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Yongfeng Lao,1,2 Yanan Bai,1,2 Xin Guan,1,2 Jian Wang,1,2 Yanan Wang,1,2 Rongxin Li,1,2 Yongqiang Ding,1,2 Zhilong Dong1,2 1Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Zhilong Dong, Department of Urology, The Second Hospital of Lanzhou University, No. 82, Cuiyingmen, Chengguan District, Lanzhou, Gansu, People’s Republic of China, Email dzl1997.student@sina.comIntroduction: Although sertraline has been widely used for chronic prostatitis (CP), the mechanisms are unclear. Herein, we explored the mechanisms of sertraline in treating CP.Methods: Network pharmacology methods were used to explore the potential targets and molecular mechanisms. LPS was used to stimulate RWPE-1 cells to construct an in vitro model of CP. An experimental autoimmune prostatitis (EAP) mice model was built. CCK-8 assay, EdU assay, BrdU detection, and Tunel assay were performed to evaluate the proliferation and apoptosis process of cells or tissues, respectively. DCFH-DA and Fluo-4 fluorescence probes were used to detect intracellular ROS and calcium concentrations. Von Frey filaments and open-field tests were utilized to evaluate pain response and depressive-like behavior of mice. Histopathology was evaluated through hematoxylin and eosin staining. RT-qPCR, Western blot, immunofluorescence, and immunohistochemistry were utilized to evaluate the transcription, expression, and location of related proteins. Molecular dynamics (MD) simulation and surface plasmon resonance (SPR) assay were performed to measure the binding capacity of sertraline and related proteins.Results: Through a network pharmacology analysis, 27 potential targets of sertraline for CP were obtained, and 5 key targets (CHRM1, ADRA1B, HTR2B, HTR2A, and TRPV1) were finally identified. Functional experiments suggested that TRPV1 was involved in the proliferation, apoptosis inhibition, and ROS production of LPS-induced RWPE-1 cells. In vitro experiments showed that sertraline significantly inhibited cell proliferation, ROS generation, and transcription of inflammation cytokines of LPS-induced RWPE-1 cells. Additionally, sertraline markedly promoted the apoptosis level of LPS-stimulated RWPE-1 cells and elevated the expression level of BAX while reducing the expression levels of Bcl2 and Caspase-3. MD simulation and SPR assay confirmed the direct binding of sertraline to TRPV1. Moreover, sertraline significantly down-regulated the expression level of TRPV1 and inhibited calcium influx of LPS-induced RWPE-1 cells. TRPV1 agonist (Capsaicin) significantly restored the effects on proliferation, apoptosis, ROS production, and calcium influx of sertraline on LPS-induced RWPE-1 cells. Mice experiments demonstrated that sertraline treatment could reduce pain response, improve depression-like symptoms, and relieve local prostate inflammation of EAP mice, as well as down-regulated the expression level of TRPV1, inhibit the proliferation, and promote apoptosis of prostate tissues in EAP mice.Discussion: The results revealed the anti-inflammatory effect of sertraline for RWPE-1 cells and EAP mice, and the potential mechanism was regulating the TRPV1 channel. It indicated that sertraline might serve as a complementary anti-inflammatory agent for CP.Keywords: chronic prostatitis, sertraline, RWPE-1, mice, TRPV1

Zhiming Mo,1 Jiayi Yuan,1 Xuelian Guan,1 Jianhong Peng2 1Department of Pharmaceutical Center, Dongguan Traditional Chinese Medicine Hospital, Dongguan, 523000, People’s Republic of China; 2Department of Internal Medicine, Dongguan Traditional Chinese Medicine Hospital, Dongguan, 523000, People’s Republic of ChinaCorrespondence: Jianhong Peng, Department of Internal Medicine, Dongguan Traditional Chinese Medicine Hospital, No. 3, Dongcheng Section, Songshan Lake Avenue, Dongcheng District, Dongguan, Guangdong Province, 523000, People’s Republic of China, Tel +86 0769-22245614, Email pengjhzyy@outlook.comAbstract: Curcumin, derived from Curcuma longa (turmeric), exhibits significant potential in dermatology, addressing conditions like atopic dermatitis, psoriasis, chronic wounds, skin cancer, and infections through its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. This review synthesizes evidence on curcumin’s mechanisms, including modulation of immune responses and promotion of wound healing, showcasing its efficacy in reducing inflammation, cytokine levels, and enhancing skin barrier functions. Studies highlight curcumin’s ability to selectively target tumor cells, suggesting a multifaceted approach to cancer therapy with minimal side effects. Despite promising therapeutic benefits, challenges remain in bioavailability, potency, and targeted delivery, underscoring the need for further research to optimize dosages, delivery methods, and assess long-term safety. The integration of curcumin into dermatological practice requires a balanced consideration of evidence-based efficacy and safety. Curcumin’s comprehensive utility in dermatology, coupled with the necessity for advanced scientific exploration, emphasizes the importance of combining traditional knowledge with contemporary research to improve patient care in dermatology. This approach could significantly enhance outcomes for individuals with skin-related conditions, marking curcumin as a versatile and promising agent in the field.Keywords: curcumin, atopic dermatitis, psoriasis, chronic wounds, skin cancer

