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Congyang Xue,1 Xiaopei Lu,2 Guangda Sun,1 Nan Wang,1 Gansheng He,1 Wenqiang Xu,1 Zhipeng Xi,1 Lin Xie1 1Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Traditional Chinese Medicine Surgery, Nanjing Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Lin Xie, Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100th. Shizi Street, Nanjing, Jiangsu Province, 210028, People’s Republic of China, Email xielin@njucm.edu.cnPurpose: To explore the validity of the thoracic spine Hounsfield Unit (HU) measured by chest computed tomography (CT) for opportunistic screening of diabetic osteoporosis. The current study attempted to establish a diagnostic threshold for thoracic spine HU in a type 2 diabetes mellitus (T2DM) population with osteoporosis.Patients and Methods: The current study retrospectively included 334 patients with T2DM. They underwent chest CT and Dual-energy X-ray (DXA) between August 2021 and January 2022 in our hospital. HU values were measured on the resulting chest CT images at thoracic spine 11 and 12 to construct regions of interest. All patients were grouped according to the lowest T-value of DXA examination: osteoporosis, osteopenia and normal bone density. HU values were compared with T-values in each group of patients, and receiver operating characteristics curves were plotted to calculate diagnostic thresholds as well as sensitivity and specificity.Results: There was a strong correlation between the HU values of chest CT and the T-values of DXA (p < 0.01). The sensitivity for osteoporosis was 88.7% for T11 attenuation≤ 98 HU and the specificity for osteoporosis was 87.5% for T12 attenuation ≤ 117HU; the specificity for normal BMD was 85.4% for T11 attenuation ≥ 147 HU and 82% for T12 attenuation ≥ 146 HU.Conclusion: Chest CT can be used to screen patients with T2DM for opportunistic osteoporosis and help determine if they need DXA screening. The current study suggests that when the HU threshold of T11 ≤ 98/T12 ≤ 117, patients may need further osteoporosis screening.Keywords: osteoporosis, T2DM, HU, thoracic vertebra, chest CT

Guiyuan He,1,&ast; Xi Wang,1,&ast; Beiqing Li,1 Lei Wang,1 Jing Zhang,2 Yang Shi,1 Wenxiu Zhu,1 Ming Shi1,3 1Centre for Reproductive and Genetic Medicine, Dalian Women and Children’s Medical Group, Dalian, People’s Republic of China; 2Department of Clinical Laboratory, Central Hospital of Dalian University of Technology, Dalian Municipal Central Hospital, Dalian, People’s Republic of China; 3Department of Clinical Laboratory, Dalian Women and Children’s Medical Group, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Shi, Centre for Reproductive and Genetic Medicine & Department of Clinical Laboratory, Dalian Women and Children’s Medical Group, Dalian, 116037, People’s Republic of China, Email zhsh6655@sohu.comPurpose: Fragile sites are specific chromosomal regions showing gaps, poor staining, contractions, or even breaks in the chromosomes. These spontaneous and heritable fragile sites are prone to structural variations which can lead to adverse reproductive outcomes. This paper aims to present a specific case study of a female patient, with a mosaic karyotype involving chromosome 16q22 fragile site which is very rare in clinic and her experience of infertility.Case Presentation: A 37-year-old woman is diagnosed with ten-year primary infertility. She worked in a factory, and she was occasionally exposed to paint. She underwent two cycles of follicular monitoring with intrauterine insemination (IUI) using her husband’s sperm six years ago but failed. Most of her prepregnancy tests were normal, except a not smooth right fallopian tube. Her G-band karyotype of peripheral blood lymphocytes was mos 46, XX, del(16)(q22)[40]/46, XX, fra(16)(q22)[29]/46, XX, fra(16)tr(16)(q22)[3]/46, XX[28] which inherited from her mother. The SCE assay detected a significantly higher frequency of SCEs in the 16q region of the patient’s chromosomes compared to her mother and a healthy control. However, the average SCEs per chromosome were quite close. Moreover, copy number variation (CNV) sequencing showed no deletion nor duplication at 16q22.Conclusion: Infertility cannot be completely attributed to the fragile site on chromosome 16q22. Assisted reproductive technology combined with preimplantation genetic testing may help in achieving a healthy live birth.Keywords: fragile sites, infertility, fra(16)(q22), del(16)(q22), SCE, CNV

Guanjin He,1,&ast; Qifeng Yang,2,&ast; Yuyang Shen,3 Lanzhi Zhang,2 Jingping Wu,2 Hongbin Cheng1 1Dermatology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Medical Aesthetic Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Traditional Chinese Medicine Department, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingping Wu; Hongbin Cheng, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shi-Er-Qiao Road, Jinniu District, Chengdu, People’s Republic of China, Tel +86 15928747715 ; +86 13880848134, Email jingpingwu2022@163.com; chenghongbin@cdutcm.edu.cnAbstract: Our team used a new kite flap preparation method to repair wounds after the removal of a benign facial tumor with satisfactory aesthetic results. Thus, this modified kite flap has significant value in facial trauma repair.Keywords: facial wound repair, modified kite flap, experience, case series

Dongning Lyu, Guangyu He, Kan Zhou, Jin Xu, Haifei Zeng, Tongyu Li, Ningbo Tang Department of Nephrology Clinic, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Dongning Lyu, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, No. 8 Qiuyue Road, Liangqing District, Nanning, Guangxi, 530200, People’s Republic of China, Tel +8613377191933, Email tsj757700@163.comPurpose: Uremia, which is characterized by immunodeficiency, is associated with the deterioration of kidney function. Immune-related genes (IRGs) are crucial for uremia progression.Methods: The co-expression network was constructed to identify key modular genes associated with uremia. IRGs were intersected with differentially expressed genes (DEGs) between uremia and control groups and key modular genes to obtain differentially expressed IRGs (DEIRGs). DEIRGs were subjected to functional enrichment analysis. The protein-protein interaction (PPI) network was constructed. The candidate genes were identified using the cytoHubba tool. The biomarkers were identified using various machine learning algorithms. The diagnostic value of the biomarkers was evaluated using receiver operating characteristic (ROC) analysis. The immune infiltration analysis was implemented. The biological pathways of biomarkers were identified using gene set enrichment analysis and ingenuity pathway analysis. The mRNA expression of biomarkers was validated using blood samples of patients with uremia and healthy subjects with quantitative real-time polymerase chain reaction (qRT-PCR).Results: In total, four biomarkers (PDCD1, NGF, PDGFRB, and ZAP70) were identified by machine learning methods. ROC analysis demonstrated that the area under the curve values of individual biomarkers were > 0.9, indicating good diagnostic power. The nomogram model of biomarkers exhibited good predictive power. The proportions of six immune cells significantly varied between the uremia and control groups. ZAP70 expression was positively correlated with the proportions of resting natural killer (NK) cells, naïve B cells, and regulatory T cells. Functional enrichment analysis revealed that the biomarkers were mainly associated with translational function and neuroactive ligand-receptor interaction. ZAP70 regulated NK cell signaling. The PDCD1 and NGF expression levels determined using qRT-PCR were consistent with those determined using bioinformatics analysis.Conclusion: PDCD1, NGF, PDGFRB, and ZAP70 were identified as biomarkers for uremia, providing a theoretical foundation for uremia diagnosis. Keywords: differential expression analysis, WGCNA, immune infiltration, nomogram, diagnosis

