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Yinxue Zhou,1,* Tingyu Wu,2,* Jiaxing Sun,1 Huanhuan Bi,1 Yuting Xiao,1 Yanmei Shao,1 Weizhong Han,1 Hongmei Wang1 1Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaxing Sun; Hongmei Wang, Email jiaxing20022001@163.com; dor.whm@163.comBackground: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries.Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics.Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as “Lung Cancer”, are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation.Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, “chemo+” treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.Keywords: EGFR-TKI, resistance, lung cancer, bibliometric, citespace, VOSviewer

Zhenghua Cao,1 Shengkun Zhao,1 Shaodan Hu,2 Tong Wu,3 Feng Sun,2 LI Shi2 1Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 2Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 3Geriatric Department, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: LI Shi, Email shili0648@163.comPurpose: To employ bioinformatics and machine learning to predict the characteristics of immune cells and genes associated with the inflammatory response and ferroptosis in chronic obstructive pulmonary disease (COPD) patients and to aid in the development of targeted traditional Chinese medicine (TCM). Mendelian randomization analysis elucidates the causal relationships among immune cells, genes, and COPD, offering novel insights for the early diagnosis, prevention, and treatment of COPD. This approach also provides a fresh perspective on the use of traditional Chinese medicine for treating COPD.Methods: R software was used to extract COPD-related data from the Gene Expression Omnibus (GEO) database, differentially expressed genes were identified for enrichment analysis, and WGCNA was used to pinpoint genes within relevant modules associated with COPD. This analysis included determining genes linked to the inflammatory response in COPD patients and analyzing their correlation with ferroptosis. Further steps involved filtering core genes, constructing TF-miRNA‒mRNA network diagrams, and employing three types of machine learning to predict the core miRNAs, key immune cells, and characteristic genes of COPD patients. This process also delves into their correlations, single-gene GSEA, and diagnostic model predictions. Reverse inference complemented by molecular docking was used to predict compounds and traditional Chinese medicines for treating COPD; Mendelian randomization was applied to explore the causal relationships among immune cells, genes, and COPD.Results: We identified 2443 differential genes associated with COPD through the GEO database, along with 8435 genes relevant to WGCNA and 1226 inflammation-related genes. A total of 141 genes related to the inflammatory response in COPD patients were identified, and 37 core genes related to ferroptosis were selected for further enrichment analysis and analysis. The core miRNAs predicted for COPD include hsa-miR-543, hsa-miR-181c, and hsa-miR-200a, among others. The key immune cells identified were plasma cells, activated memory CD4 T cells, gamma delta T cells, activated NK cells, M2 macrophages, and eosinophils. Characteristic genes included EGF, PLG, PTPN22, and NR4A1. A total of 78 compounds and 437 traditional Chinese medicines were predicted. Mendelian randomization analysis revealed a causal relationship between 36 types of immune cells and COPD, whereas no causal relationship was found between the core genes and COPD.Conclusion: A definitive causal relationship exists between immune cells and COPD, while the prediction of core miRNAs, key immune cells, characteristic genes, and targeted traditional Chinese medicines offers novel insights for the early diagnosis, prevention, and treatment of COPD.Keywords: bioinformatics analysis, Mendelian randomization, machine learning, COPD, characteristic genes, targeted traditional Chinese medicine, early diagnosis

Yuan Li,1 Tong Wu,1 Hongye Li,2 Mingming Liu,2 Haiyan Xu1 1School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Lianyungang Clinical School of Xuzhou Medical University, Lianyungang, 222006, People’s Republic of ChinaCorrespondence: Haiyan Xu, School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email xhy_8@163.comPurpose: Tanshinone IIA (Tan-IIA) is widely used in patients with diabetic nephropathy (DN), but its protective effect on podocytes in DN has not been well studied. In this study, the effects of Tan-IIA on autophagy and inflammation of glomerular podocytes in DN were observed in vivo and in vitro, and the underlying mechanisms were investigated. Irbesartan, an angiotensin II receptor blocker, is a representative medication for the clinical treatment of DN. So irbesartan was chosen as a positive control drug.Methods: Eight-week-old male db/db mice were randomly divided into a DN group, an irbesartan group, and three groups receiving different doses of Tan-IIA. The control group consisted of the db/m littermate mice. Blood, urine, and kidney samples were taken from the mice after 12 weeks of continuous administration. Renal protection of Tan-IIA was evaluated using enzyme-linked immunosorbent assay kits, haematoxylin and eosin staining, transmission electron microscopy, Western blotting, and immunohistochemistry. In vitro, the protective effect of Tan-IIA on podocytes was explored using MPC5 cells cultured with high glucose.Results: Tan-IIA significantly improved renal pathological injury and relieved the renal dysfunction in DN. Compared with the DN group, Tan-IIA could up-regulate the expression of Synaptopodin, Podocin, LC3II/I and Beclin-1 (p < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1β, TNF-α and IL-6 (p < 0.05) both in vivo and in vitro, suggesting that Tan-IIA treatment alleviated podocyte injury by promoting autophagy and inhibiting inflammation during DN. The levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in Tan-IIA group were lower than those in DN group (p < 0.05), indicating that Tan-IIA inhibited the PI3K/Akt/mTOR signalling pathway in podocytes, which was a key pathway in regulating both autophagy and inflammation.Conclusion: Tan-IIA prevented podocyte injury in DN by fostering autophagy and inhibiting inflammation, at least in part via inhibition of the PI3K/Akt/mTOR signalling pathway.Keywords: tanshinone IIA, podocyte, diabetic nephropathy, autophagy, inflammation, PI3K/Akt/mTOR signalling pathway

Hong-Mei Shu,1,&ast; Chang-Qing Lin,1 Bei He,1 Wang Wang,1 Ling Wang,1 Ting Wu,1 Hai-Juan He,1 Hui-Juan Wang,1 He-Ping Zhou,2 Guo-Zheng Ding1,&ast; 1Department of Pulmonary and Critical Care Medicine, Anqing Municipal Hospital, Anhui, People’s Republic of China; 2Neurosurgery Department, Anqing Municipal Hospital, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Mei Shu, Email shuxin501@163.comBackground: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The “ConsensusClusterPlus” package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT – PCR to detect the expression levels of eight genes in COPD patient and normal.Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.Keywords: chronic obstructive pulmonary disease, pyroptosis, gene, biomarkers, immune Infiltration

Srinivas Chava,1 Nergiz Ekmen,2 Pauline Ferraris,1 Yucel Aydin,2 Krzysztof Moroz,1 Tong Wu,1 Swan N Thung,3 Srikanta Dash1,2,4 1Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA, USA; 3Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Southeast Louisiana Veterans Health Care System, New Orleans, LA, USACorrespondence: Srikanta Dash, Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA, 70112, USA, Tel +1 504-988-2519, Fax +1 504-988-7389, Email sdash@tulane.eduIntroduction: Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC) treatment, encounters resistance in many patients. Deciphering the mechanisms underlying sorafenib resistance is crucial for devising alternative strategies to overcome it.Aim: This study aimed to investigate sorafenib resistance mechanisms using a diverse panel of HCC cell lines.Methods: HCC cell lines were subjected to continuous sorafenib treatment, and stable cell lines (Huh 7.5 and Huh 7PX) exhibiting sustained growth in its presence were isolated. The investigation of drug resistance mechanisms involved a comparative analysis of drug-targeted signal transduction pathways (EGFR/RAF/MEK/ERK/Cyclin D), sorafenib uptake, and membrane expression of the drug uptake transporter.Results: HCC cell lines (Huh 7.5 and Huh 7PX) with a higher IC50 (10μM) displayed a more frequent development of sorafenib resistance compared to those with a lower IC50 (2– 4.8μM), indicating a potential impact of IC50 variation on initial treatment response. Our findings reveal that activated overexpression of Raf1 kinases and impaired sorafenib uptake, mediated by reduced membrane expression of organic cation transporter-1 (OCT1), contribute to sorafenib resistance in HCC cultures. Stable expression of the drug transporter OCT1 through cDNA transfection or adenoviral delivery of OCT1 mRNA increased sorafenib uptake and successfully overcame sorafenib resistance. Additionally, consistent with sorafenib resistance in HCC cultures, cirrhotic liver-associated human HCC tumors often exhibited impaired membrane expression of OCT1 and OCT3.Conclusion: Intrinsic differences among HCC cell clones, affecting sorafenib sensitivity at the expression level of Raf kinases, drug uptake, and OCT1 transporters, were identified. This study underscores the potential of HCC tumor targeted OCT1 expression to enhance sorafenib treatment response.Keywords: hepatocellular carcinoma, HCC, cholangiocarcinoma, CCA, tyrosine kinase inhibitors, TKI, organic cation transporter-1, OCT1, organic cation transporter-3, OCT3, sorafenib resistance cell lines, SR huh 7