Michael Roshon,1 Paras B Khandhar,2 Manoj Biniwale,3 Rangasamy Ramanathan,3 T Patrick Frazier,4 Feng Xu,5 Linlin Zhang,6 Xiangdong Guan,7 Dai Wenling,8 Bernard Lambermont9 1Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado, Springs, CO, USA; 2Pediatric Critical Care Medicine, Beaumont Children’s Hospital, Royal Oak, MI, USA; 3Division of Neonatology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA; 4Department of Medicine, University of Alabama at Birmingham, Heersink School of Medicine, Birmingham, AL, USA; 5Department of Intensive Care, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Department of Critical Care Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 8Department of Critical Care Medicine, Yancheng First People’s Hospital, Yancheng, People’s Republic of China; 9Department of Intensive Care, University Hospital of Liege, Liege, BelgiumCorrespondence: Michael Roshon, Email MichaelRoshon@Centura.OrgPurpose: Mechanical ventilation is a life-supporting intervention but is associated with known risks and complications. To improve the efficacy and safety profile of mechanical ventilation, manufacturers have developed advanced ventilator settings, modes, and alarm strategies to optimize ventilation for patient needs while avoiding complications. However, there is little real-world data published on the deployment of ventilator technology. The main objective of this study was to assess the clinical safety and performance of the Puritan Bennett™ 980 Ventilator System (PB980) using real-world clinical data collected from a diverse, global patient population.Methods: This was a multi-center, post-market registry study that included nine sites: four in the United States of America, one in Europe, and four in China. Patients were enrolled into the registry if they were intended to be treated with a PB980. Data collection began at the start of ventilation and continued until extubation off the ventilator or up to seven days of ventilation, whichever occurred first. Subjects were divided by age into three categories: infants (0– 365 days), pediatric (1– 17 years), and adult (18 years and older). The primary outcome was device-related complication rate.Results: Two-hundred-and-eleven subjects were enrolled (41 infants, 48 pediatric, and 122 adults). Sixteen deaths, unrelated to device deficiency, occurred during the data collection timeframe (relative frequency: 7.58, 95% CI: 4.40, 12.0). Only one device-related adverse event was reported (relative frequency: 0.47% 95% CI: 0.01%, 2.61%).Conclusion: Ventilation by the PB980 was delivered safely in this multi-center observational study, which included a diverse sample of patients with broad ventilatory needs.Plain Language Summary: Mechanical ventilation is a life supporting intervention. Much progress has been made in this field thanks to a better knowledge of respiratory physiopathology and improved ventilation delivered by modern ventilators.In this global, post-market registry study, ventilation by the Puritan Bennett™ 980 Ventilator was delivered safely to a diverse sample of patients.Keywords: ventilation, PB980, safety, complications, respiratory distress, critical care

Min Zong,1 Xiaonan Guan,1 Wen Huang,1 Jing Chang,2 Jianjun Zhang1 1Department of Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Internal Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jianjun Zhang, Department of Heart Center, Beijing Chaoyang Hospital, Capital Medical University, 8th Gongtinanlu Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-13601230955, Email zmn0359@vip.sina.comBackground: To investigate the effect of frailty on the long-term prognosis of elderly patients with acute myocardial infarction (AMI).Methods: The data of 238 AMI patients (aged ≥ 75 years) were retrospectively reviewed. They were divided into two groups according to the Modified Frailty Index (mFI): frailty group (mFI≥ 0.27, n=143) and non-frailty group (mFI< 0.27, n=95). The major adverse cardiovascular and cerebrovascular events (MACEs) and Kaplan–Meier survival curves of the two groups were compared. Multivariate Cox regression analysis was used to identify the risk factors for MACEs.Results: The frailty group showed a significantly older age as well as a higher N-terminal proB-type natriuretic peptide level, Global Registry of Acute Coronary Events score, and CRUSADE bleeding score compared with the non-frailty group (P< 0.05). A significantly greater proportion of patients with combined heart failure, atrial fibrillation, comorbidity, and activities of daily living score of < 60 was also observed in the frailty group compared with the non-frailty group (P< 0.05). At 36 months after AMI, the frailty group vs the non-frailty group showed a significantly poorer survival (log-rank P=0.005), higher incidence of MACEs (50.35 vs 29.47, P=0.001), higher overall mortality rate (20.98% vs 7.37%, P=0.006), higher 30-day mortality rate (13.99% vs 5.26%, P=0.033), higher major bleeding rate (14.69% vs 5.26, P=0.018), and lower repeat revascularization rate (2.10% vs 8.42%, P=0.03). Frailty, type 2 diabetes, and N-terminal proB-type natriuretic peptide ≥ 1800 pg/mL were independent risk factors for MACEs.Conclusion: Frailty is an independent risk factor affecting the long-term prognosis of elderly patients with AMI.Keywords: myocardial infarction, frailty, MACEs, risk factors, prognosis

Yinshan Lin,1,2,&ast; Xiaoling Guan,1,2,&ast; Jianfen Su,1,2,&ast; Sheng Chen,2 Xihua Fu,1 Xiaowei Xu,2 Xiaohua Deng,2 Jishuo Chang,2 Aiping Qin,2,&ast; Ao Shen,2,&ast; Lingmin Zhang1,2,&ast; 1Pharmacy Department & Panyu Institute of Infectious Diseases, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, 511400, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingmin Zhang, Guangzhou Panyu Central Hospital, No. 8 Fuyu East Road, Guangzhou, Guangdong, 511400, People’s Republic of China, Email zhanglm@gzhmu.edu.cn Ao Shen; Aiping Qin, Guangzhou Medical University, No. 1 Xinzao Road, Guangzhou, Guangdong, 511426, People’s Republic of China, Email shenao@gzhmu.edu.cn; qinaiping_2008@163.comAbstract: Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery. Keywords: nucleic acids, bioinspired nanoparticles, non-viral vehicles, gene therapy, cell membranes

