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Yanan Qi,1,2 Yuanyuan Yan,1,2 Dawei Tang,1,2 Jingjing Han,1,2 Xinyi Zhu,1,2 Mengting Cui,1,2 Hongyan Wu,3 Yu Tao,1,2 Fangtian Fan1,2 1School of Pharmacy, Bengbu Medical University, Bengbu, People’s Republic of China; 2Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu, People’s Republic of China; 3Institute of Biomedical Technology, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224005, People’s Republic of ChinaCorrespondence: Yu Tao; Fangtian Fan, Anhui Engineering Technology Research Center of Biochemical Pharmaceutical Bengbu Medical College, 2600 Donghai Avenue, Bengbu, Anhui, 233003, People’s Republic of China, Tel +86-15852921284 ; +86-16655258065, Email YuTao@bbmc.edu.cn; 2019050@bbmu.edu.cnBackground: Chronic obstructive pulmonary disease (COPD) currently ranks among the top three causes of mortality worldwide, presenting as a prevalent and complex respiratory ailment. Ongoing research has underscored the pivotal role of immune function in the onset and progression of COPD. The immune response in COPD patients exhibits abnormalities, characterized by diminished anti-infection capacity due to immune senescence, heightened activation of neutrophils and macrophages, T cell infiltration, and aberrant B cell activity, collectively contributing to airway inflammation and lung injury in COPD.Objective: This review aimed to explore the pivotal role of the immune system in COPD and its therapeutic potential.Methods: We conducted a review of immunity and COPD published within the past decade in the Web of Science and PubMed databases, sorting through and summarizing relevant literature.Results: This article examines the pivotal roles of the immune system in COPD. Understanding the specific functions and interactions of these immune cells could facilitate the development of novel therapeutic strategies and interventions aimed at controlling inflammation, enhancing immune function, and mitigating the impact of respiratory infections in COPD patients.Keywords: COPD, immune system, inflammation, immune regulation

Li Wang, Dongling Tang, Pingan Zhang Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of ChinaCorrespondence: Pingan Zhang, Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China, Tel +86 13971196429, Email zhangpingan927@163.comPurpose: The glucose metabolic reprogramming is an important pathological mechanism in sepsis, which involves a series of enzymes including Pyruvate kinase M2 (PKM2). The purpose of this study is to explore the diagnostic and prognostic value of serum PKM2 in sepsis patients.Patients and Methods: This study recruited 143 sepsis patients, 91 non-sepsis patients, and 65 physical examiners, divided into sepsis group, non-sepsis group, and control group. Measure the serum PKM2 concentration of subjects, collect and analyze clinical and laboratory indicators of all subjects. Independent risk factors were selected by Logistic regression analysis. The area under curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve to determine the diagnostic and prognostic value of biomarkers.Results: Compared with non-sepsis and control groups, the serum PKM2 levels in the sepsis group were significantly increased (both P< 0.001). PKM2 was an independent risk factor for sepsis and had the best diagnostic efficacy when combined with procalcitonin, with the AUC value of 0.9352. Patients with high levels of PKM2 were more likely to experience organ damage and had a higher incidence of septic shock. On the 1st and 3rd days of admission, the serum PKM2 levels in the septic shock group were higher than those in the sepsis group (both P< 0.05), with AUC values of 0.7296 and 0.6247, respectively. On the 3rd and 7th days of admission, the serum PKM2 levels in the non-survival group were significantly higher than those in the survival group (both P< 0.001), with AUC values of 0.7033 and 0.8732, respectively.Conclusion: The serum PKM2 levels in sepsis patients are significantly increased and correlated with disease severity and clinical outcomes. PKM2 may be a new diagnostic and prognostic biomarker for sepsis.Keywords: sepsis, PKM2, glucose metabolic reprogramming, diagnosis, prognosis

Zhengting Jiang,1,&ast; Wenjie Zhang,1,&ast; Jie Zhang,1 Tian Liu,1 Juan Xing,1 Huan Zhang,1 Dong Tang2 1Clinical Medical College, Yangzhou University, Yangzhou, 225000, People’s Republic of China; 2Department of General Surgery, Institute of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Yangzhou, 225000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Tang, Department of General Surgery, Institute of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Yangzhou, 225000, People’s Republic of China, Email 83392785@qq.comAbstract: Cancer immunotherapy, a major breakthrough in cancer treatment, has been successfully applied to treat a number of tumors. However, given the presence of factors in the tumor microenvironment (TME) that impede immunotherapy, only a small proportion of patients achieve a good clinical response. With the ability to increase permeability and cross biological barriers, nanomaterials have been successfully applied to deliver immunotherapeutic agents, thus realizing the anti-cancer therapeutic potential of therapeutic agents. This has driven a wave of research into systems for the delivery of immunotherapeutic agents, which has resulted in widespread interest in nanomaterial-based drug delivery systems. Nanomaterial-based drug delivery systems are able to overcome the challenges from TME and thus achieve good results in cancer immunotherapy. If it can make a breakthrough in improving biocompatibility and reducing cytotoxicity, it will be more widely used in clinical practice. Different types of nanomaterials may also have some subtle differences in enhancing cancer immunotherapy. Moreover, delivery systems made of nanomaterials loaded with drugs, such as cytotoxic drugs, cytokines, and adjuvants, could be used for cancer immunotherapy because they avoid the toxicity and side effects associated with these drugs, thereby enabling their reuse. Therefore, further insights into nanomaterial-based drug delivery systems will provide more effective treatment options for cancer patients.Keywords: drug repurposing, delivery system, immunotherapy, tumor microenvironment, nanomaterial

Dijiao Tang,1 Yuetong Guo,1 Yi Tang,2 Hongxu Wang1 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Pathology, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Hongxu Wang, Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel/Fax +86 23 89012513, Email wanghx502@163.comBackground: Castleman disease (CD) is a rare and heterogeneous lymphoproliferative disorder with a spectrum of characteristic pathological abnormalities of lymph node. Furthermore, its clinical diagnosis is very challenging until pathological results are available. This study aimed to investigate the clinical presentations, treatment and prognosis of CD, thereby improving the understanding and diagnosis of CD.Methods: This study retrospectively analyzed the clinical data of 31 patients with CD admitted to the First Hospital Affiliated Hospital of Chongqing Medical University January 2013 to December 2020. The chi-square test and the Mann–Whitney rank sum test were employed to calculate between-group differences for categorical and quantitative data, respectively.Results: Clinically, patients with unicentric CD (UCD) usually present with lymphadenopathy. However, the clinical presentation of patients with multicentric CD (MCD) ranged from mild lymphadenopathy with B-symptoms (5/8, 62.5%) to intense inflammation, vascular leak syndrome (3/8, 37.5%), hepatosplenomegaly (3/8, 37.5%), organ insufficiency (3/8, 37.5%), and even death (2/8, 25.0%). Compared with UCD patients, patients with MCD had significantly lower levels of hemoglobin (104 (90,129) vs 137 (120,149), p=0.018) and plasma albumin (31.5 (27.0,37.0) vs 45.0 (40.0,46.5), p=0.001), but IgG levels were significantly increased. Patients with UCD were mainly treated with surgical resection alone, with a five-year survival rate of 95.65%. When siltuximab is not an option, steroid plus rituximab-based chemotherapy and specific supportive care are common options for MCD. Except for 2 deaths, the remaining MCD patients have stable disease or partial remission.Conclusion: CD describes a heterogeneous group of disorders characterized by morphologically benign lymphoid hyperplasia. Notably, patients with MCD present varying degrees of inflammation responses, even involving multiple systems. Surgery is a direct and effective way to diagnose and treat UCD. In the absence of IL-6 antagonists, anti-inflammatory and immunosuppressive therapeutic strategies, and cytotoxic clearance of cells responsible for hypercytokinemia could be adopted.Keywords: Castleman disease, unicentric, multicentric, heterogeneity

Di Tang,1,&ast; Duo Zhang,1,&ast; Yu Heng,1 Xiao-Ke Zhu,1 Han-Qing Lin,1 Jian Zhou,1 Lei Tao,1 Li-Ming Lu2 1Department of Otorhinolaryngology and ENT Institute, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Ming Lu, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, People’s Republic of China, Tel +86-13916235624, Fax +86-021-63846383, Email lulunew2003@163.com Lei Tao, ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Tel +86-13916944810, Email doctortaolei@163.comPurpose: Chronic inflammation contributes to tumor initiation, progression, and immune escape. Neutrophils are the major component of inflammatory response and participate in the tumorigenesis process. However, compared to other immune cells in the tumor microenvironment of laryngeal squamous cell carcinoma (LSCC), neutrophils, especially the tumor-associated neutrophils (TANs), have not yet been comprehensively explored. The mechanism for regulating the crosstalk between TANs and tumor cells still remains unclear.Materials and Methods: The distribution profiles and phenotypic features of neutrophils and other inflammatory immune cell populations from a large LSCC patient cohort were systemically analyzed. Co-culturing of peripheral blood associated neutrophils (PANs) and TANs with PBMCs was performed, and the immunosuppression effect on T-cells was examined.Results: LSCC microenvironment is highly inflammatory with remarkable TANs infiltration, which is often associated with unfavorable prognosis and advanced clinical stage. We find that TANs in LSCC display morphologically immature and lower apoptosis, exhibit distinctively immunosuppressive phenotype of high PD-L1, and suppress CD8+ T lymphocytes proliferation and activation. We subsequently discover that PD-L1+TANs induced by LSCC-derived GM-CSF potently impair CD8+ T-cells proliferation and cytokines production function, which are partially blocked by a PD-L1-neutralizing antibody. Clinical data further support GM-CSF as an unfavorable prognostic biomarker and reveal a potential association with inflammatory immune cell infiltration, in particular neutrophils.Conclusion: Tumor-infiltrating PD-L1+ neutrophils induced by LSCC-derived GM-CSF suppress T cell proliferation and activation in the inflammatory microenvironment of LSCC and predict unfavorable prognosis. These TANs cripple antitumor T cell immunity and promote tumor progression. Our findings provide a basis for targeting PD-L1+TANs or GM-CSF as a new immunotherapeutic strategy for LSCC.Keywords: laryngeal squamous cell carcinoma, LSCC, tumor-associated neutrophils, TANs, PD-L1, inflammatory microenvironment, immune suppression, granulocyte-macrophage colony stimulating factor, GM-CSF