Wenrong Zhang,1,2,&ast; Haining Wang,1,&ast; Tong Wu,1 Xintao Gao,1 Yuting Shang,1 Zhifang Zhang,1 Xingjian Liu,1 Yinü Li1 1National Key Laboratory of Agricultural Microbiology, Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, People’s Republic of China; 2College of Life Sciences, Capital Normal University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingjian Liu; Yinü Li, Tel/Fax +861082109854 ; +861082105495, Email liuxingjian@caas.cn; liyinv@caas.cnPurpose: COVID-19 is rampant throughout the world, which has caused great damage to human lives and seriously hindered the development of the global economy. Aiming at the treatment of SARS-CoV-2, in this study, we proposed a novel fenobody strategy based on ferritin (Fe) self-assembly technology.Methods: The neutralizing nanobody H11-D4 of SARS-CoV-2 fused to the C-terminus of end-modified human ferritin was expressed in E. coli and silkworm baculovirus expression systems. A large number of nanoparticles were successfully self-assembled in silkworms, while relatively few nanoparticles can be observed in the treated products from E. coli by electron microscopy. Subsequently, the fenobody’s expression level and neutralizing activity were then evaluated.Results: The results showed that the IC50 of H11-D4 and fenobody Fe-H11-D4 expressed in E. coli were 171.1 nmol L− 1 and 20.87 nmol L− 1, respectively. However, the IC50 of Fe-HD11-D4 expressed in silkworms was 1.46 nmol L− 1 showing better neutralization activity.Conclusion: Therefore, fenobodies can be well self-assembled in silkworm baculovirus expression system, and ferritin self-assembly technology can effectively improve nanobody neutralization activity.Keywords: COVID-19, ferritin, fenobody, baculovirus expression system, silkworm

Wenxuan Li,1,&ast; Zhikai Zheng,2,3,&ast; Jiongliang Wang,2,3,&ast; Tianqing Wu,2,3,&ast; Juncheng Wang,2,3 Yangxun Pan,2,3 Jinbin Chen,2,3 Dandan Hu,2,3 Li Xu,2,3 Yaojun Zhang,2,3 Minshan Chen,2,3 Zhongguo Zhou2,3 1Cancer Center, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncheng Wang; Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343115 ; +86-20-87343117, Email wangjch@sysucc.org.cn; zhouzhg@sysucc.org.cnPurpose: The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC).Patients and Methods: Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed.Results: The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P< 0.05) and 15.6 months (P< 0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P< 0.05) and 45.0 months (P< 0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P< 0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P< 0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P< 0.05) and 21.7 months (P< 0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up.Conclusion: HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.Keywords: hepatic arterial infusion chemotherapy, advanced hepatocellular carcinoma, conversion therapy

Li Chen,1,2,&ast; Qiang Liu,2,&ast; Chunlei Tan,3,&ast; Tiangen Wu,4,&ast; Meng Wu,5 Xiaosheng Tan,5 Jinwen Liu,1 Jing Wang2 1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 4Department of Hepatobiliary&Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email wangjing@cicams.ac.cn Jinwen Liu, Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email Liujinwen@tjh.tjmu.edu.cnObjective: The current study is conducted to investigate the potential prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in breast cancer patients with liver metastasis after surgery.Methods: This is a retrospective study of 178 breast cancer patients who developed liver metastasis after surgery. These patients were treated and followed up from 2000 to 2018 at our hospital. The aMAP risk score was estimated in accordance with the following formula: . The optimal cutoff value of the aMAP was evaluated via X-tile. Kaplan-Meier, Log-rank and Cox proportional hazards regression models were applied to determine the clinical influence of the aMAP score on the survival outcomes. The nomogram models were established by multivariate analyses. The calibration curves and decision curve analysis were applied to evaluate the estimated performance of the nomogram models.Results: A total of 178 breast cancer patients were divided into low aMAP score group (< 47.6) and high aMAP score group (≥ 47.6) via X-tile plots. The aMAP score was a potential prognostic factor in multivariate analysis. The median disease free survival (p=0.0013) and overall survival (p=0.0003) in low aMAP score group were longer than in high aMAP score group. The nomograms were constructed to predict the DFS with a C-index of 0.722 (95% CI, 0.673– 0.771), and the OS with a C-index of 0.708 (95% CI, 0.661– 0.755). The aMAP-based nomograms had good predictive performance.Conclusion: The aMAP score is a potential prognostic factor in breast cancer with liver metastasis after surgery. The aMAP score-based nomograms were conducive to discriminate patients at high risks of liver metastasis and develop adjuvant treatment and prevention strategies.Keywords: breast cancer, aMAP score, liver metastasis, albumin, prognosis

Huimin Du,1 Tong Wu2 1Department of Otolaryngology, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang People’s Republic of China; 2Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, People’s Republic of ChinaCorrespondence: Huimin Du, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China, Email huimindu@naver.com

Huimin Du,1 Tong Wu2 1Department of Otolaryngology, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang People’s Republic of China; 2Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, People’s Republic of ChinaCorrespondence: Huimin Du, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China, Email huimindu@naver.com

Tong Wu, Da Liu, Fanhe Meng, Jing-han Lu, Yi-feng Chen, Zheng Fan Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Da Liu, Department of Orthopedics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People’s Republic of China, Tel +86 18940257508, Email spinecmu@163.comPurpose: Here, we introduce a novel strategy of awake unilateral biportal endoscopic (UBE) decompression, which applies conscious sedation combined with stepwise local anesthesia (LA) as an alternative to general anesthesia (GA). The study aims to evaluate the feasibility of awake UBE decompression for degenerative lumbar spinal stenosis (DLSS) in elderly patients.Patients and Methods: This retrospective study included 31 consecutive patients who received awake UBE decompression for DLSS in our institution from January 2021 to March 2022. Clinical results were evaluated using patient-reported outcomes measures (PROM) including visual analog scale for leg pain (VAS-LP), Oswestry Disability Index (ODI), and modified MacNab criteria. The anesthesia effectiveness and intraoperative experience were evaluated by intraoperative VAS and satisfaction rating system.Results: UBE decompression was successfully performed in all patients under LA combined with conscious sedation. 26 (83.9%) patients rated the intraoperative experience as satisfactory (excellent or good) and 5 (16.1%) as fair. The mean intraoperative VAS was 3.41± 1.26. The VAS and ODI at each follow-up stage after surgery were significantly improved compared to preoperative scores (p < 0.01). At the last follow-up, 28 patients (90.3%) classified the surgical outcome as good or excellent, and 3 (9.7%) as fair. There were no serious complications or adverse reactions observed in the study.Conclusion: Our preliminary results suggest that awake UBE decompression is a feasible and promising alternative for elderly patients with DLSS.Keywords: awake spinal surgery, local anesthesia, degenerative lumbar disease, biportal endoscopic spine surgery, enhanced recovery after surgery