Chuangjia Huang,1,2,&ast; Yu Zhang,3,&ast; Jianfen Su,1,2,&ast; Xiaoling Guan,1,2 Sheng Chen,1,2 Xiaowei Xu,1,2 Xiaohua Deng,1,2 Lingmin Zhang,1,2 Jionghua Huang1 1Department of Cardiology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jionghua Huang; Lingmin Zhang, Email mdhjh2014@126.com; zhanglm@gzhmu.edu.cnBackground: High-level low-density lipoprotein cholesterol (LDL-C) plays a vital role in the development of atherosclerotic cardiovascular disease. Low-density lipoprotein receptors (LDLRs) are scavengers that bind to LDL-C in the liver. LDLR proteins are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), which mediates the degradation of LDLR and adjusts the level of the plasma LDL-C. The low expression of PCSK9 leads to the up-regulation of liver LDLRs and the reduction of plasma LDL-C. Hepatocytes are attractive targets for small interfering RNA (siRNA) delivery to silence Pcsk9 gene, due to their significant role in LDL-C regulation.Methods: Here, a type of liver-specific ionizable lipid nanoparticles is developed for efficient siRNA delivery. This type of nanoparticles shows high stability, enabling efficient cargo delivery specifically to hepatocytes, and a membrane-active polymer that reversibly masks activity until an acidic environment is reached.Results: Significantly, the siPcsk9 (siRNA targeting to Pcsk9)-loaded nanoparticles (GLP) could silence 90% of the Pcsk9 mRNA in vitro. In vivo study showed that the improved accumulation of GLP in the liver increased LDLR level by 3.35-fold and decreased plasma LDL-C by 35%.Conclusion: GLP has shown a powerful effect on reducing LDL-C, thus providing a potential therapy for atherosclerotic cardiovascular disease. Keywords: ionizable lipid nanoparticles, bad cholesterol, PCSK9, small interfering RNA, liver-specific delivery

Qingsong Liu,1,2,&ast; Lunyu Li,2,&ast; Dan Zheng,1 Songlin Jin,2 Xiaotian Guan,2 Zeting Fu,2 Zhigang Xiong,1 Haili Ding3 1Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China; 3Insititute of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haili Ding, No. 2, Gymnasium Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 13688467479, Email dingdingtang111@163.comPurpose: This study examined the underlying mechanisms of SJD’s anti-inflammatory and analgesic effects on acute GA flares.Methods: This study used pharmacology network and molecular docking methods. The active ingredients of ShuiJingDan (SJD) were obtained from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP), and the relevant targets of GA were obtained from the Online Mendelian Inheritance in Man (OMIM) database and Therapeutic Target Database (TTD). The core drug group–target–disease Venn diagram was formed by crossing the active ingredients of SJD and the relevant targets. Gene Ontology (GO) analysis was conducted for functional annotation, DAVID was used for Kyoto Encyclopedia of Genes, and Genomes pathway enrichment analysis, and R was used to find the core targets. The accuracy of SJD network pharmacology analysis in GA treatment was verified by molecular docking simulations. Finally, a rat GA model was used to further verify the anti-inflammatory mechanism of SJD in the treatment of GA.Results: SJD mainly acted on target genes including IL1B, PTGS2, CXCL8, EGF, and JUN, as well as signal pathways including NF-κB, Toll-like receptor (TLR), IL-17, and MAPK. The rat experiments showed that SJD could significantly relieve ankle swelling, reduce the local skin temperature, and increased the paw withdrawal threshold. SJD could also reduce synovial inflammation, reduced the concentrations of interleukin-1β (IL-1β), IL-8, and COX-2 in the synovial fluid, and suppressed the expression of IL1B, CXCL8, and PTGS2 mRNA in the synovial tissue.Conclusion: SJD has a good anti-inflammatory effect to treat GA attacks, by acting on target genes such as IL-1β, PTGS2, and CXCL8.Keywords: ShuiJingDan, gouty arthritis, network pharmacology, molecular docking, IL-1β, COX-2

Sumei Yin,1 Xiangli Guan,1 Yaqi Zhang,1 Yang Li,1 Mary C Jobe,2 Md Zahir Ahmed3 1School of Teacher Education, Yuxi Normal University, Yuxi, 653100, People’s Republic of China; 2Department of Psychological and Brain Sciences, The George Washington University, Washington, DC, 20052, USA; 3School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of ChinaCorrespondence: Xiangli Guan, School of Teacher Education, Yuxi Normal University, Yuxi, 653100, People’s Republic of China, Tel +86-15758018670, Email guanxiangli@yxnu.edu.cn Md Zahir Ahmed, School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of China, Tel +86-13919740494, Email ahmedzahirdu@gmail.comPurpose: This present study aims to explore the effects of work meaningfulness on primary school teachers’ self-reflection, self-efficacy and organizational commitment and their mechanisms of action.Methods: This study used a meaningfulness, self-reflection, self-efficacy, and organizational commitment measures. A total of 417 teachers from urban, rural, and mountainous elementary schools were recruited to complete the survey including the measures of work meaningfulness, self-reflection, self-efficacy, and organizational commitment. In this study, descriptive statistics were run using SPSS 26.0 and the relationship model between variables was tested with the SPSS macro program PROCESS.Results: The study found that work meaningfulness and self-efficacy independently predicted primary school teachers’ organizational commitment, but self-reflection did not significantly predict organizational commitment. It was found that there was a significant positive correlation between the four studied variables of work meaningfulness, self-efficacy, self-reflection, and organizational commitment with correlation coefficients ranging from 0.24 to 0.57. The study also found that work meaningfulness can directly predict elementary school teachers’ organizational commitment, and work meaningfulness can also indirectly predict elementary school teachers’ organizational commitment through self-efficacy and self-reflection.Conclusion: The results of this study are useful for understanding the value of enhancing the organizational commitment of primary school teachers from a social cognitive perspective, and have implications for how to build a stable, high-quality and dynamic primary school teaching force.Keywords: work meaningfulness, organizational commitment, self-reflection, self-efficacy, primary school teachers

Yingpeng Li,1 Ting Zhu,2,3 Jingxian Liang,2 Yuanqun Wu,2 Xiantong Guan,2 Tingting Liu,2 Shaowa Lü,2 Yongji Li,2 Yanhong Wang,2 Yang Ping4 1College of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China; 2Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China; 3Center of Pharmaceutical Engineering and Technology, College of Pharmacy, Harbin University of Commerce, Harbin, 150076, People’s Republic of China; 4College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, 154007, People’s Republic of ChinaCorrespondence: Yanhong Wang, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China, Tel +86 18845587616, Email wang.yanhong@163.com Yang Ping, College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, 154007, People’s Republic of China, Tel +86 18245482328, Email 18245482328@163.comBackground: Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine.Methods: Methods for the morphological and quantitative characterization of black plaster’s microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction.Results: In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed “branched” soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8± 59.5) μm2; after the 35 °C treatment, A2 = (259.7± 52.8) μm2; after the 45 °C treatment, A3 = (408.0± 57.7) μm2, and there were no significant differences in other pore parameters.Conclusion: The black plaster matrix’s unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.Keywords: black plaster, Goupi Gao, microstructure, quantitative characterization, release behavior, pharmacodynamics