Jing-Xiao Li,1 Jin-Shu Pang,2 Bin-Tong Yin,1 Gang Chen,1 Jun-Hong Chen,1 Jia-Yuan Luo,1 Xia Yang,1 Li-Ting Qin,1 Jiang-Hui Zeng,3 Peng Chen,4 Jia-Bo Chen,4 Deng Tang1 1Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People’s Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530031, People’s Republic of China; 4Department of Pediatric Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530031, People’s Republic of ChinaCorrespondence: Deng TangDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86-7715356534Email tdnever@163.comPurpose: The molecular mechanisms and signal pathways of ferroptosis in hepatoblastoma (HB) have not yet been clarified. In previous studies, activating transcription factor 3 (ATF3) was reported to be correlated with several tumors, but the clinical significance of ATF3 has never been determined. Herein, we investigated the clinicopathological value and mechanisms of ATF3 in regulating ferroptosis in HB.Methods: The mRNA microarray and RNA-sequencing data of 402 samples from our hospital and public databases were used to estimate ATF3 expression and assess its clinical role in HB. The standard mean difference (SMD) and summary receiver operating characteristic curves were utilized to judge the discrimination ability of ATF3 between HB and non-HB liver tissues. We examined the expression variation of ATF3 in HB cells after the treatment with erastin. We also predicted the target genes of ATF3 as a transcriptional factor from public Chromatin Immunoprecipitation-sequencing data and selected the ferroptosis-related genes for a signaling pathway analysis.Results: In ten series, the pooled SMD for ATF3 was − 0.91, demonstrating that ATF3 expression was predominantly lower in HB than in non-HB liver tissues. ATF3 down-regulation showed moderate potential to distinguish HB from non-HB liver tissues (area under curves = 0.83, 95% confidence interval = 0.79– 0.86). Altogether, 4855 putative targets of ATF3 as a transcriptional factor were collected, among which, 60 genes were ferroptosis-related.Conclusion: The down-regulated ATF3 expression may play a vital role in the occurrence of HB possible partially by regulating ferroptosis.Keywords: transcription factor, ATF3, hepatoblastoma, ferroptosis

Ding Tang,1 Xufen Zhang,1 Yani Xu,1 Linglin Dai,1 Jianlan Sun,1 Hantong Hu,2 Huangwei Jiang,3 Ping Jin,3 Lifang Chen,2 Jianqiao Fang4 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Radiological, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Third Clinical Medical College of Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lifang ChenDepartment of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, XiHu District, Hangzhou, Zhejiang, 310005, People’s Republic of ChinaEmail clfang@163.comJianqiao FangZhejiang Chinese Medical University, NO. 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail fangjianqiao7532@163.comObjective: To verify the efficacy of electroacupuncture (EA) on classical trigeminal neuralgia (CTN), and to observe the brain functional status of patients with CTN and the intervention effects of EA on brain function by resting-state functional magnetic resonance imaging (rs-fMRI).Methods and Analysis: Thirty CTN patients will be randomly divided into EA combined with carbamazepine group and carbamazepine group in 2:1 ratio by using a random number table. Patients in EA combined with carbamazepine will receive EA treatment and carbamazepine for four weeks. The carbamazepine group will only receive carbamazepine treatment. VAS (visual analogue scale), HAMA (Hamilton Anxiety Scale), HAMD (Hamilton Depression Scale) and SF-36 (short form 36 health survey) will be performed before, after four-week treatments and at three-month follow-up in CTN patients. Six CTN patients will be randomly selected from EA combined with carbamazepine group and carbamazepine group, respectively, before treatment, and twelve paired healthy participants will be recruited at the same time. The twelve CTN patients will be scanned by rs-fMRI before and after treatment, and the healthy participants will be scanned by rs-fMRI only at baseline. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analysis will be carried out to compare the dysfunctional brain regions between CTN patients and healthy participants, as well as the differences between two groups of patients with CTN after treatment.Trial Registration: ChiCTR-1900027873.Keywords: electroacupuncture, trigeminal neuralgia, pre-experimental, fMRI, randomized controlled trial, protocol

Huan Li, Juanjuan Chen, Yuanhui Hu, Xin Cai, Dongling Tang, Pingan Zhang Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Pingan Zhang Email zhangpingan927@163.comObjective: To explore the clinical application value of serum complement component C1q levels in sepsis.Methods: The clinical data and laboratory examination data of 320 research subjects (including 132 cases as sepsis group, 93 cases as nonsepsis group and 95 cases as control group) who were diagnosed and treated in Renmin Hospital of Wuhan University from July 2020 to March 2021 were collected. We compared the levels of each index among the three groups and further analyzed the C1q levels of different severity subgroups and different outcome subgroups of sepsis. Afterwards, we explored the correlation between C1q levels and SOFA score, organ damage indexes and coagulation indexes. Finally, the receiver operating characteristic curve (ROC) was used to analyze the prognostic value of C1q in patients with sepsis.Results: C1q levels were significantly reduced in the serum of patients with sepsis; the level of C1q in the death group was lower than that in the survival group (127.1 mg/L vs 153.2 mg/L, P < 0.05), and the mortality in the C1q decreased group was higher when compared with C1q normal group; in addition, serum C1q levels were correlated with SOFA score, organ damage indexes and coagulation indexes; C1q had a high area under the curve (AUC) for the prognosis of sepsis, and the combination of other indexes can further improve the prognostic value.Conclusion: Serum C1q levels have potential clinical value for the condition and prognosis of sepsis.Keywords: C1q, sepsis, infection, organ damage, prognosis

Xishuai Wang,1,2 Zhiqing Wang,1 Donghui Tang1 1Department of College of P.E and Sport, Beijing Normal University, Beijing, People’s Republic of China; 2Department of Animal Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, People’s Republic of ChinaCorrespondence: Donghui Tang; Xishuai WangDepartment of College of P.E and Sport, Beijing Normal University, No. 19, Xinjiekouwai St, Haidian District, Beijing, 100875, People’s Republic of ChinaEmail 201831070001@mail.bnu.edu.cn; 630200346@qq.comBackground: Chronic inflammation, oxidative stress, and apoptosis play critical roles in chronic obstructive pulmonary disease (COPD) pathogenesis. Here, we attempted to determine whether aerobic exercise (AE) could improve COPD by counteracting the COPD-associated inflammatory response, oxidative stress, and apoptosis in mice.Methods: Thirty male ICR mice were assigned into one of three groups: control (Con), COPD, and COPD + AE. COPD was simulated by intratracheal injection of lipopolysaccharide (LPS) for 4 weeks. Low-intensity AE was performed for 4 weeks. Bronchoalveolar lavage fluid (BALF) cell counts and the levels of inflammatory cytokine in BALF and serum were detected. Hematoxylin and eosin (HE), Masson trichrome, and Sirius Red staining as well as terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to identify the degree of pulmonary emphysema, bronchial mucus cell hyperplasia, pulmonary fibrosis, and cell apoptosis. Oxidative stress parameters were measured. Furthermore, gene expression levels for the CXCL1, IL-1β, IL-10, IL-17, matrix metalloproteinase (MMP)9, TGF-β, TNF-α, and silent information regulator (sirt)1 were detected in mice lung tissues.Results: AE improved LPS-induced emphysema, pulmonary fibrosis, bronchial mucus cell hyperplasia, bronchoconstriction, and cell apoptosis. AE prevented an LPS-induced increase in the total cell, neutrophil, and macrophage counts. AE decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels but increased glutathione (GSH) and superoxide dismutase (SOD) levels. AE decreased BALF levels of IL-1β, TNF-α, and TGF-β but increased BALF IL-10 levels. AE suppressed the gene expression levels of pro-inflammatory factors CXCL1, IL-1β, IL-17, and TNF-α and profibrotic factors MMP-9 and TGF-β but activated those of anti-inflammatory factor IL-10 and lung-protective factor sirt1.Conclusion: AE is a potential therapeutic approach for COPD. AE improved emphysema, bronchial mucus cell hyperplasia, and pulmonary fibrosis in mice with COPD by alleviating the inflammatory response, oxidative stress injury, and cell apoptosis as well as activating sirt1.Keywords: exercise, COPD, pulmonary fibrosis, emphysema, pulmonary inflammation, oxidative stress injury