Sicheng Zhao, Tingyan Wu, Mingjing Fu, Zhe Zhang Department of Dermatology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, People’s Republic of ChinaCorrespondence: Sicheng Zhao, Department of Dermatology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, No. 118 Wansheng Street, Suzhou Industrial Park, Suzhou, Jiangsu, 215028, People’s Republic of China, Email zscba@163.comBackground: Psoriasis is a chronic inflammatory skin disease characterized by erythema, papules, and plaques. Adiponectin (ADIPOQ) is an important protein hormone secreted by adipose tissue. Here, we aimed to explore the expression of ADIPOQ in psoriasis patients and the moderation effect of histone lactylation on ADIPOQ.Methods: The GSE78097 data set was downloaded from GEO database to analyze the differentially expressed genes (DEGs) in psoriasis. A total of 36 psoriasis patients were recruited to obtain the skin samples. The ADIPOQ protein levels, global lactylation and histone lactylation (H3K18lac) levels were detected by Western blot assay. Chromatin immunoprecipitation (CHIP) assay was performed to detect the combination between H3K18lac and promoter regions of the ADIPOQ. The receiver operating curve (ROC) analysis was used to evaluate the diagnostic value of ADIPOQ in psoriasis.Results: ADIPOQ was decreased in the skin tissues of psoriasis patients. In addition, the global lactylation and H3K18lac levels were significantly decreased in the skin tissues of psoriasis patients. In HaCaT cells, promoting the global lactylation and H3K18lac levels increased the ADIPOQ protein levels, while si-LDHA transfection decreased the ADIPOQ protein levels. The CHIP results indicated that lactylation promoted the binding of promoter regions of the ADIPOQ and H3K18lac. Finally, the ROC analysis showed that ADIPOQ exhibited diagnostic value in psoriasis.Conclusion: This study demonstrated ADIPOQ was decreased in the skin tissues of psoriasis patients, and ADIPOQ has diagnostic value for psoriasis. Furthermore, down-regulation of H3K18lac levels inhibited the transcription of ADIPOQ, which was the key factor of decrease of ADIPOQ levels in psoriasis patients.Keywords: psoriasis, ADIPOQ, histone, lactylation

Tianqing Wu,1,2,&ast; Zhikai Zheng,1,2,&ast; Jiongliang Wang,1,2,&ast; Minrui He,1,2,&ast; Juncheng Wang,1,2 Yangxun Pan,1,2 Jinbin Chen,1,2 Dandan Hu,1,2 Yaojun Zhang,1,2 Li Xu,1,2 Minshan Chen,1,2 Zhongguo Zhou1,2 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhouzhg@sysucc.org.cnPurpose: To assess the clinical value of the pretherapeutic systemic inflammation score (SIS) in predicting the prognosis of hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC).Methods: From February 2016 to April 2021, 415 advanced HCC patients who underwent HAIC at Sun Yat-sen University Cancer Center were randomly divided into training (n = 277) and validation cohorts (n = 138) and analyzed. The aspartate aminotransferase–alanine aminotransferase ratio (AAR), lymphocyte × albumin (L × A), and neutrophil × monocyte (N × M) were used to construct the SIS score based on a multivariate Cox analysis in the training cohort. A nomogram consisting of the SIS score was created and evaluated by calibration plot, areas under the receiver operating characteristic (AUC) curve, and decision curve analysis (DCA).Results: Univariate and multivariate Cox analyses revealed that the SIS score was an independent predictor of OS. A high SIS score was associated with large tumor size (P < 0.05), multiple lesions (P < 0.01), high AFP level (P < 0.01), extrahepatic metastasis (P < 0.05), and advanced BCLC stage (P < 0.01). Kaplan–Meier analysis showed that the patients with a high SIS had shorter OS than those with a low SIS in both the non-PD (p = 0.015) and PD group (p = 0.023). The calibration plots showed good concordance between the nomogram’s prediction and the actual observations in both the training and validation cohorts. In the training cohort, the AUCs of the nomogram predicting the 2-year and 3-year survival rates were 0.749 and 0.739, respectively; in the validation cohort, they were 0.760 and 0.681, respectively. Based on the AUC and DCA, the nomogram showed better predictive ability than other predictors.Conclusion: The pretherapeutic SIS score is a potential prognostic predictor for HCC patients undergoing HAIC.Keywords: HCC, systemic inflammation score, nomogram, prognosis

Zhikai Zheng,1,2,&ast; Jiongliang Wang,1,2,&ast; Tianqing Wu,1,2,&ast; Minrui He,1,2,&ast; Juncheng Wang,1,2 Yangxun Pan,1,2 Jinbin Chen,1,2 Dandan Hu,1,2 Li Xu,1,2 Yaojun Zhang,1,2 Minshan Chen,1,2 Zhongguo Zhou1,2 1Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongguo Zhou; Minshan Chen, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343117, Email zhouzhg@sysucc.org.cn; chenms@sysucc.org.cnPurpose: The efficacy of entecavir (ETV) versus tenofovir (TDF) on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who underwent FOLFOX-hepatic arterial infusion chemotherapy (HAIC) remains unclear. In this study, we compared the outcomes between ETV and TDF in HBV-related advanced HCC patients who underwent FOLFOX-HAIC.Methods: A total of 683 patients diagnosed with HBV-related HCC who underwent FOLFOX-HAIC and received TDF or ETV between January 2016 and December 2021 were included. Overall survival (OS), progression-free survival (PFS), HBV reactivation, and liver function of patients were compared between the ETV and TDF groups by propensity score matching (PSM).Results: In the PSM cohort, for all patients and patients with ≥ 4 cycles of FOLFOX-HAIC, the median OS in the ETV group (15.2 months, 95% CI: 13.0– 17.4 months; 16.6 months, 95% CI: 14.8– 18.5 months; respectively) was shorter than that in the TDF group (23.0 months, 95% CI: 10.3– 35.6 months; 27.3 months, 95% CI: 16.5-NA months; p=0.024, p=0.028; respectively). The median PFS in the ETV group (8.7 months, 95% CI: 7.9– 9.5 months; 8.9 months, 95% CI: 8.0– 9.8 months; respectively) was also shorter than that in the TDF group (11.8 months, 95% CI: 8.0– 15.6 months; 12.7 months, 95% CI: 10.8– 14.6 months; p=0.036, p=0.025; respectively). The rate of HBV reactivation in the ETV group was higher than that in the TDF group (12.3% vs 6.3%, p=0.040; 16.5% vs 6.2%, p=0.037, respectively). For liver function, the rate of ALBI grade that remained stable or improved in the ETV group was lower than that in the TDF group (44.6% vs 57.6%, p=0.006; 37.2% vs 53.8%, p=0.019, respectively).Conclusion: Compared with ETV, TDF was associated with a better prognosis, lower proportion of HBV reactivation, and better preservation of liver function in advanced HBV-HCC patients who underwent FOLFOX-HAIC, especially those who received ≥ 4 cycles.Keywords: tenofovir, entecavir, hepatitis B virus, hepatocellular carcinoma, hepatic arterial infusion chemotherapy

Simin Min,1,2 Weiting Tao,1 Yuchen Miao,3 Yan Li,4 Tianyu Wu,5 Xiaoyu He,6 Yijing Zhang,7 Bangye Liu,7 Zixin Meng,7 Ke Han,1 Saisai Liu,1 Li Li,1 Jie Chen,1 Shidi Zhao,1 Junjie Zhang,3 Xiaonan Zhang1 1Bengbu Medical College Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China; 2Suzhou Hospital of Anhui Medical University, Suzhou, Anhui, 234000, People’s Republic of China; 3Department of Chemistry, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China; 4School of Medicine and Health Engineering, Changzhou University, Changzhou, Jiangsu, 213164, People’s Republic of China; 5School of Public Health, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China; 6Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China; 7School of Clinical Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of ChinaCorrespondence: Xiaonan Zhang, Department of Pathophysiology, Bengbu Medical College, 2600 Donghai Avinue, Longzihu District, Bengbu, Anhui, People’s Republic of China, Tel +86-13609827842, Fax +86-552-3175283, Email zhangxn@bbmc.edu.cn Junjie Zhang, Department of Chemistry, Bengbu Medical College, 2600 Donghai Avinue, Longzihu District, Bengbu, Anhui, People’s Republic of China, Tel +86-16655208659, Fax +86-552-3175257, Email zhangjj@bbmc.edu.cnBackground: The respiratory system is intensely damaged by acute lung injury (ALI). The anti-inflammatory effects of tetramethylpyrazine (TMP) against ALI have been confirmed, but it exhibits a short half-life. miR-194-5p could directly target Rac1, but the internalization rate of miRNA cells was low.Purpose: To explore the potential of the soft mesoporous organic silica nanoplatform (NPs) as carriers for delivery of TMP and miR-194-5p through the tail vein.Methods: NPs@TMP and NPs@PEI@miR-194-5p were added to the HUVEC cell-lines, in vitro, to observe the cell uptake and cytotoxic effects. In vivo experiments were conducted by injecting fluorescently labeled NPs through the tail vein and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically.Results: In vitro study exhibited that NPs have no toxic effect on HUVECs within the experimental parameters and have excellent cellular uptake. The IVIS Spectrum Imaging System shows that NPs accumulate mainly in the lungs. NPs@TMP treatment can improved oxidative stress and inflammation levels in ALI mice and inhibited the TLR4/NLRP3/caspase 1 pathway. NPs@PEI@miR-194-5p can inhibit the Rac1/ZO-1/occludin pathway and improved endothelial cell permeability in ALI mice. The co-treatment of NPs@TMP and NPs@PEI@miR-194-5p can significantly improved the survival rates of the mice, reduced pulmonary capillary permeability and improved pathological injury in ALI mice.Innovation: This study combined traditional Chinese medicine, bioinformatics, cellular molecular biology and nanobiomedicine to study the pathogenesis and treatment of ALI. The rate of cellular internalization was improved by changing the shape and hardness of nanoparticles. NPs@TMP and NPs@PEI@miR-194-5p combined application can significantly improve the survival condition and pathological injury of mice.Conclusion: NPs loaded with TMP and miR-194-5p showed a greater therapeutic effect in ALI mice. Keywords: NPs@TMP, NPs@PEI@miR-194-5p, tight junction, pulmonary capillary, endothelial cells, inflammation, acute lung injury