While wetlands are the largest natural source of methane (CH4 ) to the atmosphere, they represent a large source of uncertainty in the global CH4 budget due to the complex biogeochemical controls on CH4 dynamics. Here we present, to our knowledge, the first multi-site synthesis of how predictors of CH4 fluxes (FCH4) in freshwater wetlands vary across wetland types at diel, multiday (synoptic), and seasonal time scales. We used several statistical approaches (correlation analysis, generalized additive modeling, mutual information, and random forests) in a wavelet-based multi-resolution framework to assess the importance of environmental predictors, nonlinearities and lags on FCH4 across 23 eddy covariance sites. Seasonally, soil and air temperature were dominant predictors of FCH4 at sites with smaller seasonal variation in water table depth (WTD). In contrast, WTD was the dominant predictor for wetlands with smaller variations in temperature (e.g., seasonal tropical/subtropical wetlands). Changes in seasonal FCH4 lagged fluctuations in WTD by ~17 ± 11 days, and lagged air and soil temperature by median values of 8 ± 16 and 5 ± 15 days, respectively. Temperature and WTD were also dominant predictors at the multiday scale. Atmospheric pressure (PA) was another important multiday scale predictor for peat-dominated sites, with drops in PA coinciding with synchronous releases of CH4 . At the diel scale, synchronous relationships with latent heat flux and vapor pressure deficit suggest that physical processes controlling evaporation and boundary layer mixing exert similar controls on CH4 volatilization, and suggest the influence of pressurized ventilation in aerenchymatous vegetation. In addition, 1- to 4-h lagged relationships with ecosystem photosynthesis indicate recent carbon substrates, such as root exudates, may also control FCH4. By addressing issues of scale, asynchrony, and nonlinearity, this work improves understanding of the predictors and timing of wetland FCH4 that can inform future studies and models, and help constrain wetland CH4 emissions.

Jinxia Li,1 Jingjun Xie,2 Xiaoqing Guo,1 Ruiyang Fu,1 Yaling Wang,1 Xinjun Guan1 1Huzhou Hospital of Traditional Chinese Medicine, Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, 313000, People’s Republic of China; 2The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of ChinaCorrespondence: Jingjun Xie, Email jingjun.1101@163.comAim: The aim of this research is to analyze the effects of mind-regulation acupuncture on serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels, fatigue, quality of sleep, depression, and quality of life in survivors of breast cancer with cancer-related fatigue.Methods: Total 136 breast cancer survivors with cancer-related fatigue were randomly allocated to the mind-regulation acupuncture group and the control group in a 1:1 ratio, with 68 cases in each group. Finally, 57 cases each in both groups completed the study. The serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels were measured in pre-treatment and post-treatment. The 20-item Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, Hamilton Depression Scale, and Karnofsky Performance Status were used to evaluate patients’ fatigue, quality of sleep, symptoms of depression, and quality of life, respectively.Results: In post-treatment, the serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels significantly reduced, 20-item Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, and Hamilton Depression scores were remarkably decreased, whereas the Karnofsky Performance Status scores were significantly increased in mind-regulation acupuncture group and control group comparing to those pre-treatment, while those in mind-regulation acupuncture group changed more significantly. The 20-item Multidimensional Fatigue Symptom Inventory, Pittsburgh Sleep Quality Index, and Hamilton Depression scores were remarkably lower, and remarkably higher Karnofsky Performance Status scores in the mind-regulation acupuncture group were seen than those in the control group.Conclusion: Mind-regulation acupuncture could reduce serum ghrelin, gastric inhibitory polypeptide, leptin, and insulin levels of breast cancer survivors with cancer-related fatigue. In addition, it alleviates cancer-related fatigue, sleep disturbance, and depression in these survivors and improves their quality of life. Therefore, mind-regulation acupuncture may have potential as an alternative and complementary therapy for breast cancer survivors with cancer-related fatigue.Keywords: mind-regulation acupuncture, traditional Chinese medicine, cancer-related fatigue, breast cancer, metabolites

Xueqing Guan, Zhijun Sun Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Zhijun Sun, Department of Cardiology, Shengjing Hospital, No. 39 of Huaxiang Road, Tiexi District, Shenyang, 110021, People’s Republic of China, Tel +86 18940251218, Fax +86 18940251218, Email sunzhijunszj8@126.comAbstract: Intestinal flora is a complex collection of microbial communities that participate in the physiological and pathological activities of the human body through various pathways. In recent years, numerous studies have reported that intestinal flora are involved in the occurrence and development of heart failure (HF) and its metabolic products could play an important role in this progression, suggesting a great value in the clinical treatment of this condition. This study reported the interaction between intestinal flora and HF, and with intestinal flora metabolites, such as short-chain fatty acids, trimethylamine N-oxide and bile acids and urotoxins, considered as the starting point, the mechanism of the roles in HF was summarized. Additionally, the current research status and the development prospects of applying flora and metabolites to the clinical therapeutic decision of HF were discussed.Keywords: intestinal flora, heart failure, trimethylamine N-oxide, inflammation, probiotics, targeted therapy, fecal microbiota transplantation

