Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

Objective To summarize and explore the current state,hotspots,and trends in the field of surgical treatment for intracerebral hemorrhage(ICH)over the past decade through a bibliometric and visualization analysis of relevant literature.Methods Relevant Chinese and English literature on the surgical treatment of ICH,published from January 1,2014 to April 1,2024,was retrieved and screened from CNKI and Web of Science databases.Visualization analysis was conducted using CiteSpace,VOSviewer,and other software to analyze the number of published papers,authors,countries,institutions,etc.Social network analysis diagrams of authors,keyword clustering network analysis diagrams,keyword burst strength,and keyword timeline maps were also utilized.Results(1)A total of 3 456 relevant papers were included,with 2 173 in Chinese and 1 283 in English.From 2014 to 2021,the annual number of Chinese publications on ICH surgery was higher than that of English publications,but the number of Chinese publications began to decline from 2016.The number of English publications showed an overall increasing trend.(2)A total of 6 367 authors were identified from the English literature,with notable collaboration networks led by researchers such as Mocco J,Hanley DF,Ziai WC,You C,and Tang ZP.The Chinese literature included 6 522authors,with prominent collaboration networks led by Wang LK,Cai Q,Ku HB,Zhang S,and Zhu SQ.(3)Analysis of the countries involved in the English literature showed that 31 countries participated in research on ICH surgery,with China leading in the number of publications(505),followed by the United States(330)and Germany(106).The top three countries in centrality were the United States(0.32),China(0.16),and Canada(0.11).The top three institutions in English literature publications were Johns Hopkins University(51 papers),Ohio State University(39 papers),and Harvard University(38 papers).In China,Sichuan University(32 papers),Huazhong University of Science and Technology(30 papers),and Capital Medical University(27 papers)had multiple English publications;Wuhan University People's Hospital(15 papers),Affiliated Hospital of Guizhou Medical University(13 papers),and Affiliated Hospital of Yan'an University(13 papers)had multiple Chinese publications.There was close collaboration among research institutions in the English literature,whereas Chinese researchers often established research teams within their medical units with relatively less collaboration between teams.(4)Research on ICH surgery primarily focused on surgical methods,complications,and comprehensive perioperative treatment.Research hotspots included hypertensive ICH,minimally invasive surgical techniques,and perioperative management and treatment."neuroendoscopy"was the most recent emergent keyword in Chinese literature with high centrality and the strongest burst strength,while"randomized trial"had the highest burst strength in English literature.Research trends included the integration of artificial intelligence with minimally invasive techniques to optimize ICH surgery management and treatment strategies,analysis of risk factors,and evaluation of imaging value.Conclusions Over the past decade,the overall publication volume on the surgical treatment of ICH has been in a stable development phase,with research directions covering surgical techniques,diagnosis and treatment,evaluation,and management.Core research teams led by key authors were the main contributors to the publications.Future research hotspots and trends in ICH surgery may include the optimization of surgical techniques,complication management,large-scale multicenter clinical trials and integration of artificial intelligence with minimally invasive techniques.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Objective:To analyze the effect of different vascular access on the outcome in peripheral blood stem cells collection by a network Meta-analysis, and to provide a reference for clinical medical staff to select the best vascular access.Methods:A systematic search was carried out in Chinese Knowledge Infrastructure database (CNKI), Wanfang Database, VIP Database, Chinese Biomedical Literature Database, Cochrane Library, Web of Science, PubMed, Embase, from inception until April 15, 2023. Two researchers independently screened literature and extracted data. Bayesian network meta-analysis was performed using R4.2.2 and Addis-1.16.6 softwares.Results:A total 7 pieces of research were included, 5 vascular access methods were peripheral artery, peripheral vein, artery-vein, femoral vein-central venous catheter (FV-CVC), and internal jugular vein-CVC (IJV-CVC). The results showed that compared with the peripheral veins, there was no significant difference on CD34 cells between other vascular accesses in the primary outcome measure when collected peripheral blood stem cell collection. On the single blood volume treatment time, peripheral vein and IJV-CVC were statistically significant ( MD = 14.80, 95% CI 2.70-22.38, P<0.05) . The SUCRA ranking probability chart showed that on CD34 cells, FV- CVC>IJV-CVC>artery-vein>peripheral artery>peripheral vein access; for a single blood volume treatment time and monocyte number, peripheral artery was superior and the next was peripheral vein. Conclusions:Current evidence suggested that Peripheral artery may be the best vascular access in peripheral blood stem cells collection, which opens a new way to establish the vascular access for peripheral blood stem cells collection, but it needs to be confirmed by large clinic trials.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia-reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia-reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGFβ1-Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10 (USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination, which provided a potential strategy for myocardial IRI and cardiac remodeling.

Objective:To investigate the differentially expressed microRNAs (miRNAs) in human gastric carcinoma SGC-7901 cell-derived exosomes induced by Helicobacter pylori ( H. pylori), providing new clues for further elucidating the carcinogenic mechanism of H. pylori. Methods:Ultracentrifugation and exosome extraction kit were used to extract the exosomes released by the H. pylori-stimulated and negative control group, and transmission electron microscope(TEM), nanoparticle tracking analysis(NTA) and Western blot experiments were employed to identify exosomes. Then, exosomes were labeled with the fluorescent dye PKH67 and co-cultured with THP-1-derived macrophages. The internalization of exosomes by macrophages was observed by laser confocal fluorescent microscopy. Additionally, miRNA microarray chips were performed to detect the differentially expressed miRNAs of exosomes from the two groups of cells. Real-time fluorescence quantitative PCR (qRT-PCR) was used to verify the expression of four differentially expressed miRNAs. Furthermore, the target genes and their functions as well as the possible signal pathways involved of partial differentially expressed miRNAs were predicted and analyzed by bioinformatics software. Differentially expressed miR-382-5p was labeled by Cy3 to observe whether it could be transferred to macrophages through exosomes. The expression of phenotype molecule CD206 and the cytokines TNF-α, IL-6 and IL-10 in miR-382-5p mimic-transfected macrophages were analyzed by qRT-PCR and ELISA, and the proportion of cells expressing CD206 and HLA-DR was analyzed by flow cytometry. Results:The extracted exosomes were consistent with exosome morphology and highly expressed the surface marker proteins CD9, CD63 and TSG101. After co-culturing with THP-1 derived macrophages for 12 h, the exosomes could be internalized by macrophages. Compared with the control group, there were 130 up-regulated miRNAs and 111 down-regulated miRNAs in the H. pylori-stimulated group. Bioinformatic analysis showed that the potential target genes of partial differentially expressed miRNAs were mainly involved in the regulation of PI3K-AKT, NF-κB, JAK-STAT, stem cell pluripotency and other inflammation and tumor-related pathways. miR-382-5p could be transferred to macrophages through exosomes, and induced the expression of M2-type phenotype molecule CD206 and cytokines IL-10 in macrophages, while inhibited the expression of TNF-α and IL-6 and increased the proportion of CD206 high HLA-DR low cells. Conclusions:H. pylori treatment caused a significant change in the expression level of exosome miRNAs in SGC-7901 cells. Bioinformatics analysis demonstrated that the prospective targets of these differentially expressed miRNAs might play an important role in the regulation of inflammation and tumor-related signaling pathways. miR-382-5p might induce the M2-type polarization of macrophages.

Objective: To investigate the expression and clinical significance of long-chain non-coding RNA brain cytoplasmic RNA 1 (BCYRN1) in serum of patients with non-small cell lung cancer. Methods: 74 patients with non-small cell lung cancer (NSCLC) diagnosed and treated in our hospital were selected as the experimental group, and 50 healthy subjects were selected as the control group. The expression of BCYRN1 in serum of NSCLC and control group was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The patients′ clinical pathology data were collected and followed up. To analyze the relationship between the expression of serum BCYRN1 and clinicopathological parameters of NSCLC patients, and the relationship between BCYRN1 expression in the diagnosis and prediction of NSCLC prognosis. Results: The relative expression of BCYRN1 in serum of NSCLC patients was 2.84±0.95, which was significantly higher than that of healthy controls (1.16±0.50) (P<0.05). The level of serum BCYRN1 in patients with NSCLC with tumor size >3 cm was significantly higher than that in patients with tumor size ≤3 cm (P<0.05). The level of BCYRN1 in patients with tumor node metastasis (TNM) Ⅲ+ Ⅳ was significantly higher than that in patients with stage Ⅰ+ Ⅱ (P<0.05). Patients with low differentiation and positive lymph node metastasis had higher serum BCYRN1 than those with moderate to high grade and lymph node metastasis (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.847 (95% CI: 0.772-0.922, P=0.000), and the sensitivity and specificity were 68.9% and 88.0%, respectively. The median progression free survival (PFS) (15 vs 21 months) and overall survival (OS) (19 vs 28 months) of patients with high and low expression of BCYRN1 were statistically significant (P<0.05). High expression of BCYRN1 was an independent risk factor for overall survival in patients with NSCLC. Conclusions BCYRN1 is highly expressed in the serum of NSCLC patients, and high expression of BCYRN1 is closely related to the poor prognosis of patients with NSCLC. It can be used as a novel biomarker and diagnostic target for NSCLC.

Objective: To screen for hotspot gene mutations associated with genetic deafness in Chinese pregnant women, and to perform risk assessment and prenatal diagnosis in high-risk families. Methods: Between November 2012 and October 2017, 26 117 pregnant women were screened by molecular hybridization microarray for 9 hot-spot mutations in 4 hereditary deafness related genes (GJB2 c. 35 del G, c. 176_191 del 16 bp, c. 235 del G, c. 299_300 del AT, GJB3 c. 538 C>T, SLC26A4 c. 2168 A>G, IVS 7-2 A>G, mitochondrial DNA 12S rRNA m. 1494 C>T, m. 1555 A>G). Genotype analysis was carried out in husbands of women carrying mutations, and prenatal diagnosis was carried out in the fetuses with high risk of deafness. Results: Among all women tested, 1 208(4.63%) were carriers of genetic deafness mutations, 7 with hearing impairment were affected by homozygous or compound heterozygous mutations, 51 were mitochondrial gene mutation carriers, 103 were carriers of GJB3 c. 538 C>T heterozygous mutation, 1 026 were carriers of GJB2 or SLC26A4 heterozygous mutations, and 21 carried heterozygous mutations in two genes simultaneously. In 394 families, the husbands accepted gene sequence testing, and 27 in which were determined as carriers of mutations in identical genes as their wives. Among which, 18 families received prenatal diagnosis, and 5 fetuses were diagnosed as hereditary deafness. In 9 families who did not receive prenatal diagnosis, 1 neonate was diagnosed as compound heterozygote after delivery. Conclusion In order to prevent birth defects with congenital hearing problems, it is effective to provide screening for hotspot mutations in pregnant women and to perform prenatal diagnosis on high risk pregnancies.

Objective To analyze the specimen types,ward distribution and risk factors for infections caused by extended-spectrum β-lactamase(ESBLs)-producing-Escherichia coli(ECO) in recent two years,so as to provide bacteriological basis for both hospital infection control and clinical anti-infection treatment.Methods Non-repetitive 443 ECO strains isolated from the hospitalized patients in the Third People′s Hospital of Shenzhen were collcted,and the phoenix100 system was employed for bacterial identification and antimicrobial susceptibility tests.ESBLs-ECO was further confirmed by the double-disk synergy test,and the risk factors caused ESBLs-ECO were statistically analyzed.Results A total of 115 strains of ESBLs-ECO were identified among the 443 strains of ECO,which accounted for 26.0%.The ESBLs-ECO strains were mainly isolated from the sputum,urine,and blood specimens.Among the isolated ESBLs-ECO strains,20.9% were isolated from the department of Tuberculosis,13.9% from the department of pediatric,12.2% from the department of live disease,and 8.7% from the department of infection.The male sex,surgery and use of the third generation cephalosporins were independent risk factors of ESBLs-ECO infection.Conclusion The isolation rate of ESBLs-ECO in this hospital is high.It is necessary for the hospital to strengthen the control of nosocomial infections according to the risk factors.More attention should be payed on male patients,the standardization of surgical operation and disinfection,and the restriction of using the third generation cephalosporins,so as to reduce the incidene of ESBLs-ECO infections.