Zheng Fan,1 Tong Wang,2 Yang Wang,3 Zimo Zhou,1 Tong Wu,1 Da Liu1 1Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Departments of Orthopedics, The 4th People’s Hospital of Shenyang, Liaoning, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Da Liu, Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China, Email spinecmu@163.comPurpose: While low back pain (LBP) constitutes a global life disorder cause, the contribution of paraspinal muscles to its pathogenicity remains elusive. We characterized the paraspinal muscles of patients with LBP using lumbar three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) mDIXON-Quant, and evaluated the risk factors combined with clinical data.Methods: A retrospective study involving 181 patients (10– 40 years) who underwent lumbar 3D-CT and MRI mDIXON from January 1, 2021 to December 31, 2022, and divided into normal, non-chronic LBP [non-CLBP], and CLBP groups. Clinical data, paraspinal muscle cross-sectional area, Hounsfield unit for CT values, and fat fraction derived from mDIXON-Quant were compared. Three readers analyzed the images independently; intra- and interobserver agreement was measured. Spearman analysis and multiple logistic regression were used to analyze the correlation between clinical data, radiologic and paraspinal muscle parameters. A nomogram was constructed for individualized prediction.Results: Correlation analysis revealed that body mass index, visual analog scale score, Pfirrmann grade, annulus fibrosus tear, lumbar lordosis (LL), and Modic changes correlated with LBP (all P< 0.05). The Pfirrmann grade and annulus fibrosus tear showed positive correlation (r=0.673, 0.559), whereas LL was negatively correlated (r=− 0.469). The multifidus CT values were negatively correlated with LBP at L4– 5/L5–S1; the multifidus fat fraction was positively correlated at L4– 5/L5–S1 (r=0.734, r=0.584, P< 0.001). The multiple logistic regression showed that L4– 5 multifidus fat fraction (P=0.046, OR=1.167), Pfirrmann grade (P=0.017, OR=0.063), LL (P=0.002, OR=0.828) and annulus fibrosus tear (P=0.005, OR=0.024) were risk factors for predicting LBP in the non-CLBP group; in the CLBP group, BMI (P=0.048 OR=1.225), L4-5 multifidus fat fraction (P=0.001 OR=1.299), LL (P=0.003, OR=0.841) and Pfirrmann classification (P=0.009, OR=0.046) were risk factors.Conclusion: BMI, L4-5 multifidus fat fraction, LL, and Pfirrmann grade are risk factors for CLBP in patients under 40; whereas annulus fibrosus tear is an independent risk factor for non-CLBP, nomograms derived from these parameters can help predict LBP and MRI mDIXON-Quant is recommended for quantitatively analyzing paraspinal muscle fat infiltration.Keywords: chronic low back pain, paraspinal muscles, fat infiltration, Pfirrmann grade, computed tomography values, mDIXON-Quant

Shengjie Xu,1 Jiaqiu Xi,2 Tao Wu,1 Zhonglin Wang3 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 3Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Zhonglin Wang, Email zydoctor7@126.comAbstract: Adipose tissue dysfunction plays an important role in metabolic diseases associated with chronic inflammation, insulin resistance and lipid ectopic deposition in obese patients. In recent years, it has been found that under the stimulation of adipocyte endoplasmic reticulum stress (ERS), the over-activated ER unfolded protein response (UPR) exacerbates the inflammatory response of adipose tissue by interfering with the normal metabolism of adipose tissue, promotes the secretion of adipokines, and affects the browning and thermogenic pathways of adipose tissue, ultimately leading to the manifestation of metabolic syndrome such as ectopic lipid deposition and disorders of glucolipid metabolism in obese patients. This paper mainly summarizes the relationship between adipocyte ERS and obese adipose tissue dysfunction and provides an overview of the mechanisms by which ERS induces metabolic disorders such as catabolism, thermogenesis and inflammation in obese adipose tissue through the regulation of molecules and pathways such as NF-κB, ADPN, STAMP2, LPIN1, TRIP-Br2, NF-Y and SIRT2 and briefly describes the current mechanisms targeting adipocyte endoplasmic reticulum stress to improve obesity and provide ideas for intervention and treatment of obese adipose tissue dysfunction.Keywords: endoplasmic reticulum stress, unfolded protein response, obesity, adipose tissue dysfunction

Yonghong Gao,1 Yan Wang,1 Dandan Zhang,2 Tingting Wu,1 Qingwei Li1 1Department of Cardiology, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of China; 2Department of General Practice, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of ChinaCorrespondence: Qingwei Li, Department of Cardiology, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of China, Email tel18930810663@163.comBackground: In the general population of the United States (U.S.), the relationship between dietary inflammatory index (DII) and mortality (all-cause, cardiovascular disease (CVD)-related, and cancer-related) is still unclear. Therefore, in this research, we examined the association of DII with mortality caused by all-cause, CVD-related, and cancer-related causes.Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from 1999– 2018 was used for exploring the link between DII and all-cause, CVD-related, and cancer-related mortality through the use of Cox proportional hazard models and restricted cubic spline model. In addition, subgroup analyses were further performed.Results: The study included 29,013 individuals from the NHANES from 1999 to 2018. The DII scores were nominated as low (T1: − 5.281– 0.724), medium (T2: 0.725– 2.513), and high-grade inflammation (T3: 2.514– 5.795), with T1 serving as the reference group. The linear positive correlation between DII and all-cause and CVD-related mortality was studied using Cox regression analysis. In the full-adjusted model, as compared with the individuals with T1 DII scores, adjusted odds ratios with 95% confidence intervals for all-cause and CVD-related mortality were 1.149 (1.059, 1.247), and 1.186 (1.084, 1.297), as well as 1.197 (1.032, 1.387), and 1.198 (1.019, 1.409), respectively. However, there was no statistical significance between DII and cancer-related mortality. The RCS plot also showed a significant increase in all-cause and CVD-related mortality with increased DII. Nevertheless, as DII scores increased, cancer-related mortality first increased and then decreased.Conclusion: All-cause and CVD-related mortality are linked independently to high DII scores, independently. Further study of the association of DII scores with mortality caused by all-cause, CVD-related, and cancer-related causes is necessary to explore.Keywords: all-cause mortality, cancer-related mortality, cardiovascular disease-related mortality, dietary inflammation index, National Health and Nutrition Examination Survey

Liuli Xu, Qing Huang, Ting Wu, Yunzhu Mu Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Yunzhu Mu, Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China, Email hymyz@126.comAbstract: Riehl’s melanosis (RM) is a contact photodermatitis, with fast progressive gray-brown skin pigmentation as the main manifestation, which can seriously affect the psychology and physiology of patients. Currently, although the etiological factors of Riehl’s melanosis is still be unknown, the existing literature proves clearly the cause of it is related to the contacting with suspected allergens. For decades, there has been no standard method for the treatment of RM, but with both conventional drug therapy and laser therapy having been attempted. Topical application of bleaching agents is mainly used as an auxiliary treatment modality. The laser treatment modality remains a hot spot, among which Q-switched Nd:YAG laser is well received for RM. Positive outcomes have been achieved by the combined treatment modalities attempted in recent years also achieve positive outcomes. The purpose of this paper is to review and summarize recent advances in the treatment of the disease.Keywords: Riehl’s melanosis, pigmented contact dermatitis, therapy