Cheng Wang,1 Hong Wang,2 Luming Dai,1 Jianqing Zhang,1 Lizhou Fang,1 Ling Liu,1 Weiping Fu,1 Dang Tang3 1Second Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Department of Burns Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 3First Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of ChinaCorrespondence: Dang Tang Email tangdangdemao@126.comBackground: Chronic obstructive pulmonary disease (COPD) is often combined with type 2 diabetes mellitus (T2DM) in clinical, and with poor prognosis. In recent years, research shows that inflammation is a common characteristic of COPD and T2DM. T-helper 17 cell (Th17)/regulatory T-cell (Treg) balance controls inflammation and may be important in the pathogenesis of COPD combined with T2DM patients. This study investigated the characteristics of Th17, Treg and related inflammatory factors in COPD combined with T2DM patients and the potential mechanism.Methods: Application of flow cytometry technology, real-time fluorescent quantitative PCR and ELISA to detect the changes in peripheral blood of Th17 and Treg number and the expression of key transcription factors and related cytokines in COPD combined T2DM patients were performed.Results: Patients with COPD combined with T2DM revealed significant increase in peripheral Th17, Th17 related cytokines (IL-17A, IL-17F, IL-21, IL-23, IL-6) and transcription factor (RORγt) levels and significant decrease in Treg, Treg-related cytokines (IL-10, TGFβ 1) and transcription factor (Foxp3) as compared with patients with COPD, T2DM and healthy controls.Conclusion: Th17/Treg functional imbalance exists in patients with COPD combined with T2DM, indicating a potential role of Th17/Treg imbalance in the formation and progression of COPD combined with T2DM.Keywords: COPD combined with T2DM, Th17/Treg, cytokine, transcription factor

Dongfang Tang,1 Tao Huang,2 Qilong Tian,2 Julei Wang2 1Department of Neurosurgery, Henan Provincial People’s Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, Xi’an City, People’s Republic of ChinaCorrespondence: Julei WangDepartment of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an City, Shaanxi Province, 710038, People’s Republic of ChinaTel +86-29-84777777Email wangjulei_wjl@163.comBackground: The role of Hydroxysafflor Yellow A (HSYA) in glioma is less studied, this research determined the effect of HSYA on glioma cells.Methods: The expressions of MYC and NBS1 in glioma tissues were detected by bioinformatics analysis and verified by RT-qPCR. The target relationship between MYC and NBS1 was predicted by bioinformatics. After treating the cells with HSYA, silenced MYC, or overexpressed NBS1, the viability, apoptosis, proliferation, invasion, migration, and DNA damage of the glioma cells were detected by MTT, flow cytometry, colony formation, transwell, wound healing, and γH2AX immunofluorescence assays, respectively. IC50 of HSYA in glioma cells was analyzed by Probit regression analysis. The expressions of MYC, NBS1, factors related to migration, invasion, apoptosis, and DNA damage of the glioma cells were determined by Western blot or RT-qPCR.Results: MYC and NBS1 were high-expressed in glioma, and NBS1 was targeted by MYC. HSYA and siRNA targeting MYC inhibited the cell viability, proliferation, invasion, migration, and induced the cell apoptosis of glioma cells. HSYA upregulated the expressions of MYC, γH2AX, E-Cadherin, Bax, and Cleaved-PARP1, stimulated the activation of NBS1, MRE11, RAD50, and ATM, and downregulated the expressions of N-Cadherin and Bcl2 in glioma cells. SiMYC decreased the IC50 of HSYA in the glioma cells, enhanced the sensitivity of glioma cells to HSYA, and inhibited the activation of NBS1 and ATM. NBS1 overexpression reversed the effect of siRNA targeting MYC on glioma cells.Conclusion: MYC silencing inhibited the DNA damage response via regulation of NBS1, leading to DNA repair deficiency, and subsequently enhanced the sensitivity of glioma cells to HSYA.Keywords: glioma, hydroxysafflor yellow A, MYC, NBS1, drug sensitivity, DNA repair

Ying Cao,1,* Du Tang,1,* Yining Xiang,1 Li Men,2 Chao Liu,1 Qin Zhou,1 Jun Wu,3 Lei Huo,3 Tao Song,3 Ying Wang,4 Zhanzhan Li,1 Rui Wei,1 Liangfang Shen,1 Zhen Yang,1 Jidong Hong1 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jidong HongDepartment of Oncology, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 731 8975 3733Fax +86 731 8975 3336Email hongjidong1966@126.comPurpose: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma.Methods: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT1/MRI1, CT2/MRI2, CT3/MRI3, and CT4/MRI4) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan1, plan2, plan3 and plan4) were made. The dose of the initial plan (plan1) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan1– 2 and plan1– 3) and by superimposing the doses to obtain the ART plans (plan10+20 and plan20+10), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans.Results: Compared with the projection plan, the D2 to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D2/Dmean to the brainstem, optic chiasm and pituitary, as well as the V20, V30, V40 and V50 to the normal brain decreased. The D2 to the pituitary and optic chiasm as well as the V20, V30, V40 and V50 to the normal brain in plan10+20 were lower than those in plan20+10, while the CI to the PTV was higher than that in plan20+10. The TCP of the PTV in plan10+20 was higher than that in plan20+10.Conclusion: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART.Keywords: adaptive radiotherapy, high-grade glioma, dosimetry, biophysical model

Dan Tang,1,2,* Haihai Luo,1,* An Xie,3 Zhichun He,1 Bin Zou,4 Fei Xu,1 Wei Zhang,1 Xinping Xu1 1Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Jiangxi Institute of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Thoracic Surgery, Jiangxi Cancer Hospital, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinping Xu; Wei ZhangJiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai St, Nanchang, Jiangxi, 330006, People’s Republic of ChinaEmail xinpingxu@ncu.edu.cn; zhangweiliuxin@163.comPurpose: Lung cancer has been recognized as the most fatal malignant tumor with the highest morbidity and mortality in recent years.Materials and Methods: In this study, we found that LMNB1, which is an important component protein of the nuclear skeleton, was significantly upregulated in lung adenocarcinoma (LUAD) and correlated with the pathological stage as well as lymphatic metastasis.Results: In vitro loss-of-function study utilizing LMNB1 knockdown LUAD cell lines demonstrated that depletion of LMNB1 inhibited development of LUAD through regulating cell proliferation, cell apoptosis, cell cycle and cell motility. Decreased tumorigenesis of LMNB1 knockdown LUAD cells was proved in mice xenograft models. Moreover, the mechanism by which LMNB1 promotes LUAD was explored through the expression evaluation of apoptosis-related proteins and cancer-related signaling pathways.Conclusion: In conclusion, our study identified LMNB1 as a tumor promotor and a potential therapeutic target in LUAD.Keywords: lung cancer, lung adenocarcinoma, LMNB1, cell proliferation, cell apoptosis

The reduction of copper content in converting slag using process control is significant to copper smelter. In this study, the slags produced from the Ausmelt Converting Process for copper matte was analyzed using X-ray diffraction and chemical analysis. Thermodynamic calculation and effects of various conditions including the lance submerging depth in molten bath, the molten bath temperature, the addition of copper matte, and airflow rate were carried out to lower the content in the slag. Thermodynamic analysis indicated that the decrease of copper content was achieved by reducing Fe3O4, CuFe2O4, and Cu2O in the slag, decreasing the magnetism of slag and lowering the viscosity of slag, which was feasible at the operating temperature of the molten bath. Experiments showed that the optimal combination of operating conditions were found to be the addition of copper matte between 5,000 – 7,000 kg/h, a lance airflow rate of 13,000-14,000 Nm3/h, and a lance submergence depth into the molten bath of 700-900 mm, in which the copper content in the slag was effectively reduced from 22.74 wt. % to 7.70 wt. %. This study provides a theoretical support and technical guidance for promoting the utilization of slags from the Ausmelt Converting Process.

Jianlong Zhou,1,2,* Dingxue Wang,3,* Dongxin Tang,3 Wenhua Huang1 1Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Oncology, The Affiliated Xinhui Hospital, Southern Medical University, Xinhui, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongxin TangThe First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, No. 71 Baoshanbei Road, Guiyang 550000, People’s Republic of ChinaEmail tangdongxin@sina.comWenhua HuangDepartment of Oncology, Zhujiang Hospital, Southern Medical University, No.253 Gongye Middle Avenue, Guangzhou 510280, People’s Republic of ChinaEmail huangwenhua88888@outlook.comBackground: Lung tumors and normal lung tissues show large differences in epigenetic modification which can affect the chromosome structure and expression of genes. However, the epigenetic reprogramming in lung adenocarcinoma remains unclear.Methods and Results: With the bioinformatics analysis, we found that some activated super-enhancers (SEs) only appear in lung adenocarcinoma cells, and 781 abnormal activated super-enhancers (AASEs) were found. Not only are the traditional oncogenes found to be activated by AASEs, such as MET and SLC2A1, but also some new genes were activated by AASEs, which probably contributes to the carcinogenic process in lung cancer. The enrichment analysis of the genes activated by AASEs shows that the glycolysis process and cell proliferation were enhanced and the apoptotic process was negatively regulated. Two AASEs were separately knockout by CRISPR/Cas9 in A549, PC-9, and H1299 cell lines and the expression of target genes decreased. The motif of CTCF, SMARCA1, SOX4, FOXM1, IRF3, IRF7, and STAT2 was enriched in AASEs, supporting that the chromosome structure changed and these transcription factors would be the master regulators on the formation of AASEs.Conclusion: This study provided comprehensive insight into the mechanisms of SEs, as well as a potential therapeutic target for lung cancer.Keywords: lung adenocarcinoma, epigenetic, super-enhancer, transcription factors