Tinghan Deng,1 Huilan Zheng,1 Ying Zhu,2 Ming Liu,3 Guanjin He,1 Ya Li,1 Yichen Liu,1 Jingping Wu,4 Hongbin Cheng1 1Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of China; 2Department of Gynecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of China; 3Department of Medical Oncology/Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Department of Medical Cosmetology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of ChinaCorrespondence: Jingping Wu; Hongbin Cheng, Email wujingping@cdutcm.edu.cn; chenghongbin@cdutcm.edu.cnBackground: Human skin microbiome is the first barrier against exogenous attack and is associated with various skin disease pathogenesis and progression. Advancements in high-throughput sequencing technologies have paved the way for a deeper understanding of this field. Based on the bibliometric analysis, this investigation aimed to identify the hotspots and future research trends associated with human skin microbiomes studied over the past decade.Methods: The published research on skin microbiome from January 2013 to January 2023 was retrieved from the Web of Science Core Collection. Data cleaning processes to ensure robust data and the bibliometrix packages R, CiteSpace, VOSviewer, Origin, and Scimago Graphica for bibliometric and visual analyses were utilized.Results: A total of 1629 published documents were analyzed. The overall publication trend steadily increased, with relatively fast growth in 2017 and 2020. The United States of America has the highest number of publications and citations and shows close collaborations with China and Germany. The University of California, San Diego, indicated a higher number of publications than other institutions and the fastest growth rate. The top three most publishing journals on this topic are Microorganisms, Frontiers in Microbiology, and Experimental dermatology. Gallo RL is the most influential author with the highest h- and g-index and most publications in skin microecology, followed by Grice EA and Kong HH. The top 10 most frequently used keywords in recent years included skin microbiome, microbiome, staphylococcus aureus, diversity, atopic dermatitis, skin, bacteria, infections, gut microbiota, and disease.Conclusion: The skin microbiome is an area of research that requires continuous analysis, and even with much-achieved progress, future research will further be aided as technology develops.Keywords: skin microbiome, bibliometric, trends, skin barrier, skin immune

Liping Mai,1,&ast; Guodong He,1,&ast; Jing Chen,1 Jiening Zhu,1 Shaoxian Chen,1 Hui Yang,1 Mengzhen Zhang,1 Xinghua Hou,1 Miaola Ke,2 Xiaohong Li1,3 1Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 2Department of Blood Transfusion, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Li, Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Email lixiaohong@gdph.org.cn Miaola Ke, Department of Blood Transfusion, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email keml@sysucc.org.cnBackground: Profilin-1 (PFN1) regulates the dynamic balance of actin and plays an important role in cell functions as a hub protein in signaling molecule interaction networks. Dysregulation of PFN1 is related to pathologic kidney diseases. Diabetic nephropathy (DN) was recently reported as an inflammatory disorder, however, the molecular mechanisms of PFN1 in DN remain unclear. Therefore, the present study was conducted to explore the molecular and bioinformatic characteristics of PFN1 in DN.Methods: Bioinformatics analyses were performed on the chip of database in DN kidney tissues. A cellular model of DN was established in human renal tubular epithelial cells (HK-2) induced by high glucose. The PFN1 gene was overexpressed or knocked-down to investigate its function in DN. Flow cytometry was used to detect cell proliferation and apoptosis. PFN1 and proteins in the related signaling pathways were evaluated by Western blotting.Results: The expression of PFN1 was significantly increased in DN kidney tissues (P < 0.001) and was correlated with a high apoptosis-associated score (Pearson’s correlation = 0.664) and cellular senescence-associated score (Pearson’s correlation = 0.703). PFN1 protein was mainly located in cytoplasm. Overexpression of PFN1 promoted apoptosis and blocked the proliferation of HK-2 cells treated with high levels of glucose. Knockdown of PFN1 led to the opposite effects. Additionally, we found that PFN1 was correlated with the inactivation of the Hedgehog signaling pathway in HK-2 cells treated with high levels of glucose.Conclusion: PFN1 might play an integral role in the regulation of cell proliferation and apoptosis during DN development by activating the Hedgehog signaling pathway. This study provided molecular and bioinformatic characterizations of PFN1, and contributed to the understanding of the molecular mechanisms leading to DN.Keywords: PFN1, diabetic nephropathy, bioinformatic characterization, Hedgehog signaling pathway, apoptosis

Guangda He,1 Runqing Ji,1 Xiqian Huo,1 Xiaoming Su,1 Jinzhuo Ge,1 Wei Li,1 Lubi Lei,1 Boxuan Pu,1 Aoxi Tian,1 Jiamin Liu,1 Lihua Zhang,1 Yongjian Wu2 On behalf of the China PEACE Collaborative Group1National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lihua Zhang, National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, 167 Beilishi Road, Beijing, 100037, People’s Republic of China, Email zhanglihua@fuwai.com Yongjian Wu, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Email wuyongjian@fuwai.comBackground: Inflammation contributes to the progression of heart failure (HF). However, long-term inflammatory trajectories and their associations with outcomes in patients with acute HF remain unclear.Methods: Data was obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, and high-sensitivity C-reactive protein (hsCRP) was used to reflect the inflammatory level. Only patients who survived over 12-month and had hsCRP data at admission, 1-, and 12-month after discharge were included. The latent class trajectory modeling was used to characterize hsCRP trajectories. Multivariable Cox regression models were used to explore the association between hsCRP trajectories and following mortality.Results: Totally, 1281 patients with a median 4.77 (interquartile range [IQR]: 4.24– 5.07) years follow-up were included. The median age was 64 years (IQR: 54– 73 years); 453 (35.4%) were female. Four distinct inflammatory trajectories were characterized: persistently low (n = 419, 32.7%), very high-marked decrease (n = 99, 7.7%), persistently high (n = 649, 50.7%), and persistently very high (n = 114, 8.9%). Compared with the persistently low trajectory, the all-cause mortality was increased in a graded pattern in the persistently high (hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.23– 2.07) and persistently very high (HR: 2.56, 95% CI: 1.83– 3.70) trajectories; nevertheless, the mortality was not significantly increased in very high-marked decrease trajectory (HR: 0.94, 95% CI: 0.57– 1.54).Conclusion: Four distinct inflammatory trajectories were identified among patients with acute HF who survived over 12-month. Patients with persistently high and very high trajectories had significantly higher mortality than those with the persistently low trajectory.Keywords: heart failure, high-sensitivity C-reactive protein, trajectory, latent class trajectory modeling, mortality

Guangyu He,1 Amos Z Dai,2 Vamiq M Mustahsan,1 Christopher L Blum,2 Imin Kao,1 Fazel A Khan2 1Department of Mechanical Engineering, Stony Brook University, Stony Brook, NY, USA; 2Department of Orthopedics, Stony Brook University Hospital, Stony Brook, NY, USACorrespondence: Fazel A Khan, Email fazel.khan@stonybrookmedicine.eduIntroduction: Computer navigation and customized 3D-printed jigs improve accuracy during bone tumor resection, but such technologies can be bulky, costly, and require intraoperative radiation, or long lead time to be ready in OR.Methods: We developed a method utilizing a compact, inexpensive, non-X-ray based 3D surface light scanner to provide a visual aid that helps surgeons accurately draw osteotomy lines on the surface of exposed bone to reproduce a well-defined preoperative bone resection plan. We tested the accuracy of the method on 18 sawbones using a distal femur hemimetaphyseal resection model and compared it with a traditional, freehand method.Results: The method significantly reduces the positional error from 2.53 (± 1.13) mm to 1.04 (± 0.43) mm (p< 0.001), and angular error of the front angle from 2.10° (± 0.83°) to 0.80° (± 0.66°) (p=0.001). The method also reduces the mean maximum deviation of the bone resection, with respect to the preoperative path, from 3.75mm to 2.69mm (p=0.003). However, no increased accuracy was observed at the back side of the bone surface where this method would not be expected to provide information.Discussion: In summary, we developed a novel 3D-LAD navigation technology. From the experimental study, we demonstrated that the method can improve the ability of surgeons to accurately draw the preoperative osteotomy lines and perform resection of a primary bone sarcoma, with comparison to traditional methods, using 18 sawbones.Keywords: computer-assist surgery, 3D light assisted drawing, osteotomy lines, structured-light scanning, surgical technique

