residents' age, degree of education, marital status, care dependence and cognitive impairment; (5) whether the elderly has suffered from a stroke or senile dementia; (6) whether the elderly carries medical catheters. Conclusion There is a lack of standardisation in the use of physical restraints in ACFs of central China. Chinese ACFs should develop guidelines and reduction measures to standardise the use of physical restraints, basing on the key factors affecting the use of physical restraints. Relevance to clinical practice The use of physical restraints in ACFs is threatening the safety of the elderly residents. Understanding the implementation of physical restraint in ACFs can provide reference for reducing the use of physical restraint.
摘要：
BACKGROUND: Circular RNAs (circRNAs) have been shown to play an important role in cerebral ischemia-reperfusion (I/R) injury. However, the role of circAsxl2 (mmu_circ_0000346) in cerebral I/R injury remains unclear. METHODS: Mouse brain neuronal cell line (HT-22) was used to perform oxygen-glucose deprivation/reperfusion (OGD/R) treatment. The levels of circAsxl2, microRNA (miR)-130b-5p and forkhead box O3 (FOXO3) were determined using quantitative real-time PCR. Cell viability and apoptosis were measured using cell counting kit 8 assay and flow cytometry. Commercial kits were used to assess cell cytotoxicity, inflammation and oxidative stress. Protein expression was analyzed by western blot. RNA interaction was verified using dual-luciferase reporter assay, RIP assay and RNA pull-down assay. RESULTS: CircAsxl2 was highly expressed in OGD/R-induced HT-22 cells, and its silencing could alleviate OGD/R-induced apoptosis, inflammation and oxidative stress in HT-22 cells. MiR-130b-5p was sponged by circAsxl2, and its inhibitor could overturn the regulation of circAsxl2 knockdown on OGD/R-induced neuronal injury. FOXO3 was targeted by miR-130b-5p and its expression was positively regulated by circAsxl2. In addition, the regulation of circAsxl2 knockdown on OGD/R-induced neuronal injury also was reversed by FOXO3 overexpression. CONCLUSION: CircAsxl2/miR-130b-5p/FOXO3 axis accelerated OGD/R-induced neuronal injury, which might provide effective strategies for treating cerebral I/R injury.
摘要：
Background: Chronic heart failure (CHF) is a common and difficult-to-treat disease in clinical practice. The efficacy and safety of Zhenyuan capsule (ZYC) in the treatment of CHF were evaluated by meta-analysis and trial sequential analysis (TSA) of published relevant data. Methods: Searched 8 databases for clinical literature on ZYC in the treatment of CHF, up to December 2022. Then the meta-analysis and TSA were performed on the studies that met the inclusion criteria. Results: Meta-analysis showed that compared with conventional treatment, combined use of ZYC could significantly increase the clinical effective rate (risk ratio 1.20, 95% confidence interval [CI] 1.14 similar to 1.26, P < .00001) by 20%, left ventricular ejection fraction (MD 8.85, 95%CI 4.57 similar to 13.12, P < .0001) by 8.85%, and 6-minutes walking distance (MD 47.91, 95%CI 18.66 similar to 77.17, P = .001) by 47.91 m, and significantly reduce brain natriuretic peptide (MD -247.86, 95%CI -330.62 similar to-165.09, P < .00001) by 247.86 pg/mL. TSA showed that the benefits suggested by the original results were conclusive. In terms of safety, the total adverse events in the combined group of ZYC were comparable to those in the conventional group, and TSA demonstrated that this result needed more research and demonstration. Conclusion: ZYC can effectively improve the clinical efficacy of treating CHF, significantly increase left ventricular ejection fraction and 6-minute walk distance, and remarkably reduce brain natriuretic peptide. ZYC, with definite efficacy and safety, has the value of clinical application and in-depth research.
