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Shuai Tang,1– 4 Wenyu Feng,2– 4 Zekun Li,1 Xinjuan Liu,1 Tong Yang,1– 4 Fulan Wei,2– 4 Gang Ding1 1School of Stomatology, Shandong Second Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Shandong Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Gang Ding, School of Stomatology, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, Shandong, 261053, People’s Republic of China, Email dinggang@sdsmu.edu.cn Fulan Wei, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Wenhua West Road No. 44-1, Jinan, Shandong, 250012, People’s Republic of China, Email weifl@sdu.edu.cnIntroduction: Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.Methods: A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.Results: The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.Conclusion: LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway. Keywords: inflammatory bowel disease, periodontal ligament stem cells, extracellular vesicles, gut microbiota, PI3K/AKT signaling pathway

Huan Tang, Wenjuan Di, Hanmei Qi, Juan Liu, Jing Yu, Jinmei Cai, Bing Lai, Guoxian Ding, Peng Cheng Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Peng Cheng, Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-25-68305171, Fax +86-25-83724440, Email cphh@sohu.comPurpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies.Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up.Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was − 0.17% in men aged 36 to 85 years, with the fastest decrease rate − 1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions.Conclusion: In men aged 36∼ 85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men.Keywords: age-related, bone loss, bone mineral density, men, osteoporosis, trabecular bone score

Sirui Song,1 Liqin Chen,1 Qianqian Ning,2 Danying Zhu,1 Feng Qiu,2 Guang Li,2 Hong Zhang,3 Tingting Xiao,1 Guohui Ding,4 Min Huang1 1Department of Cardiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Center for Bioinformation Technology, Shanghai, People’s Republic of China; 3Department of Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4International Human Phenome Institutes, Shanghai, 200235, People’s Republic of ChinaCorrespondence: Min HuangDepartment of Cardiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email huangmin@sjtu.edu.cnGuohui DingInternational Human Phenome Institutes, Shanghai, 200235, People’s Republic of China, Email dingguohui@ihup.org.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis mainly found in the medium-sized arteries, especially the coronary arteries. Immune system is involved in the pathogenesis of acute KD in children, but the functional differences in the immune system between healthy children and KD patients remain unclear.Patients and Methods: A total of 190 KD patients and 119 healthy controls were recruited for the next-generation sequencing of 512 targeted genes from 4 immune-related pathways. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated. RNA sequencing of the LPS treated PBMCs from additional 20 KD patients and 20 healthy controls was used to examine the differentially expressed genes (DEGs). Then, an expression quantitative trait locus (eQTL) analysis combined with previously analyzed RNA data were used to examine the DEGs. Finally, the serum levels of 13 cytokines were detected before and after LPS treatment in 40 samples to confirm the findings from eQTL analysis.Results: A total of 319 significant eQTL were found, and both eQTL analysis and RNA sequencing showed some DEGs were involved in the connective tissue disorders and inflammatory diseases. DEGs that function to negatively regulate immunity were closely related to the pathogenesis of KD. In addition, the serum levels of IL-10 (an inflammatory and immunosuppressive factor) and SCD25 (an important immunosuppressant) reduced significantly in the KD patients.Conclusion: Our study shows the expression of factors responsible for the negative control of innate immunity is altered, which plays an important role in the etiology of KD.Keywords: Kawasaki disease, innate immunity, inflammation, next generation sequencing, cytokines