Yucheng Fu, Guoyu He, Zhuochao Liu, Jun Wang, Zhusheng Zhang, Qiyuan Bao, Junxiang Wen, Zhijian Jin, Weibin Zhang Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaCorrespondence: Weibin ZhangDepartment of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of ChinaTel +86-21-64370045, Ext 666983Fax +86-21-54660217Email zhangweibin10368@163.comBackground: Inflammatory response took part in the progression of tumor and was regarded as the hallmark of cancer. However, the prognostic relationship between osteosarcoma and inflammatory response-associated genes (IRGs) was unclear. This research aimed to explore the correlations between osteosarcoma prognosis and IRG signature.Methods: The inflammatory response-associated differentially expressed messenger RNAs (DEmRNAs) were screened out through Gene Expression Omnibus (GEO) and Molecular Signature Database (MSigDB) databases. Univariate and multivariate cox regression analyses were utilized to construct the IRG signature. The prognostic value of signature was investigated through Kaplan–Meier (KM) survival curve and nomogram. DEmRNAs among high and low inflammatory response-associated risks were identified and functional enrichment analyses were conducted. ESTIMATE, CIBERSORT and single-sample gene set enrichment analyses (ssGSEA) were implied to reveal the alterations in immune infiltration. All the above results were validated in Target database. The expression of IRGs was also validated in different cell lines by quantitative real-time PCR (qRT-PCR) and osteosarcoma patient samples by immunohistochemistry.Results: The IRG signature that consisted of two genes (MYC, CLEC5A) was established. In training and validation datasets, patients with lower risk scores survived longer and the IRG signature was confirmed as the independent prognostic factor in osteosarcoma. The nomogram was constructed and the calibration curves demonstrated the reliability of this model. Functional analysis of risk score-associated DEmRNAs indicated that immune-related pathways and functions were significantly enriched. ssGSEA revealed that 14 immune cells and 11 immune functions were significantly dysregulated. The qRT-PCR results indicated IRGs were significantly differently expressed in osteosarcoma and osteoblast cell lines. The immunohistochemistry analyses of patients’ samples revealed the same result.Conclusion: The novel osteosarcoma inflammatory response-associated prognostic signature was established and validated in this study. This model could serve as the biomarker and therapeutic target for osteosarcoma in the future.Keywords: osteosarcoma, inflammatory response, metastasis, prognosis, immune

The purpose of this paper is to study on the power extraction of the hydrofoil by performance of the coupled oscillating heave and pitch motions. The numerical analysis is conducted by using the Reynolds Average Navier-Stokes (RANS) equations and the realizable k- ɛ turbulent model of the Star-CCM+ software. A 3D oscillating hydrofoil of NACA0015 section with aspect ratio of 7 is selected for the present analysis at two inflow velocities and three frequencies. The numerical results of lift and drag coefficients, horizontal and vertical forces coefficients, power efficiency in time domain and average value of those parameters are presented and discussed. According to the numerical results, the high efficiency of hydrofoil is found at the reduced frequency of 0.18 and the flow velocity of 1 m/s and the low efficiency is obtained at the reduction frequency of 0.06 and the flow velocity of 2 m/s. Moreover, the contour results of vorticity, streamline and pressure distribution are also presented and discussed. The computational model depicts clear vortex patterns surrounding the hydrofoil, which has a major impact on the power performance of oscillating hydrofoil.

Xiaolong Zhao,1– 3,&ast; Huajun Xu,1,3,&ast; Chuan Dong,2,&ast; Jiangang Fan,2 Gang He,2 Jianyin Zou,1,3 Lili Meng,1,3 Huaming Zhu,1,3 Kaiming Su,1,3 Mingpo Yang,4 Hongliang Yi,1,3 Jian Wang,5 Shankai Yin,1,3 Jian Guan1,3 1Department of Otolaryngology Head and Neck Surgery & Center of Sleep Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, People’s Republic of China; 4Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5School of Communication Science and Disorders/Physiol & Biophysics, Dalhousie University, Halifax, NS, Canada&ast;These authors contributed equally to this workCorrespondence: Shankai Yin; Jian Guan Email skyin@sjtu.edu.cn; guanjian0606@sina.comBackground: Cardiac autonomic dysfunction (CAD) is a common pathology in cardiovascular diseases; however, the role of glycolipid metabolic disorders in CAD development in obstructive sleep apnea (OSA) remains poorly understood.Methods: In total, 4152 patients with suspected OSA were recruited in our sleep center. Metabolic characteristics including anthropometric and glycolipid data were collected. Heart rate variability (HRV) was measured to assess the risk of CAD; its dose–response relationship with OSA severity was evaluated via restricted cubic spline (RCS) analysis. A segmented multivariate linear regression (SMLR) model was used to evaluate the roles of metabolic variables in different stages of OSA.Results: The RCS showed that CAD risk increased in a nonlinear relationship pattern with OSA severity, from slow fluctuation at earlier stages to rapid change in later stages. After integrating the clinical definition and RCS selected knots, we obtained the new four OSA severity stages. SMLR model showed that the overall value of glycolipid variables for prediction of HRV abnormalities was greater than the value of OSA variables at earlier stages, while OSA variables were more effective predictors in more severe stages. The discordance in respective relationship of HRV with metabolic and OSA variables sheds the light how metabolic disorders promoted the development of CAD in OSA, the later further in turn deteriorates cardiac function.Conclusion: These results are indicative of stage-specific involvement of glycolipid metabolic factors underlying CAD nonlinear changes in patients with OSA. Early control glycolipid disorders may help the control of CAD development in patients with OSA.Keywords: obstructive sleep apnea, autonomic nervous system, cardiac autonomic neuropathy, metabolism, heart rate variability

Xuan Feng,1,2 Feng Xue,3 Guihua He,4 Suiping Huang,4 Qing Ni1,3 1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu, People’s Republic of China; 2Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225001, Jiangsu, People’s Republic of China; 3Department of Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, 225000, Jiangsu, People’s Republic of China; 4Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of ChinaCorrespondence: Suiping Huang; Qing Ni Email gzdoctorhsp@126.com; nqingnn@163.comPurpose: Banxia xiexin decoction (BXXX) is a classical Chinese herbal compound for the treatment of gastrointestinal diseases. Its ingredients are also considered helpful for cancer rehabilitation. Here, we will explore the regulatory mechanism of BXXX acting on PD-L1 in gastric cancer (GC).Methods: GC samples and the general baseline data of the patients were collated. Immunohistochemical (IHC) detected the expression of programmed cell death-ligand 1(PD-L1), hypoxia-inducible factor-1 (HIF-1), epidermal growth factor receptor (EGFR), interferon-γ receptor (IFNGR) and Toll-like receptor 4 (TLR4). ELISA detected the expressions of EGF, IFNG and IL-6 in serum samples. Network tools were used to analyze the potential molecules of BXXX. In the cell experiment, CCK-8 detected the cell proliferation. Tunel detected the apoptosis. Western blot detected the expression of related proteins. In animal experiments, the tumor volume of GC-bearing mice was observed. Expression of EGF, IFNG and IL-6 in the serum of tumor-bearing GC mice were detected by ELISA. Western blot detected the expression of related proteins.Results: The expressions of PD-L1, HIF-1, EGFR, IFNGR and TLR4 in the tissues of GC patients were significantly increased, and the expressions of EGF, IFNG and IL-6 in serum were increased. The molecular results of the network tools showed that BXXX and its main components have a targeting effect on the key molecules of each pathway in the PD-L1 regulatory network. Cell experiments showed that BXXX can inhibit the expression of PD-L1, HIF-1, EGFR and TLR4, but has no significant effect on the expression of IFNGR, thus inhibiting the proliferation and promoting the apoptosis of GC cells. The results were consistent with the animal experiments on tumor-bearing gastric cancer mice.Conclusion: BXXX inhibited the expression of PD-L1 through multi-target and multi-pathway regulation of major oncogenes in GC, thus effect cell proliferation and apoptosis.Keywords: banxia xiexin decoction, gastric cancer, PD-L1, multi-target and multi-pathway