摘要：
BACKGROUND: Studies are ongoing to examine the versatile functions of circular RNAs (circRNAs) in human diseases. This research investigates the effects of hsa_circ_0000644 (circ_644) and its related molecules on the malignant behavior of bladder cancer (BCa) cells. METHODS: Abundant bioinformatics analyses were performed to screen the key circRNA and its related molecules in BCa. Tumor tissues and the para-tumorous tissues were collected from 58 patients with BCa. Expression of RUNX family transcription factor 3 (RUNX3), circ_644, microRNA-143-3p (miR-143-3p), and musashi RNA binding protein 2 (MSI2) in BCa tissues or cells was determined. Molecular interactions were confirmed by chromatin immunoprecipitation, RNA pull-down, and luciferase assays. Gain and loss-of function assays were performed using two BCa cell lines (T24 and HT1376). RESULTS: Circ_644 was highly expressed whereas RUNX3, which could suppress circ_644 transcription, was lowly expressed in BCa tissues and cells. Upregulation of RUNX3 suppressed proliferation, colony formation, migration and invasion, and tumorigenicity of BCa cells and induced cell cycle arrest. However, the tumor-suppressive effects of RUNX3 were blocked by circ_644 upregulation. Circ_644 served as a sponge for miR-143-3p, and miR-143-3p bound to MSI2 mRNA. The rescue experiments showed that miR-143-3p inhibition or MSI2 overexpression restored the malignant behaviors of BCa cells induced by circ_644 knockdown or RUNX3 overexpression. CONCLUSION: This study demonstrates that transcriptional activation of circ_644 upon RUNX3 downregulation drives the malignant development of BCa through the miR-143-3p/MSI2 axis. RUNX3 restoration or specific inhibition of circ_644 or MSI2 may help block BCa progression.
摘要：
Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.
作者机构：
[Zhang, Wei; Chen, Ting] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Peoples R China.;[Zhang, Yulong; Huang, Weihua; Zhang, Wei; Chen, Ting; Chen, Manyun] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Peoples R China.;[Zhang, Yulong; Huang, Weihua; Zhang, Wei; Chen, Ting; Chen, Manyun] Cent South Univ, Inst Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha, Peoples R China.;[Zhang, Yulong; Huang, Weihua; Zhang, Wei; Chen, Ting; Chen, Manyun] Minist Educ, Engn Res Ctr Appl Technol Pharmacogenom, Changsha, Peoples R China.;[Wang, Yi; Chen, Ting] Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin, Peoples R China.
通讯机构：
[Weihua Huang; Wei Zhang] D;Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China<&wdkj&>Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, People's Republic of China<&wdkj&>Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, People's Republic of China<&wdkj&>Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China<&wdkj&>Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, People's Republic of China<&wdkj&>Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, People's Republic of China
摘要：
Context The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms remain unclear. Objective This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR. Materials and methods We used a myocardial NR rat model to confirm the effect and mechanism of action of TMYX in alleviating NR. Sprague-Dawley (SD) rats were divided into Control (Con), sham, NR, TMYX (4.0 g/kg), and sodium nitroprusside (SNP, 5.0 mg/kg), and received their treatments once a day for one week. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively. Results TMYX (4.0 g/kg) showed therapeutic effects on NR by improving the cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the expression of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the HIF-1, NF-kappa B, and TNF signaling pathways. In vivo, TMYX decreased the expression of MPO, NF-kappa B, and TNF-alpha and increased the expression of GPER, p-ERK, and HIF-1 alpha. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by G-15, H-89, L-NAME, ODQ and four K+ channel inhibitors. Conclusions TMYX exerts its pharmacological effects in the treatment of NR via multiple targets. However, the contribution of each pathway was not detected, and the mechanisms should be further investigated.
期刊：
International Journal of Analytical Chemistry,2023年2023 ISSN：1687-8760
通讯作者：
He, Yongheng(2320990685@qq.com)
作者机构：
[Yao, Yanru; Ding, Ning; Luo, Hongbiao; Zhang, Tao] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Luo, Hongbiao] Chenzhou 1 Peoples Hosp, Dept Anorectal Surg, Chenzhou 423000, Peoples R China.;[Peng, Tianshu] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Anorectal Surg, Changsha 410005, Hunan, Peoples R China.;[He, Yongheng] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Anorectal Surg, Changsha 410006, Hunan, Peoples R China.