Hui Wu, Tao Li, Jian Cao, Dingwen He, Tianlong Wu, Jiahao Liu, Jinghong Yuan, Xigao Cheng Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Xigao Cheng, Department of Orthopaedics Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, 330006, Email xigaocheng@hotmail.comObjective: This study aims to compare the efficacy of percutaneous endoscopic lumbar discectomy (PELD) in treating adolescent posterior ring apophysis fracture (APRAF) accompanied by lumbar disc herniation (LDH) and lumbar disc herniation alone.Methods: Herein we present a case series of adolescent patients who underwent PELD surgery from June 2017 to September 2021. All patients were divided into two distinct groups (ie Group A and B), based on their preoperative Computed tomography (CT) scans. Group A included patients with PRAF (type III) accompanied by LDH. Group B patients had LDH alone. The general clinical characteristics, clinical outcomes, and complications in patients from the two groups were assessed and compared.Results: Compared to before surgery, the back and leg visual analog scores (VAS) and Oswestry Disability Index (ODI) were markedly improved in both groups’ patients at all follow-ups. Notably, no significant differences were observed in the back and leg VAS scores, and ODI values between the two groups at different time points after surgery. The mean intraoperative blood loss was significantly lower in Group B, relative to Group A. The mean operation time was significantly shorter in Group B, compared to Group A. There was no statistically significant difference in complication and recurrence rates between the two groups.Conclusion: APRAF (type III) accompanied by LDH and LDH alone can obtain roughly equal surgical effects through PELD surgery and turns out to be a safe and effective surgical approach.Keywords: adolescent, posterior ring apophysis fracture, percutaneous endoscopic lumbar discectomy, lumbar disc herniation

By using FactSage calculations, Fourier transform infrared spectroscopy (FTIR), rotational viscometers, and X-ray diffraction (XRD), the combined effect of MgO and Al2O3 on fluorine-free mold flux was confirmed. The viscosity of the slag at 1300 oC decreased with 2-10 wt% MgO, and higher Al2O3 increased the overall viscosity. The trend of the experimental results was consistent with the models of Riboud and Iida, while the FactSage calculation values were relatively higher. The viscosity of the slag was more influenced by the Si-O network than by the Al(B)-O structure and the MgO has a dual effect on the slag structure. The viscosity-temperature curves changed from alkaline to acidic slag characteristics when Al2O3 increased from 8 wt% to 12 wt%, and the trend was not uniform with the addition of 2-10 wt% MgO. Both FactSage calculation and XRD patterns showed that increasing MgO content gradually promoted the growth of Ca3MgSi2O8 and Ca11Si4B2O22 crystals, while the addition of Al2O3 inhibited crystal precipitation.

Bowen Chen,1,2,&ast; Linzhi Zhang,2,3,&ast; Jiamin Cheng,2,&ast; Tong Wu,2 Jin Lei,2,4 Xu Yang,5 Rongling Zhang,6 Rifaat Safadi,7 Yinyin Li,2 Tongguo Si,3 Yinying Lu1,2,8,9 1Peking University 302 Clinical Medical School, Beijing, People’s Republic of China; 2Senior Department of Hepatology, the 5th Medical Center of the PLA General Hospital, Beijing, People’s Republic of China; 3Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 4Guizhou Medical University, Guiyang, People’s Republic of China; 5Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Liver Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel; 8Center for Synthetic & System Biology, Tsinghua University, Beijing, People’s Republic of China; 9Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinying Lu, Peking University 302 Clinical Medical School, No. 100, Middle Road of the West 4th Ring, Beijing, 100039, People’s Republic of China, Email luyinying1973@163.com Tongguo Si, Tianjin Medical University Cancer Institute and Hospital, Tiyuan North Huanhu West Road, Hexi District, Tianjin, 300060, People’s Republic of China, Email sitg77@163.comPurpose: This study aimed to investigate the incidence rate and risk factors for hepatic encephalopathy (HE) among unresectable hepatocellular carcinoma (uHCC) patients with liver cirrhosis who received sorafenib or lenvatinib treatment.Patients and Methods: uHCC patients with cirrhosis who received first-line sorafenib or lenvatinib treatment between September 2014 and February 2021 were continually reviewed in our single-center retrospective study. The Hepatic Encephalopathy Scoring Algorithm was used to evaluate the occurrence and grade of HE during treatment, and logistic regression models were used to further explore the risk factors for HE.Results: A total of 454 eligible patients were enrolled in our study, with 214 and 240 patients in the sorafenib and lenvatinib groups, respectively. At time of data cut-off (2021– 12), the incidence of HE in sorafenib group (4.2%, 95% CI:2– 7%) was significantly lower than that in lenvatinib group (11.3%,95% CI:7– 15%) (p = 0.006), with alcoholic cirrhosis [OR: 5.857 (95% CI: 1.519– 22.591)], Child-Pugh > 7 [OR: 3.023 (95% CI: 1.135– 8.053)], blood ammonia ≥ 38.65 μmol/L [OR: 4.693 (95% CI: 1.782– 12.358)], total bile acid ≥ 29.5 μmol/L [OR: 11.047 (95% CI: 4.414– 27.650)] and duration of treatment ≥ 5.6 months [OR: 4.350 (95% CI: 1.701– 11.126)] to be risk factors for the occurrence of HE during first-line systemic therapy.Conclusion: In our study, for off-label uHCC patients (Child-Pugh > 7) with alcoholic cirrhosis, hyperammonemia, hypercholesterolemia, and estimated longer duration of treatment, the application of lenvatinib has to be cautious, which needs to be confirmed in future clinical trials.Keywords: hepatic encephalopathy, hepatocellular carcinoma, liver cirrhosis, sorafenib, lenvatinib

Ruipeng Zhao,1 Yupei Ji,2 Jiahui Li,1 Xinhua Li,1 Ting Wu,1 Hongru Wu,3 Cuizhen Liu2 1Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, People’s Republic of China; 2School of Psychology, Shaanxi Normal University, Xi’an, People’s Republic of China; 3Shanxi Institute of Sports Science, Taiyuan, People’s Republic of ChinaCorrespondence: Cuizhen Liu, 199 South Chang’an Road, Xi’an, 710062, People’s Republic of China, Tel +86-15129060061, Email liucuizhen28@gmail.comObjective: Knee osteoarthritis (KOA) is a painful chronic disorder. Evidence has shown that a history of chronic pain plays an important role in shaping empathy. Empathy, a valuable indicator of social functioning that refers to an individual’s ability to share the experiences of others, however, has been overlooked in KOA patients. This study aimed to investigate empathy and its association with clinical pain in KOA patients.Methods: KOA patients (n=47) and healthy controls (HCs, n=44) completed two empathy-for-pain tasks: a pain judgment task in which participants judged whether a person in an image felt pain or not, and a pain rating task in which they estimated pain intensity for themselves and others. The Interpersonal Reactivity Index was used to measure participants’ trait empathy, and clinical severity and psychological factors were assessed using relevant instruments.Results: Compared to HCs, KOA patients showed higher accuracy when judging pain and non-pain images and reported overall higher pain intensity when rating for themselves and others. KOA patients also showed greater personal distress than HCs in terms of their self-reported empathy. Moreover, pain catastrophizing particularly mediated the relationship between pain severity and pain ratings for others, and depression, anxiety, and pain catastrophizing all mediated the association between pain severity and empathy-induced personal distress.Conclusion: These findings suggest that patients with KOA have increased empathy, demonstrated by elevated sensitivity to pain-related scenes and intense emotional responses.Keywords: empathy, pain, knee osteoarthritis, pain catastrophizing, emotion

Ting Wu,1,&ast; Hao Yang,1,&ast; Liuli Xu,1 Qing Huang,1 Qi He,1 Rong Wu,2 Yun-Zhu Mu1 1Department of Dermatology, the Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China; 2Pediatric department, Women’s and Children’s hospital of GaoPing District, Nanchong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun-Zhu Mu, Department of Dermatology, the Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong, Sichuan Province, 63700, People’s Republic of China, Tel +8615984833231, Email hymyz77@163.comBackground: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder. NF1 is a multisystemic disease and its pathogenesis involves mutations in the NF1 gene on chromosome 17q11.2 causing RAS overactivation to stimulate abnormal cell proliferation.Purpose: To identify pathogenic mutation of the NF1 gene in a pedigree of NF1.Patients and Methods: Collection of clinical data from one NF1 family. Peripheral blood samples were collected from the affected persons and their family members. Potential mutations of NF1 gene were screened by exome and cDNA sequencing.Results: A splice mutation (c.4836– 10T>G) was found in exon 37 of the NF1 gene in this NFI family, and no corresponding mutation was found in healthy members of this pedigree or in the human reference genome (GRCh37/hg19).Conclusion: Mutations of NF1 gene is a major cause of NF1. The novel splice mutation in exon 37 of NF1 gene is the underlying cause of the familial c.4836– 10T>G.Keywords: neurofibromatosis type 1, gene, splicing mutation, sequencing

Li Ping Wong,1,2 Sun Tee Tay,3 Kek Heng Chua,4 Xiang Ting Goh,4 Haridah Alias,1 Zizheng Zheng,5 Qinjian Zhao,6 Ting Wu,5 Ningshao Xia,5,7 Zhijian Hu,2 Yulan Lin2 1Centre for Epidemiology and Evidence-Based Practice, Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 2Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, People’s Republic of China; 3Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 4Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 5State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, 361102, People’s Republic of China; 6College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 7The Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, 361102, People’s Republic of ChinaCorrespondence: Yulan Lin, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, People’s Republic of China, Email yulanlin@fjmu.edu.cn Li Ping Wong, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia, Email wonglp@ummc.edu.myBackground: As scant data are available about Hepatitis E virus (HEV) infection in Malaysia, this study aimed to determine the seroprevalence of HEV amongst ruminant farmworkers in Malaysia.Methods: A total of 87 farmworkers provided serum samples, which were collected from eight farms. All serum samples were tested for anti-HEV IgG and anti-HEV IgM by an enzyme-linked immunosorbent assay (ELISA) using the Wantai HEV-IgG and HEV-IgM ELISA kits from Beijing Wantai Biological Pharmacy Enterprise Co., Ltd, Beijing, China.Results: Farmworkers from six cattle farms, one sheep farm and one goat farm were investigated in this study. Only one farm practices zero-grazing, with the rest using rotational grazing. Of the 87 farmworkers, males comprised 83.9%, and almost half (47.1%) were aged 20– 35 years old. By ethnic group, the vast majority were Malay. Most of the farmworkers have good hygiene practices; washing or changing their clothes and showering after dealing with farm animals were common. None of the farmworker serum samples had anti-HEV IgM and IgG detected (95% confidence interval (CI): 0, 0.0415).Conclusion: The finding suggests that the farmworkers had no previous exposure to Hepatitis E, and were not at risk of occupational exposure to HEV infection. Our findings suggest that a zero seroprevalence of HEV infection among ruminant farmworkers in the Muslim majority country. Good farm management, hygiene practices and the absence of contact with swine-related contamination might have contributed to the no or minimal zoonotic risks of HEV amongst farmworkers surveyed in this study.Keywords: HEV, farmworkers, seroprevalence, antibody

Ting Wu, Guo-Qing Sui, Deng-Ke Teng, Qiang Luo, Hui Wang, Yuan-Qiang Lin Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of ChinaCorrespondence: Hui Wang; Yuan-Qiang Lin, Tel +86-431-84995070 ; +86-15948309530, Email whui66@jlu.edu.cn; linyuanqiang@jlu.edu.cnBackground: In recent years, papillary thyroid microcarcinoma (PTMC) has been a main cause of the high incidence of thyroid carcinoma. No existing study has reported whether microwave ablation (MWA) affects patients’ immunity. Therefore, this study explored the effects of MWA treatment on the immune functions of patients with PTMC.Methods: This study included 50 patients diagnosed with PTMC who received MWA treatment under ultrasound guidance at the ultrasound department of our hospital from January 2019 to October 2020. Changes in immune function after MWA treatment in PTMC patients were detected by T lymphocyte subsets and cytokines secreted by T helper cells.Results: At 1 day and 2 weeks after MWA treatment, the proportions of CD3+, CD4+ and CD4+/CD8+ T lymphocyte subsets and the levels of the cytokines interleukin (IL)-2 and interferon (IFN)-γ in the peripheral blood of the patients were significantly higher than those before MWA treatment (P< 0.05). The levels of CD8+ T lymphocytes, tumour necrosis factor (TNF)-α, IL-4, IL-6, IL-10 and IL-17A were not significantly different from those before MWA treatment (P> 0.05). One month after MWA treatment, the proportions of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocytes and the levels of the cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17A were not significantly different from those before MWA treatment (P> 0.05).Conclusion: The immune functions of patients with PTMC are temporarily enhanced after MWA treatment, which has important clinical significance for patients’ anti-PTMC ability.Keywords: microwave ablation, papillary thyroid microcarcinoma, T lymphocyte, cytokine

Qing Huang, Liu-li Xu, Ting Wu, Yun-Zhu Mu Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Yun-Zhu Mu, Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +8615984833231, Email hymyz77@163.comAbstract: Striae distensae (stretch marks/striae gravidarum) is one of the common cosmetic problems that can cause psychological distress and anxiety to patients due to its disfiguring damage, especially for women. The etiology of striae distensae is currently unknown, and risk factors include low maternal age, family history of stretch marks, excessive weight gain during pregnancy, and high neonatal weight. This article reviews the latest literature on the most commonly used, most popular, and novel treatment modalities and analyzes the hot spots and difficulties in striae distensae treatment in recent years. Topical treatment modalities are mainly used as an adjunctive treatment. Ablative lasers and non-ablative lasers are the most popular, among which picosecond has been tried in striae distensae treatment in the last two years. Combined treatment modalities are currently a hot spot for SD treatment, and microneedle radiofrequency and fractional CO2 laser combined with other treatments are the most common. Microneedle radiofrequency is the most commonly used and achieved therapeutic effect among the combined treatment modalities.Keywords: striae distensae, stretch marks, striae gravidarum, treatment

Jiongliang Wang,1,2,&ast; Zhikai Zheng,1,2,&ast; Tianqing Wu,1,2,&ast; Wenxuan Li,1,2,&ast; Juncheng Wang,1,2 Yangxun Pan,1,2 Wei Peng,1,2 Dandan Hu,1,2 Jiajie Hou,1,2 Li Xu,1,2 Yaojun Zhang,1,2 Minshan Chen,1,2 Rongxin Zhang,2,3 Zhongguo Zhou1,2 1Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343117, Email zhouzhg@sysucc.org.cn Rongxin Zhang, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-411-84672130, Email zhangrx@sysucc.org.cnObjective: To evaluate whether surgery-related complications are increased after hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin plus fluorouracil/leucovorin for conversion compared with primary hepatocellular carcinoma (HCC) resection and the optimal timing of conversion surgery (CS).Background: HAIC has been widely used for advanced HCC, especially initially unresectable HCC, to facilitate conversion to curative-intent resection in approximately 23.8% of cases. However, the optimal timing of surgery to reduce surgical complications must be clarified.Methods: Data from 320 HCC patients, including 107 initially unresectable patients in the HAIC-Surgery group and 213 patients in the Surgery group, were retrospectively collected and analyzed. Survival outcomes and the incidence of surgery-related complications were compared.Results: There was no significant difference in recurrence-free survival (RFS) between the HAIC-Surgery group and the Surgery group (HR: 1.140, 95% CI: 0.8027– 1.618, p=0.444). The HAIC-Surgery group had a higher incidence of surgery-related complications than the Surgery group [biliary leakage (10.3% vs 4.2%, p=0.035), abdominal bleeding (10.3% vs 3.8%, p=0.020), pleural effusion (56.1% vs 23.0%, p< 0.0001) and ascites effusion (17.8% vs 5.2%, p< 0.0001)]. In the HAIC-Surgery group, postoperative liver function decreased and abdominal bleeding increased with more preoperative HAIC cycles (Spearman=0.229, p=0.042, Spearman=0.198, p=0.041, respectively). The pathological complete remission (pCR) rate after 3– 5 HAIC cycles was significantly higher than that after 1– 2 cycles (29.4% vs 13.2%, p=0.043).Conclusion: The prognosis of advanced HCC after conversion surgery is comparable to that after direct surgery. Rather than increasing pCR, more HAIC cycles can exacerbate liver dysfunction and surgery-related complications.Keywords: hepatocellular carcinoma, conversion therapy, hepatic artery chemotherapy infusion

Xuchao Gu,1,2,&ast; Wenhao Wang,1,2,&ast; Yijing Yang,1,2,&ast; Yiming Lei,1,2 Dehua Liu,1,2 Xiaojun Wang,1,2 Tao Wu1,2 1Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Wu; Xiaojun Wang, Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan-An Road, Shanghai, 200040, People’s Republic of China, Tel +86 13641673915 ; +86 13062796919, Email taowuh@hotmail.com; 13681803275@163.comAbstract: Sarcopenia is an age-related systemic disease characterized by skeletal muscle aging that generally severely affects the quality of life of elderly patients. Metabolomics analysis is a powerful tool for qualitatively and quantitatively characterizing the small molecule metabolomics of various biological matrices in order to clarify all key scientific problems concerning cell metabolism. The discovery of optimal therapy requires a thorough understanding of the cellular metabolic mechanism of skeletal muscle aging. In this review, the relationship between skeletal muscle mitochondria, amino acid, vitamin, lipid, adipokines, intestinal microbiota and vascular microenvironment has been separately reviewed from the perspective of metabolomics, and a new therapeutic direction has been suggested.Keywords: sarcopenia, metabolomics, mitochondria, intestinal microbiota, vascular endothelium

Jiannan Tu,1,&ast; Shengchi Chen,1,&ast; Shizhen Wu,1,&ast; Ting Wu,1,&ast; Renliang Fan,1 Zhixing Kuang2 1Department of Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China; 2Department of Radiation Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixing Kuang, Department of Radiation Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353000, People’s Republic of China, Email zhixingkuang@gmail.comBackground: DNA-methylation-based machine learning algorithms have demonstrated powerful diagnostic capabilities, and these tools are currently emerging in many fields of tumor diagnosis and patient prognosis prediction. This work aimed to identify novel DNA methylation diagnostic biomarkers for differentiating cervical cancer (CC) from normal tissues, as well as a prognostic prediction model to predict survival of CC patients.Methods: The methylation profiles with the available clinical characteristics were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) program. We first screened out the differential methylation sites in CC and normal tissues and performed multiple statistical analyses to discover DNA methylation diagnostic markers that are used to distinguish CC and normal control. Then, we developed a methylation-based survival model to improve risk stratification.Results: A diagnostic prediction panel consists of five CpG markers that could predict cervical cancer versus normal tissue with highly correct rate of 100%, and cg16428251, cg22341310, and cg23316360 which in diagnostic prediction panel all could yield high sensitivity and specificity for detection of CC and normal in six cohorts (area under curve [AUC] > 0.8), in addition to excellent performance in discriminating between CC and normal sample. The diagnostic marker panel also effectively predicted the CIN3 versus normal tissue with high accuracy in two datasets (AUC = 0.80, 0.789, respectively). Furthermore, a prognostic prediction model aggregated two CpG markers that effectively stratified the prognosis of high-risk and low-risk groups (training cohort: hazard ratio [HR] 4, 95% CI: 1.7– 9.6, P = 0.0021; testing cohort: hazard ratio [HR] 1.9, 95% CI: 1.2– 3.1, P = 0.0072).Conclusion: The findings of our study showed that DNA methylation markers are of great value in the diagnosis and prognosis of CC.Keywords: cervical cancer, DNA methylation, markers, diagnosis, prognosis

Xianhua Liao,1 Qianqian Ma,1 Tingfeng Wu,1 Congxiang Shao,1 Yansong Lin,1 Yanhong Sun,2 Shiting Feng,3 Wei Wang,4 Junzhao Ye,1 Bihui Zhong1 1Department of Gastroenterology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Laboratory of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Radiology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Medical Ultrasonics of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Bihui Zhong; Junzhao Ye, Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Tel +86 135 0307 9262 ; +86 135 0151 9252, Email zhongbh@mail.sysu.edu.cn; yejzh@mail2.sysu.edu.cnPurpose: Effective treatment of dyslipidemia with lipid-lowering agents is pivotal in the management of metabolic-associated fatty liver disease (MAFLD) for preventing cardiovascular complications. We explored the associations between improvements in liver injuries indicated by changes in transaminases and a reduction in lipid levels in MAFLD patients with dyslipidemia and elevated transaminases during lipid-lowering therapies.Methods: This prospective, cohort study enrolled consecutive MAFLD patients with hyperlipidemia and elevated transaminases. Patients were divided into a group receiving lipid-lowering agents and an age-, sex- and baseline lipid level-matched control group without receiving lipid-lowering agents. Clinical visits were performed at the 1st month and then every 3 months for 1 year.Results: This study included 541 MAFLD patients (lipid-lowering group: 325 patients; control group: 216 patients). Compared with controls, there was a substantially greater reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the lipid-lowering group after 12 months (all P < 0.05). The decrease in ALT was positively correlated with the decrease in TC (r = 0.332), TG (r = 0.180), LDL-c (r = 0.253) and apolipoprotein E (ApoE) (r = 0.119), while the decrease in AST was positively correlated with the decrease in TC (r = 0.228) and LDL-c (r = 0.192) (all P< 0.05). The greater range of reduction in blood lipids (TC/TG/LDL-c), the higher the transaminase and GGT normalization rate (all P< 0.05). Multivariate analysis confirmed that a TG decrease of over 50% remained an independent predictor of transaminase and GGT normalization (OR 2.07, 95% CI 1.12– 3.84, P=0.020).Conclusion: Lipid-lowering to target levels might be beneficial to liver injury improvements in MAFLD patients with dyslipidemia when receiving lipid-lowering agents.Keywords: dyslipidemia, metabolic dysfunction-associated fatty liver disease, alanine aminotransferase, triglyceride, gamma glutamyl transpeptidase, statins

Xiaojun Wang,1,2,&ast; Xuanqi Liu,3,&ast; Yiding Qi,4,&ast; Shuyi Zhang,4 Kailei Shi,4 Huagang Lin,5 Paul Grossfeld,6 Wenhao Wang,1,2 Tao Wu,1,2 Xinkai Qu,4 Jing Xiao,5 Maoqing Ye2,4 1Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 4Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 6Division of Cardiology UCSD School of Medicine, Rady Children’s Hospital of San Diego, La Jolla, CA, 92093, USA&ast;These authors contributed equally to this workCorrespondence: Maoqing Ye, Department of Cardiology, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China, Tel +86-18930721396, Email yemaoqing@fudan.edu.cn Jing Xiao, Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China, Tel +86-13817100256, Email jingxiao13@Fudan.edu.cnBackground: Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China.Methods: A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan–Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects.Results: Based on the first year of follow-up data analysis, the elevation of SUA levels (P< 0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P< 0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups.Conclusion: Taken together, the findings in this study indicate that high SUA levels (P< 0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.Keywords: serum uric acid, calcium deposition, coronary artery calcium score, monocyte inflammation