Yuqiu Xu,* Qingyang Feng,* Yijiao Chen,* Yihao Mao,* Zhiyuan Zhang, Yang Lv, Peng Zheng, Shanchao Yu, Guodong He, Jianmin Xu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianmin Xu; Guodong HeDepartment of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People’s Republic of ChinaTel +8621-6404-1990Fax +8621-6403-8038Email xujmin@aliyun.com; angelhgd@163.comPurpose: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Ovarian metastases (OM), which are low in frequency, are reported to occur in 3– 14% of women with CRC and have a poor prognosis. Studies have shown that surgical treatment may benefit patients with ovarian metastases arising from CRC. However, the precise benefit of surgery is uncertain. This study was implemented to identify treatment outcomes associated with ovarian metastases from CRC, as well as to clarify the importance of primary and metastatic lesion resection.Patients and Methods: Between January 2008 and December 2018, the medical records of 93 patients diagnosed with CRC ovarian metastases (CRC-OM) at Zhongshan Hospital, Fudan University, Shanghai, were retrospectively analyzed. Clinicopathological characteristics as well as prognostic conditions were evaluated. Nineteen patients with only synchronous OM and 38 patients without metastases were matched to compare surgical outcomes.Results: The median overall survival (OS) of the total 93 CRC-OM patients was 26 months. The median OS times of patients with ovary-only metastases (n=37) and those with other metastases (n=56) were 49 months and 20 months, respectively. Patients with only ovarian metastases had a longer OS time (p< 0.001) than patients with other metastases. Patients with ovarian metastases resected (n=76) (p< 0.001) had a longer OS time than those unresected (n=17). Synchronous (n=54) and metachronous (n=39) metastases indicated no significant survival difference. Patients with only ovarian metastases could achieve similar OS times to those of patients without metastases after primary and metastasis surgery.Conclusion: Surgical treatment is very important for CRC-OM patients. Primary and metastatic lesion resection can help achieve longer survival times.Keywords: colorectal cancer, metastases, ovary, prognosis

Qi Luo,1,* Huidong Tang,1,* Xinxin Xu,2 Juan Huang,2 Pei Wang,1 Guiying He,1 Xiaoxuan Song,1 Yumeng Huang,1 Shengdi Chen,1 Fuhua Yan,2 Yuyan Tan,1 Jianfang Ma1 1Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfang MaDepartment of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197, Second Ruijin Road, Shanghai, 200025, People’s Republic of ChinaTel/Fax +86 21-6445-4473Email mjf10924@rjh.com.cnIntroduction: Cerebral microbleeds (CMBs) are frequently found in the healthy elderly. However, data on the prevalence and risk factors of CMBs in the general population of China are lacking.Methods: A cross-sectional study focusing on the prevalence and risk factors of CMBs was conducted in stroke-free elderly from Shanghai Wuliqiao community. MRI was performed at 3Tesla and cardiovascular risk factors (eg, age, smoking history, and hypertension), cerebral small vessel disease (CSVD) markers (eg, white matter hyperintensities, lacunar infarction, and enlarged perivascular space) and genetic information (eg, APOE, CR1) were recorded. Poisson regression was used to analyze the risk factors of the presence and location of microbleeds.Results: A total of 199 participants (70.8± 7.2 years old; male 31.2%) were finally included in our analysis. The overall prevalence of CMBs was 12.6% (25/199) and increased with age from 7.5% (55– 64 years old) to 19.3% (over 75 years old). Of those with CMBs, most of them (16/25) located in the deep/mixed region and had 1– 2 CMBs (18/25). Poisson regression analysis showed that white matter hyperintensities (OR=1.22, 95% CI: 1.16– 1.29), APOE ϵ4+ carrier (OR=2.16, 95% CI: 1.18– 3.96) and CR1 non-F/F isoform (OR=7.78, 95% CI: 4.34– 13.96) were associated with CMBs. Further analysis found that in addition to the above three risk factors, hypertension (OR=2.98, 95% CI: 1.16– 7.64), lacunar infarction (OR=2.39, 95% CI: 1.19– 4.81) also increased the risk of deep/mixed CMBs.Conclusion: The prevalence of cerebral microbleeds is similar to other countries. Cardiovascular risk factors, CSVD markers, and genetic factors (APOE ϵ4, CR1 non-F/F isoform) were associated with CMBs, suggesting an interaction of multiple pathogenesis in Chinese stroke-free community population.Keywords: cerebral microbleeds, prevalence, risk factors, community-based study

Meizhu Yan1 ,* Manru Shen1 ,* Linfang Xu1 ,* Jiying Huang,1 Guijun He,1 Min An,1 Xiaocui Li,1 Zhenjun Gao,1 Xin Meng2 1Department of Gastroenterology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, People’s Republic of China; 2Department of Hospital Infection Management, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenjun GaoDepartment of Gastroenterology, Zhongshan Hospital Qingpu Branch, Fudan University, 1158 East Gongyuan Road, Shanghai 201700, People’s Republic of ChinaEmail prom_doc@163.comXin MengDepartment of Hospital Infection Management, Zhongshan Hospital Qingpu Branch, Fudan University, 1158 East Gongyuan Road, Shanghai 201700, People’s Republic of ChinaTel +86-21-69719190-5515Email qphospital_mx@126.comBackground: Pancreatic stellate cells (PSCs) are precursor cells of cancer-associated fibroblasts that promote tumor proliferation, invasion, and metastasis. The glucagon-like peptide-1 receptor agonist exendin-4 has been reported to exhibit anticancer effects against several tumor cells; however, the function and mechanism underlying the effects of exendin-4 on pancreatic cancer cells remain unclear.Methods: Gene expression levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay. Cell viability, migration and invasion were assessed using the cell counting kit-8 (CCK-8), wound healing, and transwell assays, respectively. A xenografted tumor model was established in mouse to evaluate the effects of exendin-4 in vivo.Results: Exendin-4 treatment led to the inactivation of PSCs and suppressed their proliferation and migration. Moreover, we also found that exendin-4 attenuated NF-κB-dependent SDF-1 secretion. Furthermore, pancreatic cancer cells incubated with conditioned medium obtained from exendin-4-treated PSCs showed a decreased ability to proliferate, migrate, and invade as compared to the control cells, which is similar to the effects induced by the CXCR4 inhibitor, AMD3100. Consistent with in vitro results, we also confirmed that exendin-4 indirectly targeted pancreatic cancer cells in vivo by attenuating the function of PSCs and suppressing the deposition of extracellular matrix.Conclusion: These results revealed that exendin-4-treated PSCs could suppress pancreatic cancer cell proliferation and invasion, offering a potential strategy for the treatment of pancreatic cancer.Keywords: pancreatic cancer, pancreatic stellate cells, exendin-4, SDF-1