通讯机构：
[Hongbiao Luo; Ning Ding; Yanru Yao; Tao Zhang] H;[Yongheng He; Tianshu Peng] D;Department of Anorectal Surgery,The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine,Changsha,China<&wdkj&>Department of Anorectal Surgery,The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha,China<&wdkj&>Hunan University of Chinese Medicine,Changsha,Hunan 410208,China<&wdkj&>Department of Anorectal Surgery,Chenzhou NO. 1 People’s Hospital,Chenzhou 423000,China<&wdkj&>Hunan University of Chinese Medicine,Changsha,Hunan 410208,China
关键词：
Introduction;Materials and Methods;Results;Discussion;Conclusion;Abstract;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interests;Authors’ Contributions;Funding Statement;Acknowledgements;Acknowledgments;Supplementary Materials;Reference;Dataset Description;Dataset Files;Abstract;Introduction;Introduction and Materials;Introduction and Methods;Materials;Materials and Methods;Methods;Results;Discussion;Results and Discussion;Discussion and Conclusion;Results and Conclusion;Conclusion;Conclusions;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interest;Authors’ Contributions;Funding Statement;Acknowledgements;Supplementary Materials;References;Appendix;Abbreviations;Preliminaries;Introduction and Preliminaries;Notation;Proof of Theorem;Proofs;Analysis of Results;Examples;Numerical Example;Applications;Numerical Simulation;Model;Model Formulation;Systematic Palaeontology;Nomenclatural Acts;Taxonomic Implications;Experimental;Synthesis;Overview;Characterization;Background;Experimental;Theories;Calculations;Model Verification;Model Implementation;Geographic location;Study Area;Geological setting;Data Collection;Field Testing;Data and Sampling;Dataset;Literature Review;Related Works;Related Work;System Model;Methods and Data;Experimental Results;Results and Analysis;Evaluation;Implementation;Case Presentation;Case Report;Search Terms;Case Description;Case Series;Background;Limitations;Additional Points;Case;Case 1;Case 2 etc.;Concern Details;Retraction Details;Copyright;Related Articles
通讯机构：
[Shi, LR ] ;Cent South Univ, Xiangya Hosp, Dept Radiol, 87 Xiangya Rd, Changsha 410005, Peoples R China.
摘要：
PURPOSE: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. RESULTS: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. CONCLUSIONS: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.
摘要：
Autoimmune diseases are characterized by a breakdown of immune tolerance, leading to inflammation and irreversible end-organ tissue damage. Platelet extracellular vesicles are cellular elements that are important in blood circulation and actively participate in inflammatory and immune responses through intercellular communication and interactions between inflammatory cells, immune cells, and their secreted factors. Therefore, platelet extracellular vesicles are the "accelerator" in the pathological process of autoimmune diseases; however, this robust set of functions of platelet extracellular vesicles has also prompted new advances in therapeutic strategies for autoimmune diseases. In this review, we update fundamental mechanisms based on platelet extracellular vesicles communication function in autoimmune diseases. We also focus on the potential role of platelet extracellular vesicles for the treatment of autoimmune diseases. Some recent studies have found that antiplatelet aggregation drugs, specific biological agents can reduce the release of platelet extracellular vesicles. Platelet extracellular vesicles can also serve as vehicles to deliver drugs to targeted cells. It seems that we can try to silence or inhibit microRNA carried by platelet extracellular vesicles transcription and regulate the target cells to treat autoimmune diseases as platelet extracellular vesicles can transfer microRNA to other cells to regulate immune-inflammatory responses. Hopefully, the information presented here will provide hope for patients with autoimmune diseases. PLAIN LANGUAGE SUMMARYAutoimmune diseases patients are characterized by autoimmune disorders, whose immune system cannot distinguish between auto- and foreign-antigens. Autoimmune diseases is the third significant disease threatening human health after cardiovascular disease and cancer. However, the exact etiology of autoimmune diseases has yet to be fully elucidated. Several studies have shown that platelet extracellular vesicle content is elevated in multiple autoimmune disorders and positively correlates with disease activity. However, our knowledge about the details of the mechanisms still remains limited and fragmentary. This article updates the communication function of platelet extracellular vesicles in accelerating autoimmune and inflammatory responses. The interesting thing is every coin has two sides. We put forward a new treatment idea for AD based on the particular volume and powerful intercellular communication function of platelet extracellular vesicles. Inhibition of the communication function of platelet extracellular vesicles seems to be considered in the future, or silence or block miRNA of platelet extracellular vesicles involved in the pathogenesis of AD. We can even use it as a drug carrier to deliver the drug to the relevant target cells, thereby enhancing the role of the medicine in regulating immune response and inhibiting inflammation. This paper not only provides a deeper understanding of the pathogenesis of autoimmune diseases but also provides theoretical support for the use of platelet extracellular vesicles to achieve targeted therapy.