Lei Jin,1,&ast; Xuemei Ma,2,&ast; Nan Zhang,3 Qian Zhang,4 Xueming Chen,1 Zhongtao Zhang,2 Guoqian Ding,2 Hongzhi Yu1 1Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Radiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhi Yu; Guoqian Ding Email HongzYu@yeah.net; dingguoqiandgq@yeah.netPurpose: This study aimed to explore the value of miR-181a-2-3p in cisplatin (DDP) treatment effectiveness prediction, and to reveal the function underlying the reversal of DDP resistance in patients with gastric cancer (GC).Methods: miRNA expression dataset of three DDP-resistant GC cell lines and their DDP-sensitive parental cell lines obtained from GEO DataSets and GenBank, and functional miRNAs were annotated by bioinformatics analyses. Serum specimens and tumor samples were collected from 91 GC patients for understanding of the interrelation between chemotherapy response and miRNA expression. RT-qPCR validated these miRNAs at the transcriptional level in both gastric cancer cells and 91 gastric cancer patients. The correlation between the miRNAs expression and clinical parameters of the patients were analyzed. Receiver operating characteristics (ROC) analysis has been utilized to assess the diagnostic performance. The MTT and colony formation assays were performed to assess cell proliferation. Flow cytometry was conducted to detect cell apoptosis. DDP-resistant GC cells and their DDP-sensitive parental cells were transfected with miRNA mimic or inhibitor vector to overexpress or downregulate miRNA expression.Results: miR-181a-2-3p as a unique miRNA was found in the common differentially expressed-miRNAs (DE-miRNAs) after miRNA screening and validation from three DDP-resistant and DDP-sensitive gastric cancer cell lines. Clinical data analysis displayed that miR-181a-2-3p expression was apparently increased in larger tumor size (≥ 5 cm), higher T stage (T4), and chemotherapy resistance. miR-181a-2-3p (AUC=0.926, SE=0.028, 95% CI: 0.872– 0.980, p< 0.0001) differentiated chemosensitive GC patients from chemoresistant GC patients. miR-181a-2-3p presented a higher level in gastric cancer, and could serve as a valid biomarker to predict the overall survival of GC patients. Upregulation of miR-181a-2-3p rendered the apoptosis-inducing and anti-proliferative effects of DDP, while downregulating it decreased these effects.Conclusion: miR-181a-2-3p can function as a therapeutic target and a tumor biomarker. Targeting oncogenic miR-181a-2-3p inhibits growth and suppresses cisplatin resistance of gastric cancer.Keywords: biomarker, miR-181a-2-3p, cisplatin resistance, gastric cancer, bioinformatic analysis

Yi Wang,1 Wenhua Li,1 Hongmei Zhang,1 Qingfeng Zhang,1 Geqi Ding,1 Zhiyu Guo,2 Yan Deng,1 Chunmei Li,1 Lixue Yin1 1Key Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2GE Cardiovascular Ultrasound Clinical & Research Department, Chengdu, People’s Republic of ChinaCorrespondence: Lixue YinKey Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32#, Xierduan, 1st Ring Road, Chengdu, People’s Republic of ChinaTel +86 18981838968Email yinlixue_cardiac@163.com; yinlixue8968@126.comPurpose: Left ventricular (LV) contractile reserve is commonly used for LV systolic function assessment, while data on normal LV contractile reserve to exercise and the effect of gender on it are contradictory and limited, especially in Chinese adults. The aims of the present study are to clarify echocardiographic normal reference of LV contractile reserve during treadmill exercise stress echocardiography in healthy Chinese adults and to evaluate the sex-specific impact on it.Patients and Methods: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed.Results: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed.Conclusion: Traditional LV contractile reserve of men was much higher than that of women in a healthy Chinese population. The difference might be because of higher BSA in men. ΔGLS was less influenced by METs and CI at rest compared to ΔEF. ΔGLS, and especially the ΔGLS index, might be considered as a more preferable contractile reserve parameter for clinical cardiac function evaluation.Keywords: stress echocardiography, treadmill stress test, left ventricular contractile reserve, longitudinal strain

