Search

Yi Shao,* Yunfu Chen,* Xin Lan, Jun Lu, Guangling Tang, Sijie Tang, Ruixue Zhai, Chao Chen, Xinglong Xiong, Jing Shi Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Shi, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, No. 28 Beijing Road, Guiyi Street, Yunyan District, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-18685034016, Email shijing81@gmc.edu.cnBackground: Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells.Methods: The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting.Results: Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects.Conclusion: Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.Keywords: neuropathic pain, morin, microglia, NF-κB, neuroinflammation

Fengxing Huang,1,2,* Youwei Wang,1,2,* Yu Shao,1,2,* Runan Zhang,1,2 Mengting Li,1,2 Lan Liu,1,2,* Qiu Zhao1,2,* 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lan Liu; Qiu Zhao, Email lliugi@whu.edu.cn; qiuzhao@whu.edu.cnIntroduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored.Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework.Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk.Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations. Keywords: CRC, macrophages, metabolic classification, tumor immunity, prognosis model

Yang Zhao,1,* Yi-Han Wang,2,* Wei-Chao Tu,1 Da-Wei Wang,1 Mu-Jun Lu,3,4 Yuan Shao1 1Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People’s Republic of China; 2Department of Urology, Sixth People’s Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Shanghai Institute of Andrology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mu-Jun Lu; Yuan Shao, Email lumujun@163.com; shaoyuan10772@163.comBackground: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action.Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKβ were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models.Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKβ acted as key regulatory factor in renal injury and the expression of IKKβ was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKβ expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKβ overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKβ and attenuating IKKβ/NF-κB pathway.Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKβ/NF-κB pathway, which indicates targeting IKKβ has an enormous potential for treating CKD. Keywords: chronic kidney disease, costunolide, renal fibrosis, IKKβ/NF-κB pathway

Huiying Yan,1,* Wei Wang,2,* Tingting Cui,1 Yanxin Shao,3 Mingquan Li,1 Limei Fang,1 Lina Feng1 1Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Department of Intensive Care Unit, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Limei Fang; Lina Feng, Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China, Email fanglm008@163.com; Fenglina0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal β-amyloid deposition (Aβ), intraneuronal tau protein phosphorylation leading to the formation of ‘neurofibrillary tangles’ (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the ‘Aβ cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins’, but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aβ and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.Keywords: neuroinflammation, microglia, Alzheimer’s disease, review, Trem2

Yue Shao, Rong Li, Guangmei Chen, Lichuan Zhang Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People’s Republic of ChinaCorrespondence: Lichuan Zhang, Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People’s Republic of China, Email zlcdl2015@126.comPurpose: We explored the expression and prognostic value of GALNT6 and the tumor microenvironment of pan-cancer in humans.Methods: In this study, we explored the expression pattern of GALNT6 pan-cancer across multiple databases. The prognostic value of GALNT6 was evaluated using the Kaplan–Meier method. The types and numbers of GALNT6 gene alterations were exhibited using the cBio Cancer Genomics Portal. The correlations between GALNT6 expression and immune infiltration in cancers were analyzed using the database Tumor Immune Estimation Resource 2. We also used the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis to investigate the molecular mechanisms of the GALNT6 gene in tumorigenesis. The expression of GALNT6 was also further verified by qPCR in lung adenocarcinoma tissues.Results: In general, compared with normal tissue, tumor tissue had a higher expression level of GALNT6. GALNT6 showed a protective effect in colon carcinoma and other cancers; however, a high expression level of GALNT6 was detrimental to survival in bladder cancer and in pheochromocytoma and paraganglioma. Mutation, amplification, and deep deletion were the three main types of GALNT6 mutations in tumors. There was a significant positive correlation between GALNT6 expression and immune infiltration of CD8+ T-cells in skin cutaneous melanoma metastasis, based on most of the algorithms used. Moreover, protein processing- and glycoprotein metabolic-associated functions were involved in the functional mechanisms of GALNT6.Conclusion: This first pan-cancer study offers a relatively comprehensive understanding of the oncogenic roles of GALNT6 across different cancer types.Keywords: GALNT6, pan-cancer, survival analysis, mutation, immune infiltration, functional mechanisms

Zhanyi Zhang,1 Mengyuan Li,2 Yujia Geng,1 Wangshu Wang,1 Weihao Wang,1 Ying Shao1 1Department of Plastic and Reconstructive Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, 130000, People’s Republic of China; 2College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin Province, 130118, People’s Republic of ChinaCorrespondence: Ying Shao, Department of Plastic and Reconstructive Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, 130000, People’s Republic of China, Email shao_ying@jlu.edu.cnPurpose: Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases.Patients and Methods: We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI).Results: The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003– 1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005– 1.011; P= 2.66× 10− 6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001– 1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001– 1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000– 1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001– 1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD.Conclusion: These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.Keywords: autoimmune disease, facial aging, Mendelian randomization, ankylosing spondylitis, systemic lupus erythematosus, celiac disease

Zhihua Zhang,1 Yuhong Wang,2 Yankun Zhang,3 Shujun Geng,2 Haifeng Wu,4 Yanxin Shao,5 Guannan Kang6 1Department of Science & Education, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 2Department of Tuberculosis, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 3Department of Ophthalmology, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 4Clinical Laboratory, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 5Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 6Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanxin Shao, Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, No. 372, Sheng Li North Street, Shijiazhuang, Hebei, 050041, People’s Republic of China, Email shaoyanxin163@163.comBackground: Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging.Methods: Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set.Results: Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI.Conclusion: Our study may provide implications for the diagnosis and drug development of M. tb infections.Keywords: tuberculosis, latent tuberculosis infection, mycobacterium tuberculosis, immune, diagnostic model

Yujian Shao,1,2 Yonglu Chen,2 Mingyue Zhu,3 Yuanyuan Liu,2 Chen Fang,3 Minjun Wang,2 Peng Sun,3 Weiling Fu,2 Jing Huang,3 Shimei Sheng,2 Yanshan Huang2 1Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3First Research Institute, Zhejiang Heze Pharmaceutical Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yanshan Huang, Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China, Email yanshanhuang@doerbio.comIntroduction: Diabetes and obesity are momentous risk factors threatening people’s lives and health. Currently available incretin analogue glucagon-like peptide 1 (GLP-1) possesses huge hypoglycemic effect with the unsatisfactory effect of weight loss. Co-agonists targeting GLP-1R plus glucagon receptor (GCGR) or gastric inhibitory polypeptide receptor (GIPR) show synergistic benefits in glycaemic control and weight loss. Here, we describe a novel dual GIP and GLP-1 receptor agonist, DR10627, and performed a preclinical assessment of it.Methods: The agonistic ability of DR10627 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary (CHO) cells transfected with GLP-1R or GIPR in vitro. The plasma pharmacokinetics of DR10627 were analysed in cynomolgus monkeys. The OGTTs were performed in Sprague‑Dawley (SD) rats. The glucose lowering effects were evaluated by repeated administration of DR10627 in diabetic (db/db) mice for 4 weeks. The effects of anti-obesity and improving metabolism of DR10627 were evaluated by repeated administration of DR10627 in diet-induced obesity (DIO) mice for 57 days.Results: DR10627 had the capacity to activate both GLP-1R and GIPR in vitro. The terminal half-life of DR10627 was found to be approximately 4.19– 5.8 h in cynomolgus monkeys. DR10627 had a great improvement in oral glucose tolerance in SD rats. Moreover, DR10627 had a potent glucose-lowering effect in db/db mice, and the hypoglycemic effect of 18 nmol/kg DR10627 was better than that of 50 nmol/kg liraglutide. In addition, 10 and 30 nmol/kg DR10627 possessed the ability of potentiating the weight-loss, lipid-lowing efficacy and improving metabolism to a greater extent than 80 nmol/kg liraglutide.Conclusion: Preclinical assessment demonstrated that administration of DR10627 resulted in glucose lowering in SD rats and db/db mice, and substantial body weight reduction and metabolism improvement in DIO mice. DR10627 is a promising agent deserving further investigation for the treatment of type 2 diabetes and obesity.Keywords: glucagon-like peptide-1, gastric inhibitory polypeptide receptor, obesity, type 2 diabetes, inflammation

Zixia Wu,1,* Weibo Xia,1,* Liling Ou,1 Ling Zheng,1 Bingying Hou,1 Tonghe Pan,2 Wenjie Sun,1 Leo H Koole,1 Yongqing Shao,2 Lei Qi1 1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, the People’s Republic of China; 2Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongqing Shao, Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China, Tel +86-574 87862193, Email sunniesyq@163.com Lei Qi, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, the People’s Republic of China, 325027, Tel +86-577-88067973, Email imdoll@163.comPurpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.Keywords: dry eye disease, antioxidant, nitrogen doped graphene quantum dots, Nrf2 antioxidant pathway

Manqiao Wang,&ast; Rong Luan,&ast; Boshi Liu, Yi Gong, Jinzhi Zhao, Xiteng Chen, Qianhui Yang, Jingjie Liu, Juping Liu, Yan Shao, Xiaorong Li Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shao; Xiaorong Li, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China, Tel +86 17622651170; +86 18622818042, Email sytmueh@163.com; xiaorli@163.comPurpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR).Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion.Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05).Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).Keywords: proliferative diabetic retinopathy, ozurdex, pars plana vitrectomy, optical coherence tomography angiography, microperimetry

