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Yi Yang,1 Jingxian Wang,1 Qing Su,1 Jinhuan Yang,2,3 Zhiyuan Bo,2,3 Chongming Zheng,2,3 Yitong Xie,2,3 Kaiwen Chen,2,3 Juejin Wang,1 Gang Chen,2,3 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Nanliu Road, Chashan Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-86699-358, Email wang.yi@wmu.edu.cn Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-55579-555, Email chen.gang@wmu.edu.cnBackground: Primary liver cancer (PLC) is a fatal malignancy, sleep quality and gut microbiota were shown to be associated with PLC. However, the mechanism of how sleep quality affects PLC is unclear. This study aims to investigate the mediation/moderation effects of gut microbiota on sleep quality and the occurrence of PLC.Methods: The causality of sleep quality and the occurrence of PLC was detected through the Mendelian randomization (MR) analysis based on the data including 305,359 individuals (Finland Database) and 456,348 participants (UK Biobank). The primary method used for MR analysis was inverse-variance weighted analysis. Gut microbiota’ mediation/moderation effects were uncovered in the case–control study including 254 patients with PLC and 193 people with benign liver diseases through the mediation/moderation effect analyses. People’s sleep quality was evaluated through the Pittsburgh sleep quality index (PSQI).Results: Poor sleep quality could lead to PLC through the MR analysis (P = 0.026). The case–control study uncovered that Actinobacteria had mediation effects on the relationship between PSQI score, self-sleep quality, and the occurrence of PLC (P = 0.048, P = 0.046). Actinobacteria and Bifidobacterium could inhibit the development of PLC caused by short night sleep duration (P = 0.021, P = 0.022). Erysipelotrichales could weaken the influence of daytime dysfunction on PLC (P = 0.033). Roseburia modulated the contribution of nocturnal insomnia and poor sleep quality to PLC (P = 0.009, P = 0.017).Conclusion: Poor sleep quality was associated with PLC. Gut microbiota’ mediation/moderation effects on poor sleep quality and the occurrence of PLC prompted an insightful idea for the prevention of PLC.Keywords: primary liver cancer, sleep quality, gut microbiota, Mendelian randomization, mediation/moderation effect

Plasma-based acceleration has emerged as a promising candidate as an accelerator technology for a future linear collider or a next-generation light source. We consider the plasma wakefield accelerator (PWFA) concept where a plasma wave wake is excited by a particle beam and a trailing beam surfs on the wake. For a linear collider, the energy transfer efficiency from the drive beam to the wake and from the wake to the trailing beam must be large, while the emittance and energy spread of the trailing bunch must be preserved. One way to simultaneously achieve this when accelerating electrons is to use longitudinally shaped bunches and nonlinear wakes. In the linear regime, there is an analytical formalism to obtain the optimal shapes. In the nonlinear regime, however, the optimal shape of the driver to maximize the energy transfer efficiency cannot be precisely obtained because currently no theory describes the wake structure and excitation process for all degrees of nonlinearity. In addition, the ion channel radius is not well defined at the front of the wake where the plasma electrons are not fully blown out by the drive beam. We present results using a novel optimization method to effectively determine a current profile for the drive and trailing beam in PWFA that provides low energy spread, low emittance, and high acceleration efficiency. We parameterize the longitudinal beam current profile as a piecewise-linear function and define optimization objectives. For the trailing beam, the algorithm converges quickly to a nearly inverse trapezoidal trailing beam current profile similar to that predicted by the ultrarelativistic limit of the nonlinear wakefield theory. For the drive beam, the beam profile found by the optimization in the nonlinear regime that maximizes the transformer ratio also resembles that predicted by linear theory. The current profiles found from the optimization method provide higher transformer ratios compared with the linear ramp predicted by the relativistic limit of the nonlinear theory.