Huashan Li,1,* Jianying Sheng,1,* Jing Wang,1 Haiting Gao,1 Jing Yu,2 Guoxian Ding,2 Ning Ding,1 Weiqi He,1,3 Juanmin Zha1 1Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Geriatrics, Division of Geriatric Endocrinology, The First Affiliated Hospital to Nanjing Medical University, Nanjing, People’s Republic of China; 3State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiqi He; Juanmin ZhaCambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, 199 Ren-Ai Road, Suzhou, 205123, People’s Republic of ChinaTel +86-512-6588-3545Fax +86-6588-3562Email whe@suda.edu.cn; zhajuanmin@suda.edu.cnIntroduction: The effect of 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1) inhibition on hepatic steatosis is incompletely understood. Here, we aimed to determine the therapeutic effect of BVT.2733, a selective 11β-HSD1 inhibitor, on hepatic steatosis.Materials and Methods: C57B/6J mice were randomly divided into a low-fat diet (LFD) fed group and a high-fat diet (HFD) fed group. Mice were fed with HFD for 28 weeks which induced obesity and severe hepatic steatosis. The two groups were further divided into four groups as follows: LFD, LFD with BVT.2733, HFD, and HFD with BVT.2733. Mice in LFD+BVT and HFD+BVT groups were intraperitoneally injected with BVT.2733 daily for 30 days. Effects of BVT.2733 on mice body weight, serum lipid profile, serum free fatty acids (FFAs), glucocorticoid levels, gene expression in adipose and liver tissues were assessed.Results: Injection of a low dose of BVT.2733 (50 mg/kg/day) reduced body weight and hyperlipidemia, but did not improve glucose tolerance and insulin resistance in diet-induced obese mice. The low dose of BVT.2733 attenuated hepatic steatosis, liver injury, and liver lipolytic gene expression in diet-induced obese mice. Besides, the low dose of BVT.2733 reduced fat mass and lipolysis in visceral adipose tissues, hepatic FFAs, and serum corticosterone levels in diet-induced obese mice.Conclusion: Our study shows that moderate inhibition of 11β-HSD1 by BVT.2733 reduces FFAs and corticosterone synthesis in fatty tissues, thereby attenuates the delivery of corticosterone and FFAs to the liver. Collectively, this prevents high-fat diet-induced hepatic steatosis.Keywords: 11β-HSD1, hepatic steatosis, inhibitor, adipose tissue, free fatty acids

Sheng Cheng, Qiming Zheng, Guoqing Ding, Gonghui LiDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaPurpose: The clinical impacts of serum lipid levels on prostate cancer recurrence after radical prostatectomy have been evaluated by several observational studies with conflicting results. We performed the present meta-analysis to summarize the evidence evaluating the role of serum lipid profile in prostate cancer patients.Methods: We comprehensively searched the PubMed database for potentially relevant studies through January 2019. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for the highest versus the lowest level of serum lipid levels were calculated with the DerSimonian and Laird random-effects model.Results: A total of 12 eligible studies with 10,978 prostate cancer cases were included in this study. The pooled HRs of prostate cancer recurrence after racial prostatectomy were 0.92 (95% CI 0.73–1.16, P=0.462), 0.87 (95% CI 0.56–1.35, P=0.535), 1.09 (95% CI 0.92–1.30, P=0.320), and 1.01 (95% CI 0.78–1.31, P=0.938) for serum total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride, respectively. Sensitivity analysis was conducted by excluding each study sequentially and the results showed that all the summary risk estimates were stable and not influenced by any single study.Conclusion: The present meta-analysis indicated that serum lipid levels in patients undergoing radical prostatectomy were not associated with prostate cancer recurrence.Keywords: serum lipids, prostate cancer, recurrence, radical prostatectomy, meta-analysis

Siping Zhu,1,* Wei Lin,1,* Shu Chen,1,* Hanmei Qi,1 Siting Wang,2 Aisen Zhang,1 Jinmei Cai,1 Bing Lai,1 Yunlu Sheng,1 Guoxian Ding11Division of Geriatric Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Division of Intensive Care Unit, Nanjing Jiangning Hospital, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workBackground: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear.Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia.Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB).Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men.Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men.Keywords: B-mode ultrasound, muscle thickness, pennation angle, muscle mass, muscle strength, physical performance