Chuanlin Ning,1 Huacheng Pei,2 Youjia Huang,1 Sichen Li,1 Yiling Shao1 1School of Media and Communication, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2School of Finance, Shanghai University of Finance and Economics, Shanghai, People’s Republic of ChinaCorrespondence: Yiling Shao, School of Media and Communication, Shanghai Jiao Tong University, No. 800, Dongchuan Road, Minhang District, Shanghai, 200240, People’s Republic of China, Email sylh1996@sjtu.edu.cnBackground: The Healthy China 2030 (HC2030) policy is currently recognized as China’s most significant and influential national health policy. However, despite its implementation in 2016, the policy’s impact has yet to be comprehensively evaluated, particularly in relation to its effectiveness in enhancing population health and promoting public health equity.Methods: We utilized the Difference-in-Differences (DiD) method to evaluate the impact of the HC2030. Our analysis utilized a panel dataset derived from five longitudinal surveys conducted by the China Family Panel Studies (CFPS).Results: The implementation of HC2030 has improved the overall health status of residents, particularly in urban areas and the western and eastern regions. Mechanistic analysis has further unveiled that the policy’s beneficial impact on health outcomes is attributed to a rise in physical activity frequency and the betterment of mental health. Additionally, female, married, and medically insured individuals have demonstrated a significant positive impact of the policy on their health outcomes.Conclusion: Although the HC2030 appears to have effectively improved overall population health, it needs to promote equity in public health adequately. The study suggests adjustments are needed to address the unequal distribution of health outcomes between urban and rural areas and among different regions.Keywords: health China 2030, health policy, policy evaluation, health equity, health communication, public health

Yuming Shao,1 Wenxiang Wu,2 Fangzhou Fan,2 Haifeng Liu,3 Yongliang Ming,2 Wangwei Liao,2 Chunyu Bai,2 Yuhua Gao2 1Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Forensic Science Center of Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 2Precision Medicine Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272067, People’s Republic of ChinaCorrespondence: Chunyu Bai; Yuhua Gao, No. 133 Hehua Road, Jining, Shandong, 272067, People’s Republic of China, Tel +86-573-3616565, Email chunyu_bai@hotmail.com; anngyh@126.comAim: Acute pancreatitis is an inflammatory disorder of the pancreas, which causes abnormal activation of immune cells. The macrophages were accumulated in pancreas and infiltrated into islets during the AP process to induce abnormal glucose metabolism. However, the role of macrophages in abnormal glucose metabolism remains understood. Extracellular vesicles act in the regulation of intercellular function, but whether EVs secreted by macrophages contribute to β cell failure and apoptosis in AP is unclear. Based on this, the aim of this study was to reveal the role of macrophages-EVs in AP and develop a treatment for symptoms of hyperglycemia in AP.Methods: The AP model was established and treated by various doses of melatonin to analyze the therapeutic effect. The accumulation and polarization of macrophages in the AP pancreas were observed, and the β cells were incubated with pancreatic derived EVs to analyze the role in β cell failure and apoptosis.Results: The results showed that macrophages were recruited and polarized to M1 phenotype macrophages in the pancreas of AP mice, which obtained inflammatory EVs that contained specific miRNAs to induce β cell failure and apoptosis. Then, the EVs derived from M1 macrophages triggered β cell failure and apoptosis. Melatonin prevented polarization of macrophages to the M1 phenotype in vivo, which reduced the secretion of inflammatory EVs, changed the abundance of miRNAs in EVs, and therefore decreased inflammatory EV-mediated β cell failure and apoptosis.Conclusion: Our results demonstrate that similar to 20S proteasome inhibitor MG132, analyses indicated that melatonin prevented degradation of IκBα through the ubiquitylation pathway to restrict p50 subunits to the cytoplasm of macrophages, inhibited activation of the NF-κB pathway to downregulate the transcription of specific miRNAs, and reduced miRNA transport into EVs.Keywords: acute pancreatitis, diabetes mellitus, macrophages, EVs, melatonin

Huan He,1 Qichun Cui,1 Hengheng Chen,2,&ast; Xiao Huang,3,&ast; Shuai Wang,3,&ast; Tian Yu,2,&ast; Jinqiu Feng,3 Yun Shao1 1Department of Anesthesiology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China; 2Department of Preventive Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China; 3Department of Pediatric Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Shao, Department of Anesthesiology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, No. 356 East Beijing Road, Shanghai, 200002, People’s Republic of China, Tel/Fax +86 2163295852, Email shaoyun07078@sina.com Jinqiu Feng, Department of Pediatric Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, No 356 East Beijing Road, Shanghai, 200002, People’s Republic of China, Tel/Fax +86 2163601149, Email feng_jinqiu356@fudan.edu.cnPurpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane.Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 μg/kg dexmedetomidine, 1 μg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit.Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P< 0.001). Intranasal administration of 2 μg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents.Conclusion: Both 2 μg/kg and 1 μg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 μg/kg is more effective in preventing severe ED and providing better mask acceptance.Keywords: intranasal dexmedetomidine, emergence delirium, sevoflurane anesthesia, pediatric patients, dental rehabilitation

Dawei Wang,1 Lingchao Sun,1 Yunru Shao,1 Xiaoyan Zhang,1 Phil Maguire,2 Yixin Hu1 1School of Psychology, Shandong Normal University, Ji’nan, Shandong, People’s Republic of China; 2Department of Computer Science, National University of Ireland, Galway, IrelandCorrespondence: Yixin Hu, School of Psychology, Shandong Normal University, Jinan, Shandong Province, 250358, People’s Republic of China, Email huyixin2005@163.comPurpose: Cyberchondria is a problematic or unhelpful behavior pattern that describes excessive or repetitive online health-related information searching related to an enhanced level of health anxiety. Such internet-derived medical anxiety can manifest itself in different ways across cultures. This study explores the unique nature of cyberchondria in the context of Chinese culture, identifying the risk factors for the condition and the possible negative outcomes.Methods: An exploratory factor analysis (EFA) was used to explore whether the structure of the Chinese version of the Cyberchondria Severity Scale (C-CSS) is different from that in western context. Subsequently, a confirmatory factor analysis (CFA) was used to verify the model fit of the C-CSS. Finally, a series of regression analysis were used to test the relationship between cyberchondria and its antecedent variables and consequence variables in Chinese context.Results: Retained 18 items and revised to 3 dimensions (Negative Effects, Excessiveness and Reassurance Seeking), the Chinese version of the Cyberchondria Severity Scale (C-CSS) was developed. In the context of China, the three antecedents were also effective predictors of cyberchondria, and C-CSS is also related to theoretically relevant outcomes.Conclusion: This study initially demonstrated the validity, reliability and applicability of C-CSS to assess the severity of cyberchondria among Chinese undergraduates.Keywords: cyberchondria severity scale, medical anxiety, Chinese health system, validity, reliability

Xiao-Yu Wang,1– 3,&ast; San-Hua Xu,3,&ast; Hong Wei,3,&ast; Min Kang,3 Jie Zou,3 Qian Ling,3 Hui Huang,3 Xu Chen,4 Yi-Xin Wang,5 Yi Shao,3 Yao Yu1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Branch of National Clinical Research Center for Ocular Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Department of Ophthalmology and Visual Sciences, Maastricht University, Maastricht, Limburg Province, 6200MA, Netherlands; 5School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF244HQ, UK&ast;These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email freebee99@163.com Yao Yu, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email yuyao1234562023@163.comPurpose: This study aimed to explore the spontaneous brain activity in patients with diabetic optic neuropathy (DON) by using the amplitude of low-frequency fluctuation (ALFF) technique.Methods: Sixteen DON patients and 16 age- and sex-matched healthy controls (HCs) were recruited. ALFF along with functional MRI method was used to detect the intrinsic brain activity alterations. The mean values of ALFF in DON patients and HCs were analyzed by receiver operating characteristic (ROC) curves. Pearson’s correlation analysis was used to determine the correlation between Hospital Anxiety and Depression Scale (HADS) and ALFF values of DONs.Results: The DON group showed significantly increased ALFF values in the fusiform gyrus, and decreased ALFF values in the medial frontal gyrus/left frontal superior orbit/right frontal medial orbit, and left frontal inferior triangle. ROC curve analysis indicated that the accuracy of AUC was good. The anxiety scale and depression scale of the DON group were negatively correlated with the ALFF values of the medial frontal gyrus.Conclusion: DON is a neurodegenerative disease involving multiple brain regions. The abnormal activity of neurons in these brain regions helps to reveal the underlying neural mechanisms of brain activity related to DON.Keywords: ALFF, fMRI, diabetic optic neuropathy, spontaneous brain activity

Qingyan Liu,1,2,&ast; Shuo Sun,1,&ast; Zhengwei Yang,1,&ast; Yan Shao,1 Xiaorong Li1 1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China; 2Department of Ophthalmology, Anhui NO.2 Provincial People’s hospital, Hefei, 230041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shao; Xiaorong Li, Email 13820179302@163.com; xiaorli@163.comBackground: Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV.Methods: Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis.Results: A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls.Conclusion: This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.Keywords: serum amyloid A 4, inflammation, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy

Xulin Liao,1,2 Chu Qi Li,1 Qian Min Ge,1 Li Ying Tang,3 Ting Su,4 Qiu Yu Li,1 Yi Cong Pan,1 Hui Ye Shu,1 Li Juan Zhang,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, People’s Republic of China; 4Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USACorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comPurpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients.Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity.Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients’ anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus.Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.Keywords: herpes zoster keratitis, resting-state functional magnetic resonance imaging, brain activity patterns, brain region, the percent amplitude of fluctuation