Yitian Lang,1 Bin Wu,2 Zhilin Sun,3 Erjia Ye,4 Guanshen Dou,4 Xin Guan3 1Department of Pharmacy, Huangpu Branch, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 2Medical Decision and Economic Group, Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201100, People’s Republic of China; 3Department of Dermatology, Peking University Third Hospital, Peking University, Haidian District, Beijing, People’s Republic of China; 4Lilly China Drug Development and Medical Affairs Center, Eli Lilly and Company, Shanghai, People’s Republic of ChinaCorrespondence: Xin Guan, Department of Dermatology, Peking University Third Hospital, Peking University, No. 49, Huayuan North Road, Haidian District, Beijing, People’s Republic of China, Email guanxin1@sina.comObjective: Assessments of patients’ preferences can support in clinical decision-making regarding biologic therapies for psoriasis. Our objective was to investigate patient preference for biologic treatments in patients with psoriasis in China.Methods: From October 2020 to January 2021, psoriasis patients were recruited for a survey that included demographic and disease-related questions, as well as a discrete choice experiment to measure their preferences for biologic therapy. A discrete-choice experiment was used in which respondents selected psoriasis treatments based on benefits (ie, early onset of efficacy, long-term efficacy, sustained efficacy) and treatment costs. We analyzed choice data using conditional logit model.Results: This study included 236 patients with moderate-to-severe psoriasis. The relative importance of the cost of biologic treatments, probability of keeping PASI100 at 5 years, probability of achieving PASI100 at 3 months and time to achieve PASI50 after initiation the biologic treatment were 0.593, 0.137, 0.185 and 0.085. Over 50% of patients regarded the cost of biologic treatments as the most important attribute. High-income and low-income subgroups had higher preference weight in probability of achieving PASI100 at 3-month and monthly cost.Conclusion: The cost of biologic treatments was found as the most important attribute for Chinese patients with psoriasis. Among efficacy attributes, the probability of achieving PASI100 at 3 months showed most sensitive. These results may be helpful to understand patient preference for biologic treatments used for psoriasis in China.Keywords: biologics, discrete choice experiment, Chinese setting, patient preference, psoriasis

Xiudong Guan,1,2,&ast; Yangyang Wang,1,2,&ast; Yueqian Sun,2,3 Chuanbao Zhang,1,2 Shunchang Ma,2,4 Dainan Zhang,1,2 Deling Li,1,2 Wang Jia1,2,4 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, People’s Republic of China; 3Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Neurosurgical Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wang JiaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of ChinaTel +86 18810671839Fax +86-10-67051377Email jwttyy@126.comPurpose: CTLA4, the immune checkpoint, has been widely reported to contribute to immune evasion in anti-tumor activity. The inhibitors of CTLA4 provide a novel strategy to improve the outcome of peripheral cancer, but their clinical effects are limited in glioblastoma (GBM), thus the comprehensive role of CTLA4 needs to be addressed.Patients and Methods: A total of 471 GBM cases were enrolled in this study from 5 cohorts. In our works, the Cancer Genome Atlas (TCGA) cohort was divided into the training set, and the Chinese Glioma Genome Atlas (CGGA), REMBRANDT, and GSE84465 cohorts were divided into validation sets. Tissues from our cohort were collected for histopathologic validation. Then, the role of CTLA4 in the TME of GBM was comprehensively investigated.Results: Significant differences exist in immunological characteristics between the low and high CTLA4 expression groups. Mutation analysis found different genomic patterns associated with CTLA4 expression. Next, network analysis found the module named c1-1562 including CTLA4 correlated with over survival (OS) in GBM. We also developed a predictive model to calculate the risk score for every GBM case and the risk score was independently related to OS. Furthermore, the expression of CTLA4 was positively related to the infiltration level and function of macrophage in GBM TME based on seven independent algorithms, single-cell RNA-seq data and immunohistochemistry.Conclusion: These findings implicate that CTLA4 could serve as a novel target for prognosis and therapy in GBM patients. CTLA4-mediated immune suppression may be attributed to the infiltration of macrophages in the tumor microenvironment.Keywords: glioblastoma, tumor microenvironment, CTLA4, macrophage, multi‐omics

MicroRNAs (miRNA) are important regulators of oocyte maturation, playing a key role in modulating gene expression both in a temporal- and spatial-specific manner. These small non-coding RNAs are involved in important processes during oocyte maturation, acting as messengers between the oocyte and its surrounding cumulus cells. Despite its significance, the bidirectional communication mechanism is still unknown. To test miRNA communication between oocyte and surrounding cumulus cells through the gap junctions the gap junctions were either blocked with carbenoxolone or not. MiRNA sequencing of oocytes at 1, 6, and 22 h of in vitro maturation was then performed. Among the differentially expressed miRNAs, bta-miR-21-5p, a regulator of cumulus cell viability and oocyte maturation, was the only previously known miRNA. Furthermore, by labeling a bta-miR-21-5p mimic with FAM, crossing of this miRNA through the gap junctions within the cumulus-oocyte complex could be visualized and internalization in the oocyte was confirmed by RT-qPCR. In conclusion, this study provides, for the first time, evidence that miRNA communication within the bovine cumulus-oocyte complex is enabled through the gap junctional network. [ABSTRACT FROM AUTHOR]

Source‐to‐sink systems respond to and therefore potentially record topographic and tectonic changes. North of the Tian Shan Belt, the Sikeshu subbasin of the SW Junggar Basin transitioned from active extension in the Triassic to post‐extensional subsidence in the Jurassic‐Cretaceous. Sediment in the Sikeshu subbasin has been shown to be derived from the Tianshan. However, the details of the source‐to‐sink system remain unclear and discrepancies exist between proxy records. The heavy minerals in the Middle Triassic in the Sikeshu subbasin are dominated by garnets. To investigate the garnet sources and decipher the Mesozoic source‐to‐sink evolution, we conducted petrological and sedimentary analysis and detrital garnet and tourmaline geochemistry. We found that the geochemistry of garnets in the Middle Triassic sandstone is most consistent with that of the skarns in the Yili Block (YB) in Tianshan, while the geochemistry of 55%–84% of garnets in other Mesozoic sandstones is consistent with that of garnets in amphibolites in the YB. The geochemistry of the tourmalines since the Upper Triassic is consistent with that of the meta‐sedimentary rocks in the YB and Central Tianshan Block. The dominance of garnets sourced from skarns in the Middle Triassic probably indicates a near‐source point provenance and the broader range of garnet compositions from the Upper Triassic–Lower Cretaceous suggests multiple sources. We infer that the point source changed to multiple sources, which is consistent with the zircon spectra changing from unimodal to multimodal. This change reflects the expansion of the drainage that accompanies a change from active rifting to a post‐rift stage. Key Points: Provenance changed from a point source from skarns during the syn‐rift stage to multiple sources during the post‐rift stageHigher relief in the Tianshan in the Triassic was reduced during the Jurassic‐CretaceousSediment recycling took place in the Early Cretaceous [ABSTRACT FROM AUTHOR]