Junhui He,1,* Jiaxiu Xie,1,* Guili Zhou,2,* Chunlian Jia,2 Dongbo Han,2 Dongmei Li,1 Jie Wei,1 Yi Li,1 Renshan Huang,1 Chunlian Li,1 Bo Wang,3 Chao Wei,3 Qibiao Su,4 Kedao Lai,1 Guining Wei1 1Department of Pharmacology, Key Laboratory of Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Guangxi Shuangyi Pharmaceutical Co., Ltd, Nanning, Guangxi, 530021, People’s Republic of China; 4College of Health Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guining Wei, Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China, Email weiguining2013@163.com Qibiao Su, College of Health Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Tel +8618376664440, Email suqibiao@163.comPurpose: Neuroinflammation is a significant etiological factor in the development of depression. Traditional Chinese medicine (TCM) has demonstrated notable efficacy in the treatment of inflammation. Our previous study surfaces that the active fraction of Polyrhachis vicina Roger (AFPR) has antidepressant and anti-neuroinflammatory effects, but the specific mechanisms remain to be elucidated. The objective of this study was to examine the impact of AFPR on inflammation in depression via the FTO/miR-221-3p/SOCS1 axis.Methods: Chronic unpredictable stress (CUMS)-induced rats and LPS-induced BV2 cells were employed to simulate depression models in vivo and in vitro. The levels of inflammatory factors were detected using the ELISA assay. The expression of genes and proteins was detected using qRT-PCR and Western blot. Gene interactions were detected using the dual luciferase reporter gene. Protein-RNA interactions were investigated using RNA methylation immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP). Neuroinflammation in the brain was examined through H&E staining, while neuronal apoptosis was assessed using TUNEL staining.Results: The results showed that AFPR ameliorated depression induced inflammation by increasing SOCS1 expression. However, SOCS1 was identified as a target of miR-221-3p. Overexpression of miR-221-3p decreased the expression of SOCS1 and increased the levels of NF-κB, IL-7, and IL-6. In addition, we found that miR-221-3p was regulated by FTO-mediated m6A modification through MeRIP and RIP experiments. Interference with miR-221-3p and overexpression of FTO resulted in increased SOCS1 gene expression and decreased levels of NF-κB, IL-7, and IL-6, which were reversed by AFPR.Conclusion: AFPR inhibits the maturation of pri-miR-221-3p through FTO-mediated m6A modification, reduces the production of miR-221-3p, increases the expression of SOCS1, and reduces the level of inflammation, thereby improving depressive symptoms. Keywords: depression, FTO, SOCS1, inflammation, Polyrhachis vicina Roger

Qing Su,1 Chen Jin,2 Yi Yang,1 Jingxian Wang,1 Juejin Wang,1 Hao Zeng,1 Yaqing Chen,1 Junxi Zhou,1 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Chashan High Education Zone, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86-577-8669-9358, Email wang.yi@wmu.edu.cnPurpose: Observational studies have reported that autoimmune diseases are closely related to sarcopenia, but the causalities of autoimmune diseases with sarcopenia have not been established. We conducted this Mendelian randomization (MR) study to reveal the causal associations of overall autoimmune disease and five common autoimmune diseases with sarcopenia-related traits.Methods: The publicly available summary-level data of autoimmune diseases and three sarcopenia-related traits were used for analysis. The causal effects of autoimmune diseases on sarcopenia-related traits were first identified in discovery samples using the inverse-variance-weighted method as the primary method, and the robustness of results was examined by additional sensitivity analyses. Replication MR analyses were then conducted using replication samples of five autoimmune diseases. Finally, the possibility of reverse causation was assessed by reverse MR analyses.Results: In both the discovery and replication samples, we identified potential causal effects of rheumatoid arthritis (RA) on appendicular lean mass (ALM) and low grip strength (OR = 0.979, 95% CI: 0.964– 0.995 for ALM; OR = 1.042, 95% CI: 1.013– 1.072 for low grip strength), but not on walking pace. We also found that inflammatory bowel disease (IBD) and type 1 diabetes (T1D) were only causally negatively associated with ALM in the discovery stage (OR = 0.986, 95% CI: 0.974– 0.999 for IBD; OR = 0.987, 95% CI: 0.975– 0.999 for T1D), whereas systemic lupus erythematosus, multiple sclerosis, and overall autoimmune disease were not associated with any of the three sarcopenia-related traits. Additionally, reverse MR analysis only found an association between walking pace and overall autoimmune disease, but this association did not remain in the weighted-median method.Conclusion: This study demonstrates that RA is causally associated with low grip strength and reduced ALM, and that IBD and T1D may be causally negatively related to ALM.Keywords: Mendelian randomization, autoimmune disease, sarcopenia, rheumatoid arthritis, grip strength, appendicular lean mass