Yiyang Shu,1 Yuting Shao,1 Qi Zhou,2 Lixia Lu,3 Zhiyue Wang,1 Li Zhang,1 Yanlong Bi1,4 1Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Exam Center of Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Tongji Eye Institute, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yanlong Bi, Email biyanlong@tongji.edu.cnAim: To explore the trends in the prevalence and disease burden of cataract from 1990 to 2019, evaluate attributable risk factors, and predict trends over the next decade in China and globally.Methods: Data was obtained from Global Burden of Disease Study 2019. We calculated the age-standardized prevalence rate (ASR) and annual percentage change (EAPC) to show the trends of cataract in China and different regions. We calculated and reported the proportion of disability adjusted life years (DALYs) attributable to risk factors by sex in China and different regions. Then, the Bayesian age-period-cohort (BAPC) analysis model was also used to predict the prevalence trends from 2020 to 2030 in China and globally.Results: The ASR increased from 867.09 in 1990 to 991.56 in 2019 per 100,000 with an EAPC of 0.88 in China. The age-standardized DALY rate of females was higher than males. DALY rates were correlated to household air pollution from solid fuels, tobacco, high fasting plasma glucose and high body-mass index. The projective model indicates that the ASR for cataracts will rise to 1101.35× 106 for male and 1616.63× 106 for female by 2030.Conclusion: The trends from 1990 to 2030 suggested that the burden of cataract remains high in China. Maintaining good lifestyle habits such as switching to clean energy, reducing cigar intake, controlling blood glucose and weight can reduce the risk of cataracts. As aging increases, China should pay more attention to cataract-induced low vision and blindness and develop public policies to reduce the disease burden.Keywords: China, cataract, disease burden, risk factors

Yuanyuan Pan,1,&ast; Yifan Shao,2,&ast; Zhanghuan Chi,3,&ast; Shenhui Jin,1 Junlu Wang1 1Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Anesthesia, Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Anesthesia, Wenzhou People’s Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junlu Wang, Departments of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86 13806689854, Fax +86 0577-55578999-689854, Email wangjunlu973@163.comPurpose: To evaluate transcutaneous electrical acupoint stimulation (TEAS) on the perioperative rehabilitation of patients undergoing laparoscopic myomectomy.Patients and Methods: One hundred and five women undergoing laparoscopic hysteromyomectomy were randomly divided into TEAS group (Group T) and control group (Group C). Propofol and remifentanil were used to stabilize patient blood pressure and keep BIS between 40 and 60. Group T patients received TEAS at LI4/PC6 30 minutes before the operation and lasting until the end of anesthesia, followed by TEAS at ST36/SP6 for 30 minutes in PACU. All required indicators were recorded.Results: Group T patients required lower dosages of remifentanil and vasoactive drugs, and had a reduced incidence of propofol injection pain and intraoperative hypotension compared to Group C. Group T also had a lower maximum NRS score in PACU, lower NRS scores at 1 hour and 24 hours, and a lower incidence of vomiting within 24 hours. In addition, the QoR-40 score for Group T at 24 hours after operation was higher in terms of physical comfort, emotional state, pain and total score.Conclusion: TEAS can reduce the amount of anesthetic, maintain hemodynamic stability, reduce postoperative pain, reduce postoperative vomiting, enhance the recovery of gastrointestinal function, increase the quality of postoperative recovery and thus accelerate overall patient recovery.Keywords: TEAS, laparoscopic myomectomy, QoR-40

Gaoyuan Wang,1 Xiaoyu Chen,2 Yubao Shao,2 Bin Xu1 1Department of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Histology and Embryology, Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Bin Xu, Email youchen100@126.comIntroduction: To explore the role of PINK1/Parkin-mediated mitochondrial autophagy in H2O2-induced abnormal proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS).Methods: Firstly, we isolated fibroblast like synoviocytes (RA-FLS) from RA patients. H2O2-induced oxidative stress, and NAC (a ROS inhibitor) or FCCP (a mitochondrial autophagy activator) treatment inhibited ROS level or activate mitochondrial autophagy in RA-FLS. MitoSOX Red, JC-1 kit, DCFH-DA kit and CCK8 kit were used to evaluate mitochondrial redox status, mitochondrial membrane potential, intracellular ROS level and cell activity, respectively. Western blot was used to detect the protein expression. The rat model of Freund’s complete adjuvant arthritis (AA) was established and treated with NAC and FCCP, respectively. The pathological changes of synovium and the percentage of apoptotic cells in synovium were detected by H&E and TUNEL staining, respectively.Results: We have successfully isolated synovial cells from RA patients. Using 5μM H2O2 to stimulate RA-FLS could induce mitochondrial abnormalities of RA-FLS and inhibit RA-FLS autophagy. FCCP could reverse the effect of H2O2 on RA-FLS cell proliferation and apoptosis. NAC could reverse the effect of H2O2 on PINK1/Parkin. Overexpression of PINK1 or Parkin reversed the effect of H2O2 on RA-FLS mitochondrial autophagy, proliferation and apoptosis. The in vivo experiment results showed that both NAC and FCCP could prevent the pathogenesis of RA, reduce RA-FLS cell viability and increase RA-FLS cell apoptosis.Conclusion: The PINK1/Parkin-mediated mitochondrial autophagy participates in H2O2-induced abnormal proliferation of RA-FLS, and targeting of PINK1/Parkin-mediated mitochondrial autophagy may be the key mechanism in the treatment of RA.Keywords: mitochondrial autophagy, rheumatoid arthritis, PINK1, Parkin

Zheng J, Shao Y, Jiang Y, et al. Cancer Manag Res. 2019;11:5231–5242. We, the Editors and Publisher of Cancer Management and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2, 3 and 4. Specifically, The images for Figure 2A, Control, 30µg/ml, and 90µg/ml have been duplicated with images from Figure 4D, +-0, -+0, -+90 and +-90, respectively. The graph for Figure 3B has been duplicated with the graph for Figure 4G. When approached for an explanation, the authors were cooperative but were unable to provide a sufficient explanation for the image duplication or provide sufficient original data for their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Xin Xiong,1,&ast; Rong Rong,2,&ast; Li-Ying Tang,3,&ast; Tie Sun,1 Yi-Cong Pan,1 Hui-Ye Shu,1 Li-Juan Zhang,1 Qian-Min Ge,1 Rong-Bin Liang,1 Yi Shao1 1Department of Pathology and Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Centre of Natural Ocular Disease Clinical Research Center, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, 361004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comObjective: To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers.Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student’s t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM.Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L.Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125+Hb has potentially greater utility in diagnosing hepatocellular carcinoma.Keywords: hepatocellular carcinoma, ocular metastases, CA-125, Hb, risk factors

Manhong Xu,1,&ast; Ruiyan Fan,1,&ast; Xiaoe Fan,2 Yan Shao,1 Xiaorong Li1 1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China; 2Department of Ophthalmology, Jincheng People’s Hospital, Jincheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Li; Yan Shao, No. 251 Fukang Road, Nankai Distinct, Tianjin, 300384, People’s Republic of China, Tel +86 186 2281 8042 ; +86 186 2281 8042, Fax +86 022-86428777, Email xiaorli@163.com; sytmueh@163.comAbstract: Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.Keywords: anti-vascular endothelial growth factor, retinal angiogenesis, anti-VEGF drugs, sustained-release strategies, ranibizumab, bevacizumab

Ju Zhu,1 Haoming Shi,1 Haoyu Ran,1 Qiancheng Lai,2 Yue Shao,1 Qingchen Wu1 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Cardiothoracic Surgery, Chengdu Fifth People’ Hospital, Chengdu, People’s Republic of ChinaCorrespondence: Qingchen Wu, Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Email wuqingchencqmu@126.comBackground: Non-small cell lung cancer (NSCLC) survivors are at an increased risk of developing second primary malignancies, such as small cell lung cancer. This paper sought to establish a prognostic nomogram to assess overall survival (OS) in patients with second primary small cell lung cancer (SPSCLC) after NSCLC.Methods: 420 patients who developed SPSCLC after NSCLC were randomly split into the training and validation groups. A nomogram was established by stepwise regression. Area under the curve (AUC) and calibration plots were applied to assess the prognostic performance of the nomogram. Concordance index (C-index), integrated discrimination improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA) were performed to compare the nomogram with the American Joint Committee on Cancer (AJCC) 8th staging system. Survival risk classification was constructed based on the nomogram.Results: Five variables were chosen to construct the nomogram. The AUC showed that it had a satisfactory discrimination ability. All calibration plots displayed good concordance between nomogram and observation. The C-index, IDI, NRI and DCA showed the nomogram was superior to the AJCC 8th staging system. The Kaplan-Meier curves suggested huge differences in prognosis among the three risk groups.Conclusion: This study build a nomogram and risk stratification system for predicting probabilities of OS in patients with SPSCLC after NSCLC, which can help clinicians in individualized survival assessment and treatment decisions.Keywords: nomogram, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), SEER database