Yulu Zhang,1,* Songyu Liu,1,* Jinyan Wan,1,* Qiyue Yang,2 Yan Xiang,1 Li Ni,1 Yu Long,1 Mingquan Cui,1 Zhimin Ci,1 Donglei Tang,1 Nan Li1 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nan LiCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, People’s Republic of ChinaTel +86-28-61801001Email 55743198@qq.comPurpose: Baicalin (BA) has a good neuroprotective effect, but it is eliminated quickly in the body and does not easily reach the brain. In this experiment, borneol (BO) was used as an auxiliary drug to prepare borneol-baicalin-liposomes (BO-BA-LP) to prolong the efficacy time of BA, synergistically synergize, introduce drugs into the brain, and better exert the therapeutic effect on cerebral ischemia-reperfusion (I/R) injury.Methods: Through single-factor inspection and response surface optimization analysis, obtained the best preparation process of BO-BA-LP and characterized by various analytical techniques. Validated the long-term effectiveness of BA-BO-LP through pharmacokinetic studies and conducted pharmacodynamic studies on the middle cerebral artery occlusion (MCAO) rat model to verify the therapeutic effect of BO-BA-LP on cerebral I/R injury.Results: The optimum preparation conditions of BO-BA-LP were as follows: the dosage of BO was 9.55 mg, the ratio of phospholipid to drug was 4.02:1, the ratio of phospholipid to cholesterol was 7.25:1, the entrapment efficiency (EE) was 41.49%, and the drug loading (DL) was 4.29%. The particle size range of the liposomes was 167.1 nm, and the polydispersity index (PDI) range was 0.113. The results of pharmacokinetic experiments showed that the combination of BA and BO liposomes effectively improved the pharmacokinetic parameters of BA and prolonged the half-life of BA. Pharmacodynamic studies have found that, compared with BA-LP, BO-BA-LP can significantly improve neurological deficits, cerebral infarction volume, and brain pathological states on MCAO rats.Conclusion: These results demonstrated that BO-BA-LP can improve the circulation of drugs in the blood, and the addition of BO can enhance the therapeutic effect of BA and effectively improve cerebral I/R.Keywords: borneol-baicalin-liposome, pharmacokinetics, pharmacodynamics, MCAO

Guo-feng Xie,1,* Luo-dan Zhao,2,3,* Qiang Chen,4,* Dong-xiao Tang,4 Qiong-yu Chen,4 Hong-fei Lu,4 Jia-rong Cai,5 Zheng Chen4 1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province 510095, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangzhou Higher Education Institutes, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, People’s Republic of China; 5Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-rong CaiDepartment of Urology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of ChinaTel +86-20-82179727Fax +86-20-85253336Email caijiar@mail.sysu.edu.cnZheng ChenDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of ChinaFax +86-20-85253336Email chenzh68@mail.sysu.edu.cnPurpose: Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral cavity. As the survival rate of OSCC patients is low, it is crucial to explore new markers and therapeutic targets for early diagnosis of the disease. A high level of actinin alpha 1 (ACTN1) in patients could serve as an independent prognostic factor of acute myeloid leukemia. However, the role of ACTN1 in OSCC remains unclear. In the present study, we aimed to investigate the role of ACTN1 in OSCC.Methods: ACTN1 protein levels in tissues were determined by immunohistochemical (IHC) staining. The correlation of ACTN1 expression with clinicopathological features and prognosis was analyzed. Univariate and multivariate analyses were performed. The effect of ACTN1 knockdown on cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and the cell cycle was evaluated using Western blotting, Cell Counting Kit‑8 (CCK8) assays, flow cytometry analysis, transwell assays, wound-healing assays, and nude mouse models of subcutaneous xenograft and pulmonary metastasis.Results: Based on the total score of ACTN1 IHC staining analysis, ACTN1 expression was found to be low in 10 normal mucosal tissues, 48 normal mucosal tissues adjacent to OSCC, and 19 OSCC tissues, but high in 29 OSCC tissues. ACTN1 protein levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 expression was an independent predictor of poor prognosis of OSCC. Using in vitro assays, we found that ACTN1 knockdown could induce cell cycle arrest, promote apoptosis, and inhibit EMT and cell proliferation, migration, and invasion in the OSCC cell lines, SCC-15 and HSC-3. Moreover, ACTN1 knockdown inhibited subcutaneous tumor growth and pulmonary metastasis in vivo.Conclusion: ACTN1 levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 knockdown could suppress cell proliferation and metastasis of OSCC. Our results suggested that ACTN1 may serve as a diagnostic and prognostic marker of OSCC.Keywords: actinin alpha 1, poor prognosis, oral squamous cell carcinoma, knockdown, proliferation, metastasis

Dianjun Tang,*,1,2 Yanshuo Han,*,3 Yu Lun,1 Han Jiang,1 Shijie Xin,1 Zhiquan Duan,1 Jian Zhang11Department of Vascular Surgery, The First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm Liaoning Province, Shenyang, People’s Republic of China; 2Department of Vascular Surgery, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China*These authors contributed equally to this workPurpose: Abdominal aortic aneurysm (AAA) demonstrates many features of autoimmune diseases. Y chromosome, sex-determining region of the Y chromosome (SRY) gene, androgen receptor (AR) gene, and androgen appear as potential candidates for influence of the male immune function. This study investigated Y chromosome numbers, SRY gene, AR gene, and androgen levels in male AAAs. We also investigated the correlation between Y chromosome loss (LOY) ratio, SRY expression, androgen levels, and age.Patients and methods: We investigated LOY by fluorescence in situ hybridization (FISH) in 37 AAAs and compared with 12 patients with abdominal aortic atherosclerotic occlusive disease (AOD) and 91 healthy controls (HC). We investigated SRY and AR expression at mRNA level by real-time PCR in peripheral T lymphocytes in AAA compared with AOD and HC, and AR protein levels by immunohistochemistry (IHC) in AAA. LOY, SRY expression, androgen levels, and age were examined for correlations using the Spearman’s rank correlation coefficient.Results: LOY ratio in peripheral T lymphocytes was significantly higher in the AAA group compared with the HC (9.11% vs 5.56%, P

Defeng Tang,1,2 Tianlong Lin,1 Yangyang Wang,1 Hui Cao11Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, People’s Republic of China; 2Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, People’s Republic of ChinaPurpose: The aim of this study was to elucidate the prognostic value of proenkephalin (PENK) in gastrointestinal stromal tumors (GISTs).Patients and methods: We collected data on 268 eligible postoperative patients diagnosed with GIST between January 1, 2002, and December 31, 2011. PENK expression was detected in GIST tissues classified using the United States National Institutes of Health (NIH) risk classification system. The associations between high PENK expression and the clinicopathological characteristics were assessed. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan–Meier analysis, and the log-rank test was used to compare the differences between groups. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of PENK in GIST patients.Results: High PENK expression was more common in the low- and intermediate-risk GIST groups compared with the high-risk group (P

Cheng Wang,1 Jun-Xiong Li,1 Dang Tang,2 Jian-Qing Zhang,1 Li-Zhou Fang,1 Wei-Ping Fu,1 Ling Liu,1 Lu-Ming Dai1 1Second Department of Respiratory Medicine, 2First Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China Background: Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system. Metabolic profiling of different high-resolution computed tomography (HRCT) phenotypes of COPD patients before and after treatment may identify discriminatory metabolites that can serve as biomarkers and therapeutic agents. Patients and methods: 1H nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics was performed on a discovery set of plasma samples from 50 patients with stable COPD. Patients were assigned into two groups on the basis of HRCT findings including phenotype E (n=22) and phenotype M (n=28). After budesonide–formoterol treatment (160/4.5 µg ×2 inhalations twice daily for 3 months), clinical characteristics and metabolites were then compared between phenotype E pretreatment and posttreatment, phenotype M pretreatment and posttreatment, phenotype E pretreatment and phenotype M pretreatment, and phenotype E posttreatment and phenotype M posttreatment. Results: Inhaled budesonide–formoterol therapy for both phenotype E (emphysema without bronchial wall thickening) and phenotype M (emphysema with bronchial wall thickening) was effective. However, phenotype E and phenotype M were different in response to therapy. Patients with phenotype M in response to therapeutic effects were significantly greater compared with phenotype E. Certain metabolites were identified, which were closely related to the treatment and phenotype. Metabolic changes in phenotype E or phenotype M after treatment may be involved with adenosine diphosphate (ADP), guanosine, choline, malonate, tyrosine, glycine, proline, l-alanine, l-valine, l-threonine leucine, uridine, pyruvic acid, acetone and metabolism disturbance. Metabolic differences between phenotype E and phenotype M in pretreatment and posttreatment covered glycine, D-glucose, pyruvic acid, succinate, lactate, proline, l-valine and leucine. Conclusion: Bronchial wall thickening in COPD may be an indicator for predicting the better response to the treatment with bronchodilator and corticosteroid. The identification of metabolic alterations provides new insights into different HRCT phenotypes and therapeutic assessment of COPD. Keywords: COPD, metabolomics, budesonide–formoterol, HRCT

The frequency of the Robertonian (ROB) translocation in newborn babies is approximately one in 1000. Robertsonian translocation is an unusual type of chromosome rearrangement caused by two particular chromosomes joining together. The aim of the study was to analyze the segregation of the ROB translocations in 13 male carriers, and to verify a possible inter-chromosomal effect (ICE) of the ROB translocation on chromosomes 18, X, and Y. Thirteen male patients were included in the study. Multicolor fluorescent in situ hybridization (FISH) was used to analyze chromosomes 13, 14, 15, 21, 22, 18, X and Y in sperm. Among the heterozygous ROB translocation carriers, the frequency of normal/balanced spermatozoa resulting from alternate segregation varied between 70.4 and 85.2%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 14.8 and 29.6%. Increased frequencies of aneuploidy for a sex chromosome were found in 10 ROB translocation carriers (P2-P8, P10-P12). Increased frequencies of aneuploidy for chromosome 18 were found in10 ROB translocation carriers (P3-P9, P11-P13). In addition, increased frequencies of diploid were found in 11 ROB translocation carriers (P2-P9, P11-P13). Among the homozygous ROB translocation carriers, the rate of balanced spermatozoa was 99.7% and the frequency of unbalanced spermatozoa was 0.3%. However, the frequencies of aneuploidy for a sex chromosome and chromosome 18 were normal. Despite the high number of normal/balanced frequencies, there remained many unbalanced spermatozoa resulting from alternate segregation. The ROB translocation carriers may be at an increased risk for ICE. Robertsonian translocation homozygosity could be seen as a potential speciation in humans with 44 chromosomes.