Xialu Zhang,1,* Chenguang Zhang,1,2,* Qingfang Zhao,1 Shanshan Wang,3 Liyong Wang,4 Yang Si,1 Qiang Su,5 Shan Cheng,1 Wei Ding1 1School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory for Cancer Invasion and Metastasis Mechanism Research, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Institute of Hepatology, Beijing You’An Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Core Facilities for Molecular Biology, Capital Medical University, Beijing, People’s Republic of China; 5Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chenguang Zhang; Wei Ding, Email chzhang@ccmu.edu.cn; weiding@ccmu.edu.cnObjective: To investigate the involvement and transcriptional targets of zinc finger protein 281 (ZNF281) in the progression of hepatocellular carcinoma (HCC).Methods: The expression of ZNF281 in HCC was detected in tissue microarray and cell lines. The role of ZNF281 in aggressiveness of HCC was examined using wound healing, matrigel transwell, pulmonary metastasis model and assays for expression of EMT markers. RNA-seq was used to find potential target gene of ZNF281. Chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (Co-IP) were employed to uncover the mechanism of the transcriptional regulation of ZNF281 on the target gene.Results: ZNF281 was increased in tumor tissues and positively correlated with vascular invasion in HCC. Knockdown of ZNF281 suppressed the migration and invasion with significant alteration of EMT marker expression in HLE and Huh7 HCC cell lines. RNA-seq screening showed that the tumor suppressor gene Annexin A10 (ANXA10) was a most up-regulated gene in response to ZNF281 depletion and responsible for the attenuation of aggressiveness. Mechanistically, ZNF281 interacted with the ANXA10 promoter region harboring ZNF281 recognition sites, and recruited components of nucleosome remodeling and deacetylation (NuRD) complex. By knocking down such components like HDAC1 or MTA1, ANXA10 was released from transcriptional repression by ZNF281/NuRD, and in turn reversed the EMT, invasion and metastasis driven by ZNF281.Conclusion: ZNF281 drives invasion and metastasis of HCC partially through transcriptional repression of tumor suppressor gene ANXA10 by recruiting NuRD complex.Graphical Abstract: Keywords: zinc finger protein 281, Annexin A10, nucleosome remodeling and deacetylation complex, hepatocellular carcinoma, invasion and metastasis, transcription

Abstract Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic stress resulting in proteinuria and glomerulosclerosis, implying that GV increase could serve as a therapeutic target to prevent progression. In this report we examine how Angiotensin Converting Enzyme inhibition (ACEi), started before uninephrectomy can reduce compensatory GV increase in wild-type Fischer344 rats. An unbiased computer-assisted method was used for morphometric analysis. Urine Insulin-like growth factor-1 (IGF-1), the major diver of body and kidney growth, was used as a readout. In long-term (40-week) studies of uni-nephrectomized versus sham-nephrectomized rats a 2.2-fold increase in GV was associated with reduced podocyte density, increased proteinuria and glomerulosclerosis. Compensatory GV increase was largely prevented by ACEi started a week before but not after uni-nephrectomy with no measurable impact on long-term eGFR. Similarly, in short-term (14-day) studies, ACEi started a week before uni-nephrectomy reduced both GV increase and urine IGF-1 excretion. Thus, timing of ACEi in relation to uni-nephrectomy had significant impact on post-nephrectomy “compensatory” glomerular growth and outcomes that could potentially be used to improve kidney transplantation and live kidney donation outcomes.

Yichao Liang, Xin Wu, Qi Su, Yujie Liu, Hong Xiao Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xin WuDepartment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaEmail wux5@sj-hospital.orgPurpose: The inflammatory response plays a crucial role in the occurrence and development of colon cancer. In this study, we aimed to explore a novel prognostic model for patients with colon cancer (COAD) based on inflammatory response-related genes.Methods: Inflammatory response-related genes were obtained from Molecular Signatures database. Univariate and multivariate Cox regression analyses were used for model construction based on TCGA dataset. GSE39582 dataset and qRT-PCR dataset were used for validation. Gene set variation analysis and gene set enrichment analysis were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT. Immunohistochemistry analysis and experiments were used to explore the function of genes in model.Results: In this study, a novel prognostic signature was identified using stepwise Cox proportional hazards regression analysis based on TCGA dataset. The results were subsequently validated in 562 patients from GSE39582 and a qRT-PCR data set from 70 tumor samples. Functional analysis indicated that the tumor microenvironment and immune cell infiltrate were different between high- and low-risk groups. Additionally, IHC results showed that the protein levels of prognostic genes were significantly different between COAD tissues and adjacent non-tumorous tissues, and prognostic genes could regulate the malignant phenotype of COAD cells.Conclusion: Overall, the inflammation-related gene signature can be used for prognostic prediction in patients with COAD.Keywords: colon cancer, prognosis, inflammation