Alei Feng,1,2 Ning Yang,1 Ruoying Yu,3 Jingwen Liu,3 Jiaohui Pang,3 Xue Wu,3 Yang Shao,3,4 Zhe Yang,1 Honghai Dai1 1Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Shandong Qidu Pharmaceutical Co. Ltd., Shandong Provincial Key Laboratory of Neuroprotective Drugs, Zibo, 255400, People’s Republic of China; 3Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China; 4School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Honghai Dai; Zhe YangTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaEmail dhhcp@163.com; sdslyyyz@sina.comBackground: Esophageal cancer (EC), especially esophageal squamous cell carcinoma, remained as one of the most aggressive tumors in China with a five-year survival rate of around 40%. Molecular characteristics through next-generation sequencing are becoming an emerging method in identifying prognostic biomarkers for better treatment management for EC patients.Methods: Targeted next-generation sequencing using a 422-gene pan-cancer panel was performed with tumor tissue samples from a total of 69 Asian non-surgical esophageal carcinoma patients (AEC) treated with chemoradiotherapy. A TCGA cohort of 143 EC patients and another Asian ESCC cohort of 47 patients were employed for validation.Results: In the AEC cohort, alterations in TP53 (94.2%) and NOTCH1 (55.1%) were the two most frequently observed alterations, whereas in the TCGA cohort, only TP53 alterations were observed at a high ratio (85.3%). Co-amplifications of FGF19 and CCND1 were found at a similar ratio in both cohorts. Multiple alterations in the DNA damage pathway were identified but not associated with overall survival in AEC. Using univariate and multivariate Cox regression analyses, six gene alterations including YAP1 amplification, RB1 alteration, BAP1 mutation, MYC amplification, WRN mutation, and BRIP1 mutation were identified as adverse prognostic factors in the AEC cohort. A Cox proportional hazard model based on the six prognosis-related genes was constructed and showed the ability in distinguishing EC patients with poorer disease outcomes in AEC and two validation cohorts.Conclusion: Six gene alterations were found to be potential unfavorable prognostic markers that might provide guidance in the treatment management for EC patients.Keywords: esophageal cancer, YAP1, RB1, BAP1, MYC, BRIP1, WRN, overall survival, chemoradiotherapy

Ao Duan,1,&ast; Zemeng Ma,2,&ast; Wanshun Liu,1,&ast; Kai Shen,1,&ast; Hao Zhou,1,&ast; Shunbing Wang,3 Renyi Kong,4 Yuqi Shao,5 Yunzi Chen,2 Wei Guo,6 Feng Liu1 1Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 2Key Laboratory of Immune Microenvironment and Disease, Department of Immunology, Nanjing Medical University, Nanjing, 211100, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 4Department of Orthopedics, Xincheng Hospital of Traditional Chinese Medicine, Maanshan, 243131, Anhui, People’s Republic of China; 5Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, People’s Republic of China; 6Department of Urology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Guo; Feng Liu Email weiguo_gavin@163.com; njliuf@163.comBackground: Osteoarthritis (OA) is the most prevalent chronic joint disease globally. Loss of extracellular matrix (ECM) by chondrocytes is a classic feature of OA. Inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), secreted mainly by macrophages, promote expression of matrix degrading proteins and further aggravate progression of OA. 1,25-dihydroxyvitamin D (1,25VD) modulates inflammation thus exerting protective effects on cartilage tissue. However, the underlying mechanisms of 1,25VD activity have not been fully elucidated.Methods: The destabilization of the medial meniscus (DMM)-induced mice model of OA was established to investigate the protective effects of 1,25VD by micro-CT and Safranin-O and Fast Green staining. And the co-culture system between THP-1 cells and primary chondrocytes was constructed to explore the effects of vitamin D receptor (VDR) and 1,25VD on chondrogenic proliferation, apoptosis, and migration. The immunofluorescence staining and Western blot analysis were used to detect the expressions of ECM proteins and matrix degradation-associated proteases. Enzyme-linked immunosorbent assay (ELISA) was used to examine the expression levels of inflammatory cytokines.Results: The findings of the study showed that 1,25VD prevented cartilage degeneration and osteophyte formation by inhibiting secretion of inflammatory cytokines in OA mice model. These protective effects were exerted through the vitamin D receptor (VDR). Further studies showed that 1,25VD increased ubiquitination level of NLRP3 by binding to VDR, resulting in decrease in IL-1β and IL-18 secretion. These findings indicate that 1,25VD binds to VDR thus preventing chondrogenic ECM degradation by modulating macrophage NLRP3 activation and secretion of inflammatory cytokines, thus alleviating OA progression.Conclusion: Here, our study suggests that 1,25VD, targeting to VDR, prevents chondrogenic ECM degradation through regulating macrophage NLRP3 activation and inflammatory cytokines secretion, thereby alleviating OA. These findings provide information on a novel molecular mechanism for application of 1,25VD as OA therapy.Keywords: osteoarthritis, 1,25-dihydroxyvitamin D, vitamin D receptor, NLRP3, inflammatory cytokines

Weilong Xiao1,2 &ast;, Binghai Sun1 &ast;, Hui Zhou,3 Liting Fan,1,2 Changkang Sun,1 Yanhong Shao4 1College of Teacher Education, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Key Laboratory of Intelligent Education Technology and Application of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 3Jinhua Advanced Research Institute, Jinhua, Zhejiang, People’s Republic of China; 4Zhejiang International Studies University, Hangzhou, Zhejiang, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Changkang SunCollege of Teacher Education, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, Zhejiang, People’s Republic of ChinaEmail 1158067980@qq.comYanhong ShaoZhejiang International Studies University, 299 Liuhe Road, Xihu District, Hangzhou, 310013, Zhejiang Province, People’s Republic of ChinaEmail yhshao2003@126.comPurpose: People choose actions that maintain their moral self-regard. This paper explains how one’s moral actions influence moral self-regard. The moral threshold model (MTM) has been proposed by scholars and tested using a limited sample. However, whether the MTM is universally applicable among people is still unknown.Participants and Methods: Our sample comprised 1761 individuals living in China, a collectivist culture, who were recruited to test the two main hypotheses of the MTM. Participants engaged in a hypothetical investment task.Results: 1) When the beneficiary was a prosocial cause, participants showed stronger preferences for smaller guaranteed positive payouts over larger uncertain ones; 2) as compared to making decisions for charities, when a participant made decisions exclusively for themselves, the maximum potential benefit was more likely to influence participant behavior.Conclusion: The current study provides initial evidence for the validity of using the worst outcome avoidance (WOA) hypothesis of MTM among members of China’s collectivist culture, indicating that the WOA hypothesis of MTM may have universal application.Keywords: collectivist culture, morality, moral self-regard, prosocial behavior, egoistic behavior

Yue Shao,1 Jun Luo,1 Liu Ye,2 Hao-Yu Ran,1 Hao-Ming Shi,1 Cheng Zhang,1 Qing-Chen Wu1 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2The First Branch, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Cheng Zhang; Qing-Chen WuDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaEmail zhangchengcqmu@126.com; wuqingchencqmu@126.comBackground: Long non-coding RNAs (lncRNAs) can act as a competitive endogenous RNA (ceRNA) to regulate gene expression by sequestering the microRNA (miRNA). However, the lncRNA-miRNA-mRNA ceRNA network in thoracic aortic dissection (TAD) has been rarely documented.Methods: Three Gene Expression Omnibus (GEO) datasets were used to detect differentially expressed mRNAs, miRNAs, and lncRNAs in TAD. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the differentially expressed mRNAs. A protein–protein interaction network for differentially expressed mRNAs was also constructed, and hub genes were identified. We established a ceRNA network of TAD based on the differentially expressed miRNAs, mRNAs and lncRNAs, and verified our results using an independent dataset and quantitative real-time PCR (qRT-PCR).Results: In TAD, 267 lncRNAs, 81 miRNAs, and 346 mRNAs were identified as differentially expressed. The established ceRNA network consisted of seven lncRNA nodes, three mRNA nodes, and three miRNA nodes, and the expression of miRNAs in TAD was opposite to that of lncRNAs and mRNAs. Subsequently, an independent GEO dataset and qRT-PCR were used to validate the expression of three mRNAs. In addition, the expression differences in SLC7A5, associated miRNA and lncRNA were verified. According to gene set enrichment analysis of SLC7A5, the most significant KEGG pathway was considerably enriched in spliceosome and pentose phosphate pathway.Conclusion: We established a novel ceRNA regulatory network in TAD, which provides valuable information for further research in the molecular mechanisms of TAD.Keywords: bioinformatics analysis, ceRNA, expression profile, thoracic aortic dissection

Wanyong Huang,&ast; Bo Zhou,&ast; Yingwei Li,&ast; Yuansheng Shao, Bo Peng, Xianchun Jiang, Tao Xiang Department of Neurosurgery, People’s Hospital of Guanghan City, Guanghan City, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanyong HuangDepartment of Neurosurgery, People’s Hospital of Guanghan City, 75 Hankou Road, Luocheng Town, Guanghan City, Sichuan Province, People’s Republic of ChinaEmail huangwy459088699@163.comObjective: Decompressive craniectomy as a treatment is often used in the rescue treatment of critically ill patients in neurosurgery; however, there are many complications after this operation. Subdural effusion is a common complication after decompressive craniectomy. Once it occurs, it can cause further problems for the patient. Therefore, the purpose of this study was to explore the safety and effectiveness of pressure dressings for subdural effusion after decompressive craniectomy.Methods: Patients who underwent decompressive craniectomy in our hospital from January 2016 to January 2021 were included in this study, and all patients were followed up for 6 months or more. After the operation, the patients were divided into two groups according to whether they received a pressure dressing or a traditional dressing. Subdural effusion, cerebrospinal fluid leakage, hydrocephalus and other complications were compared between the two groups, and the differences in hospital duration, cost and prognosis between the two groups were analyzed.Results: A total of 123 patients were included in this study. Among them, 62 patients chose pressure dressings, and 61 patients chose traditional dressings. The incidence of subdural effusion in the pressure dressing group was significantly lower than that in the traditional dressing group (P< 0.05). There was no difference between the two groups in cerebrospinal fluid leakage and hydrocephalus (P > 0.05). In addition, the length of hospital stay and the total cost in the pressure dressing group were significantly lower (P< 0.05).Conclusion: Pressure dressing can effectively reduce the occurrence of subdural effusion after decompressive craniectomy, and it does not increase the occurrence of other cerebrospinal fluid-related complications.Keywords: decompressive craniectomy, complication, pressure dressing, subdural effusion