Zhan Gu,1,* Yan Bi,2,* Fan Yuan,2,* Ruirui Wang,1 Dong Li,3 Jianying Wang,1 Xiaojuan Hu,1 Guang He,2 Lei Zhang,1 Bao-cheng Liu1 1Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 2Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 3Zhangjiang Community Health Service Center of Pudong New District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bao-cheng Liu Email baochliu@shutcm.edu.cnBackground: As fat and obesity play a vital role in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD), this study aims to investigate the association between the fat mass and obesity-associated gene (FTO) and MAFLD.Methods: Six SNPs (rs6499640, rs1421085, rs8050136, rs3751812, rs9939609 and rs9930506) within FTO were genotyped for 741 MAFLD patients (median age, 69.98; interquartile range, 66.55– 75.93) and 825 healthy people (median age, 69.94; interquartile range, 66.39– 75.64). Allele and genotype frequencies, pairwise linkage disequilibrium (LD) and haplotype analysis were calculated.Results: BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglyceride, alanine transaminase, glutamyl transpeptidase and the prevalence of diabetes were found to be higher in the MAFLD individuals comparing to the control ones (P < 0.05). For rs1421085, the C allele frequency was remarkably higher in MAFLD after Bonferroni correction (OR [95% CI] =1.353 [1.095– 1.671]; Pcorr =0.030), and a significantly different genotype result was observed in log-additive model (OR [95% CI] =1.369 [1.108– 1.691]; Pcorr =0.024). For rs8050136, significantly increased A allele frequency was observed in MAFLD (OR [95% CI] =1.371 [1.109– 1.695]; Pcorr =0.024), and A-allele carriers showed increased MAFLD risk (OR [95% CI] =1.393 [1.103– 1.759]; Pcorr =0.030). For rs3751812, the T allele frequency was remarkably higher in MAFLD (OR [95% CI] =1.369 [1.108– 1.691]; Pcorr =0.024), and T-allele carriers demonstrated high MAFLD risk (OR [95% CI] =1.392 [1.103– 1.756]; Pcorr =0.030). For rs9939609, A allele frequency was also remarkably high in MAFLD (OR [95% CI] =1.369 [1.108– 1.691]; Pcorr =0.024), and A-allele carriers were more susceptible to MAFLD (OR [95% CI] =[1.103– 1.756]; Pcorr =0.030). A strong LD was found among rs1421085, rs8050136, rs3751812 and rs9939609 (r2 > 0.8), and individuals with C-A-T-A haplotype had an elevated MAFLD risk (P =0.005).Conclusion: The case-control study indicated that C variant of rs1421085, A variant of rs8050136, T variant of rs3751812 and A variant of rs9939609 are associated with elevated MAFLD risk in the older Chinese Han population.Keywords: MAFLD, FTO, polymorphism, genetic association, susceptibility

Dan Song,1 Doris SF Yu,2 Polly WC Li,2 Guijuan He,1 Qiuhua Sun1 1School of Nursing, ZheJiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The Nethersole School of Nursing, The Chinese University of Hong Kong, HKSARCorrespondence: Qiuhua SunSchool of Nursing, ZheJiang Chinese Medical University, Room 807, 23 Building, Hangzhou, People’s Republic of ChinaTel/Fax +86-571- 86613674Email sunqiuhua@zcmu.edu.cnPurpose: This study aimed to assess the health-related quality of life (HRQoL) and identify the important correlates of HRQoL in older Chinese adults with mild cognitive impairment (MCI).Patients and methods: A cross-sectional study design was adopted. A total of 204 older adults with MCI were enrolled in this study. HRQoL was evaluated by the Quality of Life–Alzheimer’s disease. Hierarchical regression analysis was conducted to investigate the sociodemographic, disease-related, psychological, and behavioral factors associated with the HRQoL of individuals with MCI.Results: Hierarchical regression analysis indicated that old age (Beta = −0.131, p =0.024), low income (Beta = 0.128, p = 0.032), depressive symptoms (Beta = −0.564, p < 0.001), and poor sleep quality (Beta = −0.169, p =0.004) were significantly associated with the HRQoL of individuals with MCI.Conclusion: Caring for older Chinese adults with MCI should focus on sociodemographically disadvantaged groups with advanced age and low income. Rehabilitation programs that effectively alleviate depressive symptoms and improve sleep quality should be applied to older adults with MCI to enhance their HRQoL.Keywords: mild cognitive impairment, health-related quality of life, correlates

Yang Bao,1,* Yijun Zhu,1,* Guangbao He,1 Hongwei Ni,1 Chenxia Liu,1 Limin Ma,1 Lifeng Zhang,2 Dongping Shi1 1Department of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai 201800, People’s Republic of China; 2Department of Anesthesiology, Jiading Maternal and Child Health Hospital, Shanghai 201821, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongping ShiDepartment of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No.1 Chengbei Road, Jiading District, Shanghai, Shanghai 201800, People’s Republic of ChinaEmail dongpingshi@yandex.com Lifeng ZhangDepartment of Anesthesiology, Jiading Maternal and Child Health Hospital, No 1216 Gaotai Road, Jiading District, Shanghai, Shanghai 201821, People’s Republic of ChinaEmail zhanglifeng2019@126.comBackground: Dexmedetomidine (Dex) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which Dex exhibits anti-inflammation effects on LPS-stimulated BV2 microglia cells remains unclear. Thus, this study aimed to investigate the role of Dex in LPS-stimulated BV2 cells.Methods: The BV2 cells were stimulated by lipopolysaccharides (LPS). BV2 cells were infected with short-hairpin RNAs targeting NF-κB (NF-κB-shRNAs) and NF-κB overexpression lentivirus, respectively. In addition, miR-340 mimics or miR-340 inhibitor was transfected into BV2 cells, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of miR-340 and NF-κB in BV2 cells. CCK-8 was used to detect the viability of BV2 cells. In addition, Western blotting was used to detect the level of NF-κB in LPS-stimulated BV2 cells. The levels of TNF-α, IL-6, IL-1β, IL-2, IL-12, IL-10 and MCP-1 in LPS-stimulated BV2 cells were measured with ELISA.Results: The level of miR-340 was significantly upregulated in Dex-treated BV2 cells. Meanwhile, the level of NF-κB was significantly increased in BV2 cells following infection with lenti-NF-κB, which was markedly reversed by Dex. LPS markedly increased the expression of NF-κB and proinflammatory cytokines in BV2 cells, which were reversed in the presence of Dex. Moreover, miR-340 mimics enhanced the anti-inflammatory effects of Dex in LPS-stimulated BV2 cells via inhibiting NF-κB and proinflammatory cytokines. Furthermore, Dex obviously inhibited LPS-induced phagocytosis in BV2 cells.Conclusion: Taken together, our results suggested that Dex might exert anti-inflammatory effects in LPS-stimulated BV2 cells via upregulation of miR-340. Therefore, Dex might serve as a potential agent for the treatment of neuroinflammation.Keywords: NF-κB, dexmedetomidine, BV2 microglia cells, postoperative cognitive dysfunction

Qian Liu,1,* Qing Zhong,2,* Guoqiang Tang,1,* Guanghong He11Department of Anesthesiology, First People’s Hospital, Zigong, Sichuan, People’s Republic of China; 2Department of Anesthesiology, People’s Hospital, Jianyang, Sichuan, People’s Republic of China*These authors contributed equally to this workObjective: To examine the effectiveness and safety of ultrasound-guided glossopharyngeal nerve block via the styloid process for primary glossopharyngeal neuralgia.Methods: This retrospective study included all patients receiving glossopharyngeal nerve block via the styloid process under ultrasound guidance for primary glossopharyngeal neuralgia between January 2015 and May 2018 at our hospital. The primary outcome of the study was pain relief as assessed using the visual analog scale (VAS). Treatment was considered effective if the VAS score decreased by more than 2 points.Results: Twelve patients were included in the analysis. The baseline VAS scores ranged from 5 to 9. All patients received previous pharmacotherapy. Other previous treatments included pulsed mode radiofrequency (n=4), microvascular decompression (n=2), and glossopharyngeal nerve block (not under ultrasound guidance; n=2). The patients completed a total of 48 injections for glossopharyngeal nerve block. At discharge from the hospital, and at 6, 12, and 18 months thereafter, 10/12, 10/12, 7/12, and 4/12 patients achieved pain relief and the effective rate was 83.3% at discharge, 83.3% at 6 months, 58.3% at 1 year, and 33.3% at 18 months, respectively.Conclusion: Ultrasound-guided glossopharyngeal nerve block via the styloid process is a safe, radiation-free, repeatable, convenient, and effective treatment. It can provide a treatment option for patients with glossopharyngeal neuralgia.Keywords: ultrasound, glossopharyngeal neuralgia, styloid process, glossopharyngeal nerve block