Heng Yin,1,&ast; Gaoxiang Wang,2,&ast; Jianwei Wang,1 Yong Ma,2 Mao Wu,1 Songming Qiu,2 Qiuju Su3 1Department of Orthopedics Wuxi Traditional Chinese Medicine Hospital affiliated to Nanjing University of Chinese Medicine, Wuxi, 214071, People’s Republic of China; 2Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 3Department of Rehabilitation & Acupuncture, Wuxi People’s Hospital Affiliated Nanjing Medical University, Wuxi, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuju SuDepartment of Rehabilitation & Acupuncture, Wuxi People’s Hospital Affiliated Nanjing Medical University, No. 299 of Qingyang Road, Wuxi, 214023, People’s Republic of ChinaTel +86 15 9618 17218Fax +86 510-8270 0775Email suqiuju_336@163.comObjective: To analyze the prevalence and risk factors of constipation after thoracolumbar vertebral compression fractures (TVCFs).Methods: This retrospective study reviews the records of patients hospitalized between January 1, 2017 and December 31, 2018 with TVCFs. A total of 117 patient’s records are included (n = 117). Univariate and multivariate analysis using the logistic regression method are carried out to identify the prevalence and potential risk factors for constipation after TVCF, including gender, age, number of fractured vertebrae, major segment of vertebral fracture, degree of compression, use of painkillers, diabetes, and the intervention of Zengyechengqi decoction.Results: Among the 117 patients with TVCFs that were included in this study, 83 (70.9%) patients developed constipation. Univariate analysis showed that the factors of degree of vertebral compression and the preintervention of Zengyechengqi decoction had statistically significant effects on the incidence of constipation after TVCF (P < 0.05), indicating that they might contribute to the incidence of constipation after TVCF. Multivariate logistic regression analysis showed that degree of vertebral compression was a risk factor (P < 0.05), while preintervention of Zengyechengqi decoction was a protective factor (P < 0.05), for constipation after TVCF.Conclusion: Patients with vertebral fractures featuring a higher degree of compression may have a higher risk of constipation. Preintervention of Zengyechengqi decoction can reduce the incidence of constipation after TVCF.Keywords: constipation, degree of vertebral compression, risk factors, thoracolumbar vertebral compression fractures, Zengyechengqi decoction

Wu J, Wang J, Su Q, et al. Onco Targets Ther. 2018;11:2685–2698. The authors have advised the incorrect images were inadvertently selected for Figure 2A, on page 2690, due to the dark background and relatively low resolution of photos captured for the wound healing assay. For Figure 3A on page 2691, all Transwell images were captured and saved in one folder labelled by experimental date. Two overlapping images from different visual fields were captured from one well but labelled incorrectly and inadvertently selected for Figure 3A. The correct Figures 2 and 3 are shown in Download Article. The authors apologize for these errors and advise they do not affect the results of the paper. Read the original article

Jie Song,1 Yuan Gao,2 Pengbin Yin,3 Yi Li,1 Yang Li,2 Jie Zhang,4 Qingqing Su,1 Xiaojie Fu,2 Hongying Pi5 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Fouth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Medical Service Training Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Hongying PiMedical Service Training Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of ChinaTel/Fax +86 010-66939159Email pihongying@301hospital.com.cnPurpose: Build machine learning models for predicting pressure ulcer nursing adverse event, and find an optimal model that predicts the occurrence of pressure ulcer accurately.Patients and Methods: Retrospectively enrolled 5814 patients, of which 1673 suffer from pressure ulcer events. Support vector machine (SVM), decision tree (DT), random forest (RF) and artificial neural network (ANN) models were used to construct the pressure ulcer prediction models, respectively. A total of 19 variables are included, and the importance of screening variables is evaluated. Meanwhile, the performance of the prediction models is evaluated and compared.Results: The experimental results show that the four pressure ulcer prediction models all achieve good performance. Also, the AUC values of the four models are all greater than 0.95. Besides, the comparison of the four models indicates that RF model achieves a higher accuracy for the prediction of pressure ulcer.Conclusion: This research verifies the feasibility of developing a management system for predicting nursing adverse event based on big data technology and machine learning technology. The random forest and decision tree model are more suitable for constructing a pressure ulcer prediction model. This study provides a reference for future pressure ulcer risk warning based on big data.Keywords: pressure ulcer, adverse event, machine learning, risk management

Shu Ye,1,* Hui Ran,1,* Hongmei Zhang,1 Hui Wu,2 Wen Li,1 Shichun Du,1 Qing Su1 1Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People’s Republic of China; 2Department of Endocrinology, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shichun DuDepartment of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Kong Jiang Road 1665#, Shanghai, 200092, People’s Republic of ChinaEmail dushichun@xinhuamed.com.cnPurpose: Ketosis-prone type 2 diabetes (KPT2D) is increasingly recognized in young adults. However, the role of blood lipids in KPT2D, especially serum triglycerides (TGs), is not yet clearly understood.Patients and Methods: We retrospectively evaluated 409 young patients diagnosed with KPT2D or classical type 2 diabetes (T2D) attending an academic tertiary hospital. Clinical characteristics and laboratory findings were compared between KPT2D and T2D patients. ANOVA or a non-parametric test analyses were used to evaluate differences in clinical characteristics and laboratory findings. Multivariate regression analyses and stratified analyses were used to further investigate differences in serum TGs levels between KPT2D and T2D individuals.Results: KPT2D is a subtype of T2D with traits of overweight or obesity. However, hyperglycemia and impaired β-cell functions were more severe in KPT2D patients. Serum TGs levels were significantly higher (P = 0.0003) in KPT2D individuals. Furthermore, the proportion of very high serum TGs levels was 6-fold higher (P < 0.0001) in KPT2D than in T2D patients. Elevated serum TGs were associated with young KPT2D patients.Conclusion: Lifestyle changes as well as lipid-lowering treatments might be effective in lowering the incidence of ketosis as well as stabilizing disease progression.Keywords: ketosis, triglycerides, hypertriglyceridemia

Yao Yao,* Qian Xu,* Liyong Yan, Yan Jiao, Qingqi Su, Xiaoguang Li, Cong Liu, Feng Zhao Department of Stomatology, Central Hospital of Taian, Taian, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Zhao Tel +86-538-6298546Email zxyyzhaofeng@163.comBackground: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cavity cancers, and the 5-year survival rate for OSCC patients remains unsatisfactory. MiRNA-128/miRNA-142 has been reported to work as a tumor suppressor in diverse tumors. However, the biological function of miR-128/miR-142 in OSCC is still unknown.Methods: The expression of miR-128/miR-142 and homeobox A10 (HOXA10) in OSCC tissues and cells was measured by quantitative real-time polymerase chain reaction (RT-qPCR). The effects of miR-128/miR-142 or HOXA10 on proliferation, migration, invasion and apoptosis were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), transwell and flow cytometry assays, respectively. The expression levels of epithelial–mesenchymal transition (EMT)-associated proteins (E-cadherin, N-cadherin and Vimentin), proliferation-associated protein ki-67 and HOXA10 were detected by Western blot assay. The interaction between HOXA10 and miR-128/miR-142 was predicted by TargetScan, and then confirmed by dual-luciferase reporter assay.Results: MiR-128/miR-142 was downregulated in OSCC tissues and cells. Overexpression of miR-128/miR-142 inhibited proliferation, migration, invasion and EMT and induced apoptosis in OSCC cells. HOXA10 as the target of miR-128/miR-142 was verified in OSCC cells. Knockdown of HOXA10 also repressed proliferation, migration, invasion and EMT and boosted apoptosis in OSCC cells. Upregulation of miR-128/miR-142 hindered the expression level of HOXA10, while introduction of HOXA10 weakened the effect.Conclusion: MiR-128/miR-142 suppressed OSCC tumorigenesis and metastasis by targeting HOXA10, providing a new promising therapeutic approach for OSCC patient diagnosis and treatment.Keywords: miR-128, miR-142, oral squamous cell carcinoma, HOXA10, tumorigenesis, EMT