Kangjun Zhang,1 Taishi Fang,1 Yajie Shao,2 Yanhui Wu3 1Hepatic Surgery Department, The Third People’s Hospital of Shenzhen, Shenzhen City, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People’s Republic of China; 3Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People’s Republic of ChinaCorrespondence: Yanhui WuHepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan City, Hubei Province, 430030, People’s Republic of ChinaTel +86-027-83665313Email Wuyanhai_yhiw@163.comIntroduction: Enhancer of zeste homolog 2 (EZH2) is implicated in hepatocellular carcinoma (HCC), but whether transforming growth factor-β (TGF-β)-metastasis associated 1 (MTA1)-SMAD7-SMAD3-SRY-Box Transcription Factor 4 (SOX4)-EZH2 signaling axis, in which EZH2 participates, is also involved in HCC remained unknown.Methods: Data on EZH2 expression in liver hepatocellular carcinoma (LIHC) and its relation with prognosis of HCC patients were predicted and analyzed using online databases. Following transfection with or without TGF-β 1, HCC cell viability, migration and invasion were determined with MTT, Scratch and Transwell assays. Relative expressions of epithelial-to-mesenchymal transition (EMT)-related factors (N-Cadherin, Vimentin, and E-Cadherin) and TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 signaling axis factors (TGF-β, MTA1, SMAD7, phosphorylated-SMAD3, SOX4 and EZH2) were calculated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot.Results: EZH2 was upregulated in HCC, which was related to poor prognosis. Silencing EZH2 suppressed EZH2 expression and HCC cell viability, migration, and invasion, and increased E-Cadherin expression yet decreased N-Cadherin and Vimentin expression, whereas EZH2 overexpression did conversely. Also, silencing EZH2 reversed the effects of TGF-β 1 on promoting viability, migration, and invasion, as well as N-Cadherin and Vimentin expressions, yet suppressing E-Cadherin expression in HCC cells. In addition, TGF-β 1 promoted TGF-β, MTA1, SOX4 and EZH2 expressions and p-SMAD3/SMAD3 ratio yet suppressed SMAD7, whereas silencing EZH2 solely reversed the effects of TGF-β 1 on EZH2 expression in HCC cells.Conclusion: The present study provides a theoretical basis for TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 signaling cascade in viability, migration, invasion, and EMT of HCC cells. Inhibiting these signals may represent a therapeutic pathway for the treatment of metastatic HCC.Keywords: hepatocellular carcinoma, enhancer of zeste homolog 2, transforming growth factor-β, metastasis, metastasis associated 1-SMAD7-SMAD3-SRY-box transcription factor 4 axis, MTA1-SMAD7-SMAD3-SOX4 axis

Yanxiang Shao,1,&ast; Xiang Tu,1,&ast; Yang Liu,1,&ast; Yige Bao,1 Shangqing Ren,1,2 Zhen Yang,1,3 Xu Hu,1 Kan Wu,1 Hao Zeng,1 Qiang Wei,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, Sichuan, People’s Republic of ChinaTel +86 18980601428Email xiangli87@hotmail.comObjective: To investigate the predictive factors of lymph node metastasis (LNM) and evaluate the usefulness of prediction nomograms.Methods: This study included 300 patients diagnosed with penile squamous cell carcinoma at West China Hospital (WCH) of Sichuan University (Chengdu, China) and 412 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis was performed on these cohorts to investigate the predictive factors of LNM. We evaluated a recently developed prediction nomogram for LNM, which was established based on the National Cancer Database (NCDB). Moreover, we developed a novel nomogram using cases from the WCH for the prediction of lymphatic metastasis.Results: Logistic analysis identified that younger age at diagnosis, invasion of the penis body, poorer pT stage, cN stage, nuclear grade and the presence of lymph vascular invasion (LVI) were significantly correlated with LNM in WCH cases; however, only race, poorer T stage and cN stage were significantly associated with LNM among the cases from the SEER. Multivariate analysis demonstrated that younger age, poorer T stage, cN stage and nuclear grade were independent predictors of LNM. Receiver operating characteristic curve analysis of WCH cases showed that the tumor T stage 8th edition has better area under the curve than 7th stage (0.672 vs 0.636, respectively). Moreover, well AUC was seen in external validation of NCDB nomogram in WCH cohorts and SEER series (0.833 vs 0.795). The new nomogram included the aforementioned independent predictors and the bootstrap-corrected concordance was 0.876.Conclusion: Younger diagnose age, poorer pT stage, cN stage, nuclear grade and LVI were the most important predictors of LNM in patients with penile cancer. 8th T stage performed better than 7th version in predicting LNM. NCDB nomogram has some application values in both WCH and SEER cases, and our novel model further improved the predictive accuracy.Keywords: penile cancer, lymph node metastasis, prediction model, nomogram, SEER

Jushan Sun,1 Yibiao He,1 Lei Bai,1 Zhipeng Wang,1 Zhu Cao,1 Yingmei Shao,2 Jinming Zhao1 1Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 2Xinjiang Uyghur Autonomous Region Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of ChinaCorrespondence: Jinming ZhaoDepartment of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137 of Liyushan Street, Xinshi District, Urumqi, Xinjiang, 830054, People’s Republic of ChinaTel/Fax +86-991-4364529Email zhaojm_m@outlook.comObjective: To investigate the risk factors related to new-onset diabetes mellitus (NODM) and the significance of IL-6.Methods: A retrospective analysis was conducted on clinical data from 64 patients who received either a living donor liver transplantation or a donation after circulatory death from September 2013 to October 2020 and attended regular follow-up visits for six or more months. During follow-up, patients were randomized into groups and followed up until the completion of the study or the death of the patient.Results: The incidence of NODM was 31.25% (n = 20). The median age in the NODM group was 52.15 years (p < 0.01). Age (OR = 1.089; 95% CI: 0.0211– 0.1495, p = 0.003) and elevated preoperative IL-6 (OR = 1.122; 95% CI: 0.0619– 0.1677, p = 0.029) were found to be independent risk factors for NODM. HBV-induced liver cirrhosis, warm ischemia time (WIT), body mass index (BMI), and high preoperative fasting blood glucose (FBG) were also found to be risk factors for NODM. The recipient had a higher risk of NODM if the donor had a high BMI and poor hepatic function. The concentrations of IL-6, procalcitonin (PCT), FBG, and tacrolimus (TAC) in the first month postoperatively were significantly higher in the NODM group than in the NO-NODM group. The survival rate of the patients was not affected by NODM.Conclusion: HBV-induced liver cirrhosis, WIT, BMI, and high preoperative FBG levels are risk factors for NODM, and age and preoperative IL-6 levels are independent risk factors. To a certain extent, higher BMI and poor hepatic function had reference significance for the incidence of NODM. Patients with a high concentration of FBG, IL-6, and TAC in the first month postoperatively had an increased risk of suffering from NODM.Keywords: liver transplantation, HBV, IL-6, immunosuppressants, NODM

Ang Xiao,1,&ast; Qian-Min Ge,1,&ast; Hui-Feng Zhong,2 Li-Juan Zhang,1 Hui-Ye Shu,1 Rong-Bin Liang,1 Yi Shao,1 Qiong Zhou1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Intensive Care, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shao; Qiong ZhouDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88692520; +86 791-88694639Email freebee99@163.com; qiongz-ms@126.comObjective: To explore the changes in gray matter volume (GMV) and white matter volume (WMV) in proliferative diabetic retinopathy (PDR) patients using voxel-based morphometry (VBM).Participants and Methods: In total, 15 patients (10 males, 5 females) with PDR were enrolled to the patient group and 15 healthy controls (10 males, 5 females) to the control group, matched for age, sex, handedness, and education status. All individuals underwent voxel-based morphometry scans. GMV and WMV were compared between the two groups.Results: GMV in bilateral superior temporal gyrus, sixth area of left cerebellum, left middle temporal gyrus, left orbital inferior frontal gyrus and left middle cingulum gyrus and WMV in left thalamus and left precuneus were significantly lower in patients than controls (P< 0.01). Conversely, WMV was significantly higher in bilateral lenticular putamen of patients than controls (P< 0.01).Conclusion: Abnormal GMV and WMV in many specific areas of the cerebrum provide new insights for exploration of the occurrence and development of DR and its pathophysiology.Keywords: voxel-based morphometric, white matter, gray matter, proliferative diabetic retinopathy

Yanxiang Shao,1,&ast; Thongher Lia,1,&ast; Yaohui Wang,1,&ast; Kan Wu,1 Xu Hu,1 Yang Liu,1 Shuyang Feng,1 Shangqing Ren,1,2 Zhen Yang,1,3 Sanchao Xiong,1 Weixiao Yang,1 Qiang Wei,1 Hao Zeng,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People’s Republic of ChinaEmail xiangli87@hotmail.comObjective: To evaluate the prognostic factors of penile cancer and the utility of prognostic models.Methods: We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan–Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models.Results: Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results.Conclusion: Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.Keywords: penile cancer, TNM stage, survival, nomogram, external validation