Zhihua Guo, Jing Liu, Hui Zeng, Guoping He, Xiaohong Ren, Jia GuoXiangya School of Nursing, Central South University, Changsha 410013, Hunan, People’s Republic of ChinaAim: The aim of this study was to examine the feasibility and efficacy of nurse-led team management (NLTM) intervention at improving the self-management of patients with type 2 diabetes (T2D) at community settings in Changsha, Hunan, China.Background: China has become the country with the largest number of patients with diabetes, and that number is growing, causing increasing pressure on the health care system. At present, the main diabetes management model in China is teamwork guided by general practitioners. However, the number of general practitioners is insufficient, and their work is overloaded, which leads to poor outcomes of diabetes management. Therefore, it is important to explore alternative methods of diabetes management, such as NLTM.Patients and methods: In a randomized controlled trial, 171 T2D patients were randomized into the control or intervention arm. Participants in the control group received routine management from the community health service center, whereas the intervention group received 12 months NLTM intervention in addition to the standard care. The diabetes self-management scale, fasting blood sugar, and glycosylated hemoglobin A1c (HbA1c) were assessed at baseline and at 6 and 12 months after the start of the intervention.Results: Baseline data were comparable between arms. Repeated-measurement analysis showed that self-management of the intervention group improved compared with the control group after the intervention (P

Huifang Zhu,1–3 Guoyang He,1–3 Yongqiang Wang,1–3 Yuhan Hu,1–3 Zheying Zhang,1–3 Xinlai Qian,1–3 Yongxia Wang1–31Department of Pathology, Xinxiang Medical University, Xinxiang City 453000, Henan, People’s Republic of China; 2Department of Pathology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang City 453000, Henan, People’s Republic of China; 3Opening Laboratory for Key Discipline of Tumor Reversal Molecular Biology of Henan Higher Education, Xinxiang Medical University, Xinxiang City 453000, Henan, People’s Republic of ChinaBackground: The incidence and mortality of colorectal cancer (CRC) are rising worldwide. Long-noncoding RNAs (lncRNAs) are known to play key roles in the development of human cancers, including CRC. However, the function and underlying mechanism of long intergenic noncoding RNA 00707 (LINC00707) in the development of CRC are unknown.Materials and methods: The expression of LINC00707 and miR-206 in tissue samples or cell lines was measured by quantitative reverse transcription PCR (qRT-PCR). The protein expression of neurogenic locus notch homolog protein 3 (NOTCH3) and transmembrane 4 L6 family member 1 (TM4SF1) was assessed by Western blotting. Cell proliferation, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Luciferase reporter assay and biotin-coupled miRNA capture assay were used to explore the relationship between LINC00707 and miR-206 expression.Results: The expression of LINC00707 was significantly upregulated in CRC tissues as compared with the adjacent non-CRC tissues. LINC00707 expression was significantly correlated with tumor size, lymphatic metastasis, and distant metastasis, but not significantly correlated with age and gender. Knockdown of LINC00707 expression significantly inhibited LoVo and HCT116 cell proliferation, migration, and invasion. LINC00707 acted as a molecular sponge by competing for miR-206 and indirectly modulating the expression of its targets, NOTCH3 and TM4SF1.Conclusion: LINC00707 promotes CRC cell proliferation and metastasis by sponging miR-206, suggestive of its potential application for CRC treatment.Keywords: long intergenic noncoding RNA 00707, colorectal cancer, miR-206, NOTCH3, TM4SF1

Qianqian Sun,1,2 Fan Yuan,1,2 Decheng Ren,1,2 Gaini Ma,1,2 Fengping Yang,1,3 Xi Wu,1,3 Lin He,1,3 Guang He1,21Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, P.R. China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Institute of Mental Health, Shanghai Jiao Tong University, Shanghai 200030, P.R. China; 3Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. ChinaPurpose: Venlafaxine is one of the commonly prescribed antidepressants for major depressive disorder (MDD). Accumulated evidence revealed the involvement of glutamatergic system in the pathophysiology of MDD and antidepressant treatment. Methods: We recruited 193 MDD patients who have been taking venlafaxine for 6 weeks, and investigated whether single nucleotide polymorphisms (SNPs) in GSK-3β and BDNF were associated with treatment response. Nine SNPs were selected randomly depending on association studies. Efficacy of treatment was determined by 17-item Hamilton Rating Scale. Allele and genotype frequencies were compared between responders and nonresponders.Results: After adjusting the false discovery rate, no significant difference was observed between response and nonresponse groups in allele or genotype distributions after venlafaxine treatment for 6 weeks.Conclusion: Our results indicated that genetic variants in the GSK-3β and BDNF may not be associated with treatment response in MDD patients treated with venlafaxine.Keywords: association, GSK-3β, BDNF, major depressive disorder, venlafaxine

Bao Hai,1 Yunlong Ma,2 Xiaoyu Pan,1 Lei Yong,1 Chen Liang,1 Guanping He,1 Chenlong Yang,1 Bin Zhu,2 Xiaoguang Liu1 1Department of Orthopedics, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2The Center for Pain Medicine, Peking University Third Hospital, Beijing 100191, People’s Republic of China Background: Disc degeneration (DD) is one of the common diseases worldwide, which deeply influences normal life and leads to excruciating pain. However, an effective treatment for DD is still not identified.Method: The present study systemically examined the effect of melatonin on annulus fibrosus (AF) cells of patients with DD.Results: Melatonin had the effect of promoting proliferation, inducing autophagy, and suppressing apoptosis on AF cells of patients with DD. Moreover, melatonin contributed to the translation and transcription of autophagy-related protein ATG7 and inhibited the function of miR-106a-5p in AF cells. In addition, the results suggested that miR-106a-5p mediated the expression of ATG7 by directly binding to its 3'UTR in AF cells.Conclusion: This research not only gained a deep insight of melatonin mode of action, but also indicated its potential target signaling pathway in AF cells. Keywords: disc degeneration, melatonin, ATG7, miR-106a-5p

Yang Li,1,* Fei Wang,2,* Limin Wu,3 Min Zhu,4 Guiqing He,5 Xinchang Chen,1 Feng Sun,1 Qihui Liu,1 Xiaomeng Wang,2 Wenhong Zhang1 1Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China; 2Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, China; 3Hangzhou Center for Disease Control and Prevention, Hangzhou, Zhejiang 310021, China; 4Tuberculosis Treatment Center, Hangzhou Red Cross Hospital, Hangzhou 310003, China; 5Department of Infectious Diseases, Wenzhou Center Hospital, Wenzhou 325000, China *These authors contributed equally to this work Purpose: Cycloserine has been used in multidrug-resistant tuberculosis (MDR-TB) treatment since the 1950s. We evaluated the efficacy and safety of cycloserine and sought to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB).Materials and methods: A retrospective observational study was performed in Zhejiang Province, China. We enrolled 144 cycloserine-treated and 181 cycloserine-nontreated patients consecutively and determined the treatment outcome as the primary outcome. The proportion of patients with sputum culture conversion and the frequency of adverse drug reactions were also assessed.Results: One-hundred (69.4%) out of 144 patients in the cycloserine group successfully completed treatment. The HR of any unfavorable treatment outcome after the introduction of cycloserine was 0.58 (95% CI: 0.38–0.86, P=0.008). Subgroup analysis showed that cycloserine could benefit simple MDR-TB cases reducing the risk of unfavorable treatment outcomes (HR: 0.43, 95% CI: 0.24–0.76, P=0.004), but not pre-XDR-TB (HR: 0.65, 95% CI: 0.30–1.38, P=0.263) or XDR-TB (HR: 0.73, 95% CI: 0.22–2.37, P=0.589). The culture conversion rate at the intensive phase was similar whether cycloserine was administered or not (P=0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side effects attributed to cycloserine.Conclusion: Cycloserine is an attractive agent for the treatment of MDR-TB, and its safety profile warrants its use in most MDR-TB cases. Cycloserine significantly improved the chance of a favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. Thus, more aggressive regimens might be required for pre-XDR-TB or XDR-TB patients. Keywords: cycloserine, multidrug-resistant tuberculosis, efficacy, safety, extensively drug-resistant tuberculosis, treatment outcome