期刊：
Frontiers in Pharmacology,2023年14:1137609 ISSN：1663-9812
通讯作者：
Liu, BY;Yuan, CY
作者机构：
[Yi, Jian; Tian, Fengming; Xu, Yaqian; Liu, Baiyan; Liu, BY; Chen, Bowei; Ouyang, Yin; Liu, Yingfei] Hunan Univ Chinese Med, Hosp 1, Changsha, Peoples R China.;[Yi, Jian; Tian, Fengming; Xu, Yaqian; Liu, Baiyan; Liu, BY; Chen, Bowei; Ouyang, Yin; Liu, Yingfei] Hunan Univ Chinese Med, MOE Key Lab Res & Translat Prevent & Treatment Maj, Changsha, Peoples R China.;[Yuan, Chunyun] Hunan Hosp Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Yuan, Chunyun] Hunan Acad Chinese Med, Affiliated Hosp, Changsha, Peoples R China.;[Liu, Baiyan; Liu, BY] Hunan Acad Chinese Med, Changsha, Peoples R China.
通讯机构：
[Liu, BY ; Yuan, CY ] H;Hunan Univ Chinese Med, Hosp 1, Changsha, Peoples R China.;Hunan Univ Chinese Med, MOE Key Lab Res & Translat Prevent & Treatment Maj, Changsha, Peoples R China.;Hunan Hosp Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Hunan Acad Chinese Med, Affiliated Hosp, Changsha, Peoples R China.
作者机构：
[Zhong, Dayuan; Liu, Pingwen; Liu, Deliang; Ou, Xueming] Guangzhou Univ Chinese Med, Guangdong Prov Hosp Integrated Tradit Chinese & We, Foshan 528200, Peoples R China.;[Zheng, Mengxue; Gan, Zhenyu; Luo, Hongsheng] Guangzhou Univ Chinese Med, Guangzhou 510006, Peoples R China.;[Deng, Yihui; Li, Lan] Hunan Univ Tradit Chinese Med, Changsha 410208, Peoples R China.;[Cheng, Hui] Jinan Univ, Guangzhou 510632, Peoples R China.;[Li, Huanjie] Foshan Hosp Tradit Chinese Med, Foshan 528099, Peoples R China.
通讯机构：
[Zhong, DY ] G;Guangzhou Univ Chinese Med, Guangdong Prov Hosp Integrated Tradit Chinese & We, Foshan 528200, Peoples R China.