Yingbei Weng, Ripeng Yin, Lala Qian, Zhi Chen, Jie Wang, Huaqiang Xiang, Yangjing Xue, Kangting Ji, Xueqiang Guan Department of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaCorrespondence: Kangting Ji; Xueqiang GuanDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Xueyuanxi Road, No. 109, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaEmail jikt@wzmc.edu.cn; wzsgxq@163.comObjective: The aims of this study were to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and all-cause mortality in coronary care unit (CCU) patients, adjusting for a wide range of potential confounding factors, to examine the potential of LDL-C in predicting the prognostic value of CCU patients.Methods: Clinical data were extracted from Medical Information Mart for Intensive Care-III database (MIMIC-III database version v.1.4). Baseline data were collected within 24 hours after the patient was first admitted to the hospital. The primary endpoint of our study is 30-day all-cause mortality. The secondary endpoints are 90-day and one-year all-cause mortality and infections. Cox proportional hazard regression and propensity score-matched (PSM) analysis were used to analyze the association between LDL-C levels and prognostic value of CCU patients.Results: We included a total of 1476 patients with an average age of 66.7 ± 14.1 years (66% male). For 30-day all-cause mortality, the hazard ratio (95% confidence interval) of high LDL-C level group (≥ 55 mg/dl) was 0.42 (0.29, 0.62), which was compared with low LDL-C level group (< 55 mg/dl) in unadjusted model. After adjusting for age, gender and race, the association still existed (P < 0.05), and the HR (95% CI) was 0.49 (0.33, 0.72). Further adjustment of possible covariates showed similar correlation (P < 0.05), and HR (95% CI) was 0.65 (0.43, 0.97). Similar correlations were observed for 90-day and one-year all-cause mortality. The relationship between all-cause mortality and LDL-C levels in CCU patients was further verified by propensity score-matched (PSM) analysis. In addition, the higher the LDL-C level, the lower the risk of infection, odds ratio (OR) values in the three models were less than 1 (P < 0.05).Conclusion: Our data suggest that high LDL-C level is associated with a reduced risk of 30-day, 90-day, and one-year mortality of patients in the CCU. And this result is still stable in the PSM model. The results need to be verified in prospective trials.Keywords: low-density lipoprotein cholesterol, coronary care unit, all-cause mortality, cardiovascular disease

Xuehai Guan,1,&ast; Ziyin Jiao,1,&ast; Xiaofang Gong,1 Huiyu Cao,1 Susu Liu,1 Hongmeng Lan,1 Xiaofang Huang,1 Yanmeng Tan,1 Bing Xu,2 Chengxin Lin1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Rehabilitation, The People`s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuehai Guan; Chengxin LinDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of ChinaTel/Fax +86-771-5356250Email guan_xh@aliyun.com; lin.chx@163.comBackground: Propofol-induced injection pain (PIP) is a well-known problem in general anesthesia. We hypothesized that pre-treatment with remimazolam prevents PIP in patients undergoing abortion or curettage.Materials and Methods: In this prospective, single-center, double-blinded, randomized, placebo-controlled clinical trial, adult patients aged 18 to 60 undergoing abortion or curettage were randomly assigned to three groups. Group Lido received system lidocaine (a bolus of 0.5 mg kg− 1, iv). Group Remi received remimazolam (a bolus of 0.1 mg kg− 1, iv). Group NS received identical volumes of 0.9% normal saline. Sixty seconds after the injection of lidocaine, remimazolam or saline, patients were injected with propofol at a rate of 12 mL/min until the loss of consciousness. The primary outcome was the incidence of PIP at the time of induction using 4-point scale. Secondary outcomes included propofol-induced injection pain, vital signs, the characteristics of anesthesia and surgery, and adverse events.Results: The incidence of patients with PIP was higher in group NS than that in group Lido and group Remi (75.7, 44.3, and 42.9%, respectively, p < 0.001). The percentages of patients with moderate PIP were higher in group NS than that in group Lido and group Remi (20.0, 2.9, and 1.4%, respectively, p < 0.001). Moreover, the consumption of propofol and the incidence of adverse event (hypoxemia and chin lifting) in group Remi were lower than that in group NS and Lido, and less patients got physical movement and cough in group Remi. The recovery time in group NS was longer than that in group Lido and Remi.Conclusion: Our findings indicate that pre-treatment with remimazolam reduced the incidence and intensity of PIP in abortion or curettage patients, equivalent to that of lidocaine without severe adverse effects.Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2100041805).Keywords: lidocaine, remimazolam, propofol injection pain, abortion, curettage

Wenqiang Chen,1 Mingxia Jiang,1 Wenjing Yu,1 Zhiwei Xu,1 Xinyue Liu,1 Qingmiao Jia,1 Xiuwen Guan,1– 3 Weifen Zhang1– 3 1College of Pharmacy, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, 261053, People’s Republic of ChinaCorrespondence: Xiuwen Guan; Weifen Zhang Tel +86-536-8462490Email gxw2603@wfmc.edu.cn; zhangwf@wfmc.edu.cnAbstract: Cancer has been a serious health hazard to the people all over the world with its high incidence and horrible mortality. In recent years, tumor vaccines in immunotherapy have become a hotspot in cancer therapy due to their many practical advantages and good therapeutic potentials. Among the various vaccines, nanovaccine utilized nanoparticles (NPs) as the carrier and/or adjuvant has presented significant therapeutic effect in cancer treatment. For tumor nanovaccines, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) is a commonly used adjuvant. It has been reported that CpG ODN was the most effective immune stimulant among the currently known adjuvants. It could be recognized by toll-like receptor 9 (TLR9) to activate humoral and cellular immunity for preventing or treating cancer. In this review, the topic of CpG-based nanovaccines for cancer immunotherapy will be focused. The types and properties of different CpG will be introduced in detail first, and then some representative tumor nanovaccines will be reviewed according to the diverse loading modes of CpG, such as electrostatic adsorption, covalent bonding, hydrophilic and hydrophobic interaction, and DNA self-assembly, for summarizing the current progress of CpG-based tumor nanovaccines. Finally, the challenges and future perspectives will be discussed. It is hoped that this review will provide valuable references for the development of nanovaccines in cancer immunotherapy.Keywords: cancer immunotherapy, nanovaccine, nanoparticle, adjuvant, CpG

Li Cai,1,2 Lixian Wang,3 Xuhua Guan,4 Lei Wang,4 Xinyi Hu,5 Yang Wu,4 Yeqing Tong,4 Peigang Wang1 1School of Health Sciences, Wuhan University, Wuhan, 430071, People’s Republic of China; 2Wuhan Center for Disease Control and Prevention, Wuhan, 430015, People’s Republic of China; 3Xiaonan Center for Disease Control and Prevention, Xiaogan, 432100, People’s Republic of China; 4Hubei Center for Disease Control and Prevention, Wuhan, Hubei, 430079, People’s Republic of China; 5Global Study Institute, University of Geneva, Geneva, SwitzerlandCorrespondence: Peigang Wang Email wpg926@163.comYeqing Tong Tel +8627 87652010Email t_yeqing@163.comObjective: The study aimed to timely grasp the epidemiologic status of rabies in Central China from 2013 to 2018 and provide scientific evidence for the implementation of follow-up prevention and control measures.Methods: We initiated a retrospective observational and descriptive study of bite-related injuries data and rabies disease data in Hubei province from 2013 to 2018, managed by the Center for Disease Control and Prevention.Results: A total of 2,028,691 individuals were exposed to bites from 2013 to 2018, of which 221 were diagnosed with rabies and deceased. Among those cases, the incubation periods of rabies varied from 3 days to 18,406 days, which has been shown to be statistically associated with where the infected person was exposed and whether the wound care has been conducted.Conclusion: Epidemiological studies have shown that from 2013 to 2018, the current situation of rabies in Central China is still severe. The case fatality rate keeps virtually 100%. The rural population is still the most vulnerable group to rabies, characterized by a high exposure ratio and low treatment rate as well as poor vaccination compliance. Hoewever, larger populations are warranted to validate our findings.Keywords: rabies, epidemiology, China

Xiangqian Guan, Yuyan Lu, Heping Zhu, Shuqi Yu, Wenxiu Zhao, Xiaoqin Chi, Chengrong Xie, Zhenyu Yin Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, Fujian, People’s Republic of ChinaCorrespondence: Chengrong Xie; Zhenyu YinDepartment of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, 209 South Hubin Road, Xiamen, Fujian Province, 361004, People’s Republic of ChinaEmail eason_xiecr@126.com; yinzy@xmu.edu.cnBackground: Emerging evidences have highlighted the roles of neutrophils, as the major host microenvironment component, in the development of hepatocellular carcinoma (HCC). Neutrophils extracellular traps (NETs) produced in the infection can strengthen the behavior of cancer metastasis. Here, we investigated the roles of NETs in HCC metastasis and further explore the underlying mechanism of how NETs interact with cancer.Methods: The neutrophils were isolated from whole blood of HCC patients and used to evaluate the formation of NETs. NET markers were detected in tissue samples, plasma and cell climbing slice. Mouse models were used to evaluate the roles of NETs in HCC metastasis in vivo, and the corresponding mechanisms were explored using in vivo and in vitro assays.Results: An increase in the release of NETs in patients with HCC, particularly those with portal vein tumor thrombosis (PVTT). The presence of NETs in HCC tumor tissues closely correlated with a poor prognosis. Functionally, the invasion ability of HCC cells was enhanced by co-culture with HCC neutrophils, through NETs formation, while the neutrophils from a healthy donor (HD) exhibited the inhibition of the invasion ability. Furthermore, we observed an enhanced ability of forming NETs in neutrophils from HCC patients in vitro, especially patients with PVTT or extra-hepatic metastasis. An in-vivo animal study demonstrated that neutrophils of HCC facilitated the metastatic behavior towards the lung. The further mechanistic investigation unveiled that HCC cells-derived cytokine IL-8 triggered NETs formation in an NADPH oxidase-dependent manner, and NETs-associated cathepsin G (cG) promoted HCC metastasis in vitro as well as vivo. Clinically, the expression of the cG protein in tumor tissues displayed a close correlation with the disease prognosis of HCC patients.Conclusion: Our findings implicated that the induction of NETs by HCC cells is a critical metastasis-supporting cancer–host interaction and that NETs may serve as an immune-based potential therapeutic target against HCC progression.Keywords: hepatocellular carcinoma, neutrophils extracellular traps, cathepsin G, IL-8, E-cadherin, metastasis, NADPH