Hong Peng,1 Jie Zheng,2 Qiang Su,3 Xueya Feng,1 Mingsha Peng,1 Lei Gong,4 Hong Wu,1 Xue Pan5 1Department of Anorectal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Anesthesiology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 3Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan, 637000, People’s Republic of China; 4Department of Gastrointestinal Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 5Scientific Research Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Xue PanScientific Research Department, The First Affiliated Hospital of Chongqing Medical University, No. 1 of Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86 13594002025Email panxue89012705@163.comBackground: Many studies found that VPS53, one of the subunits of the golgi-associated retrograde protein (GARP) complexes, was aberrantly expressed in human diseases.Aim: This study investigated the functions and molecular mechanisms of VPS53 in colorectal cancer (CRC).Methods: Expression and correlation of Beclin 1 and VPS53 were analyzed by RT-qPCR and Pearson’s correlation in CRC tissues, and VPS53 expression was also determined in CRC cells. The changes of proliferation, migration, invasion, apoptosis, and autophagy of CRC cells were examined by a succession of functional experiments including CCK-8, flow cytometry, transwell assay, and electron microscopy. The levels of autophagy related proteins were evaluated by Western blotting analysis.Results: RT-qPCR results found that VPS53 was downregulated in CRC tissues and cells, and Beclin 1 expression was also decreased in CRC tissues. There was a positive correlation between VPS53 and Beclin 1. Functional results showed that overexpression of VPS53 could suppress proliferation, migration, and invasion, and accelerate apoptosis and autophagy of CRC cells. Also, VPS53 could upregulate Beclin 1 and LC3BII, suggesting the inductive effect of VPS53 on CRC cell autophagy. Furthermore, it was found that the autophagy inhibitor (Inhb) could attenuate the inhibition of VPS53 on CRC progression.Conclusion: VPS53 repressed CRC progression by regulating the autophagy signaling pathway, suggesting that VPS53 might be a promising therapeutic target for CRC.Keywords: colorectal cancer, VPS53, autophagy, cell migration, cell invasion

Shichun Du,1,* Hongmei Zhang,1,* Hui Wu,2 Shu Ye,1 Wen Li,1 Qing Su1 1Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People’s Republic of China; 2Department of Endocrinology, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing SuDepartment of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Kong Jiang Road 1665#, Shanghai 200092, People’s Republic of ChinaTel/ Fax +86 2125077538Email suqing@xinhuamed.com.cnPurpose: This study aimed to identify the prevalence and gender differences of metabolic syndrome in young new-onset ketosis-prone type 2 diabetic (KPT2D) individuals.Patients and Methods: A retrospective study was conducted in Shanghai Xin Hua Hospital from 2007 to 2019. A total of 304 patients from 12 to 40 years of age with newly diagnosed diabetes presenting with ketosis were analyzed. The clinical features and laboratory results of KPT2D and type 1 diabetic (T1D) individuals were compared. Prevalence and gender differences of metabolic syndrome in the KPT2D subjects were analyzed.Results: The prevalence of metabolic syndrome (P < 0.0001) was significantly higher in young KPT2D than T1D subjects. The prevalence of high blood pressure (P < 0.0001), central obesity (P < 0.0001), low plasma HDL-C concentration (P = 0.045), and hypertriglyceridemia (P < 0.0001) was elevated in the KPT2D subjects compared with T1D. Male predominance (89%) was presented in the KPT2D subjects. The prevalence of metabolic syndrome (P = 0.0002) was significantly higher in young male than female KPT2D subjects. The presence of central obesity (P < 0.0001) and high blood pressure (P =0.03) was higher in male KPT2D subjects than female. The presence of serum triglyceride concentrations ≥ 2.3mmol/L was significantly higher (P = 0.011) in male KPT2D subjects than female.Conclusion: Significantly higher prevalence of metabolic syndrome in young KPT2D patients compared with T1D patients could be an important reference for diabetic differential diagnosis. KPT2D presented a higher predominance in young males, who had higher prevalence of metabolic syndrome than young females.Keywords: ketosis, glucose, overweight, hyperglycemia

Jihan Huang,1,* Yingchun He,1,* Qianmin Su,2 Juan Yang1 1Center for Drug Clinical Research, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 2Department of Computer in College of Electronic and Electrical Engineering, Shanghai University of Engineering Science, Shanghai 201620, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jihan Huang; Juan YangCenter for Drug Clinical Research, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, #1200 Cailun Road, Pudong New District, Shanghai 201203, People’s Republic of ChinaTel +86 21 51322420Email huangjihan@shutcm.edu.cn; janeyang5006@163.comObjective: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China.Methods: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated.Results: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included ≤ 100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy.Conclusion: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.Keywords: COVID-19, clinical trial, interventional, randomized, blinding