Yihao Mao,1,* Qingyang Feng,1,2,* Peng Zheng,1,* Liangliang Yang,1,* Tianyu Liu,1 Yuqiu Xu,1 Dexiang Zhu,1,2 Wenju Chang,1,2 Meiling Ji,1,2 Li Ren,1,2 Ye Wei,1,2 Guodong He,1,2 Jianmin Xu1,2 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, China; 2Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai 200030, China *These authors contributed equally to this work Purpose: Tumor purity is defined as the proportion of cancer cells in the tumor tissue. The impact of tumor purity on colon cancer (CC) prognosis, genetic profile, and microenvironment has not been thoroughly accessed.Materials and methods: Clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA, were retrospectively collected (n=1,248). Tumor purity of each sample was inferred by a computational method based on transcriptomic data. Survival-related analyses were performed on microarray dataset containing GSE17536/17537 and GSE39582 (n=794), whereas TCGA dataset was utilized for subsequent genomic analysis (n=454).Results: Right-sided CC patients showed a significantly lower tumor purity. Low purity CC conferred worse survival, and tumor purity was identified as an independent prognostic factor. Moreover, high tumor purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumor purity, with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumor purity. Furthermore, immune-related pathways and immunotherapy-associated markers (programmed cell death protein 1 [PD-1], programmed death-ligand 1 [PD-L1], cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Lymphocyte-activation gene 3 [LAG-3] and T-cell immunoglobulin and mucin-domain containing-3 [TIM-3]) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumor purity.Conclusion: Tumor purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing. Keywords: adjuvant chemotherapy, colon cancer, prognosis, tumor microenvironment, tumor purity

Peng Zheng,* Li Ren,* Qingyang Feng,* Dexiang Zhu,* Wenju Chang, Guodong He, Meiling Ji, Mi Jian, Qi Lin, Tuo Yi, Ye Wei, Jianmin Xu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate differences in clinical characteristics and mutational patterns between synchronous and metachronous colorectal liver metastases (CLMs). Patients and methods: From June 2008 to December 2014, patients with RAS wild-type CLMs treated at Zhongshan Hospital, Fudan University were included. DNA extracted from formalin-fixed paraffin-embedded tissue of primary tumors was sequenced with next-generation sequencing for single-nucleotide polymorphism of 96 genes according to custom panel. Mutations were compared between synchronous and metachronous liver metastases and correlated with clinical characteristics. Results: A total of 161 patients were included: 93 patients with synchronous CLM and 68 patients with metachronous CLM. Patients with metachronous CLM were obviously elder. For pathology of primary tumors, synchronous CLMs were larger in size, poorly differentiated, and more frequently local advanced and lymph node positive. For evaluation of liver metastases, synchronous CLM had more and larger metastatic lesions. The median number of mutations in synchronous CLMs was significantly higher than in metachronous group (22 vs. 18, p

Yanhua Chen,1,* Xu Zhang,2,* Bingdong Zhang,1 Guodong He,2 Lifang Zhou,2 Yubo Xie2 1Department of Anesthesiology, Cardiovascular Institute, 2Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China *These authors contributed equally to this work Abstract: Cardiopulmonary bypass (CPB) constitutes one of the primary methodologies pertaining to cardiac surgery. However, this form of surgery can cause damage to the body. Many studies have reported that dexmedetomidine confers cerebral protection. In this study, we aimed to investigate the effect and mechanism of dexmedetomidine on neuronal apoptosis caused by CPB. Here, rats were treated with different doses of dexmedetomidine by intravenous infusion 2 hours after CPB. We observed that dexmedetomidine treatment to rats reduces the S100ß, NSE levels in plasma, and neuronal apoptosis following CPB in a dose-dependent manner. Furthermore, we observed that the beneficial effect of dexmedetomidine treatment following CPB was associated with a reduction in IL6, an inflammatory cytokine in plasma and cortex. Our results suggest that dexmedetomidine provides neuroprotective effects by inhibiting inflammation and reducing neuronal apoptosis. There was a correlation between the protective effect on the brain and the dose of dexmedetomidine. In addition, dexmedetomidine administration inhibits phosphorylation of JAK2 and STAT3 proteins in the hippocampus of rats 2 hours after CPB. Therefore, we speculate that the JAK2–STAT3 pathway plays an important role in the neuroprotective effects of dexmedetomidine following brain injury induced by CPB. Keywords: apoptosis, cardiopulmonary bypass, dexmedetomidine, neuroprotective effect, JAK2, STAT3

Wentao Tang,* Meiling Ji,* Guodong He,* Liangliang Yang, Zhengchuan Niu, Mi Jian, Ye Wei, Li Ren, Jianmin Xu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression. Intriguingly, ectopic expression of miR-7 in CRC cells consistently inhibited proliferation and invasion, and the miR-7 inhibitor was able to rescue the function of CDR1as knockdown. Mechanistic studies demonstrated that CDR1as silencing suppressed EGFR and IGF-1R expression, which could be partially blocked by the miR-7 inhibitor. Finally, positive correlations between CDR1as expression and EGFR and IGF-1R expression were observed in CRC samples. Thus, given the importance of CDR1as in blocking miR-7 and positively regulating EGFR and IGF-1R, dysregulated CDR1as expression may play an important role in CRC progression. Keywords: CDR1as, colorectal cancer, microRNA-7, proliferation

Matthew R Peterson, Samantha E Haller, Jun Ren, Sreejayan Nair, Guanglong He School of Pharmacy, University of Wyoming, College of Health Sciences, Laramie, WY, USA Abstract: Systemic inflammation and localized macrophage infiltration have been implicated in cardiovascular pathologies, including coronary artery disease, carotid atherosclerosis, heart failure, obesity-associated heart dysfunction, and cardiac fibrosis. Inflammation induces macrophage infiltration and activation and release of cytokines and chemokines, causing tissue dysfunction by instigating a positive feedback loop that further propagates inflammation. Cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) is a protein expressed primarily by dendritic cells, neutrophils, and macrophages, in which it mediates cytokine secretion. The purpose of this review is to highlight the role of CARD9 as a potential target in inflammation-related cardiovascular pathologies. Keywords: inflammation, heart failure, pressure-overload, hypertension

Zai-Quan Dong,1,* Xi-Rong Li,2,* Lin He,3,4 Guang He,3,4 Tao Yu,3,4 Xue-Li Sun1 1Psychological Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 2Mental Health Center, First Affiliated Hospital, Chongqing Medical University, Chongqing, 3Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 4Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs. Methods: Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system. Results: There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing. Conclusion: Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission. Keywords: genetic association, major depressive disorder, SSRIs

Yongxin Wu,1,2 Guichao Li,1,2 Dong He,3 Fengping Yang,3 Guang He,3 Lin He,3 Hui Zhang,1,2 Yun Deng,1,2 Ming Fan,1,2 Lijun Shen,1,2 Daizhan Zhou,3 Zhen Zhang1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People’s Republic of China Purpose: Telomerase activity is associated with cellular immortalization and is present in most human tumors but absent in normal tissues. The activity of telomerase reverse transcriptase (TERT), a catalytic telomerase subunit, correlates with telomerase activity in tumors. The objective of this study was to investigate TERT promoter methylation and its prognostic impact in gastric cancer (GC).Patients and methods: The analysis of TERT promoter methylation was performed in tumors and corresponding normal tissues of 116 patients with GC using a highly sensitive Sequenom Epityper assay. The expression of TERT in GC tissues was measured by quantitative real-time polymerase chain reaction.Results: The levels of TERT promoter methylation in GC samples were significantly higher than in normal adjacent tissues (P=0.002). Hypermethylation of TERT promoter was associated with high T-stage (P=0.024), late N-stage (P=0.006), and lymphovascular/neural invasion (P=0.035), without correlation with age, sex, or histological grade. Simple linear regression analysis showed that TERT mRNA correlated positively with TERT methylation (R2=0.562, P=0.001). Also, higher TERT mRNA expression was related to hypermethylation of TERT promoter in GC samples (P=0.005). Univariate analysis demonstrated that N-stage (P=0.002) and TERT promoter methylation (P=0.004) were predictive of overall survival. Furthermore, multivariate analysis confirmed that N-stage (P=0.013) and TERT promoter methylation (P=0.031) were independent prognostic indicators for overall survival.Conclusion: Our data suggested that hypermethylation of TERT promoter may contribute to gastric wall invasion, lymph node metastasis, lymphovascular/neural invasion, and poor prognosis in GC. GC patients with hypermethylation of TERT promoter could be eligible for close follow-up. Keywords: telomerase reverse transcriptase, gastric cancer, methylation, prognosis, lymph node metastasis

Can Chen,1,2,* Ting Wang,1,3,* Fengbo Wu,1,* Wei Huang,4 Gu He,1 Liang Ouyang,1 Mingli Xiang,1 Cheng Peng,4 Qinglin Jiang1,2 1State Key Laboratory of Biotherapy and Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 2College of Pharmacy and the First Affiliated Hospital, Chengdu Medical College, Chengdu, 3Department of Cardiology, Genenal Hospital of Chengdu Military Command, Chengdu, 4State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workAbstract: Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2) to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS) production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important information for further research on novel PKM2 activators as antitumor agents.Keywords: pharmacophore, molecular docking, pyruvate kinase, virtual screening

The safety of mooring systems on offshore platforms seems more and more significant with the utilization of offshore space and resources, so the reduction of wave drift force is the key issue in this wave-body interaction problem. The wave drift force acting on the inner floating body surrounded by multiple small floating bodies can be reduced obviously with the occurrence of a phenomenon, which is called the Cloaking phenomenon. The Cloaking phenomenon refers to the reduction or complete elimination in amplitude of the scattered waves. In this paper, a real-coded genetic algorithm was used to optimize the parameters of outer floating bodies to minimize the scattered wave energy, and then the wave drift force acting on the inner body can be reduced. Furthermore, associated CFD simulations and experimental research were conducted with the above optimized parameters to investigate and verify the Cloaking phenomenon more systemically. It is shown that the wave drift force acting on the inner floating body in the Cloaking configuration can be reduced obviously both in numerical and experimental research, and the reduction of the wave drift force is closely related to the change of wave field around the structure.

Electricity is an important output of the global energy system. Large amounts of water can be consumed in the process of producing electricity. This article focuses on how that water is virtually transferred from power-generating regions to electricity-consuming areas. We propose two metrics, i.e., water substitution ratio and virtual water transfer loss, to assess the efficiency of water use for power generation and virtual transmission of water through the power transmission system, respectively. These metrics are used to estimate the effects of the West–East Electricity Transmission project in China on the water resources used in power-generating regions. Results show that the electricity delivered by the project increased from 228 TWh in 2008 to 683 TWh in 2017. With the construction of wind and solar energy projects, the growth rate of virtual water was slightly slower than that of the electricity transmitted. In 2017, 2.4 km3 of virtual water was transmitted eastward. The corresponding virtual water transfer loss throughout the transmission system was approximately 100 million m3. We estimate that the virtual water footprint of the project will exceed 4.4 km3 by 2030, which may affect the sustainability of water resources and the ecological environment in western regions of China.

Organic aerosols generated from the smoldering combustion of wood critically impact air quality and health for billions of people worldwide; yet, the links between the chemical components and the optical or biological effects of woodsmoke aerosol (WSA) are still poorly understood. In this work, an untargeted analysis of the molecular composition of smoldering WSA, generated in a controlled environment from nine types of heartwood fuels (African mahogany, birch, cherry, maple, pine, poplar, red oak, redwood, and walnut), identified several hundred compounds using gas chromatography mass spectrometry (GCMS) and nano-electrospray high-resolution mass spectrometry (HRMS) with tandem multistage mass spectrometry (MSn). The effects of WSA on cell toxicity as well as gene expression dependent on the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) were characterized with cellular assays, and the visible mass absorption coefficients (MACvis) of WSA were measured with ultraviolet-visible spectroscopy. The WSAs studied in this work have significant levels of biological and toxicological activity, with exposure levels in both an outdoor and indoor environment similar to or greater than those of other toxicants. A correlation between the HRMS molecular composition and aerosol properties found that phenolic compounds from the oxidative decomposition of lignin are the main drivers of aerosol effects, while the cellulose decomposition products play a secondary role; e.g., levoglucosan is anticorrelated with multiple effects. Polycyclic aromatic hydrocarbons (PAHs) are not expected to form at the combustion temperature in this work, nor were they observed above the detection limit; thus, biological and optical properties of the smoldering WSA are not attributed to PAHs. Syringyl compounds tend to correlate with cell toxicity, while the more conjugated molecules (including several compounds assigned to dimers) have higher AhR activity and MACvis. The negative correlation between cell toxicity and AhR activity suggests that the toxicity of smoldering WSA to cells is not mediated by the AhR. Both mass-normalized biological outcomes have a statistically significant dependence on the degree of combustion of the wood. In addition, our observations support the fact that the visible light absorption of WSA is at least partially due to charge transfer effects in aerosols, as previously suggested. Finally, MACvis has no correlation with toxicity or receptor signaling, suggesting that key chromophores in this work are not biologically active on the endpoints tested.

The finite volume method (FVM) is used to numerically investigate the sloshing behaviors of dual liquid tanks with gas inflow in this study. The sloshing process of a single liquid tank is simulated to verify the feasibility of the numerical method. Three different inlet boundary conditions are then discussed in order to obtain a reasonable gas flow rate. The sloshing process of a dual liquid tank with the gas inflow is simulated, and the effects of three different factors on the sloshing behaviors are investigated. The results indicate that the overload, flow rate, and filling ratio can affect the peak value of the impact force acting on the tank wall. The impact force is positively proportional to the overload (1G, 3G, or 5G). An increase in flow rate (50 g/s, 1000 g/s, or 5000 g/s) or a decrease in filling ratio (99.52%, 75.64%, or 63.69%) can increase the size and number of bubbles, leading to intensified sloshing behavior and increased impact force. [ABSTRACT FROM AUTHOR]

Electrospray (ES) has attracted significant interest due to its advantages in generating uniform droplets and enabling controlled deposition. However, the complex interactions and droplet motion mechanisms between fluids and electric fields are still not well understood. Herein, this study presents a three-dimensional numerical model based on the volume of fluid and Lagrangian approaches to simulate the ES process in the pulsed jet mode. The model accurately captures the morphology and the atomization characteristics in the pulsed jet mode of ES. The effects of voltage and Reynolds number on the length of the non-atomized zone (including quasi-static Taylor cone, transition zone, and jet), diameter of the jet breakup, and atomization characteristics are discussed. Also, the mechanism of atomized droplets is revealed by analyzing the magnitudes of different types of forces imposing on the droplets in the electric field. The results indicate that higher Reynolds numbers lead to increased length of non-atomized zone and diameter of jet breakup, while the elevated voltages enhance atomization. Electric and Coulomb forces are, respectively, the dominant forces of forming the jet and expanding the atomization angle. Coulomb force increases the atomization angle, and electric field force increases the velocity of atomized droplets. Gravity and drag-force effects are relatively negligible throughout the atomization process. These findings contribute to a better understanding of the electrospray mechanisms and provide insights for optimizing electrospray applications. [ABSTRACT FROM AUTHOR]