Changrun Guo,1 Gang Ding,2 Wenzhe Huang,2 Zhenzhong Wang,2 Zhaoqing Meng,1,2 Wei Xiao2 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang City, People’s Republic of China Background: Diabetic nephropathy has become the most common cause of morbidity and mortality in diabetic patients. Therefore, there is an urgent need for more effective and safer drugs for use in this condition.Purpose: The aims of this study were to investigate the ameliorative effects of total saponin of Dioscoreae hypoglaucae rhizoma (TSD) on diabetic nephropathy and to explore the potential underlying mechanism(s).Methods: Rats with streptozotocin-induced diabetes were orally treated with TSD at 40, 80, and 160 mg/kg/d for 12 weeks. At the end of the treatment, blood, urine, and kidneys were collected for biochemical and histological examination.Results: The results demonstrated that TSD significantly decreased the fasting blood glucose, glycosylated hemoglobin, urinary protein, serum creatinine, and blood urea nitrogen levels in diabetic rats. The results of histological examinations showed that TSD ameliorated glomerular and tubular pathological changes in diabetic rats. Furthermore, TSD significantly prevented oxidative stress and reduced the renal levels of advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and tumor necrosis factor-α.Conclusion: This study demonstrated the renoprotective effects of TSD in experimental diabetic nephropathy via a number of different mechanisms. Keywords: total saponin of Dioscoreae hypoglaucae rhizoma, diabetic nephropathy, oxidative stress, AGEs, TGF-β1

Jihai Chen,1,2 Lijun Wei,2 Xiaoxia Zhu,2 Wenli Xu,2 Yuxin Zou,2 Xinyu Qi,2 Jia Fang,2 Xiaodong Wang,2 Xiaolan Shi,1 Yunlu Sheng,2 Guoxian Ding,2 Xiaojun Ouyang,1 Yu Duan2 1Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Nanjing, 210024, People’s Republic of China; 2Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Yu Duan, Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email duanyujsph@163.com Xiaojun Ouyang, Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Luojia Road 30, Nanjing, 210024, People’s Republic of China, Email xiaojun_ouyang@aliyun.comBackground and Aims: Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population.Subjects and Methods: A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty.Results: Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk.Conclusion: There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.Graphical Abstract: Keywords: sarcopenia, thyroid hormone, elderly, muscle strength

Gonglin Tang,1,&ast; Kai Sun,2,&ast; Guixin Ding,1 Jitao Wu1 1Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, People’s Republic of China; 2Urology Department, Shandong Province Hospital, Shandong University, Jinan, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jitao Wu, Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, People’s Republic of China, Email wjturology@163.comIntroduction: Kidney renal clear cell carcinoma (KIRC) is a common cancer in people worldwide, and one of the main issues is developing suitable biomarkers. This study aims to investigate the expression of TSTD2 in KIRC and its impact on prognosis.Methods: RNA sequencing data from TCGA and GTEx were gathered to examine the functional enrichment of TSTD2-related differentially expressed genes (DEGs) using GO/KEGG, GSEA, immunocyte permeation analysis, and protein–protein interaction (PPI) network analysis. The Kaplan‒Meier-Cox regression model and the prognostic nomograph model were used to assess the clinical importance of TSTD2 in KIRC. R software was used to analyze the included studies. Finally, verification of cells and tissues was performed using immunohistochemical staining and quantitative real‒time PCR.Results: In contrast to normal samples, it was discovered that TSTD2 was underexpressed in a number of malignancies, including KIRC. Furthermore, in 163 KIRC samples, low expression of TSTD2 was linked to a poor prognosis, as were subgroups with age greater than 60, the integrin pathway, the development of elastic fibers, and high TNM stage, pathologic stage, and histologic grade (P < 0.05). Age and TNM stage were included in the nomogram prognostic model, and low TSTD2 was a prognostic predictor that could be used independently in Cox regression analysis. In addition, 408 DEGs with 111 upregulated genes and 297 downregulated genes were found between the high- and low-expression groups.Conclusion: The diminished expression of TSTD2 may serve as a biomarker for unfavorable outcomes in KIRC, and holds potential as a target for therapeutic interventions.Keywords: kidney renal clear cell carcinoma, TSTD2, the cancer genome atlas, R packages

