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Dong Zhang,1,2 Zeming Zhu,3 Zhangyou He,4 Siwei Duan,3 Qincheng Yi,4 Min Qiu,3 Xingzhen Dai,3 Guang Su,4 Kexin Li,1,2 Lin Xu,1,2 Donghou Liu,1,2 Yabin Wu,1,2 Yong Gao,3 Ruliu Li,3 Shaoju Guo1,2 1Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 2Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China; 4Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of ChinaCorrespondence: Ruliu Li, Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou City, Guangdong Province, 510000, People’s Republic of China, Tel +86-020-39357088, Email lrl@gzucm.edu.cn Shaoju Guo, Gastroenterology Department, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Shenzhen City, Guangdong Province, 518000, People’s Republic of China, Tel +86-0755-82571384, Email gsj1080@163.comPurpose: Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis.Methods: A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg− 1) and high-dose (10 g·kg− 1), and mesalazine (50 mg·kg− 1) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome.Results: Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways.Conclusion: Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways. Keywords: ulcerative colitis, enema therapy, neutrophil extracellular traps, Chinese medicine, inflammation

Guomiao Su,1,* Juan Wang,2,* Shiyue Liu,1,* Xiaonan Fu,1 Yanxi Li,1 Guoqing Pan1 1Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yun Nan, People’s Republic of China; 2Clinical Laboratory, Yunnan Province Third People’s Hospital, Kunming, Yun Nan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanxi Li; Guoqing Pan, Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yun Nan, People’s Republic of China, Email liyanxicuhk@163.com; guoqing_pan@163.comPurpose: To identify the epithelial cell centre regulatory transcription factors in the gastric cancer (GC) microenvironment and provide a new strategy for the diagnosis and treatment of GC.Methods: The GC single-cell dataset was downloaded from the Gene Expression Omnibus (GEO) database. The regulatory mechanisms of transcription factors in both pan-cancer and GC microenvironments were analysed using the Cancer Genome Atlas (TGCA) database. Real-time quantitative PCR (RT-qPCR) was used to determine the mRNA expression levels of Prospero homeobox gene 1 (PROX1) and Endothelial PAS domain-containing protein 1 (EPAS1) in the human gastric mucosal normal epithelial cell line (GES-1) and the GC cell line (AGS). Immunohistochemistry (IHC) was used to determine the amounts of PROX1 and EPAS1 protein expression in GC and adjacent tissues. GC patients’ overall survival (OS) was tracked through outpatient, Inpatient case inquiry, or phone follow-up.Results: The single-cell data from GSE184198 was re-annotated, resulting in nine cell subsets: T cells (13364), NK cells (606), B cells (2525), Epithelial cells (2497), DC cells (1167), Fibroblast cells (372), Endothelial cells (271), Neutrophils cells (246) and Macrophage cells (420). Analysis of cell subgroup signalling pathways revealed that communication intensity between epithelial cells and smooth muscle cells was highest. Transcription factors PROX1 and EPAS1 were notably active in epithelial cells. Cell communication analysis indicated that IFNG may interact with IFNGR1/2 and LIF with IL6ST and LIFR to regulate the downstream PROX1 and EPAS1. PROX1 and EPAS1 were upregulated and negatively correlated with tumour mutation burden (TMB). They also exhibited high positive correlations with immune checkpoints CTLA4 and PDCD1LG2, as well as with chemokines CCL24 and CXCL12 and their receptors CCR3 and CCR4. Additionally, PROX1 and EPAS1 were positively correlated with immunosuppressive factors ADORA2A, CD160, IL10, TGFBR1, KDR and CSF1R, as well as with immunostimulators CD276, PVR, TNFRSF25, ULBP1, CXCL12 and ENTPD1. In GC tissues and AGS, PROX1 and EPAS1 were both substantially expressed. In the meantime, they showed a positive correlation with clinicopathological features such TNM stage and degree of differentiation. In GC patients, the up-regulated group’s PROX1 and EPAS1 prognosis was noticeably poorer than the down-regulated group’s.Conclusion: PROX1 and EPAS1 are likely central regulatory transcription factors in the epithelial cells of the GC environment, regulated by IFNG and LIF. They may contribute to GC progression by modulating the tumour’s immune microenvironment.Keywords: PROX1, EPAS1, GC, tumour microenvironment, transcription factor, cell communication