Yue Chen,1,&ast; Yan-Chang Yang,2,&ast; Li-Ying Tang,3,&ast; Qian-Min Ge,4 Wen-Qing Shi,1,4 Ting Su,3,5 Hui-Ye Shu,1,4 Yi-Cong Pan,1,4 Rong-Bin Liang,4 Qiu-Yu Li,4 Yi Shao4 1Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People’s Republic of China; 2Department of Anesthesiology, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People’s Republic of China; 4Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 5Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA&ast;These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, Jiangxi, 330006, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comObjective: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma.Methods: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients.Results: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001).Conclusion: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.Keywords: gastric adenocarcinoma, serological indicators, ocular metastases, risk factors, ROC curve

Yuan Ning,1 Yushuang Shao,1 Jiangyue Zhao,1 Jinsong Zhang,1 Mingwu Wang,2 Yu Qin1 1Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang, 110005, People’s Republic of China; 2Department of Ophthalmology and Vision Science, The University of Arizona College of Medicine, Tucson, Arizona, 85711-1824, USACorrespondence: Yu QinDepartment of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, No. 11 Xinhua Road, Heping District, Shenyang, 110005, People’s Republic of ChinaTel +86 24 62035015Fax +86 24 62035015Email yuqin_3620@163.comObjective: The aim of the present study was to evaluate the stability of four different types of aspheric intraocular lenses (IOLs) after implantation.Methods: This retrospective study included 124 eyes implanted with four different types of aspheric IOLs including a one-piece four-loop fixed hydrophilic acrylic IOL, a one-piece flat fixed acrylic IOL, a one-piece two-loop fixed acrylic IOL, and a three-piece two-loop fixed silicone IOL. IOL decentration, tilt, and ocular coma‐like aberration (coma) at one-week, one-month, three-month, and one-year time points were evaluated postoperatively.Results: IOL decentration, tilt, and coma in the AO, 36A, IQ, and KS-AiN implantation groups were statistically significantly different one week and one year postoperatively (p < 0.01). There were significant differences between each of the pairs of groups (p < 0.01), except for coma between the AO and 36A implantation groups one week postoperatively (p > 0.05). When comparing the different time points (ie, one week, one month, three months, and one year postoperatively), IOL decentration, tilt, and coma were significantly different in each group (p < 0.05). IOL decentration, tilt, and coma in each group increased over the period from one week to one year postoperatively. A positive linear correlation was observed between IOL decentration or tilt and coma one year postoperatively (p < 0.01).Conclusion: One-piece multi-point fixed acrylic IOLs demonstrate better stability when compared with three-piece two-point fixed silicone IOLs. IOL decentration, tilt, and coma increase gradually over time. Ocular coma‐like aberrations are influenced by the stability of IOLs.Keywords: stability, aspheric intraocular lens, IOL, decentration, tilt, coma

Si-Wen Tan,1,2,* Guo-Qian Cai,3,* Qiu-Yu Li,1,* Yu Guo,3 Yi-Cong Pan,1 Li-Juan Zhang,1 Qian-Min Ge,1 Hui-Ye Shu,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comXian-Jun ZengDepartment of Radiology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88694639Email 375135747@qq.comPurpose: Previous research suggests that diabetic optic neuropathy (DON) can cause marked anatomical and functional variations in the brain, but to date altered functional synchronization between two functional hemispheres remains uncharacterized in DON patients. Voxel mirrored homotopic connectivity (VMHC) is a voxel-based method to evaluate the synchronism between two mirrored hemispheric by determining the functional connectivity between each voxel in one hemisphere and its counterpart. In this study, we aim to assess abnormal changes in interhemispheric functional connectivity in DON patients via the VMHC method.Methods: The study included 28 adult DON patients (12 male, 16 female) and 28 healthy controls (12 male, 16 female) who were closely matched for sex and age. Participants were examined using resting-state functional magnetic resonance imaging. The VMHC method was applied to investigate the abnormal state in bilateral hemispheres in DON patients and the same regions in healthy controls, as well as the receiver operating characteristic (ROC) curves were used to evaluate characteristics. Associations between altered VMHC values in distinct cerebral regions and clinical features were assessed via correlational analysis.Results: Markedly lower VMHC values were evident in the right temporal inferior, the left temporal inferior, the right mid-cingulum, the left mid-cingulum, the right supplementary motor region, and the left supplementary motor region in DON patients compared with healthy controls. ROC curve analysis suggested that the application of VMHC is reliable for the diagnosis of DON.Conclusion: Anomalous interhemispheric functional connectivity in specific brain areas caused by DON may indicate neuropathologic mechanisms of vision loss and blurry vision in patients with DON.Keywords: diabetes, diabetic optic neuropathy, magnetic resonance imaging, resting-state functional MRI

Xianghui Zhang,1,* Yusong Ding,1,* Yinbao Shao,1 Jia He,1 Jiaolong Ma,1 Heng Guo,1 Mulatibieke Keerman,1 Jiaming Liu,1 Huili Si,2 Shuxia Guo,1,3 Rulin Ma1 1Department of Public Health, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China; 2Department of Neurology, Shihezi People’s Hospital, Shihezi, Xinjiang, People’s Republic of China; 3Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuxia GuoDepartment of Public Health, Shihezi University School of Medicine, Suite 721, Building No. 1, Beier Road, Shihezi, 832000, Xinjiang, People’s Republic of ChinaTel +86 1800-9932-625Fax +86 993-2057-153Email gsxshzu@sina.comRulin MaDepartment of Public Health, Shihezi University School of Medicine, Suite 816, Building No. 1, Beier Road, Shihezi, 832000, Xinjiang, People’s Republic of ChinaTel +86 1330-9930-561Fax +86 993-2057-153Email marulin@shzu.edu.cnBackground: Few studies have focused on the predictive ability of visceral obesity-related indices for metabolic syndrome (MetS), especially in different ethnic groups. This study aimed to evaluate the applicability of visceral obesity-related indices for MetS screening among three major ethnic groups living in remote rural areas of Xinjiang.Methods: Based on multistage stratified cluster random sampling method, 3,192 Uyghurs, 3,054 Kazakhs, and 3,658 Hans were recruited from Xinjiang, China. The Joint Interim Statement (JIS) criteria were used to define MetS. The receiver operating characteristic curve (ROC), area under the ROC curve (AUC), and predictive value of each visceral obesity-related index were used to evaluate the predictive ability of MetS.Results: After adjusting for potential confounding factors, the lipid accumulation product (LAP), Chinese visceral adiposity index (CVAI), waist-to-height ratio (WHtR), and atherogenic index of plasma (AIP) were significantly correlated with MetS for each ethnic group, and the odds ratios (ORs) for MetS increased across quartiles. LAP was best able to identify MetS status in Kazakhs (AUC=0.853) and Uyghurs (AUC=0.851), with optimal cut-offs being 36.3 and 28.2, respectively. Both LAP (AUC=0.798) and CVAI (AUC=0.791) most accurately identified MetS status in Hans, with the optimal cut-offs being 27.3 and 85.0, respectively. Moreover, the AUC of the combination of these visceral obesity-related indices is higher for each ethnic group. However, compared with LAP, the improved value of combined screening was not significant.Conclusion: LAP had the best discriminative capability for the screening of MetS among Kazakhs, Uyghurs, and Hans. The screening ability of CVAI for MetS was similar to that of LAP in Hans. Thus, LAP may be a complementary indicator for assessing MetS in various ethnic groups.Keywords: metabolic syndrome, visceral obesity-related indices, screening, ethnic groups

Mingfei Zhao,1,* Yijie Shao,1,* Jinfang Xu,1 Buyi Zhang,2 Chenguang Li,1 Jie Gong3 1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurointerventional, Zhejiang Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Gong Tel +86-15168248628Fax +86571-88098123Email orchidwave@163.comPurpose: LINC00466 is a newfound long non-coding RNA (lncRNA) that has been rarely explored in cancers. However, the specific role and molecular mechanism of LINC00466 in glioma remain to be further elucidated.Methods: Bioinformatic analysis was used to screen differentially expressed genes. Quantitative real-time PCR (qRT-PCR) was used to determine the expression of LINC00466, microRNA-137 (miR-137) and protein phosphatase 1 regulatory subunit 14B (PPP1R14B). Dual-luciferase reporter gene assay and RNA binding protein Immunoprecipitation (RIP) assays were employed to verify the binding relationship among LINC00466, miR-137 and PPP1R14B. The sensitivity of glioma cells to temozolomide (TMZ) was measured by cell counting kit-8 (CCK8) assay. The xenograft nude models were used to test the effects of LINC00466 on glioma tumor growth in vivo.Results: Highly expressed LINC00466 and PPP1R14B and lowly expressed miR-137 were eventually revealed in glioma tissues. Overexpression of LINC00466 could promote proliferation, metastasis and drug sensitivity to TMZ of glioma cells. LINC00466 could bind to miR-137, and up-regulation of miR-137 could attenuate the enhancing effects caused by LINC00466 overexpression. We took a further step and found that miR-137 could bind to PPP1R14B. Besides, LINC00466 could function as a sponge to miR-137 to regulate PPP1R14B. In addition, overexpression of LINC00466 could promote tumor growth in vivo.Conclusion: These findings validate LINC00466 could restrain the miR-137 expression to up-regulate PPP1R14B and therefore promote proliferation, metastasis and resistance to TMZ of glioma.Keywords: LINC00466/miR-137/PPP1R14B, glioma, proliferation and metastasis, temozolomide; TMZ