Huijuan Wang,1 Yinmin Shi,2 Jiying Ma,1 Wenxia Wang,2 Jianrong Gao,3 Lili Zhao,1 Ting Zhao,2 Guifeng Ding4 1The National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 2Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 3Department of Obstetrics, Xi’an International Medical Center Hospital, Xi’an, Shaanxi, 710018, People’s Republic of China; 4Department of Obstetrics and Gynecology, Urumqi Maternal and Child Health Care Hospital, Urumqi, Xinjiang, 830001, People’s Republic of ChinaCorrespondence: Guifeng Ding, Department of Obstetrics and Gynecology, Urumqi Maternal and Child Health Care Hospital, No. 344 Jiefang South Road, Urumqi, Xinjiang, People’s Republic of China, Tel +86 1 331 988 0258, Fax + 86 991-8554656, Email dingguifeng123@126.comBackground: Preeclampsia (PE) is a multi-system disorder of pregnancy that poses a serious threat to maternal and perinatal health worldwide. This study aims to evaluate the global alterations of protein expression and N-glycosylations that are crucial for PE pathogenesis. Here, tandem mass tag labeling combined with LC-MS/MS was employed to determine the global expression of all proteins and intact glycopeptide in placentas from three healthy pregnant women, three patients with early-onset severe PE, and three patients with late-onset severe PE.Results: A total of 2260 proteins were quantified across 9 placental tissues, of which 37 and 23 were differentially expressed in the early-onset and late-onset PE groups, compared to the controls. A total of 789 glycopeptides were accurately quantified, which were derived from 204 glycosylated sites in 159 glycoproteins and were modified by 59 N-Linked glycans. A total of 123 differently expressed glycopeptides, which were from 47 glycoproteins were identified among three groups. Through a combined analysis of proteomic and glycoproteomic data, it was found that the changes in 10 glycoproteins were caused by the difference in glycosylation level but not in the protein abundance level.Conclusion: This is the first study to conduct an integrated proteomic and glycoproteomic characterization of placental tissues of PE patients. Our findings suggest that glycosylation modification may affect the molecular function of proteins through changes in the glycosylation structure or the occupancy of glycosylation, which will provide new insights to help elucidating the pathogenic mechanism of PE.Keywords: preeclampsia, placenta, proteomics, glycoproteomics, glycosylation

Lingsong Feng, Guodong Ding, Yang Zhou, Haiyuan Zhu, Huiming Jiang Department of Urology, Meizhou People’s Hospital, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, People’s Republic of ChinaCorrespondence: Huiming Jiang, Tel +86-13560990839, Email jianghm0228@163.comBackground: Clear cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer subtype, has a high mortality rate. Crystallin lambda 1 (CRYL1) encodes an enzyme that catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in uronate cycle. CRYL1 dysregulation has been linked to the progression of several cancers. This research aimed to evaluate the prognostic significance of CRYL1 expression in ccRCC prognosis.Methods: Clinical data and gene expression profiles on ccRCC were retrieved from the University of California Santa Cruz Xena platform. Differences (variations) in the expression profiles of CRYL1 in ccRCC and healthy tissues were found using RNA-sequencing data, and these findings were validated using qPCR with real-world samples. CRYL1 expression levels were also linked to clinicopathological characteristics, survival, and immune microenvironments. The potential pathway via which CRYL1 expression levels impact the prognosis of patients with ccRCC was investigated using gene set enrichment analysis (GSEA).Results: In ccRCC tissues, CRYL1 expression levels were lower compared to healthy renal tissues in TCGA cohort (n = 535, P < 0.001), which was validated in another real-world cohort (n = 14, P < 0.001). Lower CRYL1 expression levels were linked to unfavorable clinicopathological characteristics and prognoses (P < 0.001). According to multivariate Cox regression analysis (P < 0.001), CRYL1 expression levels in patients with ccRCC could serve as an independent prognostic indicator. Furthermore, a strong link between CRYL1 expression levels and immune microenvironment was observed (P < 0.001). Finally, GSEA revealed that CRYL1 expression levels (P < 0.001) were associated with fatty acid metabolism, G2M checkpoint delays, and epithelial-mesenchymal transitions in ccRCC.Conclusion: Our study found that lower levels of CRYL1 expression were linked to unfavorable clinicopathological characteristics and worse prognoses, and CRYL1 could serve as a new target for the treatment of ccRCC, which is useful for personalized medicine.Keywords: clear cell renal cell carcinoma, CRYL1, prognosis, biomarker