Abstract Background Cephalanthera nanchuanica is a terrestrial orchid species and has been red listed as a second-grade protected plant due to its limited distributions in China. Initially classified within a monotypic genus Tangtsinia, this species was later reassigned to Cephalanthera based on morphological and molecular data. However, previous phylogenetic analyses of Cephalanthera using several segment sequences exhibited a low discriminatory power in delineating its relationships. Results In this study, we characterized and comparatively analyzed the complete chloroplast (cp) genome of C. nanchuanica with those of six previously reported Cephalanthera species. Our findings revealed that the cp genome of C. nanchuanica had the typical quadripartite structure, with a size of 161,365 bp and a GC content of 37.27%. A total of 113 unique genes were annotated, among which nearly half of protein-encoding genes (RSCU > 1) showed a preference in codon usage. No structural rearrangements were observed among the cp genomes of Cephalanthera species, except for C. humilis, which displayed structural alterations due to gene loss, relocation, and inverted repeat (IR) expansion/contraction. The cp genomes of Cephalanthera species were highly conserved, with only a small number of SSRs detected, most of which preferred A/T bases. Comparative analysis of cp genomes indicated that IR and coding regions were less divergent than single copy and non-coding regions and eight mutational hotspots were identified. Phylogenetic analysis suggested that the tribe Neottieae was a monophyletic group, divided into five clades. Palmorchis was the earliest-diverging lineage, followed by Cephalanthera. Diplandrorchis was deeply nested within Neottia, forming a clade. Aphyllorchis and Limodorum formed another clade, sister to Epipactis. Within the Cephalanthera clade, C. nanchuanica was sister to C. falcata with a strong support. Conclusions This study demonstrated that the cp genome characters of C. nanchuanica are highly similar to those of other Cephalanthera species, except for the mycoheterotrophic species C. humilis. Although the cp genomes of Cephalanthera species (excluding C. humilis) exhibited conservation in genome structure and sequence, SSR repeats and mutational hotspots were identified, which could potentially serve as as molecular markers for distinguishing Cephalanthera species. The phylogenetic analysis based on the protein-coding genes provided high-resolution support for the infrageneric classification. Therefore, cp genome data will be instrumental in resolving the phylogeny of the genus Cephalanthera.

Abstract Lower limb arterial occlusive disease is treated with intraluminal devices, such as paclitaxel (PTX)-coated balloons (PCBs); however, post-procedural restenosis remains a significant challenge. NLRP3 activation is known to play a significant role in atherosclerosis, but its involvement in restenosis following PCB intervention remains to be investigated. We identified that NLRP3 was differentially expressed in lower-limb arterial tissues sourced from healthy controls and patients with arterial occlusive disease. Through cell experiments, we confirmed that PTX is involved in the activation of NLRP3. Subsequently, we demonstrated that NLRP3 activation promotes the proliferation and migration of vascular smooth muscle cell (VSMC), thereby reducing their sensitivity to PTX. NLRP3 activation also stimulates the secretion of the inflammatory cytokine interleukin IL-1β. RNA sequencing of IL-1β-treated VSMC revealed the upregulation of BRD4 and LIN9. Further mechanistic investigations confirmed that IL-1β facilitates BRD4 recruitment, leading to enhanced LIN9 expression. The transcription factor LIN9 binds to the promoter region of the cell-cycle regulator AURKA, thereby promoting its transcription and subsequently upregulating the expression of the cell proliferation-associated molecule FOXM1. These processes ultimately mediate the proliferation, migration, and PTX resistance of VSMC. Additionally, we discovered that JQ1 inhibited the overexpression of the above molecules, and exhibited a synergistic effect with PTX. Our conclusions were validated through in vivo experiments in Sprague-Dawley rats. Collectively, our findings provide insights into the molecular mechanisms underlying restenosis following PCB therapy, and suggest that the combined use of JQ1 and PTX devices may represent a promising therapeutic strategy. Graphical Abstract

Trichloroacetic acid is a common nonvolatile byproduct of drinking water disinfection and poses carcinogenic risks to the human body. In this study, four types of nano-oxide@microcrystalline-cellulose-based adsorbents (P25@microcrystalline cellulose, SiO₂@microcrystalline cellulose (MCC-g-GMA@SiO2), Fe3O4@microcrystalline cellulose, and Fe2O3@microcrystalline cellulose) were successfully prepared by the pre-radiation grafting-embedding method. Subsequently, their ability to remove trichloroacetic acid from drinking water was investigated. The micro zonation morphology and surface properties of the materials were characterized and tested using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), Thermogravimetric (TG) analysis, and Scanning electron microscopy (SEM) characterization methods. The effects of monomer concentration, embedding concentration, and absorbed dose on the weight gain rate were systematically investigated. A complete static adsorption equilibrium curve was obtained on the basis of the results of adsorption experiments of four buried nano-oxides. The performance of SiO2@microcrystalline cellulose was found to be significantly higher than that of the other three adsorbents. When the volum percentage of monomer concentration was 30%, the mass percentage of embedding concentration was 4%, and the absorbed dose was 60 kGy, the removal rate of trichloroacetic acid in drinking water reached 83.27%. This series of adsorbent materials present significant potential for practical application in drinking water purification.

[ Objective ] The front piedmont belt of the northern slope of the Tianshan Mountains in Xinjiang is a crucial component of the mountain-oasis-desert ecosystem of the Tianshan northern slope. Investiga- ting the dynamic physiological adaptations of plants to drought stress and assessing methods for drought resistance , as well as selecting suitable tree species for vegetation restoration holds significant importance for the ecological restoration in this region. [ Methods ] 12 plant species planted in the piedmont belt of the northern slope of the Tianshan Mountains in Xinjiang were selected as the subjects. The study observed the spatiotemporal distribution of soil moisture following irrigation and analyzed the impact of drought stress and rewatering treatment on plant photosynthetic and physiological indicators. The drought resist- ance of these 12 species was evaluated using principal component analysis. [ Results ] ( 1 ) Following drought stress , soil moisture depletion occurred most rapidly in the 0-20 cm layer , followed by the 20- 40 cm layer , and was slowest in the 40-60 cm layer. Different plants employed different strategies to adapt their growth to drought stress. ( 2 ) Following drought stress , net photosynthetic rate ( P n ), stoma- tal conductance ( G s ), transpiration rate ( T r ), intercellular CO 2 concentration ( C i ), potential activity of PSⅡ ( F v / F o ), maximum photochemical efficiency of PSⅡ ( F v / F m ), electron transport rate ( ETR ), and chlorophyll content were decreased , while the activity of superoxide dismutase ( SOD ), proline content , malondialdehyde ( MDA ) content , and non-photochemical quenching coefficient ( q N ) were increased. Af- ter rehydration , there was a certain degree of recovery in each parameter , but none of them reached the in- itial levels. ( 3 ) The results of principal component analysis highlighted that factors like P n , chlorophyll content , ETR , and MDA content were major contributors. Species such as Haloxylon ammodendron , Tamarix chinensis , Rosa acicularis , and Caragana korshinskii demonstrated significant drought resili- ence. Hippophae rhamnoides , H . rhamnoides ‘ Xinji 5 ’, H . rhamnoides ‘ Xinji 1 ’, and Prunus sibirica showed moderate levels of drought resistance , while H . rhamnoides ‘ Xinji 4 ’, H . rhamnoides ‘ Xinji 3 ’, Xanthoceras sorbifolium , and H . rhamnoides ‘ Xinji 2 ’ exhibited relatively lower drought tolerance. [ Conclusion ] P n , chlorophyll content , ETR , and MDA content were crucial indicators for evaluating the adaptability of various plant species to drought stress. In the context of ecological restoration efforts in the piedmont belt of the Tianshan Mountains􀆴 northern slope in Xinjiang , prioritizing the cultivation of H . ammodendron , T . chinensis , R . acicularis , and C . korshinskii were recommended.

Abstract Background Ruptured atherosclerotic plaques often precipitate severe ischemic events, such as stroke and myocardial infarction. Unraveling the intricate molecular mechanisms governing vascular smooth muscle cell (VSMC) behavior in plaque stabilization remains a formidable challenge. Methods In this study, we leveraged single-cell and transcriptomic datasets from atherosclerotic plaques retrieved from the gene expression omnibus (GEO) database. Employing a combination of single-cell population differential analysis, weighted gene co-expression network analysis (WGCNA), and transcriptome differential analysis techniques, we identified specific genes steering the transformation of VSMCs in atherosclerotic plaques. Diagnostic models were developed and validated through gene intersection, utilizing the least absolute shrinkage and selection operator (LASSO) and random forest (RF) methods. Nomograms for plaque assessment were constructed. Tissue localization and expression validation were performed on specimens from animal models, utilizing immunofluorescence co-localization, western blot, and reverse-transcription quantitative-polymerase chain reaction (RT-qPCR). Various online databases were harnessed to predict transcription factors (TFs) and their interacting compounds, with determination of the cell-specific localization of TF expression using single-cell data. Results Following rigorous quality control procedures, we obtained a total of 40,953 cells, with 6,261 representing VSMCs. The VSMC population was subsequently clustered into 5 distinct subpopulations. Analyzing inter-subpopulation cellular communication, we focused on the SMC2 and SMC5 subpopulations. Single-cell subpopulation and WGCNA analyses revealed significant module enrichments, notably in collagen-containing extracellular matrix and cell-substrate junctions. Insulin-like growth factor binding protein 4 (IGFBP4), apolipoprotein E (APOE), and cathepsin C (CTSC) were identified as potential diagnostic markers for early and advanced plaques. Notably, gene expression pattern analysis suggested that IGFBP4 might serve as a protective gene, a hypothesis validated through tissue localization and expression analysis. Finally, we predicted TFs capable of binding to IGFBP4, with Krüppel-like family 15 (KLF15) emerging as a prominent candidate showing relative specificity within smooth muscle cells. Predictions about compounds associated with affecting KLF15 expression were also made. Conclusion Our study established a plaque diagnostic and assessment model and analyzed the molecular interaction mechanisms of smooth muscle cells within plaques. Further analysis revealed that the transcription factor KLF15 may regulate the biological behaviors of smooth muscle cells through the KLF15/IGFBP4 axis, thereby influencing the stability of advanced plaques via modulation of the PI3K-AKT signaling pathway. This could potentially serve as a target for plaque stability assessment and therapy, thus driving advancements in the management and treatment of atherosclerotic plaques.

The present study explores the function of FANCA gene, a pivotal member of the Fanconi anaemia (FA) pathway crucial for preserving genomic stability and preventing cancer, particularly in the context of gastric cancer (GC). Using immunohistochemistry, quantitative real-time PCR, and western blot analysis, we evaluate FANCA mRNA and protein expressions in GC cell lines. The relationship between FANCA expression and clinicopathological characteristics is also explored. Various assays, including CCK8, colony formation, wound healing, and Transwell assays, are used to assess functional changes in cells associated with FANCA. Flow cytometry is utilized to evaluate alterations in the cell cycle resulted from FANCA knockdown and overexpression. Our findings show elevated FANCA expression in GC cell lines, with levels correlated with pathologic stage and lymphatic metastasis. FANCA knockdown impedes cell proliferation, migration, and invasion and induces G1/S phase cell cycle arrest. Conversely, FANCA overexpression stimulates cell proliferation, migration, and invasion. In vivo xenograft experiments confirm the promotional role of FANCA in GC tumor progression. Moreover, FANCA overexpression is associated with the activation of cell cycle. Collectively, our results suggest that FANCA drives malignant cell behaviors in GC through the cell cycle pathway, highlighting its potential as a therapeutic target for the treatment of GC.

Objective·To explore the value of miR-499 expression levels in the serum of patients with acute coronary syndrome (ACS) in predicting the severity of coronary artery disease.Methods·Seventy-four patients with ACS admitted to Xinhua Hospital, Shanghai Jiao Tong University School of Medicine were included and divided into a mild group of 30 cases, a moderate group of 21 cases, and a severe group of 23 cases according to the Gensini score. Real-time quantitative polymerase chain reaction (qPCR) technology was used to detect the expression level of serum miR-499, while troponin (cTnI), creatine kinase isoenzyme (CK-MB), myoglobin (Mb), brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), and other laboratory indicators were measured. Spearman correlation analysis was used to analyze the correlation between the expression level of miR-499 and Gensini score, as well as the number of vessel branches in coronary artery disease. The evaluation value of miR-499 in assessing the severity of coronary artery disease was analyzed by using receiver operating characteristic (ROC) curve.Results·The expression level of miR-499 increased with the severity of coronary artery disease (P=0.000). The expression level of miR-499 was positively correlated with Gensini score and cTnI (r=0.331, r=0.143, P0.05), while Gensini score was not correlated with cTnI and LVEF (P>0.05). ROC analysis showed that the AUC of miR-499 for assessing the severity of coronary artery disease was 0.802 (95% CI 0.698‒0.906), with sensitivity of 65.2% and specificity of 80.4%. The expression level of miR-499 increased with the increase of the number of coronary artery lesions, and was positively correlated with the number of coronary artery lesions (r=0.368, P

SPDL1 (spindle apparatus coiled-coil protein 1), also referred to as CCDC99, is a recently identified gene involved in cell cycle regulation. SPDL1 encodes a protein, hSpindly, which plays a critical role in the maintenance of spindle checkpoint silencing during mitosis. hSpindly coordinates microtubule attachment by promoting kinesin recruitment and mitotic checkpoint signaling. Moreover, the protein performs numerous biological functions in vivo and its aberrant expression is closely associated with abnormal neuronal development, pulmonary interstitial fibrosis, and malignant tumor development. In this review, we provide an overview of studies that reveal the characteristics of SPDL1 and of the protein encoded by it, as well as its biological and tumor-promoting functions.

Embodied intelligence transcends the boundaries of traditional artificial intelligence by emphasizing the importance of interaction between machines and the physical world, facilitating the development of intelligent entities that combine hardware and software to learn from and adapt to their environments, thereby solving real-world problems. Inspired by this philosophy, the concept and framework of embodied intelligent driving are introduced, aiming at integrating the idea of embodied intelligence into the development and application of autonomous vehicles. Through the continuous interaction between physical agents, virtual agents, and real traffic scenes, intelligent driving systems can achieve precise perception, efficient execution, and autonomous evolution in complex scenes, enhancing the long-term adaptability of autonomous vehicles in open traffic environments. Based on the embodied intelligent driving framework, the relevant technologies are summarize and the development status and existing problems of such technologies are analyzed. Furthermore, thoughts and prospects in this field are demonstrated by exploring the important roles and application potential of virtual-real interactive data intelligence, foundation models and foundation intelligence, continuous learning and parallel intelligence. This paper is expected to promote innovative research and the application on embodied intelligent driving in a wider range of scenarios, and provide new ideas and solutions for the development of mobile robot systems such as intelligent vehicles.

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P

AbstractContext Our previous studies have found that total flavonoid of Alpinia officinarum Hance (Zingiberaceae) (F.AOH) had protective effects on gastric ulcer (GU).Objective To investigate the protective mechanism of F.AOH on acetic acid-induced chronic GUs in rats and ethanol-induced GES-1 cells damage.Materials and methods In vivo: Gastric damage was induced in SD rats by administering acetic acid after oral treatment with F-AOH at 54, 27 and 13.5 mg/kg (2 weeks of continuous gavage). After a comprehensive evaluation of rats’ serum and gastric tissue-related indicators, gene transcriptome sequencing, qPCR and Western blotting were used to investigate the mechanism further. In vivo: GES-1 cells were incubated with F-AOH (8, 4 and 2 μg/mL) for 16 h and treated with 7% ethanol for 4 h. Transwell and flow cytometry were employed to detect migration and apoptosis of cells.Results F.AOH effectively reduced the area of GUs in rats (from 11.2 ± 1.89 to 2.19 ± 0.95), reversing ethanol-induced cells apoptosis (from 23 ± 1.3 to 8.11 ± 0.93%). It also inhibited the expression of endothelin-1 (ET-1) and iNOS proteins, decreasing the levels of TNF-α IL-6 in serum, improving oxidative stress levels and increasing the expression of Bcl-2/Bax dimer genes. In addition, 4005 differentially expressed genes between the acetic acid model and the drug groups. Through experimental verification, F.AOH can inhibit the activation of TLR4/NF-κB signalling pathway and TRPV1 receptor.Conclusions F.AOH, as an effective gastric protective plant component, had potential therapeutic value in anti-inflammatory pain and antioxidative stress gastrointestinal diseases.

As an important resource on the demand side, air-conditioning load can flexibly participate in the power system and promote new energy consumption. In the process of air-conditioning load scheduling, there are differences in thermal comfort requirements and scheduling potential among different users. How to satisfy the user differentiated thermal comfort and tap their scheduling potential is a difficult problem to consider. In response to the above problem, the thermal comfort model is firstly introduced to comprehensively quantify the user′s thermal comfort experience. Secondly, according to the human parameters in the thermal comfort model, the K-means clustering method is used to divide the user groups with different characteristics of thermal tolerance. On this basis, the air-conditioning direct load control strategy based on user differentiated thermal comfort is proposed and validated by simulation. The example analysis shows that, compared with the traditional strategy, the strategy proposed in this paper fully taps the scheduling potential of different user groups on the basis of completing the consumption task, and guarantees the thermal comfort of them.