Qingqing Xu, Xue Cheng, Hong Sun, Guangyuan Su, Yuanhui Fei, Chunhui Wang, Chao Han Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, People’s Republic of ChinaCorrespondence: Chao Han, Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +8613961568178, Email staff940@yxph.comPurpose: This study aimed to compare the impact of remimazolam-based versus propofol-based intravenous anesthesia on surgical stress and post-operative immune function in patients undergoing gastric radical surgery.Patients and Methods: Sixty-eight patients aged 50 to 80 undergoing gastric radical surgery were randomly assigned to the remimazolam group (group R) or the propofol group (group P), receiving remimazolam or propofol-based intravenous anesthesia, respectively. The primary outcome measured was peri-operative serum stress indicators and lymphocyte subtypes. Secondary outcomes included hemodynamic vitals, recovery quality, postoperative pain profiles and potential adverse effects.Results: The demographic and surgical characteristics of the 60 analyzed patients were comparable. The absolute counts of CD3+CD4+ and CD3+CD8+ cell decreased significantly on POD1 compared with baseline. On POD3, the numbers of CD3+CD4+ cells in group R were lower than baseline and Group P, whereas the CD3+CD8+ cell counts in both groups were lower than baseline, with group R higher than group P. The CD3-CD16+CD56+ cell numbers in both groups on POD1 and POD3 decreased significantly compared to baseline with group P lower than group R on POD3. The serum levels of IL-1β, IL-6, TNF-α, ACTH and COR rose sharply 2 hours after the beginning of surgery compared to baseline. Notably, all these parameters in group R were higher than those in group P. Additionally, blood pressure and intra-operative vasoactive drug frequency in group R were higher than that in group P. No significant differences in recovery quality, postoperative pain profiles, and potential adverse effects were observed.Conclusion: Remimazolam-based intravenous anesthesia might favour the recovery of cellular immune function in early postoperative period compared to propofol. On the contrary, remimazolam was inferior to propofol in suppressing surgical stress. Further studies with larger sample sizes are needed to confirm our findings.Keywords: remimazolam, propofol, surgical stress, post-operative immune function, gastric radical surgery

Guomiao Su,&ast; Zifan Xu,&ast; Shiyue Liu,&ast; Dou Hao, Yanxi Li, Guoqing Pan Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqing Pan, Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email guoqing_pan@163.comPurpose: Semaphorin 5A (SEMA5A) and autophagy-related genes (ARGs) are pivotal in the pathogenesis of gastric cancer (GC). However, the potential regulatory role of SEMA5A in autophagy via its associated ARGs and the underlying molecular mechanisms remain unresolved.Patients and Methods: GC-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) between GC and control samples. The intersection of DEGs with ARGs produced candidate genes, which were further analyzed using Spearman correlation with SEMA5A to identify signature genes. Stratification of GC samples based on signature gene expression, followed by Kaplan-Meier survival analysis, identified key genes. Subsequent analyses, including gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint evaluation, were conducted on the key genes and SEMA5A. The mRNA expression level was quantified using real-time quantitative polymerase chain reaction (RT-qPCR).Results: Ninety candidate genes were identified for Spearman correlation with SEMA5A, revealing TNFSF11, BMP6, ITPR1, and DLC1 with correlation coefficients exceeding 0.3. Survival analysis underscored DLC1 and BMP6 as key genes due to significant prognostic differences. GSEA implicated SEMA5A, BMP6, and DLC1 in the ECM receptor interaction pathway. Immune infiltration analysis indicated a negative correlation of SEMA5A and BMP6 with M1 macrophages, while DLC1 exhibited the strongest association with the immune checkpoint PDCD1LG2 (p < 0.05, cor = 0.43). The mRNA expression level of SEMA5A was significantly upregulated in AGS parental cells compared to GES-1 cells (p < 0.01), whereas DLC1 and BMP6 mRNA levels were markedly downregulated in AGS parental cells relative to GES-1 (p < 0.0001).Conclusion: ARGs BMP6 and DLC1, associated with SEMA5A, were identified, and their prognostic significance in GC was demonstrated. Additionally, their regulatory mechanisms were further elucidated through immune infiltration analysis and molecular network construction, providing a theoretical foundation for future research on the molecular mechanisms in patients with GC.Keywords: GC, SEMA5A, autophagy, ARGs, bioinformatics analysis

Yaolin Wang,1– 3,&ast; Kai Zhao,4,5,&ast; Nanling Wu,1– 3 Tao Ji,1– 3 Gaowei Su,1– 3 Xiaojie Cui,1– 3 Yushan Dong,1– 3 Xiuxia Chen1– 3 1NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui, People’s Republic of China; 5Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Email cxxlxy@sina.comPurpose: This study was designed to investigate the effects of different doses of butorphanol on postoperative shivering and quality of recovery in elderly patients.Patients and Methods: A total of 147 elderly patients (aged 60 or older) scheduled for elective transurethral resection of the prostate were enrolled in the current study. Patients were randomly and evenly assigned into four groups: Group C (0.9% normal saline), Group B1 (butorphanol 0.01 mg/kg), Group B2 (butorphanol 0.02 mg/kg) and Group B3 (butorphanol 0.03 mg/kg). All drugs were diluted to 5mL and injected intravenously slowly 5 min before induction of anesthesia. The primary outcome measure was the incidence of postoperative shivering in the post-anesthesia care unit. Quality of Recovery-40 (QoR-40) scores were assessed on postoperative day (POD) 1, 2 and 3. Perioperative core and skin temperature, extubation time and adverse events were also recorded.Results: Patients among the four groups had comparable baseline characteristics. Compared with Group C, the incidence of shivering was significantly lower in Group B2 and B3 (P = 0.006 and P = 0.005, respectively). The QoR-40 scores on POD1 were significantly higher in all butorphanol groups than that in Group C (P < 0.0083). In Group B2 and B3, patients experienced lower pain intensity (P < 0.001). In addition, the incidence of catheter-related bladder discomfort (CRBD) was lower in all butorphanol groups than in Group C (P < 0.0083).Conclusion: Butorphanol 0.02 or 0.03 mg/kg could effectively prevent the occurrence of postoperative shivering in elderly patients scheduled for transurethral resection of the prostate, provided effective postoperative recovery and postoperative analgesia.Keywords: butorphanol, elderly patients, postoperative shivering, recovery quality, postoperative pain

Jie Zhang,1,&ast; Jingfei Zhao,1,&ast; Shuichun Wei,2 Peipei Huang,2 Xinyue Tu,2 Guimin Su,2 Yu Gan,2 Wenfeng Gong,1 Bangde Xiang1 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2College of Basic Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang; Wenfeng Gong, Email xiangbangde@gxmu.edu.cn; gwf0771@163.comBackground: Hepatocellular carcinoma (HCC), a major type of cancer affecting the lives of people across the world, is one of many diseases whose advancement is thought to be influenced by autophagy dysfunction. Here, the prognostic significance of autophagy in HCC will be investigated.Methods: The Cancer Genome Atlas (TCGA) database was employed in this work to identify 62 differentially-expressed Autophagy-Related Genes (ARGs) in HCC patients. Functional enrichment studies revealed that autophagy played a tumor-promoting role in the advancement of HCC. Based on RNA sequencing of 116 tumor samples and 114 paracancerous tissue samples acquired from HCC patients at the Guangxi Medical University Cancer Hospital, 866 differentially expressed prognosis-related genes were identified. Using lasso regression analysis, two ARGs (BIRC5 and BAK1) linked to prognosis were discovered after intersecting the differential genes derived from the prognosis-related groups. A risk score based on ARGs was developed using a Cox proportional hazards regression model. RNA sequencing data were used to construct this model. Finally, the TCGA and The Human Protein Atlas Databases (THPA) were used to validate the clinical data of 116 HCC patients.Results: Elevated expression level of the BAK1 and BIRC5 genes is linked to poor prognosis. The two ARGs were used to calculate the risk score as follows: (0.0253&ast;BAK1) + (0.0051&ast;BIRC5). Risk score served as the independent prognostic factor as per the multivariate analysis. TCGA, THPA, and data from the Guangxi Medical University Cancer Hospital were used to confirm the predictive validity of risk scores for the prognosis of HCC patients.Conclusion: This study offers molecular insights regarding the involvement of autophagy in HCC patients, along with a probable prognostic signature for determining the outcome (prognosis) of HCC patients.Keywords: hepatocellular carcinoma, risk score, The Cancer Genome Atlas, autophagy-related genes, RNA sequencing

To better understand the application of IVR (In-Vessel Retention), extensive experiments have been conducted on the heat transfer characteristics of molten pool. However, most research mainly focuses on hemispherical lower heads, and the research on ellipsoidal lower head suitable for small pressurized water reactors is relatively lacking. In order to provide some reference for the implementation of IVR with ellipsoidal lower head, this paper conducted the experimental study on the heat transfer characteristics of a three-dimensional double-layer molten pool based on the design of a small pressurized water reactor. The test section consists of two parts: ellipsoidal and cylindrical, with a span of 1150 mm and a total height of 700 mm. The molten material is simulated by nitrate mixture (20mol%NaNO3-80mol%KNO3), and electric heating wire is chosen to simulate the oxide layer decay heat. The effects of heating power, oxide layer height and layered partition thickness on heat transfer characteristics of two-layer molten pool under static conditions were studied. The results show that the thermal stratification phenomenon mainly occurs in the lower and middle regions of the oxide layer, with a smaller dimensionless temperature gradient in the upper region; with the similar volumetric power densities, the height of the oxide layer has little effect on the wall heat flux density; the layered partition increases the thermal resistance between the two layers and reduces the upward heat transfer to the ceramic pool. In addition, the heat transfer relationships in the oxide layer, both downward and upward, are fitted for the internal Rayleigh number range of 3.43 × 1012 to 1.54 × 1013. [ABSTRACT FROM AUTHOR]

Zhangluxi Liu, Jing Xu, Hongxi Li, Jia Shu, Guannan Su, Chunjiang Zhou, Peizeng Yang The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, People’s Republic of ChinaCorrespondence: Peizeng Yang, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, People’s Republic of China, Tel/Fax +86-23-89012851, Email peizengycmu@126.comBackground: Effector T cells, especially T helper 1 (Th1) cells and T helper 17 (Th17) cells, are involved in the pathogenesis of many autoimmune diseases such as uveitis. Under hyperactive immune conditions, these effector T cells pathologically maintain a high expression level of programmed cell death protein 1 (PD-1) receptors and distinctively engage aerobic glycolysis via cellular energy metabolism mediated by pyruvate kinase M2 (PKM2). Therefore, we proposed that the synergy of metabolic inhibition and receptor guidance might target and down-regulate these hyperactive effector T cells to achieve anti-immune effects.Methods: PD-1 antibody and TEPP-46 were integrated by polyethylene glycol (PEG) modified poly (lactic-co-glycolic acid) (PLGA) as a nanoplatform (TPP). Characteristics of TPP were basically detected. The biosafety of TPP was evaluated in vitro and in vivo. The targeting effect of TPP was detected by laser scanning confocal microscopy and flow cytometry (FCM). Interleukin-2 (IL-2)/interleukin-17A (IL-17A)/interferon-gamma (IFN-γ) producing cells were detected by FCM. Experimental autoimmune uveoretinitis (EAU) was induced in C57BL/6J mice as the inflammatory model.Results: TPP had homogeneous distribution, good stability in vitro, and high biosafety in vitro and in vivo. Encapsulated TEPP-46 showed a sustained release profile with burst, steady and slow release periods. Early activation and proliferation of effector T cells was inhibited by TPP treatment in vitro. Th1 and Th17 cells were suppressed by TPP in vitro and in vivo. EAU was alleviated in mice by systemic administration of TPP.Conclusion: The novel nanoplatform TPP could suppress Th1 and Th17 cells and exhibited an anti-inflammatory effect on EAU, providing an alternative approach to ameliorate autoimmune diseases mediated by these cells.Graphical Abstract: Keywords: anti-inflammation, experimental autoimmune uveitis, sustained release, aerobic glycolysis, biomaterial, Th1 and Th17 cells

Kai Zhao,1,&ast; Yushan Dong,1,&ast; Gaowei Su,1 Yaolin Wang,1 Tao Ji,1 Nanling Wu,1 Xiaojie Cui,1 Wenzhan Li,1 Yanming Yang,1 Xiuxia Chen1,2 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuxia Chen, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86 18052268332, Fax +0516-8346-9496, Email cxxlxy@sina.comPurpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia.Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded.Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P < 0.001) in group L (165.5± 3.8 vs 173.7± 4.7) than those in group C (155.6± 4.0 vs 163.2± 4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P < 0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P < 0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality.Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.Keywords: lidocaine, brain neoplasm, supratentorial tumor resection, recovery quality, brain protection, postoperative pain

Shasha Duan,1– 3,&ast; Chao Wang,1,2,&ast; Xiangli Xu,4 Xiaoshan Zhang,3 Gaofeng Su,1,2 You Li,1,2 Shuai Fu,1,2 Ping Sun,1,2 Jiawei Tian1 1Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, People’s Republic of China; 3Department of Ultrasound, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4Department of Ultrasound, the Second Hospital of Harbin city, Harbin, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiawei Tian; Ping Sun, Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150086, People’s Republic of China, Tel +86 451-86605811, Fax +86 451-86605745, Email jwtian2004@163.com; sunpinghmu@163.comPurpose: Angiogenesis is required for improving myocardial function and is a key factor in long-term prognosis after an acute myocardial infarction (AMI). Although exosomes are known to play a crucial role in angiogenesis, the role of peripheral exosomes in angiogenic signal transduction in patients with AMI remains unclear. Here, we explored the effect of exosomes extracted from the peripheral serum of AMI patients on angiogenesis and elucidated the downstream pathways.Patients and Methods: Serum exosomes were obtained from patients with AMI (AMI-Exo) and healthy individuals (Con-Exo). The exosomes were cocultured with human umbilical vein endothelial cells (HUVECs) in vitro, with aortic rings ex vivo, and were used to treat mouse hind-limb ischemia and mouse AMI model in vivo.Results: AMI-Exo raised HUVEC proliferation, tube formation, and migration, and enhanced microvessel sprouting from aortic rings compared to Con-Exo, both in vitro and ex vivo. Quantitative reverse transcription-polymerase chain reaction revealed that the abundance of miR-126-3p, a crucial regulator of angiogenesis, was increased in AMI-Exo. The inhibition of miR-126-3p decreased the benefits of AMI-Exo treatment, and miR-126-3p upregulation enhanced the benefits of Con-Exo treatment in HUVECs, aortic rings, the mouse hind-limb ischemia model, and the mouse AMI model. Knockdown and overexpression analyses revealed that miR-126-3p regulated angiogenesis in HUVECs by directly targeting tuberous sclerosis complex 1 (TSC1). Moreover, we found that miR-126-3p could inhibit TSC1 expression, which further activated mTORC1 signaling and increased HIF-1α and VEGFA expression, ultimately promoting angiogenesis.Conclusion: Collectively, our results provide a novel understanding of the function of exosomes in angiogenesis post AMI. We demonstrated that exosomes from the peripheral serum of AMI patients promote angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α signaling pathway.Keywords: acute myocardial infarction, angiogenesis, exosomes, miR-126-3p, tuberous sclerosis complex 1

Swelling characteristics of compacted bentonite when hydrated with a hypersaline pore fluid (332 g/L total dissolved solids; 6.6 mol/L ionic strength) are reported. The pore fluid mimics the multiple constituents and their concentrations found for the Cobourg limestone of the Michigan Basin and is dominated by sodium (25% mole fraction) with some potassium, calcium, and magnesium (10%, 5%, and 4% mole fractions). Measurements of swell pressure for two sodium bentonites when hydrated under conditions of zero volume increase are reported. Swell pressure reached a peak within 10-30 h from the onset of hydration, followed by a continual decrease over 1 year of testing from chemical interaction between the bentonite and pore fluid. After 1 year, the swell pressure of the MX-80 bentonite tested decreased by a factor of nine relative to the peak swell pressure with deionized water when the dry density was 1.6 Mg/[m.sup.3]. Swell pressures increased as dry density increased. However, chemical interactions appear to have more influence on swell pressure than density for the pore fluid examined as a swell pressure of just under 1200 kPa was measured for MX-80 after 1.8 years of hydration when compacted to the highest dry density of 1.8 Mg/[m.sup.3] examined. Key words: bentonite, swelling soil, MX-80, hypersaline pore fluid, chemical interaction. Les caracteristiques de gonflement de la bentonite compactee lorsqu'elle est hydratee avec un liquide poreux hypersalin (332 g/L de solides dissous totaux; 6,6 mol/L de force ionique) sont signalees. Le liquide interstitiel imite les multiples constituants et leurs concentrations trouves pour le calcaire de Cobourg du bassin du Michigan et est domine par le sodium (25% de la fraction molaire) avec un peu de potassium, de calcium et de magnesium (10, 5 et 4% des fractions molaires). Des mesures de la pression de gonflement pour deux bentonites sodiques sont rapportees lorsqu'elles sont hydratees dans des conditions d'augmentation de volume nulle. La pression de gonflement a atteint un pic dans les 10 a 30 h suivant le debut de l'hydratation, suivi d'une diminution continue pendant un an d'essais due a l'interaction chimique entre la bentonite et le liquide interstitiel. Apres un an, la pression de gonflement de la bentonite MX-80 testee a diminue par un facteur de neuf par rapport a la pression de gonflement maximale avec de l'eau deionisee lorsque la densite seche etait de 1,6 Mg/[m.sup.3]. La pression de la houle augmente a mesure que la densite seche augmente. Cependant, les interactions chimiques semblent avoir plus d'influence sur la pression de gonflement que sur la densite pour le liquide interstitiel examine, car une pression de gonflement d'un peu moins de 1200 kPa a ete mesuree pour le MX-80 apres 1,8 an d'hydratation lorsqu'il etait compacte a la plus haute densite seche de 1,8 Mg/[m.sup.3] examinee. [Traduit par la Redaction] Mots-cles: bentonite, gonflement du sol, MX-80, liquide poreux hypersalin, interaction chimique., Introduction Swelling characteristics are of interest for compacted bentonite used as the clay mineral component of barrier systems that are being contemplated, or proposed, for the management of nuclear wastes [...]

Tianwen Lai,* Xiaoxia Wen,* Dong Wu,* Guomei Su, Yun Gao, Cuifen Chen, Weiquan Wu, Yingying Lv, Zhanghui Chen, Quanchao Lv, Wen Li, Dongming Li, Min Chen, Bin WuDepartment of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, People’s Republic of China*These authors contributed equally to this workPurpose: Particulate matter (PM) has been implicated as a risk factor for airway injury. However, the molecular mechanisms remain largely unclear. The goal of this study was to determine whether sirtuin1 (SIRT1), an anti-inflammatory and antiaging protein, protects against PM-induced airway inflammation.Methods: The effect of SIRT1 on PM-induced airway inflammation was assessed by using in vivo models of airway inflammation induced by PM and in vitro culture of human bronchial epithelial (HBE) cells exposed to PM, resveratrol (SIRT1 activator), or both.Results: PM-stimulated HBE cells showed a significant decrease in SIRT1 but a notable increase in inflammatory cytokines. SIRT1 gene silencing further enhanced PM-induced expression of inflammatory cytokines. In contrast, resveratrol, a SIRT1 activator, reduced the expression of these cytokines compared with the control cells. In vivo, SIRT1 expression was significantly decreased in lung tissues of PM-exposed mice. Interestingly, resveratrol treatment reversed the enhanced total cells, neutrophils and inflammatory cytokines in PM-induced mice. Moreover, SIRT1 mediated PM-induced inflammatory cytokines expression at least partly through MAPK pathways.Conclusion: These findings suggest that SIRT1 is involved in the pathogenesis of PM-induced airway inflammation and activation of SIRT1 could prevent airway disorders or disease exacerbations induced by airborne particulate pollution.Keywords: particulate matter, SIRT1, resveratrol, airway inflammation

Jiansong Wang,1 Wencheng Che,2 Weimin Wang,1 Gongzhang Su,3 Tianchang Zhen,3 Zhongmin Jiang31Graduate Department, Weifang Medical University, Weifang, Shandong 261031, People’s Republic of China; 2Department of Thoracic Surgery, Zibo Central Hospital, Zibo, Shandong 255022, People’s Republic of China; 3Department of Thoracic Surgery, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, People’s Republic of ChinaPurpose: Esophageal cancer (ESCA) progression and chemoresistance are critical factors that impact the survival of patients with esophageal cancer. Cyclin dependent kinase inhibitor 3 (CDKN3) is an important regulator of the cell cycle that has received little attention, therefore the purpose of this study was to investigate CDKN3 involvement in ESCA.Methods: We first explored the public database in addition to our cohort to evaluate the expression of CDKN3 in ESCA patients. We performed bioinformative analysis on specific processes regulated by CDKN3, then we investigated the role of CDKN3 in ESCA progression and chemoresistance in vitro and in vivo. Finally, we sought to elucidate the mechanism of CDKN3 regulation of chemoresistance in ESCA.Results: We discovered that CDKN3 was highly expressed in ESCA and serves as an independent prognostic factor of this disease. Bioinformatic analysis showed CDKN3 involvement in DNA replication, the cell cycle G2/M phase transition, DNA damage repair (DDR) signaling pathways, et al Functional experiments in vitro and in vivo demonstrated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance. Furthermore, CDKN3 inhibition resulted in reduced expression of RAD51, which plays a pivotal role in DDR. Overexpression of RAD51 reversed cisplatin-induced DNA damage and chemosensitivity in CDKN3 inhibited ESCA cell lines.Conclusion: The present research indicated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance via RAD51, thereby influencing overall patient survival.Keywords: esophageal cancer, chemoresistance, CDKN3, RAD51, DNA damage repair

Zhen-gang Wei,1–3 Feng-xian Wei,1–3 Zi-wei Shao,1–3 Guo-hong Su,1–3 Xue-ping Qi,3 You-cheng Zhang1–3 1Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China; 2Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, Lanzhou 730030, China; 3Lanzhou University Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730030, China Objective: Carvedilol is nonselective beta-blocker with a mild anti-alpha-1-adrenergic effect. Several studies proposed improved hemodynamic effects of carvedilol compared with propanolol. Our study was to perform a systematic review and meta-analysis of randomized control trials comparing carvedilol with variceal banding ligation (VBL).Methods: Studies were searched on online databases MEDLINE, EMBASE(Ovid), the Cochrane Library, Chinese Wanfang Database, and China National Knowledge Infrastructure between January 2000 and May 2018. Incidence of bleeding and mortality were main outcome measures. Subgroup analysis and sensitivity analysis were conducted to ensure the robustness of pooled estimates.Results: Ten randomized control trials including 1,269 cirrhotic patients were chosen. Compared with VBL, carvedilol showed similar preventive efficacy of risk ratios (RRs) in variceal bleeding, and bleeding-related mortality over different follow-up periods from 6 months to 24 months. Also, significant differences between carvedilol and VBL in overall mortality and other causes of mortality were failed to be found. Carvedilol achieved a lower incidence of portal hypertension gastropathy in both 6 months (RR=0.49, 95% CI: 0.38–0.64, P

Yanyan Yu, Gaoxing Su, Hongyan Zhu, Qing Zhu, Yong Chen, Bohui Xu, Yuqin Li, Wei Zhang School of Pharmacy, Nantong University, Nantong, People’s Republic of China Abstract: In this study, we fabricated a novel electrochemical biosensing platform on the basis of target-triggered proximity hybridization-mediated isothermal exponential amplification reaction (EXPAR) for ultrasensitive protein analysis. Through rational design, the aptamers for protein recognition were integrated within two DNA probes. Via proximity hybridization principle, the affinity protein-binding event was converted into DNA assembly process. The recognition of protein by aptamers can trigger the strand displacement through the increase of the local concentrations of the involved probes. As a consequence, the output DNA was displaced, which can hybridize with the duplex probes immobilized on the electrode surface subsequently, leading to the initiation of the EXPAR as well as the cleavage of duplex probes. Each cleavage will release the gold nanoparticles (AuNPs) binding sequence. With the modification of G-quadruplex sequence, electrochemical signals were yielded by the AuNPs through oxidizing 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. The study we proposed exhibited high sensitivity toward platelet-derived growth factor BB (PDGF-BB) with the detection limit of 52 fM. And, this method also showed great selectivity among the PDGF isoforms and performed well in spiked human serum samples. Keywords: electrochemical biosensor, proximity hybridization, PDGF-BB, isothermal exponential amplification, G-quadruplex