Yan-Chang Yang,1,* Qiu-Yu Li,2,* Min-Jie Chen,2 Li-Juan Zhang,2 Meng-Yao Zhang,1 Yi-Cong Pan,2 Qian-Min Ge,2 Hui-Ye Shu,2 Qi Lin,2 Yi Shao2 1Department of Ophthalmology, Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, 17 Yongwaizheng Street, Donghu, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail freebee99@163.comPurpose: The percent amplitude of fluctuation (PerAF) method was used to study the changes in neural activities and functions in specific brain regions of patients with a retinal detachment (RD).Patients and Methods: In this study, we recruited 15 RD patients (nine males and six females) and 15 healthy controls (HCs) matched for gender, age, and weight. All participants were scanned with resting functional magnetic resonance imaging (rs-fMRI). The PerAF method was then used for data analysis to evaluate and detect changes in neural activity in relevant brain regions. Receiver operating characteristic (ROC) curve analysis was used to evaluate the two groups.Results: The PerAF signal values of the right fusiform gyrus and the left inferior temporal gyrus of RD patients were significantly higher than those of HCs. This may indicate changes in neural activity and function in the related brain regions. The anxiety and depression scores of hospital anxiety and depression scale (HADS) and the durations in RD patients were positively correlated with the PerAF values of the left inferior temporal gyrus.Conclusion: In this study, we demonstrated that there were significant changes in the PerAF values in specific areas of the brain in patients with RD. The change of PerAF values represent the changes of BOLD signal intensity, which reflect the hyperactivity or weakening of specific brain regions in RD patients, which are helpful to predict the development and prognosis of RD patients, and play an important role in the early diagnosis of RD. In addition, according to the results, changes in neural activity in specific brain regions of RD patients increase the risk of brain dysfunction related diseases, which may help to understand the pathological mechanism of vision loss in RD patients.Keywords: retinal detachment, the percent amplitude of fluctuation, resting-state, functional magnetic resonance imaging, hospital anxiety and depression scale

Weijian Li,1,* Yang Zhang,1,2,* Youjian Li,1,3,* Yuepeng Cao,4 Jun Zhou,1 Zhongxu Sun,1 Wanke Wu,5 Xiaofang Tan,5 Yang Shao,5 Kaipeng Xie,5,6 Xiang Yan1,2 1Department of Nephrology and Urology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, People’s Republic of China; 3Department of Urology Surgery, The People’s Hospital of Xuancheng City, Xuancheng, People’s Republic of China; 4Department of Critical Care Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, People’s Republic of China; 5Nanjing Maternity and Child Health Care Institute, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 6Department of Women’s Health Care, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang YanDepartment of Nephrology and Urology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of ChinaEmail yanxiang@zju.edu.cnKaipeng XieNanjing Maternity and Child Health Care Institute, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing 210004, People’s Republic of ChinaTel/Fax +86-25-5222-6264Email kaipengxienjmu@163.comBackground: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study.Methods: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases.Results: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, P < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that 45HFNPRFNAHGDAN 57 derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.Conclusion: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.Keywords: peptide, therapeutic target, progression, bladder cancer

Cuiyun Su,1 Ya Jiang,2 Wei Jiang,1 Huilin Wang,1 Sisi Liu,2 Yang Shao,2 Wenhua Zhao,1 Ruiling Ning,1 Qitao Yu1 1Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China; 2Department of Research and Development, Nanjing Geneseeq Technology Inc, Nanjing, Jiangsu, ChinaCorrespondence: Qitao Yu Email yqt133@126.comAbstract: Non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) rearrangement benefit from treatment with ALK inhibitors. Therefore, the identification of druggable ALK fusions is necessary for NSCLC treatment. More than 90 fusion partners of ALK have been reported in NSCLC patients, but the striatin gene (STRN)-ALK fusion has rarely been reported. Moreover, the response of STRN-ALK fusion patients treated with ALK inhibitors remains to be explored. A 64-year-old Chinese male with no history of smoking or alcohol consumption was diagnosed as stage IVB lung adenocarcinoma (LADC) (cT4N3M1c) in October 2018. Next-generation sequencing (NGS) targeting 425 cancer-related genes was performed on the plasma and supernatant of pleural effusion samples and revealed an STRN-ALK fusion. The patient received alectinib (600 mg, twice daily) as the first-line treatment with an excellent response exceeding 19 months. This is the first report of a NSCLC patient harboring an STRN-ALK fusion and exhibiting an excellent response to alectinib treatment. This case provides valuable information for therapeutic decision-making of patients with STRN-ALK fusions. Furthermore, this case also highlighted the advantage of performing targeted NGS on circulating tumor DNA for the identification and analysis of rare, druggable genomic alterations.Keywords: lung adenocarcinoma, STRN-ALK fusion, ctDNA, alectinib, targeted NGS

Lijun Huang,1 Qiusheng Ren,1 Shenghui Yu,1 Ya Shao,1 Yijun Chen,2 Xin Huang1 1Department of Anesthesiology, Ningbo Yinzhou People’s Hospital, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Lijun HuangDepartment of Anesthesiology, Ningbo Yinzhou People’s Hospital, The Affiliated People’s Hospital of Ningbo University, No. 251, East Baizhang Road, Ningbo, Zhejiang Province 315040, People’s Republic of ChinaEmail huanglijunyz@163.comObjective: The goal of the study was to investigate the efficacy of lipid supplement to epinephrine-based therapy in resuscitation of asphyxia-induced cardiac arrest in aged rats.Methods: The study included two parts: in experiment A, rats underwent asphyxial cardiac arrest and cardiopulmonary resuscitation, randomized to receive epinephrine and normal saline (control group, n=22), epinephrine and intralipid 20% (long-chain triglycerides (LCT) group, n=22) or epinephrine and lipovenoes 20% (LCT/medium-chain triglcerides (MCT) group, n=22). Return of spontaneous circulation, recurrence of asystole after resuscitation, hemodynamic metrics, arterial blood gas values, neurological assessment score and indexes of pulmonary transudation were recorded. In experiment B, rats using the same model and resuscitation protocol were randomly divided into 21 groups: Control 0, Control 20, Control 40, Control 60, Control 80, Control 100, Control 120, LCT 0, LCT 20, LCT 40, LCT 60, LCT 80, LCT 100, LCT 120, LCT/MCT 0, LCT/MCT 20, LCT/MCT 40, LCT/MCT 60, LCT/MCT 80, LCT/MCT 100 and LCT 120 (n=10, the subscripts represent respective endpoint of observation in minutes). Myocardial bioenergetics were determined.Results: In experiment A, the LCT and LCT/MCT groups had a shorter time to return of spontaneous circulation (ROSC) (P=0.001and P< 0.001, respectively) and higher survival rate (P=0.033 and P=0.014, respectively) compared with the Control group. The LCT/MCT group had higher MAP (P< 0.001 and P=0.001, respectively), HR (P< 0.001 and P=0.004, respectively) and RPP (P< 0.001 and P< 0.001, respectively) compared with the Control and LCT groups, respectively. In experiment B, the LCT/MCT group had a higher energy charge compared with the control group at 20 (P< 0.001) and 40 (P< 0.001) minutes. The LCT group had higher energy charge compared with the Control group at 40 (P< 0.001) and 60 (P< 0.001) minutes.Conclusion: The supplement of lipid emulsion to epinephrine improves resuscitation outcomes of asphyxia-induced cardiac arrest than epinephrine alone in our in vivo model of aged rat. LCT/MCT emulsion may be superior to LCT emulsion in epinephrine-based resuscitation.Keywords: asphyxia, cardiac arrest, epinephrine, lipid emulsion, cardiopulmonary resuscitation

Wenwu He,1,* Xuefeng Leng,1,* Yanyu Yang,2,* Lin Peng,1 Yang Shao,3,4 Xue Li,3 Yongtao Han1 1Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Department of Radiology, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Medicine, Nanjing Geneseeq Technology, Inc, Nanjing, Jiangsu, People’s Republic of China; 4School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongtao Han Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of MedicineUniversity of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of ChinaTel +86-28-85420229Email yongtao_han@126.comBackground: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with significant geographical variation and familial aggregation. However, the potentially different mechanisms underlying tumorigenesis in patients with ESCC with and without a family history of the disease remain unclear. In this study, the genes mutated in familial and nonfamilial ESCC were analyzed. Further, we aimed to explore the genes related to ESCC and attempt to identify potential patients in families with a history of ESCC.Methods: Next-generation sequencing technology was used to examine germline mutations and mutation profiles in 36 matched tumor-normal ESCC specimens. Additionally, tumor mutational burden (TMB) values were measured in two cohorts.Results: We identified four novel germline mutations in patients with familial ESCC, in BAX (c.121dupG: p.E41G), CDKN2A (c.374dupA: p.D125E), TP53 (c.856G>A: p.E286K), and CHEK1 (c.923+1G>A). Mutation profiles revealed that patients with and without a family history of ESCC had similar high-frequency gene mutation profiles, among which TP53 was the most commonly mutated gene. Additionally, tumor-specific mutated genes in patients with a positive family history of ESCC were APC, AKT3, DPYD, EP300, NFE2L2, PPP2R1A, RUNX1, and VEGFA, while those in patients without a family history of ESCC were CXCR4, PIK3R2, SMARCA4, and TTF1. Moreover, patients with positive family history had significantly higher TMB values (7.8 ± 4.1 vs 5.0 ± 2.4, for patients with and without a family history, respectively; P = 0.038).Conclusion: Our results identified mutation profiles in patients with familial and nonfamilial ESCC, and identified germline mutations in patients with positive history. TMB values may be informative for immunotherapy approaches in familial ESCC.Keywords: esophageal squamous cell carcinoma, genetic heterogeneity, family heredity

Ya-Jie Yu,1,* Rong-Bin Liang,1,* Qi-Chen Yang,2,* Qian-Min Ge,1 Qiu-Yu Li,1 Biao Li,1 Wen-Qing Shi,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong 999077, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Shao Tel/ Fax +86 791-88692520Email freebee99@163.comObjective: Previous studies demonstrated that myopia could result in alterations of brain activity in specific areas. However, whether the visual function could improve by Lasik surgery, with the brain activity alterations also change, is still unknown. Here, we intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in pre-Lasik (PRL) and post-Lasik (POL) patients.Methods: A total of 15 patients with myopia (nine male and six female) were recruited in our study, who were matched according to age, weight, and height. These patients comprised both the PRL and POL groups, which is self-controlled. The patients all underwent resting-state functional magnetic resonance imaging (MRI), and the spontaneous brain activity changes were recorded by the ALFF technique. The data were recorded and arranged in the receiver operating characteristic (ROC) curve, which presented how intrinsic activities altered in different brain regions. Moreover, by Graphpad prism 8, we can analyze the linear correlation between HADS (Hospital Anxiety and Depression Scale) and ALFF values as well.Results: Differences in ALFF values existed in brain regions between the same patient before and after the Lasik operation. The regions with increased ALFF values after Lasik surgery were the left parahippocampal gyrus, cerebellar vermis, and left posterior cingulate cortex. The regions with decreased ALFF values after Lasik surgery were the left supramarginal gyrus and right trigonometric inferior frontal gyrus.Conclusion: We demonstrated significant fluctuations of ALFF values in specific brain areas between the same patients before and after the Lasik surgery. The altered ALFF values reflected the hyperactivity or hypoactivity of the specific brain areas, which may help predict the recovery level of patients’ vision after Lasik surgery. Furthermore, based on the experimental results that presented significant activity alterations in specific brian regions, patients could be speculated equipped with a better visual function.Keywords: myopia, Lasik, resting-state functional MRI, amplitude of low-frequency fluctuation

Zhou Zhou,1– 3 Pei-Wen Zhu,3 Wen-Qing Shi,3 You-Lan Min,3 Qi Lin,3 Qian-Min Ge,3 Biao Li,3 Qing Yuan,3 Yi Shao3 1Institute of Pathogenic Biology, Medical College, University of South China, Hengyang 421001, Hunan, People’s Republic of China; 2Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, Hunan, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of ChinaCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Tel/ Fax +86 791-88692520Email freebee99@163.comPurpose: Brain function in patients with acute eye pain (EP) has not been extensively studied. An understanding of the alterations in short-range functional connectivity density (shortFCD) and long-range functional connectivity density (longFCD) in patients with EP remains elusive. The aim of the present study was to compare the functional connectivity density (FCD) between patients with EP and healthy controls (HCs) using resting-state functional connectivity.Methods: A total of 40 patients with EP (26 males and 14 females) and 40 HCs (26 males and 14 females) of similar age underwent functional magnetic resonance (MR) examination at the resting state. The shortFCD and longFCD values were compared using the one-sample t-test. The differences between patients with EP and the HCs were evaluated using receiver operating characteristic (ROC) curves.Results: In the patients with EP, significantly reduced shortFCD values were observed in the left posterior lobe of the cerebellum, right inferior parietal lobule, and left anterior lobe of the cerebellum, and significantly reduced longFCD values were observed in both the left and right posterior lobe of the cerebellum. Significantly increased shortFCD values were also observed in both superior frontal gyri (Brodmann area 6), and increased longFCD values were observed in the left inferior temporal gyrus and left superior frontal gyri (Brodmann area 11). Compared with the HCs, less reduction was noted among the shortFCD values of patients with EP in the right posterior lobe of the cerebellum, right supramarginal gyrus, left middle temporal gyrus, bilateral superior frontal gyri, and bilateral caudate nuclei.Conclusion: EP patients shown variation of binarized shortFCD and long FCD in brain areas including premotor cortex, ventral cortical visual system, newest part of the cerebellum, cerebellum control unconscious proprioception, inhibition of involuntary movement, somatosensory association cortex, nucleus involving reward system and ventral cortical visual system which might provide an explanation of brain functional compensation for chronic eye pain and visual impairment in the EP patients.Keywords: eye pain, magnetic resonance imaging, functional connectivity density

Shuo Wu, Liucheng Ding, Hewei Xu, Jie Gao, Yunpeng Shao, Sicong Zhang, Zhongqing Wei Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Zhongqing WeiDepartment of Urology The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaEmail weizq1@163.comPurpose: Long non-coding RNAs (lncRNAs) are involved in the development of various tumors including prostate cancer. The purpose of this study was to explore the function of a natural antisense RNA, IDH1-AS1, exerting potential carcinogenic effects in prostate cancer through a novel molecular mechanism.Materials and Methods: GEPIA and CCLE databases were searched to identify alterations in the expression of IDH1-AS1, which were then verified by RT-qPCR in 20 pairs of matched tumor and normal tissue samples. Subsequently, CCK-8, EdU, and transwell assays were conducted to investigate the carcinogenic effect of IDH1-AS1. RT-qPCR, Western blot, and isocitrate dehydrogenase 1 (IDH1) enzyme activity assays were used to explore the functional relationship between IDH1-AS1 and its sense gene IDH1.Results: IDH1-AS1 expression was found to be significantly increased in prostate cancer tissues and cell lines. IDH1-AS1 knockdown significantly inhibited the proliferation and migration of prostate cancer cells. Interestingly, RT-qPCR and Western blot analyses revealed that IDH1-AS1 did not significantly affect the expression of IDH1 mRNA or protein but was involved in the regulation of IDH1 enzyme activity in prostate cancer cells.Conclusion: Our experiments revealed that the carcinogenic effects of IDH1-AS1 in prostate cancer may depend on a new molecular mechanism, which directly alters IDH1 enzyme activity. Our findings indicate that IDH1-AS1 is a novel candidate target for prostate cancer treatment.Keywords: antisense RNA, divergent transcription, bioinformatics analysis, enzyme activity

Jingjing Dai,1,* Longfeng Jiang,1,* Lei Qiu,2,* Yuyun Shao,1,* Ping Shi,1 Jun Li1 1Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of General Surgery, The Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Li Email dr-lijun@vip.sina.comBackground: Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1) plays key regulatory roles in cancer development and progression. However, its specific functions and potential mechanisms of action remain to be described in hepatocellular carcinoma (HCC).Materials and Methods: WHSC1 expression in HCC was evaluated using The Cancer Genome Atlas and verified in HCC tissues and cell lines using qRT-PCR, Western blotting, and immunohistochemistry. Functional assays were performed to explore the role of WHSC1 in HCC progression. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, immunofluorescence, and immunohistochemistry were conducted to evaluate the interaction between WHSC1 and prolyl 4-hydroxylase subunit beta (P4HB). Pathway enrichment was performed using gene set enrichment analysis.Results: WHSC1 was markedly overexpressed in HCC tissues and cell lines. The level of expression was strongly associated with adverse clinicopathological characteristics. Survival analyses revealed that WHSC1 upregulation predicted poor overall survival and higher recurrence rates in patients with HCC. Functional studies revealed that WHSC1 significantly stimulated HCC proliferation, migration, and invasion in vitro and in vivo. WHSC1 was shown to interact with P4HB to stimulate P4HB expression and subsequently activate mTOR1 signaling.Conclusion: We determined the oncogenic role of WHSC1 in HCC, via P4HB interaction, which activates mTOR1 signaling, and identified WHSC1 as a promising therapeutic target for HCC.Keywords: apoptosis, metastasis, P4HB, poor prognosis, hepatocarcinogenesis

Shou-Long Hu,1,2,* Li-Ying Tang,3,* Jian-Wen Fang,2,* Ting Su,3 Qian-Min Ge,2 Qi Lin,2 Biao Li,2 Wen-Qing Shi,2 Qiu-Yu Li,2 Rong-Bin Liang,2 Yi Shao2 1National Center for Children’s Health, MOE Key Laboratory of Major Diseases in Children, Department of Ophthalmology, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006, Jiangxi, People’s Republic of China; 3Department of Ophthalmology, Xiang’an Hospital of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Eye Institute of Xiamen University; Xiamen University School of Medicine, Xiamen 361102, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Shao Email freebee99@163.comPurpose: To investigate differences in the functional connectivity (FC) of the primary visual cortex between patients with corneal ulcer (CU) and healthy controls (HCs) using resting-state functional magnetic resonance imaging.Patients and Methods: A total of 30 patients with CU and 30 HCs were closely matched in terms of sex, age, and level of education. Two-sample t-test, receiver operating characteristic curve, and Pearson’s correlation coefficient analyses were used to determine the differences in FC between the two groups, the mean FC value of patients with CU and HCs, and the correlation between FC signal values and clinical manifestations in different brain regions of patients.Results: The CU group showed significantly elevated FC in the left and right middle frontal gyri and lower FC with the right cuneus compared with the HC group. In addition, the FC of the right cingulate and left superior frontal gyri also increased in the CU group. The receiver operating characteristic curve revealed high diagnostic value in those brain regions.Conclusion: CU involves aberrant FC of the primary visual cortex in different brain areas, including visual-related and cognitive-related regions. This finding may unveil the underlying neural mechanisms of impaired visual function in CU.Keywords: corneal ulcer, functional magnetic resonance imaging, resting state, spontaneous brain activity, primary visual cortex