Chao Ma,1 Zongming Zhuang,1 Qisheng Su,2 Jianfeng He,1 Haoyu Li1 1Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Haoyu LiDepartment of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaEmail med.dr.lihy@gmail.comPurpose: This study focused on the mechanism underlying the therapeutic effect of curcumin against tongue cancer (TC).Methods: Target genes of TC and curcumin were identified, respectively. Three datasets of TC from Gene Expression Omnibus were included, and then the differentially expressed genes were collected. After combing the data from The Cancer Genome Atlas, bioinformatics analyses were performed to investigate hub genes in terms of the functions and correlations. The proliferation and migration of TC cells were evaluated with CCK-8 assay and scratch wound healing assay, respectively. Cell apoptosis was evaluated by TUNEL assay, flow cytometry and Western blot. Cell cycle was determined by flow cytometry.Results: In this study, 15 hub genes were identified (TK1, TDRD3, TAGLN2, RNASEH2A, PDE2A, NCF2, MAP3K3, GPX3, GPD1L, GBP1, ENO1, CAT, ALDH6A1, AGPS and ACACB). They were mainly enriched in oxygen-related processes, such as oxidation-reduction process, reactive oxygen species metabolic process, hydrogen peroxide catabolic process, oxidoreductase activity and Peroxisome-related pathway. The expression levels of hub gene mRNAs were positively correlated with each other’s expression levels. None of the hub genes was correlated with prognosis (P > 0.05). Curcumin significantly inhibited CAL 27 cell proliferation and migration (P < 0.05), but significantly promoted cell apoptosis (P < 0.05).Conclusion: Curcumin has potential therapeutic effect on treating TC by suppressing cell proliferation and migration, as well as promoting apoptosis through modulating oxygen-related signaling pathways.Keywords: tongue neoplasms, curcumin, proliferation, apoptosis, migration, computational biology

Jun Xu,1,* Qiang Su,2,* Mingxia Gao,3 Qingsong Liang,1 Junfeng Li,1 Xu Chen1 1Department of Cardiothoracic Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan 637000, People’s Republic of China; 2Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu ChenDepartment of Cardiothoracic Surgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, #97 of Renmin South Road, Nanchong City, Sichuan 637000, People’s Republic of ChinaTel +86 139 9089 8058Email Ncchchen@hotmail.comObjective: Cancer stem-like cells (CSC) are thought to be involved in the cisplatin resistance of tumors. This study was designed to investigate the effect of PRDX6 on CSCs present in cisplatin-resistant non-small cell lung cancer (NSCLC) tumors.Materials and methods: CD133+/ABCG2+ H1299 CSCs and A549 CSCs were isolated. The IC50 values for cisplatin in treatment of CSCs were detected using the CCK8 assay. Then the isolated cells were identified using CD133. Wnt/β-catenin expression was evaluated by Western blot assays. Specimens of tumor and adjacent para-carcinoma tissue were collected from 30 NSCLC patients and examined by immunohistochemistry (IHC), qRT-PCR, and Western blotting to determine and compare their levels of PRDX6 and CD133 expression. Finally, siRNA-mediated silencing of PRDX6 was employed with both types of CSCs to determine the impact of PRDX6 on CD133 enrichment by flow cytometry, cell viability, and sphere formation ability.Results: High levels of PRDX6 and CD133 expression were detected in samples of tumor tissue from NSCLC patients, and expression of PRDX6 and CD13 presented a positive relationship. Increasing levels of cisplatin resistance and upregulated levels of PRDX6, ABCG2, Wnt, and β-catenin expression were detected in CD133+/ABCG2+ H1299 and A549 CSCs. Transfection with siRNA targeting PRDX6 changed these cellular characteristics by decreasing the levels of PRDX6, ABCG2, Wnt, and β-catenin expression. We further demonstrated that exogenous silencing of PRDX6 effectively inhibited the sphere formation ability of CSCs and re-sensitized them to cisplatin.Conclusion: Our results strongly suggest that PRDX6 promotes cisplatin resistance in human lung cancer cells by promoting the stem-like properties of cancer cells. Our findings also suggest PRDX6 as a target for treating cisplatin resistant NSCLC.Keywords: PRDX6, CSCs, cisplatin-resistance, NSCLC, cancer stem-like cell