Wei Xu, Changsheng Teng, Guoqian Ding, Ning Zhao Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ning Zhao, Email 13811926363@163.comBackground: This study aimed to compare the risk of hypoparathyroidism between the transoral vestibular approach (TOVA) and the breast approach (BA) in patients undergoing total endoscopic thyroidectomy (TET) for papillary thyroid carcinoma (PTC).Methods: The medical records of 121 PTC patients (all women) who underwent total TET from January 2015 to January 2021 were retrospectively analyzed. Patients were grouped according to surgical approach (BA or TOVA). Clinical status and concentrations of parathyroid hormone (PTH) and calcium were monitored in the perioperative period and 1, 6, and 12 months after surgery.Results: The BA and TOVA groups comprised 101 and 20 patients, respectively. Clinicopathologic and characteristics and surgical data were comparable between the groups. Incidence of transient hypoparathyroidism was significantly lower in the TOVA group than the BA group (10% vs 63.4%; p < 0.01). Incidence of permanent hypoparathyroidism was comparable (5% vs 6.9%). Two days after TET, mean PTH concentration was significantly higher and incidence of abnormal PTH was significantly lower in the TOVA group. The incidence of abnormal calcium concentration 2 days after surgery was significantly lower in the TOVA group. One month after surgery, the mean calcium concentration was significantly higher in the TOVA group. Univariate and multivariate Cox regression analysis suggested that patients who underwent TOVA had a lower risk of transient hypoparathyroidism (hazard ratio 0.05, 95% confidence interval, 0.01– 0.23; p< 0.01). No clinicopathological factors examined were significantly associated with permanent hypoparathyroidism.Conclusion: In patients undergoing TET for PTC, the incidence of transient hypoparathyroidism may be lower with the TOVA than the BA. Surgeons should be aware of the relatively high risk of transient hypoparathyroidism when performing the BA.Keywords: hypoparathyroidism, endoscopic, thyroidectomy, papillary thyroid carcinoma, parathyroid hormone, surgery

Feng Su,1,&ast; Yong Fang,1,&ast; Jinjie Yu,1 Tian Jiang,1 Siyun Lin,1 Shaoyuan Zhang,1 Lu Lv,2 Tao Long,2 Huiwen Pan,2 Junqing Qi,2 Qiang Zhou,3 Weifeng Tang,4 Guowen Ding,2 Liming Wang,5 Lijie Tan,1 Jun Yin1 1Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China; 3Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan, People’s Republic of China; 4Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Jiangsu, People’s Republic of China; 5Department of Respiratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yin; Lijie Tan, Zhongshan Hospital of Fudan University, 180 Fenglin road, Xuhui District, Shanghai, 200032, People’s Republic of China, Email jun_yin@fudan.edu.cn; tan.lijie@zs-hospital.sh.cnBackground: The σ 1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population.Methods: A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P< 0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.Results: AP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers.Conclusion: AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.Keywords: AP1S1, single nucleotide polymorphism, SNP, esophageal squamous cell carcinoma, ESCC

Targeted therapy for patients with advanced non-small cell lung cancer (NSCLC) is often challenged by the arising of drug resistance. After progression to targeted therapy, treatment options include continued targeted therapy, definitive local therapy, and the combination of both. While there is evidence that local ablative radiotherapy may prolong the disease control by targeted therapy, little is known regarding the relevance of salvage thoracic surgery in this setting. Herein, we presented a case of stage IV lung adenocarcinoma with concurrent EML4-ALK and TAC1-ALK fusion who had long-term survival after salvage thoracic surgery. The patient underwent a multidisciplinary treatment scheme that consisted of radiotherapy, ALK inhibitor crizotinib, and surgery, with blood-based genomic profiling for monitoring disease progression. Notably, salvage thoracic surgery was performed after progression on the crizotinib therapy and acquired ALK F1174C mutation was identified, which has been shown to be resistant to crizotinib and possibly sensitive to ceritinib. The patient benefited from salvage thoracic surgery with a remarkable progression-free survival of 31 months at last follow-up, and the patient maintained high-performance status throughout the course of management. To the best of our knowledge, this is the first case reporting on the long-term survival outcome from salvage thoracic surgery after crizotinib treatment in an NSCLC patient carrying double ALK fusion., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Ren et al.)

Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1), locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77 ± 32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%± 7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%± 5.29% and 43.49%± 9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients.