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.
作者机构：
[Chen, Xi; Liu, Ying; Cao, Hui; Qiu, Huiwen; Xu, Caijuan; Li, Sixin; Li, Xinyu; Tan, Rongrong] Hunan Univ Chinese Med, Sch Clin Med, Dept Psychiat, Changsha, Hunan, Peoples R China.;[Chen, Xi; Liu, Ying; Cao, Hui; Qiu, Huiwen; Xu, Caijuan; Li, Sixin; Li, Xinyu; Tan, Rongrong] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Dept Psychiat, Changsha, Hunan, Peoples R China.;[Huang, Wei] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Cheng, Quan] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Hunan, Peoples R China.;[Cheng, Quan] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Hunan, Peoples R China.
通讯机构：
[Hui Cao; Quan Cheng] D;Department of Psychiatry, The School of Clinical Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China<&wdkj&>Department of Psychiatry, Brain Hospital of Hunan Province (The Second People’s Hospital of Hunan Province), Changsha, Hunan, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, China
摘要：
Disorders of central nervous system (CNS) disorders are considered serious health issues. The most common CNS diseases include neurodegenerative diseases, mental disorders, demyelinating disease, ischemia-reperfusion injury, and neuroinflammation. As a natural phenolic compound, hesperidin is a flavanone glycoside with various biological effects. Increasing evidence show that the growth of CNS diseases is hindered by hesperidin. Here, we have reviewed the related literature on neuropharmacological mechanisms for the preventive and therapeutic effects of hesperidin on CNS diseases. Several cellular and animal models have been developed to evaluate the underlying neuropharmacological mechanisms of hesperidin. Additionally, clinical evidence has confirmed its neuroprotective function. Hesperidin exerts its neuroprotective properties by decreasing neuro-inflammatory and apoptotic pathways. Hesperidin function has been studied in preclinical models for CNS diseases, but little is known about its definite effect in humans. Hesperidin can effectively alleviate depression and improve cognition and memory. It is urgent to explore and discover clinical trials for further confirmation of the neuroprotective efficacy of hesperidin and to evaluate its safety profile.
作者机构：
[Wang, Xiaofan; Wu, Hongzheng; Chen, Zhenni; Peng, Huanqie; Chen, Wanxin; Wang, Bingqi; Wang, Min] Cent South Univ, Dept Lab Med, Second Xiangya Hosp, Changsha 410011, Hunan, Peoples R China.;[Huang, Yiran] Hunan Univ Chinese Med, Sch Clin Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Wang, M ] C;Cent South Univ, Dept Lab Med, Second Xiangya Hosp, Changsha 410011, Hunan, Peoples R China.
摘要：
Bipolar disorder (BD) is a distinctly heterogeneous and multifactorial disorder with a high individual and social burden. Immune pathway dysregulation is an important pathophysiological feature of BD. Recent studies have suggested a potential role for T lymphocytes in the pathogenesis of BD. Therefore, greater insight into T lymphocytes' functioning in patients with BD is essential. In this narrative review, we describe the presence of an imbalance in the ratio and altered function of T lymphocyte subsets in BD patients, mainly in T helper (Th) 1, Th2, Th17 cells and regulatory T cells, and alterations in hormones, intracellular signaling, and microbiomes may be potential causes. Abnormal T cell presence explains the elevated rates of comorbid inflammatory illnesses in the BD population. We also update the findings on T cell-targeting drugs as potentially immunomodulatory therapeutic agents for BD disease in addition to classical mood stabilizers (lithium, valproic acid). In conclusion, an imbalance in T lymphocyte subpopulation ratios and altered function may be involved in the development of BD, and maintaining T cell immune homeostasis may provide an overall therapeutic benefit.
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.
作者机构：
[Xia, Zi-An] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha 410008, Peoples R China.;[Xia, Zi-An; He, Jiang; Sun, Lunquan] Cent South Univ, Natl Clin Res Ctr Geriatr Disorders, XiangyaHosp, Changsha 410008, Peoples R China.;[Lu, Can] Cent South Univ, Xiangya Hosp, Dept Pathol, Changsha 410078, Peoples R China.;[Pan, Can] Hunan Univ Tradit Chinese Med, Sch Clin Med, Changsha 410208, Peoples R China.;[Li, Jia] Cent South Univ, Xiangya Hosp, Dept Emergency, Changsha 410008, Peoples R China.
通讯机构：
[Sun, LQ ; He, J ; Sun, LQ] ;Cent South Univ, Natl Clin Res Ctr Geriatr Disorders, XiangyaHosp, Changsha 410008, Peoples R China.;Cent South Univ, Xiangya Canc Ctr, Dept Oncol, XiangyaHosp, Changsha 410008, Peoples R China.;Key Lab Mol Radiat Oncol Hunan Prov, Changsha 410008, Peoples R China.;Hunan Int Sci & Technol Collaborat Base Precis Med, Changsha 410008, Peoples R China.
关键词：
Large-scale data analysis;Tumour-infiltrating lymphocytes;CD103;LAG3;Immunotherapy;Chemotherapy
摘要：
Tumour-infiltrating lymphocytes (TILs), including T and B cells, have been demonstrated to be associated with tumour progression. However, the different subpopulations of TILs and their roles in breast cancer remain poorly understood. Large-scale analysis using multiomics data could uncover potential mechanisms and provide promising biomarkers for predicting immunotherapy response. Single-cell transcriptome data for breast cancer samples were analysed to identify unique TIL subsets. Based on the expression profiles of marker genes in these subsets, a TIL-related prognostic model was developed by univariate and multivariate Cox analyses and LASSO regression for the TCGA training cohort containing 1089 breast cancer patients. Multiplex immunohistochemistry was used to confirm the presence of TIL subsets in breast cancer samples. The model was validated with a large-scale transcriptomic dataset for 3619 breast cancer patients, including the METABRIC cohort, six chemotherapy transcriptomic cohorts, and two immunotherapy transcriptomic cohorts. We identified two TIL subsets with high expression of CD103 and LAG3 (CD103+LAG3+), including a CD8+ T-cell subset and a B-cell subset. Based on the expression profiles of marker genes in these two subpopulations, we further developed a CD103+LAG3+ TIL-related prognostic model (CLTRP) based on CXCL13 and BIRC3 genes for predicting the prognosis of breast cancer patients. CLTRP-low patients had a better prognosis than CLTRP-high patients. The comprehensive results showed that a low CLTRP score was associated with a high TP53 mutation rate, high infiltration of CD8 T cells, helper T cells, and CD4 T cells, high sensitivity to chemotherapeutic drugs, and a good response to immunotherapy. In contrast, a high CLTRP score was correlated with a low TP53 mutation rate, high infiltration of M0 and M2 macrophages, low sensitivity to chemotherapeutic drugs, and a poor response to immunotherapy. Our present study showed that the CLTRP score is a promising biomarker for distinguishing prognosis, drug sensitivity, molecular and immune characteristics, and immunotherapy outcomes in breast cancer patients. The CLTRP could serve as a valuable tool for clinical decision making regarding immunotherapy.
摘要：
BACKGROUND: The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends. METHODS: The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace. RESULTS: During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years. CONCLUSION: The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation.
摘要：
BACKGROUND: Severe SARS-CoV-2 infection results in lymphopenia and impaired function of T, B, and NK (TBNK-dominant) lymphocytes. Mitochondria are essential targets of SARS-CoV-2 and the efficacy of lymphocyte mitochondrial function for immunosurveillance in COVID-19 patients has not been evaluated. METHODS: Multi-parametric flow cytometry was used to characterize mitochondrial function, including mitochondrial mass (MM) and low mitochondrial membrane potential (MMP(low)), in TBNK-dominant lymphocytes from severe (n=93) and moderate (n=77) hospitalized COVID-19 patients. We compared the role of novel lymphocyte mitochondrial indicators and routine infection biomarkers as early predictors of severity and death in COVID-19 patients. We then developed a mortality decision tree prediction model based on immunosurveillance indicators through machine learning. RESULTS: At admission, the MM of circulating NK cells (NK-MM) was the best discriminator of severe/moderate disease (AUC=0.8067) compared with the routine infection biomarkers. The NK cell count and NK-MM displayed superior diagnostic effects to distinguish patients with non-fatal or fatal outcomes. Interestingly, NK-MM was significantly polarized in non-survivors, with some patients showing a decrease and others showing an abnormal increase. Kaplan-Meier analysis showed that NK-MM had the optimal predictive efficacy (hazard ratio=11.66). The decision tree model has the highest proportion of importance for NK-MM, which is superior to the single diagnostic effect of the above indicators (AUC=0.8900). CONCLUSION: NK-MM was not only associated with disease severity, its abnormal increases or decreases also predicted mortality risk. The resulting decision tree prediction model is the first to focus on immune monitoring indicators to provide decision-making clues for COVID-19 clinical management.
摘要：
The inhibitory role of curcumin on sperm-associated antigen 5 (SPAG5) and its effects on the cancer‑related Wnt classical signaling pathway has been previously demonstrated. Nevertheless, research on the modulatory role of curcumin on the Wnt signaling pathway by acting on SPAG5 has yet to be reported. The activation of the Wnt/β‑catenin pathway is frequently observed in patients suffering from hepatocellular carcinoma (HCC), suggesting that small molecular drugs that target Wnt could present a promising therapeutic strategy. However, these drugs often result in substantial side effects. In the present study, the presence of SPAG5 in the cancer tissues of patients with HCC and cell lines was validated using immunohistochemistry, cellular immunofluorescence, reverse transcription‑quantitative polymerase chain reaction, and western blot analyses. Subsequently, the effect of SPAG5 and the regulatory role of curcumin on SPAG5 and the Wnt/β‑catenin pathway were examined using cell function tests, flow cytometry, and western blotting. Techniques of gene knockout and overexpression were employed. The findings revealed a significant overexpression of SPAG5 in the cancer tissues of patients with HCC. Both the mRNA and protein levels of SPAG5 in Huh7 and HCCLM3 cell lines were markedly elevated. Treatment with curcumin led to a decrease in SPAG5 expression, while also inhibiting cell migration and promoting apoptosis. Additionally, suppression of SPAG5 expression resulted in the decreased expression of β‑catenin. Furthermore, curcumin was observed to reduce the expression of cyclin D1 in SPAG5‑overexpressing cell lines. However, the degree of inhibition was diminished once SPAG5 expression was silenced. These initial findings indicate that SPAG5 may function as an upstream regulatory protein of the Wnt/β‑catenin pathway, hence offering a potential alternative target for HCC. Moreover, as curcumin has the capacity to inhibit Wnt via suppressing SPAG5, it could potentially serve as a natural drug component for early intervention and treatment of HCC.
摘要：
BACKGROUND: Increasing evidence has highlighted that systemic immune-inflammation index (SII), a recently developed prognostic biomarker that utilizes peripheral platelet, lymphocyte and neutrophil counts, is associated with unfavorable prognosis in various tumors. Nevertheless, the prognostic significance of SII in high-grade gliomas patients undergoing radical resection remains unclear. Therefore, the present study aimed to assess the potential of SII as a prognostic biomarker in this patient population. METHODS: A total of 111 adult patients with high-grade gliomas who underwent radical resection were consecutively enrolled in this investigation. The study involved the categorization of patients into high and low SII groups using predetermined cut-off values. Subsequently, forward stepwise logistic regression was employed to identify autonomous predictors for early gliomas recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was performed between high and low SII patients. Finally, the Kaplan-Meier approach was utilized to compare the progression-free survival (PFS) and overall survival (OS) of the two groups. RESULTS: The study involved the categorization of patients into two groups based on their SII levels, namely high SII (> 604.8) and low SII (≤ 604.8) groups. Forward stepwise logistic regression revealed that high SII (p < 0.001) and tumor size ≥ 50 mm (p < 0.001) were significantly related to early recurrence of gliomas. Furthermore, the results indicate that PFS and OS were significantly shorter in the high SII group compared to the low SII group, both before and after PSM (p < 0.05). CONCLUSION: Preoperative biomarker SII can serve as a prognostic biomarker for early recurrence and prognosis in patients with high-grade gliomas undergoing radical resection. Furthermore, the combination of tumor size and SII demonstrates a robust predictive capacity for early recurrence and prognosis in this patient population.
摘要：
BACKGROUND: Spinal cord injury (SCI) refers to the interruption of the tracts inside the spinal cord caused by various factors. The repair of damaged axons has always been a difficult point in clinical treatment and neuroscience research. The treatment of SCI with Buyang huanwu decoction (BYHWD), a well-known recipe for invigorating Qi (a vital force forming part of any living entity in traditional Chinese culture) and promoting blood circulation, shows a good effect. METHODS: The rubrospinal tract (RST) transection model in rats was established in this study and rats were administrated with low (BL), medium (BM), or high (BH) doses of BYHWD. RESULTS: Compared with the SCI group, BL, BM moderately, and BH significantly improved the motor function of forelimbs and increased the number of red nucleus neurons in SCI rats. As for the possible molecular mechanism, BL, BM moderately, and BH significantly increased mTOR whereas decreased Beclin-1 and LC3 in the red nucleus. CONCLUSION: In conclusion, low, medium, and high doses of BYHWD could promote neural recovery in SCI rats through improving motor function and neuron survival in the red nucleus. The neuroprotective effects of BYHWD might be associated with affecting the mTOR signaling pathway and autophagy.
期刊：
Cell Death & Disease,2023年14(4):235 ISSN：2041-4889
通讯作者：
Cheng, Q.;Liu, G.
作者机构：
[Cheng, Yuan; Liu, Guodong; Zhang, Hao; Luo, Hong; Zhao, Guanjian; Xie, Zongyi; Tao, Yihao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China.;[Mao, Jinning] Chongqing Med Univ, Affiliated Hosp 2, Hlth management Ctr, Chongqing, Peoples R China.;[Cao, Hui] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Changsha, Peoples R China.;[Cao, Hui] Hunan Univ Chinese Med, Sch Clin Med, Changsha, Peoples R China.;[Zhang, Zhiwen] Fudan Univ, Sch Pharm, Shanghai, Peoples R China.
通讯机构：
[Cheng, Quan; Liu, Guodong] D;Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
摘要：
Exosomes, the cell-derived small extracellular vehicles, play a vital role in intracellular communication by reciprocally transporting DNA, RNA, bioactive protein, chains of glucose, and metabolites. With great potential to be developed as targeted drug carriers, cancer vaccines and noninvasive biomarkers for diagnosis, treatment response evaluation, prognosis prediction, exosomes show extensive advantages of relatively high drug loading capacity, adjustable therapeutic agents release, enhanced permeation and retention effect, striking biodegradability, excellent biocompatibility, low toxicity, etc. With the rapid progression of basic exosome research, exosome-based therapeutics are gaining increasing attention in recent years. Glioma, the standard primary central nervous system (CNS) tumor, is still up against significant challenges as current traditional therapies of surgery resection combined with radiotherapy and chemotherapy and numerous efforts into new drugs showed little clinical curative effect. The emerging immunotherapy strategy presents convincing results in many tumors and is driving researchers to exert its potential in glioma. As the crucial component of the glioma microenvironment, tumor-associated macrophages (TAMs) significantly contribute to the immunosuppressive microenvironment and strongly influence glioma progression via various signaling molecules, simultaneously providing new insight into therapeutic strategies. Exosomes would substantially assist the TAMs-centered treatment as drug delivery vehicles and liquid biopsy biomarkers. Here we review the current potential exosome-mediated immunotherapeutics targeting TAMs in glioma and conclude the recent investigation on the fundamental mechanisms of diversiform molecular signaling events by TAMs that promote glioma progression.
摘要：
Objective Paraquat (PQ) is a toxic compound that selectively accumulates in the lungs, inducing severe pulmonary inflammation and fibrosis. However, data on the metabolomic changes induced by the PQ remain scant. This study aimed to determine the metabolic changes in Sprague-Dawley rats subjected to PQ using UPLC-Q-TOF-MS/MS. Methods We established groups of PQ-induced pulmonary injury rats for 14 or 28 days. Results Our data showed that PQ decreased the survival of the rats and induced pulmonary inflammation at day 14 or pulmonary fibrosis at day 28. There was upregulation of IL-1 beta expression in the inflammation group as well as upregulation of fibronectin, collagen and alpha-SMA in the pulmonary fibrosis group. OPLS-DA revealed differential expression of 26 metabotites between the normal and the inflammation groups; 31 plasma metabotites were also differently expressed between the normal and the fibrosis groups. There was high expression of lysoPc160-, hydroxybutyrylcarnitine, stearic acid, and imidazolelactic acid in the pulmonary injury group compared to the normal group. Conclusion Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. This study gives insights into the mechanisms of PQ-induced lung injury and highlights the potential therapeutic targets. Nonstructured abstract The effect of PQ on lung injury in rats was detected by metabonomics, and the possible metabolic mechanism was investigated by KEGG analysis. OPLS-DA revealed the differential expression of 26 metabotites and 31 plasma metabotites between the normal and the pulmonary injury groups. Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. Oleoylethanolamine, stearic acid, and imidazolelactic acid are potential molecular markers in PQ-induced pulmonary injury.
期刊：
Journal of Analytical Methods in Chemistry,2022年2022 ISSN：2090-8865
通讯作者：
Wang, DS
作者机构：
[Wang, Wenbo; Wang, Dongsheng; Chen, Han] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha 410008, Peoples R China.;[Wang, Wenbo; Wang, Dongsheng; Chen, Han] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Dis, Changsha 410008, Peoples R China.;[Zhu, Shuangquan] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Gynecol, Changsha 410005, Peoples R China.;[Chen, Hao] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Clin Lab, Changsha 410007, Peoples R China.;[Wu, Ning] Changsha Social Work Coll, Changsha 410116, Peoples R China.
通讯机构：
[Wang, DS ] C;Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha 410008, Peoples R China.;Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Dis, Changsha 410008, Peoples R China.
摘要：
A rapid, accurate, and sensitive method for the simultaneous determination of 10 main components, namely puerarin, daidzin, coptisine, epiberberine, jatrorrhizine, berberine, palmatine, coumarin, daidzein, and cinnamic acid in Ge-Gen-Jiao-Tai-Wan, was developed based on ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Analysis was performed on an Agilent 1290 Infinity II series UHPLC system, equipped with a Waters ACQUITY UPLC HSS T3 column (100 × 2.1 mm, 1.8 <i>μ</i>m) by using (A) 0.1% acetic acid and (B) methanol as mobile phase. The flow rate was 0.3 mL/min, and the injection volume was 1 <i>μ</i>L. Mass spectrometry was operated in multiple reaction monitoring mode using an Agilent 6460 triple quadrupole mass spectrometer equipped with an AJS-ESI ion source. Agilent Mass Hunter Work Station Software was employed for data acquisition and processing. All calibration curves showed excellent linear regressions (<i>R</i><sup>2</sup> > 0.9992). The precision, repeatability, and stability of the ten compounds were below 4.56% in terms of relative standard deviation. The average extraction recovery ranged from 96.53% to 102.69% with a relative standard deviation of 1.14–3.78% for all samples. This study potently contributes to the quantitative evaluation of Ge-Gen-Jiao-Tai-Wan, thereby providing a scientific basis for further studies and clinical application of Ge-Gen-Jiao-Tai-Wan.
期刊：
Current Neurovascular Research,2022年19(2):137-149 ISSN：1567-2026
作者机构：
[Ren, Biqiong; Li, Sijin; Li, Huiyang; Yang, Huan] Hunan Univ Chinese Med, Sch Clin Med, Changsha, Hunan, Peoples R China.;[Chen, Xing] Loudi Cent Hosp, Dept Blood Transfus, Loudi 417000, Hunan, Peoples R China.;[Ren, Biqiong] Second Peoples Hosp Hunan Prov, Dept Lab Med, Changsha 410007, Hunan, Peoples R China.
关键词：
Acute ischemic stroke;Ischemia-modified albumin;Middle cerebral artery stenosis;Ratio of IMA to albumin;Severe stenosis or occlusive;albumin-adjusted ischemia modified albumin index
摘要：
Objective: In this study, we investigated the relationship between serum ischemic modified albumin (IMA) levels and other hematologic features and middle cerebral artery (MCA) severe stenosis/occlusion in acute ischemic stroke (AIS) patients.<&wdkj&>Methods: The levels of serum IMA and Albumin (ALB) of 169 AIS patients were measured, and the ratio of IMA to albumin (IMAR) and the albumin-adjusted ischemia-modified albumin index (IMA index) were calculated. Different combinations of other hematologic changes and clinical features of the patients were analyzed.<&wdkj&>Results: The results indicated that the levels of blood IMA and IMAR were significantly higher in the group with severe intracranial stenosis/occlusion than in the group with non-severe stenosis/ occlusion in AIS patients, while the CHE levels were significantly lower than those in the other groups. In the MCA severe stenosis/occlusion group, the levels of blood IMA and IMAR were significantly higher than that in the other vascular severe stenosis/occlusion groups, while the IMA index, ALB, and CHE were significantly lower than that in the other groups. Multiple linear regression analysis showed a significant negative correlation between IMA and albumin. A combined diagnostic ROC curve analysis showed that among AIS patients, the best combination for determining severe stenosis/occlusion of the great intracranial arteries was the admission NIHSS score + CHE (AUC = 0.783). The best combination for determining severe stenosis or occlusion of the MCA in AIS patients was IMAR combined with the admission NIHSS score and CHE (AUC = 0.827).<&wdkj&>Conclusion: The combined use of IMA, IMAR, and the IMA index has some diagnostic value in AIS caused by severe stenosis or occlusion of the MCA. IMAR, CHE, and the admission NIHSS scores are the best combinations to determine whether an AIS patient has severe stenosis or occlusion of the MCA.
通讯机构：
[Zhixiong Liu; Quan Cheng] D;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
摘要：
Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.
摘要：
ObjectiveIn this study, we aimed to characterize the plasma metabolic profiles of brain atrophy and alcohol dependence (s) and to identify the underlying pathogenesis of brain atrophy related to alcohol dependence. MethodsWe acquired the plasma samples of alcohol-dependent patients and performed non-targeted metabolomic profiling analysis to identify alterations of key metabolites in the plasma of BA-ADPs. Machine learning algorithms and bioinformatic analysis were also used to identify predictive biomarkers and investigate their possible roles in brain atrophy related to alcohol dependence. ResultsA total of 26 plasma metabolites were significantly altered in the BA-ADPs group when compared with a group featuring alcohol-dependent patients without brain atrophy (NBA-ADPs). Nine of these differential metabolites were further identified as potential biomarkers for BA-ADPs. Receiver operating characteristic curves demonstrated that these potential biomarkers exhibited good sensitivity and specificity for distinguishing BA-ADPs from NBA-ADPs. Moreover, metabolic pathway analysis suggested that glycerophospholipid metabolism may be highly involved in the pathogenesis of alcohol-induced brain atrophy. ConclusionThis plasma metabolomic study provides a valuable resource for enhancing our understanding of alcohol-induced brain atrophy and offers potential targets for therapeutic intervention.
作者机构：
[Xu, Huilan; Tang, Kun] Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Changsha 410008, Peoples R China.;[Tang, Kun] Cent South Univ, Xiangya Hosp, Dept Discipline Construct, Changsha 410008, Peoples R China.;[Zhang, Jingwei; Wang, Zeyu; Zhang, Hao; Zhang, Xun; Cheng, Quan; Xiao, Gelei] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Peoples R China.;[Zhang, Jingwei; Wang, Zeyu; Zhang, Hao; Zhang, Xun; Cheng, Quan; Xiao, Gelei] Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Peoples R China.;[Cao, Hui] Second Peoples Hosp Hunan Prov, Brain Hosp Hunan Prov, Changsha 410007, Peoples R China.
通讯机构：
[Quan Cheng; Huilan Xu] D;Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha 410008, China<&wdkj&>remove Hide full affiliation list<&wdkj&>Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>National Clinical Research Center for Geriatric Disorders, Changsha 410008, China<&wdkj&>Clinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China<&wdkj&>remove Hide full affiliation list
摘要：
Abstract: Simple Summary Immunotherapy targeting immune checkpoints and stromal cells in the tumor microenvironment is currently one of the most promising directions for tumor therapy. Ongoing studies suggest that CD73 plays an important role in the tumor immune process in certain tumors, however, the exact mechanism is unknown. We aim to fully reveal the prognostic value of CD73 in pan-cancer and its role in tumor immunity through large-scale single-cell and bulk sequencing analysis. We found that high CD73 expression was significantly associated with poor prognosis in many tumors. It is also strongly associated with immune scores, stromal cell infiltration, and immune-related pathways. CD73 can regulate the biological behavior of immune cells in the tumor microenvironment, especially macrophages and T cells. Immunotherapy targeting CD73 has obvious effects, and CD73 may shine as a new immune checkpoint in future tumor immunotherapy. Abstract CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient’s prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy. Keywords: CD73; cancer; immunotherapy; macrophages; T cells