关键词：
Blood-brain barrier;Nanoparticle drug delivery system;Nanomedicine;Bibliometric analysis;Central nervous system
摘要：
BACKGROUND: The blood-brain barrier (BBB) is a natural physiological barrier that protects the central nervous system from foreign substances and limits the delivery of drugs to the brain. Nanotechnology has opened up new possibilities for drug delivery in the brain. Over several decades, various Nanoparticle Drug Delivery Systems (NDDS) that can cross the BBB have been developed for targeted delivery in the brain. To gain a comprehensive understanding of the current research hotspots and trends of NDDS across the BBB, this paper employs bibliometric analysis of articles published in the core database of Web of Science (WOS) from 1996 to 2022. METHOD: A search for relevant research literature on NDDS that can cross the BBB was conducted in the Web of Science database, covering the period from 1996 to 2022. The Bibliometrix R-4.0 software package was used to analyze data related to the countries of publication, research institutions, journals, citations, and keywords. The analysis aimed to identify the co-occurrence of keywords in the documents, including their titles and abstracts. Additionally, cooperative network analyses of authors, institutions, and countries of publication were conducted. RESULTS: A total of 436 articles were analyzed, originating from 174 journals and 13 books, with the majority published in Q1 and Q2 journals. Contributors from 53 countries or regions participated in the publication of these articles, with China, the United States, and India having the highest number of articles by correspondent authors, and China, the United States, and Germany being the most cited countries. Fudan University, Hacettepe University, and Sichuan University were the top three institutions with the most publications. Among the 436 articles analyzed, 1337 keywords and 1450 keywords plus were identified. Factor analysis grouped the keywords plus into two categories: drug delivery systems, polymeric nanoparticles, gold nanoparticles, transferrin, and others, and drug, delivery, efficiency, expression, and mechanism. CONCLUSION: The research on NDDS that can cross the BBB is gradually receiving attention, and the recognition and cooperation in this field have increased.
摘要：
Background: Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone (GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1 from NPC cells and its regulatory mechanism.<&wdkj&>Methods: NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments. HNE1 cells were treated with GS (20, 40, 60 μmol/L). The expressions of miR-125a-5p and circFIP1L1 were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs.<&wdkj&>Results: miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a- 5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting the VEGFA pathway to repress HUVECs angiogenesis.<&wdkj&>Conclusions: GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis affecting tumor angiogenesis.
通讯机构：
[Li, L; Tan, Y ] H;Hunan Univ Chinese Med, Pharm Coll, Changsha 410208, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410208, Peoples R China.
摘要：
Protocatechuic acid (PCA) is a natural component with multiple biological activities. However, the underlying mechanisms of the effects of PCA on anti-ulcerative colitis (UC) are unclear. A UC mouse model was established by allowing the mice to freely drink a dextran sulfate sodium solution. The mice were administered PCA intragastrically for 7 days. Histological pathology, intestinal flora, and ferroptosis regulators were determined in vivo. Additionally, ferroptotic Caco-2 cells were modeled to investigate the role of PCA in ferroptosis. Our results showed that PCA reduced the levels of the disease activity index, inflammatory factors, and histological damage in UC mice. We also found that the regulation of intestinal flora, especially Bacteroidetes, was one of the potential mechanisms underlying the protective effects of PCA anti-UC. Moreover, PCA downregulated the level of ferroptosis in the colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production compared with the model group. Similar effects of PCA on ferroptosis were observed in Erastin-treated Caco-2 cells. The results obtained using reactive oxygen species assays and the changes in mitochondrial structure observed via scanning electron microscopy also support these results. Our findings suggested that PCA protected against UC by regulating intestinal flora and ferroptosis.
通讯机构：
[Guo, ZH ] H;Hunan Univ Chinese Med, 300 Xue Shi Rd, Changsha 410208, Peoples R China.
关键词：
bile acids;gut microbiota;heart failure;metabolites
摘要：
Heart failure (HF) is the terminal manifestation of various cardiovascular diseases. Recently, accumulating evidence has demonstrated that gut microbiota are involved in the development of various cardiovascular diseases. Gut microbiota and their metabolites might play a pivotal role in the development of HF. However, previous studies have rarely described the complex role of gut microbiota and their metabolites in HF. In this review, we mainly discussed bile acids (BAs), the metabolites of gut microbiota. We explained the mechanisms by which BAs are involved in the pathogenesis of HF. We also discussed the use of gut microbiota and BAs for treating HF in Chinese medicine, highlighting the advantages of Chinese medicine in treating HF.