Recently, multiple-cross polarization (multiCP) has attracted much interest owing to its favorable performance as a solid-state nuclear magnetic resonance quantitative method. Relating investigations revealed that the setup of multiCP parameters relies on the properties of the samples. Diverse types of samples require different parameters. To improve the tolerance to sample properties, an improved method named MLGCP-1 was proposed in this work, which employed Lee-Goldburg cross polarization technique. L-alanine, L-valine and their mixtures were chosen as model samples to evaluate the performance of MLGCP-1 method. multiCP experiments were also conducted for comparison. Based on the test of molecular group ratio, it was revealed that the range of contact time tp of MLGCP-1 was larger than that of multiCP, which improved from 1.0~1.3 ms to 0.8~2.0 ms. Moreover, according to the study of L-valine and mixtures, it was revealed that the range of tp was influenced by the difference of cross relaxation time TCH. Large TCH difference limited tp range for quantification. This manner was in accordance with multiCP. However, the tp range of MLGCP-1 was markedly enlarged in comparison with multiCP, presenting higher tolerance to the sample properties.

Objective: To study the effects of soil environment on the growth, yield, and quality of Sharen (Amomi Fructus) under different planting patterns. Methods: Soil physical and chemical indices and enzyme activities in four periods including early flowering (March), full flowering (June), fruit ripening (September), and late fruit picking (December), were measured under three planting patterns including natural forest, greenhouse, and rubber forest in Xishuangbanna, China. The changes in soil indices during the growth periods of Sharen (Amomi Fructus) under different planting patterns were analyzed, and the differences in plant growth, yield, and quality under different planting patterns were explored. Pearson correlation analysis was used to analyze the relationship between soil indices and Sharen (Amomi Fructus) growth, yield, and quality. Principal component analysis was used to investigate the effects of soil environment under different planting patterns on Sharen (Amomi Fructus) growth, yield, and quality. Results: The soil moisture, available potassium content, and urease activity of the three planting patterns of Sharen (Amomi Fructus) increased initially and decreased afterwards throughout the year; pH and organic matter content showed little change in the whole year. Exchangeable manganese content and acid phosphatase activity gradually increased throughout the year. Hydrolyzed nitrogen content, exchangeable calcium content, available zinc content, protease activity, and sucrase activity decreased initially and increased afterwards throughout the year. Exchangeable magnesium content, available iron content, and catalase activity decreased annually. Total nitrogen content, total phosphorus content, and available phosphorus content fluctuated throughout the year. The total potassium content under natural forest and greenhouse planting decreased throughout the year, while the total potassium content under rubber forest showed an upward trend all year round. The organic matter content, total nitrogen content, total potassium content, available potassium content, available zinc content, urease activity, acid phosphatase activity, and catalase activity under greenhouse were significantly lower than those under natural and rubber forests (P < 0.05). Correlation analysis showed that plant growth, yield, and quality of Sharen (Amomi Fructus) were significantly correlated with soil organic matter, total nitrogen, hydrolyzed nitrogen, total phosphorus, available phosphorus, total potassium, available potassium, exchangeable manganese, exchangeable magnesium, exchangeable calcium, available zinc, urease, acid phosphatase, and invertase (P < 0.05). The results of the principal component analysis indicated that the soil environment of Sharen (Amomi Fructus) under natural forest was the best, followed by rubber forest and greenhouse. The order of its advantages and disadvantages is consistent with the growth index of Sharen (Amomi Fructus), but contrary to the yield of Sharen (Amomi Fructus), indicating that the soil environment directly affects the growth index and nutritional components of plants. Conclusion: Different planting patterns of Sharen (Amomi Fructus) have different soil nutrient content, and the change rules in the growths period are not similar, with some differences. Soil indices have impacts on plant growth, yield, and quality of Sharen (Amomi Fructus). Soil ecological environment is positively correlated with the growth characteristics of Sharen (Amomi Fructus) plants, but has no direct correlation with yield and quality.

With the in-depth application of Internet technology in the field of English education, the connection between Internet technology and the reverse dialing effect of English teaching in colleges and universities has become increasingly close. The theory of the reverse dialing effect is introduced in this paper, and an Internet technology framework is proposed that incorporates an online English learning platform and a personalized recommendation model of English resources. The viscous binary particle swarm algorithm with nonlinear factors is used as the algorithm for recommending learning paths to build the online learning platform. At the same time, the online learning platform is also used as the background, and the S-CNN model is constructed by relying on the convolutional neural network model framework to propose a personalized course resource recommendation algorithm based on deep learning. University Q in Changchun City, Jilin Province, China, was used as the research site for practice. The English scores of the students in the experimental class were significantly improved, and the mean values of cooperative communication ability, problem-solving ability, and information literacy in English learning ability were higher than those of the control class by 4.427, 4.394 and 3.918, respectively, which showed significant differences (P

Nautical talents are the first resource and fundamental guarantee for the development of marine careers, strengthening the construction of nautical talents and realizing the effective supply of nautical talents have become the urgent task of building a strong marine country. This paper combines the basic situation of the current nautical personnel training and the training requirements of nautical personnel, constructs the vocational literacy and ability enhancement path of nautical students based on the integration of post-course, race, and certificate under the guidance of the OBE concept, and constructs the corresponding index system. Subsequently, combining the hierarchical analysis method and entropy weight method, the weights of the indicators in the evaluation system of nautical students’ vocational quality and talent ability are calculated, and the cloud model is utilized to evaluate the vocational quality and talent ability of nautical talents after cultivation. The results of the study show that the comprehensive evaluation level of the vocational quality and talent ability of the maritime students of Jimei University after the implementation of the pathway is “good”. Among the secondary evaluation indexes, the vocational concept evaluation cloud has the highest degree of affiliation, which is 9.31. This indicates that the vocational concept of navigation students is being cultivated at a very high level. The evaluation result of “vocational behavior” also belongs to the “good” level. The cultivation path proposed in this paper provides a reference for the enhancement of the vocational quality and ability of nautical talents, and it can improve the cultivation of nautical talents through the synergistic approach of government, industry, enterprise, and school, and guarantee the enhancement of the vocational ability and career expansion of nautical talents.

Traditional particulate embolic agents are small in diameter, but can easily embolize the ends of blood vessels, resulting in ischemia and necrosis of normal tissues and organs. The metal spring embolic agent has a larger diameter, but it cannot be degraded and can easily cause permanent damage to blood vessels. Ideally, a bleeding embolism should achieve rapid hemostasis without causing long-term necrosis of organs and tissues. In this study, a modified sodium alginate hydrogel (MSAH) was prepared by mixing an oxidized sodium alginate (OSA) aqueous solution with a carboxymethyl chitosan (CMC) aqueous solution at a ratio of 1:6 in a 38°C bath for 8 min. The feasibility of this modified hydrogel was then tested in an internal iliac artery hemorrhage model using New Zealand rabbits. The MSAH had good adhesion. The hydrogel was injected through a single curved 4F catheter without obvious effects on uterine smooth muscle cell proliferation and apoptosis. The blood flow of the internal iliac artery was restored by long-term degradation of the sodium alginate hydrogel, and no ischemia and necrosis were observed by histopathology. The MSAH prepared using a mixture of OSA and CMC had good adhesion, biocompatibility, and injectability and could be used for target-vessel embolization in an internal iliac artery hemorrhage model. The MSAH can achieve main artery embolization without affecting the peripheral artery blood supply, resulting in both short-term rapid hemostasis and long-term degradation, with no target organ necrosis.

Background and purpose: The recurrence rate of non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT) is high. There are few studies on the risk factors of recurrence in NMIBC patients after initial TURBT. Our study aimed to screen the high-risk population and take corresponding preventive intervention measures by analyzing the risk factors of recurrence in NMIBC patients after initial TURBT. Methods: A total of 197 NMIBC patients who received initial TURBT in The Cancer Hospital of the University of Electronic Science and Technology of China from December 2015 to May 2020 were selected and followed up for 24 to 77 months. Patients were divided into recurrence group (48 cases) and non-recurrence group (149 cases) according to the results. Univariate analysis was performed on the clinical data of the two groups, and the indicators with statistical significance were included in the multivariate logistic regression analysis to screen the possible risk factors of recurrence. Results: Univariate analysis showed that the difference was statistically significant between two groups in gross hematuria, secondary resection, T1 stage, high grade tumor, multiple tumor and lack of immediate intravesical therapy (P 0.05). The receiver operating characteristic (ROC) curves of the ratio of neutrophils to lymphocytes and the ratio of neutrophils and hemoglobin to lymphocytes showed no statistically significant difference between two groups (P>0.05). Multivariate logistic regression analysis showed that T1 stage, high grade tumor, multiple tumor and lack of immediate intravesical therapy were independent risk factors of recurrence in NMIBC patients after initial TURBT (P 1). Conclusion: The recurrence of NMIBC patients after initial TURBT is closely related to tumor stage, tumor grade, tumor number and immediate intravesical therapy. Corresponding intervention measures can be taken to reduce the postoperative recurrence rate in initial NMIBC patients.

Mercury intrusion experiment is widely used in porous material characterization because of its simple model, wide testing range, high speed and high precision. However, lignite samples are easy to be affected by Hemp skin effect and matrix compression effect due to low metamorphic degree, weak compaction and soft coal quality, resulting in large error in test results. In order to improve the test accuracy, the mercury injection data of lignite samples in Erlian basin were corrected. Firstly, based on the cumulative mercury injection curve and fractal characteristics, the displacement pressure and hemp skin coefficient are determined. Secondly, aiming at the deficiency of traditional matrix compression correction method in low-pressure section and over correction in high-pressure section, a new method based on cubic spline interpolation and subsection to obtain matrix compression coefficient of coal sample is proposed to improve data utilization and accuracy of correction results. Finally, the pore development of lignite samples in this area was analyzed by combining mercury injection and liquid nitrogen adsorption experimental data. The results show that the hemp skin effect mainly affects the pressure range of < 0.0274 MPa, and the average hemp skin coefficient is 16.9%. Based on the new method, the average matrix compressibility of lignite samples in this area ranges from 1.73 to 3.48 × 10−4 MPa−1, with an average of 2.28 × 10−4 MPa−1. With the increase of pore fluid pressure, organic matter content and mineral based humic group content, the matrix compressibility increases. Before and after correction, the mercury intake decreases by 0.0383-0.079 2 mL/g, with an average decrease of 35.1%. The pore volume (> 1.7 nm) of lignite in the study area is between 0.03-0.25 cm3/g, with an average of 0.15 cm3/g. The average pore volume from micropore to macropore is 12.5%, 16.8%, 16.2% and 54.5%, respectively. The specific surface area of B-E-T is between 2.4-37.19 m2/g, with an average of 13.85 m2/g, which is mainly provided by micropores. The pore size distribution curve of coal sample can be divided into I (>5 μm), Ⅱ(0.1-5 μm), Ⅲ(

C5H6O3N2, monoclinic, P21/c (no. 14), a = 11.3451(10) Å, b = 4.9505(5) Å, c = 10.3200(8) Å, β = 99.220(3)°, V = 572.12(9) Å3, Z = 4, R gt(F) = 0.0429, wR ref(F 2) = 0.1031, T = 170 K.

In order to study the characteristics of porosity, permeability and stress sensitivity of middle rank coal reservoir in Tucheng syncline and their influence on coalbed methane exploitation, coal core samples of coal seams 1#, 3#, 5#, 15#, 17#, 291# and 292# in Tucheng syncline were collected. Based on the overburden porosity and permeability test, the variation law of porosity and permeability with effective stress of each coal reservoir is compared, and the sensitivity of effective stress of each coal reservoir is analyzed by using the parameters of porosity stress damage rate, permeability stress damage rate and permeability curvature. The results show that: with the increase of effective stress, the coal reservoir porosity and gas permeability were negative exponent; the stress sensitivity coefficient of test coal reservoir is 0.035-0.073 MPa-1, and the stress sensitivity regression coefficient of 3# coal sample is the largest; the stress damage rate of porosity increases with the increase of effective stress, and the stress damage rate of 3# coal sample with shallow burial depth is relatively large. The permeability stress damage rate increases exponentially with the increase of effective stress, and the permeability damage rate of 3# coal sample is obviously larger than that of other coal samples. The permeability curvature of coal reservoir decreases exponentially with the increase of effective stress.Under the same effective stress, the stress sensitivity of 3# coal seam is greater than that of 5#, 15# and 29# coal seam, and the stress sensitivity of 1# and 17# coal seam is the weakest.

The dry skin tortures numerous patients with severe itch. The transient receptor potential cation channel V member 1 (TRPV1) and A member 1 (TRPA1) are two essential receptors for peripheral neural coding of itch sensory, mediating histaminergic and nonhistaminergic itch separately. In the dorsal root ganglion, transmembrane protein 100 (TMEM100) is structurally related to both TRPV1 and TRPA1 receptors, but the exact role of TMEM100 in itch sensory coding is still unknown. Here, in this study, we find that TMEM100 + DRG neurons account for the majority of activated neurons in an acetone-ether-water (AEW)-induced dry skin itch model, and some TMEM100 + DRG neurons are colocalized with both TRPA1 and the chloroquine-related Mrgpr itch receptor family. Both the expression and function of TRPA1 channels, but not TRPV1 channels, are upregulated in the AEW model, and specific DRG Tmem100 gene knockdown alleviates AEW-induced itch and rescues the expression and functional changes of TRPA1. Our results strongly suggest that TMEM100 protein in DRG is the main facilitating factor for dry skin-related chronic itch, and specific suppression of TMEM100 in DRG could be a novel effective treatment strategy for patients who suffer from dry skin-induced itch.

Objective To investigate the effect of Liu-Shen-Wan on transplanted tumors in mice with colon cancer based on the polarization of M2 macrophages in the tumor microenvironment. Methods We established a subcutaneous transplantation tumor model of mice with CT26 colon cancer. Mice were randomly divided into vehicle, oxaliplatin, and oxaliplatin combined with Liu-Shen-Wan groups. Treatment was administered for three weeks, and tumor volume was measured. All mice were weighed during the administration. After the end of the treatment, the mice were dissected and tumors were photographed and weighed. Spleen index was calculated. The expression levels of IFN-γ and IL-12P40 in serum and related blood biochemical indices were measured. The expression levels of M2 macrophage polarization indices, namely, IL-10 and TGF-β, in serum and tumor tissues were detected. The infiltration degree of M2 macrophages in each group was observed by immunohistochemical experiments. Results The tumor volume and mouse weight in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased compared with those in the vehicle group. The spleen index increased, and the expression levels of IFN-γ and IL-12P40 in serum also significantly increased. The mice had no obvious side effects after the drug treatment. In addition, the expression levels of IL-10 and TGF-β in the serum and tissues of mice in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased. The expression levels of CD68 and CD206 in tumor tissues also decreased. Conclusion The anti-tumor effect of Liu-Shen-Wan on the transplanted tumors of mice with colon cancer is related to the inhibition of M2 macrophage polarization in the tumor microenvironment.

Objective: To develop selenium-enriched （Se-enriched） Moringa oleifera seed protein resources. Methods: Using Se-enriched Moringa oleifera seed protein powder as raw material, the enzymatic hydrolysis conditions of Se-enriched Moringa oleifera seed protein antihypertensive peptides from Se-enriched Moringa oleifera seed protein were obtained by single factor and response surface optimization, and the ACE inhibitory activity, Se content and stability of the optimal enzymatic hydrolysate were analyzed. Results: The optimal enzymatic hydrolysis conditions of Se-enriched Moringa oleifera were as follows: enzymatic hydrolysis time 3 h, temperature 34 ℃, pH 8, concentration of substrate 7%, enzyme to substrate ratio 0.3%. Under these conditions, the semi-inhibitory concentration of ACE of the peptides was 1.956 mg/mL. The Se content of the antihypertensive peptide was 1.394 mg/kg, which was 1.1 times that of the raw protein. Moreover, the antihypertensive peptides （5 mg/mL） had good thermal stability and acid-base stability, and could still maintain good ACE inhibitory activity after digestion by gastrointestinal enzyme system in vitro. Conclusion: The Se-enriched Moringa oleifera seed protein antihypertensive peptides obtained by response surface optimization showed strong ACE inhibitory activity and good stability.

In this paper, we consider stochastic dynamics of a two-dimensional stochastic differential equation with additive noise. When the strength of the noise is zero, this equation undergoes a Bautin bifurcation. We obtain the main conclusions including the existence and uniqueness of the solution, synchronization of system and property of the random equilibrium, where going through some processes like deducing the stationary probability density of the equation and calculating the Lyapunov exponent. For better understanding of the effect under noise, we make a clear comparison between the stochastic system and the deterministic one and make precise numerical simulations to show the slight changes at Bautin bifurcation point. Furthermore, we take a real model as an example to present the application of our theoretical results.

The twenty-first century is the century of marine resources. The ocean is a treasure of biological resources, energy, water resources and mineral resources, and it would gradually become the “second space” of mankind. In the next few years, it would be more and more relevant to human life. Many scholars have realized the importance of the ocean and began to vigorously develop and use the ocean. Underwater robot is a means for human beings to explore and develop the ocean, and it would be widely used in this field. The development and promotion of underwater vehicles are of great significance to resource development, economic development, and national security. With the increasing shortage of land resources, the development and utilization of marine resources have received increasing attention. The direct exploitation of marine resources by humans would have adverse effects, so the underwater robot technology has developed rapidly in recent years. However, at present, most underwater robots are driven by electric turbines. The underwater working environment requires that the underwater motor has good sealing performance, so its structure is complex and expensive, and it is rarely used in ordinary underwater operations. In recent years, intelligent robots have been used more and more, but because of the complexity and uncertainty of the underwater working environment, there are many uncertain factors. Therefore, it is very meaningful to carry out stability control for it. The research results showed that the displacement, stability, and other corresponding test curves of each component can be obtained by establishing a simple model with software and through ADAMS (Automatic Dynamic Analysis of Mechanical Systems) simulation analysis. This can simulate the movement of real objects in the real environment and find the existing problems, so as to provide a reference for the actual underwater robot design. In this way, the development cycle and production costs can be reduced. This article analyzed the structure and control system of the underwater vehicle based on ADAMS simulation. The results showed that the dynamic stability of the underwater vehicle based on ADAMS simulation analysis was improved by 4.67% compared with the underwater vehicle before optimization.

With the diesel particulate filter more and more widely applied on engine, the particulate matter (PM) sensor is used to detect malfunctions of diesel particulate filter (DPF) in on board diagnostics (OBD). This paper focused on the new leakage current particulate matter sensor, which has more practical significance. The electric field and flow field were simulated by the COMSOL Multihysics, and the influence rules of sensor electrode parameters on the electric field and flow field were analyzed. The dynamic characteristics of particulate matters with different charges was studied. The simulation results showed that the average electric field strength was higher with higher electrode voltage and larger electrode spacing, which made the motion trend of charged particulate matter to electrodes more obvious. The decrease of electrode spacing or the increase of electrode length made the exhaust flow more stable, and the motion trend of charged particulate matters to electrodes is more obvious with the increase of electrode length. It was concluded that the flow of the exhaust and particulate matter was in good condition when the electrode spacing was 12.5mm, the electrode length is 12.5mm and the electrode voltage ranged between 1000V and 1500V.