Chunxiang Li,1 Hengchang Liu,2 Ran Wei,2 Zheng Liu,2 Haipeng Chen,2 Xu Guan,2 Zhixun Zhao,2 Xishan Wang,2 Zheng Jiang2 1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Zheng JiangDepartment of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, People’s Republic of ChinaTel +86 10-87787110Email zr7780@163.comBackground/Aims: Long non-coding ribonucleic acids (lncRNAs) are involved in the progression of cancers and affect the response to radiation therapy. This study was to investigate the mechanism of lncRNA EGOT in the radiosensitivity of rectal cancer.Methods: The mRNA expression of EGOT, miR-211-5p and ErbB4 in rectal cancer tissues and cells was detected by qRT-PCR. The protein expression of ErbB4 was detected by Western blot. Dual-luciferase reporter assay and ribonucleic acid immunoprecipitation (RIP) were used to confirm the interaction between EGOT and miR-211-5p or miR-211-5p and ErbB4. Transfection technology was used to down-regulate and up-regulate the expression of EGOT and miR-211-5p in rectal cancer cells, respectively. MTT, colony formation and flow cytometry were used to detect the effect of EGOT and miR-211-5p on proliferation, invasion, migration and apoptosis of rectal cancer cells.Results: The expression of EGOT was up-regulated in rectal cancer tissues and cells, and the expression of EGOT was related to the late stage of pathology. EGOT knockdown inhibited the proliferation and colony formation of rectal cancer cells and induced the apoptosis of rectal cancer cells. Moreover, EGOT knockdown was significantly enhanced the effects of radiotherapy on rectal cancer in vivo and in vitro. Furthermore, EGOT was found to serve as a sponge of miR-211-5p, and ErbB4 was a downstream target of miR-211-5p. EGOT enhanced the expression of ErbB4 by regulating miR-211-5p. MiR-211-5p inhibitor restored the effect of EGOT knockdown on the radiosensitivity of rectal cancer.Conclusion: Down-regulation of EGOT could inhibit the growth of rectal cancer cells by regulating the miR-211-5p/ErbB4 axis and improve the radiosensitivity of rectal cancer cells. EGOT may be a new therapeutic target for rectal cancer.Keywords: EGOT, miR-211-5p, ErbB4, rectal cancer, radiosensitivity

Liang Yan,1,* Xiuyun Tian,1,* Chunxiang Ye,1,2 Xiaoya Guan,1 Bin Dong,3 Min Zhao,4 Jianhui Wu,1 Chunyi Hao1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunyi HaoKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, People’s Republic of ChinaTel +86-10-88196182Fax +86-10-88196548Email haochunyi@bjmu.edu.cnPurpose: Pancreatic cancer is associated with a high mortality rate owing to insufficient approaches for early diagnosis and the invasive biological behavior of the cancer. CD26 is a membrane-anchored protein involved in multiple physiological and pathological processes. Here, we investigated correlations between CD26 expression and clinicopathological features in patients with pancreatic tumors.Methods: We collected 170 tumor tissue specimens and 138 paired paratumoral tissues from patients with pancreatic tumors and evaluated CD26 expression using immunohistochemistry.Results: CD26 was expressed in 79.4% of pancreatic tumors, which was significantly (P < 0.001) higher than that in paratumoral pancreatic tissues (23.2%). High expression of CD26 was correlated with ABO blood type (P = 0.035), malignancy degree (P = 0.001), CA199 (P = 0.01), and CA242 (P = 0.027). In pancreatic malignancies, CD26 expression was observed in 80.7% (130/161) of cases. Lower CD26 expression was correlated with longer disease-free survival (P = 0.048) and overall survival (P = 0.024) and was an independent predictor of overall survival (hazard ratio [HR]: 1.713; P = 0.042). Similar results were observed in pancreatic ductal adenocarcinoma (PDAC) tissues, and CD26 expression level (HR: 2.117; P = 0.008) was an independent predictor of overall survival in patients with PDAC. CD26 expression was significantly increased in pancreatic tumors and gradually increased with increasing malignancy degree, suggesting that CD26 may be involved in the tumorigenic proliferation of pancreatic tumors.Conclusion: Therefore, CD26 is a potential marker for early diagnosis and a promising therapeutic target in pancreatic tumors.Keywords: biomarker, CD26, immunohistochemistry, pancreatic cancer, prognosis

Hengchang Liu,1,* Ran Wei,1,* Chunxiang Li,2 Zhixun Zhao,1 Xu Guan,1 Ming Yang,1 Zheng Liu,1 Xishan Wang,1 Zheng Jiang1 1Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zheng Jiang; Xishan Wang Tel +86-010-88788798Email Jiangzheng@cicams.ac.cn; wangxishan@cicams.ac.cnObjective: This study aims to develop feasible nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of the local advanced rectal cancer (LARC) patients who were treated with neoadjuvant chemoradiotherapy (nCRT) and operation.Methods: A total of 243 LARC patients undergoing nCRT followed by total mesorectal excision (TME) were enrolled. Preoperative clinical features and postoperative pathological characteristics were collected. A Cox regression analysis was performed, and Cox-based nomograms were developed to predict the OS and CSS. We assessed the predictive performance of the nomogram with concordance index and calibration plots.Results: A total of 243 patients were included with a median follow-up period of 46 months (range from 9 to 86 months). Cox regression analysis showed that low BMI (BMI < 18.5, HR= 21.739, P < 0.05), high level of preoperative CA19-9 (HR = 3.369, P = 0.036), high ypStage (HR = 19.768, P < 0.001), positive neural invasion (HR = 4.218, P = 0.026) and no adjuvant chemotherapy (HR = 5.495, P < 0.001) were independent predictors of poor OS. Age ≥ 70 (HR = 2.284, P < 0.001), low BMI (BMI < 18.5, HR = 3.906, P < 0.05), positive preoperative CA19-9 (HR = 1.920, P = 0.012), high ypStage (HR = 5.147, P < 0.001) and positive neural invasion (HR = 2.873, P = 0.022) were independent predictors of poor CSS. The predictive nomograms were developed to predict the OS and CSS with a C-index of 0.837 and 0.760. Good statistical performance on internal validation was shown by calibration plots.Conclusion: In conclusion, this study demonstrated that BMI was an independent prognostic factor for OS and CSS in LARC patients treated with nCRT followed TME. A nomogram incorporating BMI, neural invasion, pre-CA19-9, ypStage, age, and adjuvant chemotherapy could be helpful to predict the OS and CSS.Keywords: local advanced rectal cancer, neoadjuvant chemoradiotherapy, nomogram, body mass index, prognosis, overall survival, cancer-specific survival