Cong Su,1,&ast; Ting Wu,2,&ast; Bao Meng,2 Chengcheng Yue,2 Yating Sun,2 Lingling He,2 Tingting Bian,2 Yanyan Liu,3,4 Ying Huang,5 Yanhu Lan,4 Jiabin Li2– 4,6 1Department of Infection Management, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Department of Infectious Diseases, The Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital and the Chaohu Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, People’s Republic of ChinaEmail lijiabin@ahmu.edu.cnYanhu LanInstitute of Bacterial Resistance, Anhui Medical University, Jixi Road 218, Hefei, 230022, People’s Republic of ChinaEmail zixinhu@163.comBackground: Klebsiella pneumoniae (K. pneumoniae) causes community-acquired and hospital-acquired pneumonia. The mortality rates of invasive infections caused by hypervirulent K. pneumoniae (HvKP) are extremely high. However, the microbiological characteristics and clinical manifestations of K. pneumoniae in AnHui province still remain unclear.Purpose: To show the high prevalence of HvKP infections regarding clinical characteristics and antimicrobial resistance in Anhui province.Patients and Methods: A retrospective analysis was conducted to study the clinical data of 115 strains of K. pneumoniae from July 2019 to March 2020 in The First Affiliated Hospital of AnHui Medical University. The virulence genes, capsular types, carbapenemase genes, and molecular subtypes of these hypervirulent isolates were detected.Results: Overall, 59.1% (68/115) cases were HvKP infections, mainly from the department of intensive care unit (ICU, n=14, 20.6%) and the department of respiratory and critical care (n=13, 19.1%). K2 was the most prevalent capsular serotype (n=26), followed by K1 (n=21). The results of MLST identification of 68 strains showed that ST23 (n=15, 22.1%) was the most common type of ST, followed by ST11 and ST65 (n=12, 17.6%), ST86 (n=9, 13.2%), and ST412 (n=6, 8.8%). Among 68 hvKP strains, 12 isolates were carbapenem resistant, and all except two harboured KPC.Conclusion: The high incidence of carbapenemase producing HvKP in the Anhui province, especially the higher mortality of HvKP, should be paid more attention. Meanwhile, epidemiological surveillance and clinical treatment strategies should be continuously determined and implemented.Keywords: Klebsiella pneumoniae, virulence genes, capsular types, antimicrobial resistance

Ti Wu,1,&ast; Haipeng Zhang,2,&ast; Xiaolin Tian,3 Yang Cao,2 Dianjun Wei,4 Xiangkun Wu4 1Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 4Department of Clinical Laboratory, Hebei Yanda Hospital, Langfang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangkun Wu Tel +8615613682051Email wuxiangkun_2021@163.comPurpose: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) without fever and to clarify whether NLR has an advantage over high-sensitivity C-reactive protein (hs-CRP) in predicting SAP.Patients and Methods: A total of 434 patients with AIS without fever were assessed in this study. Multivariable analysis was used to evaluate the relationship between NLR and SAP, and the receiver operating characteristic (ROC) curve was used to compare the predictive value of NLR and hs-CRP.Results: Among the total patients, 18 (4.1%) developed SAP. After adjusting for confounders, NLR (adjusted odds ratio [aOR] = 1.60; 95% confidence interval [CI], 1.30– 1.96; p < 0.001) remained independently associated with an increased risk of SAP. In addition, the area under the curve (AUC) of NLR (0.862 [0.826– 0.893]) was higher than that of hs-CRP (0.738 [0.694– 0.779]).Conclusion: We found that compared with hs-CRP, NLR was significantly associated with the occurrence of SAP in patients with AIS without fever and showed a more effective predictive value for SAP.Keywords: stroke, pneumonia, neutrophil, lymphocyte, high-sensitivity C-reactive protein, inflammation

Xin-Tian Cai,1,2,&ast; Qing Zhu,1,2,&ast; Sha-Sha Liu,2 Meng-Ru Wang,2 Ting Wu,2 Jing Hong,2 Jun-Li Hu,2 Nanfang Li1,2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang LiGraduate School, Xinjiang Medical University; Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of ChinaEmail lnanfang2016@sina.comPurpose: The metabolic score for insulin resistance (METS-IR) index is an emerging surrogate predictor of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the METS-IR index and the risk of T2DM in non-obese Japanese adults.Methods: A total of 12,290 non-obese participants were selected from the NAGALA prospective cohort study conducted from 2004 to 2015. Cox proportional hazards models were used to assess the association between the baseline METS-IR index and risk of T2DM. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During a median follow-up of 2050 days, 176 (1.43%) incident T2DM occurred. The fully adjusted HR (95% CI) for the incidence of T2DM in non-obese adults was 1.17 (HR=1.17, 95% CI: 1.09– 1.27, P< 0.001) for every 1-unit increase in the METS-IR index. The risk of developing T2DM increased with the quartile of change in the METS-IR index, after adjustment for multiple potential confounding, the HRs for the Q4 group versus the Q1 group was 4.01 (95% CI, 1.39– 11.57). Generalized additive models also showed a cumulative increase in the risk of T2DM with increasing the METS-IR index. Time-dependent receiver operating curve suggested helpful discriminative power of the METS-IR index for T2DM. The C-statistics by the clinical risk factors significantly improve with the addition of the METS-IR index (from 0.862 to 0.875, P = 0.035); the discriminatory power and risk reclassification also appeared to be substantially better, with the category-free NRI of 0.216, and the IDI of 0.011.Conclusion: The METS-IR index was a significant and independent predictor for future T2DM development in non-obese adults. The METS-IR index may have clinical significance in identifying groups at high risk of T2DM.Keywords: metabolic score for insulin resistance index, type 2 diabetes mellitus, non-obese, population-based cohort study

Yun-Hua Chai,1 Hui Yang,2 Gai-Ping Huang,1 Ting Wu,1 Yan Dong3 1Department of Geriatrics, First Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, People’s Republic of China; 2Nursing College of Shanxi Medical University, Jinzhong City, Shanxi Province, People’s Republic of China; 3Department of Respiratory and Critical Illness, First Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, People’s Republic of ChinaCorrespondence: Yun-Hua ChaiDepartment of Geriatrics, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan City, Shanxi Province, 030001, People’s Republic of ChinaTel +86 15203405557Email chai_121yh@126.comBackground: Chronic obstructive pulmonary disease (COPD) is a physical and mental disease, and there is currently no cure, so the health guidance of COPD patients after discharge from hospital is crucial. The purpose of this study is to investigate the nursing outcomes and risk factors for patients with COPD discharged from hospital.Methods: In this study, a total of 200 patients with COPD who were stable and ready to be discharged from two tertiary hospitals in Taiyuan were surveyed by the Nursing Outcome Evaluation Form for COPD patients, and the relevant risk factors of these patients were analysed.Results: The results of this study showed that patients with COPD who were to be discharged from hospital had low scores in the perceived health domain (1.9708 ± 0.70525) and psychosocial health domain (1.5267 ± 0.68289), while the scores in the rest of the domains were above the medium level. The main factors affecting the two domains of the nursing outcome were degree of education, dietary habits, complications (perceived health domain), drinking, marital status, medical insurance and smoking (psychosocial health domain) (p < 0.05).Conclusion: Clinical nurses should pay attention to the perceived and psychosocial health domains when educating COPD patients who are to be discharged from hospital, and should primarily focus on the risk factors of smoking and drinking status, degree of education, dietary habits, complications, marital status and medical insurance.Keywords: chronic obstructive pulmonary disease, COPD, discharge, core nursing outcomes, risk factors

Tingting Wu,&ast; Dandan Xie,&ast; Xiaotong Zhao, Murong Xu, Li Luo, Datong Deng, Mingwei Chen Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwei ChenDepartment of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230032, People’s Republic of ChinaEmail chmw1@163.comObjective: To explore the correlation between the expression of miR-34c in peripheral blood of patients with type 2 diabetes mellitus (T2DM) and the onset of diabetic foot ulcer (DFU) and diabetic foot osteomyelitis (DFO).Methods: Sixty newly diagnosed patients with T2DM without DFU (T2DM group), 112 T2DM patients with DFU (DFU group) and 60 controls with normal glucose tolerance (NC group). The DFU group patients were subdivided into DFO (n=64) and NDFO (n=48) groups. Quantitative real-time PCR (qRT-PCR) method was used to determine miR-34c expression levels in the peripheral blood of subjects to analyze the clinical characteristics of DFU and DFO risk factors.Results: MiR-34c expression level in the T2DM group was marked higher than the NC group [2.99 (1.45– 6.22) vs 1.01 (0.89– 1.52)] (P < 0.05). However, the expression level of miR-34c in the DFU group was significantly higher than the T2DM group [9.65 (6.15– 18.63) vs 2.99 (1.45– 6.22)] (P < 0.01). Compared with the NDFO group, the expression level of miR-34c in the DFO group was also obviously increased [13.46 (8.89– 19.11) vs 6.02 (5.93– 14.72)] (P < 0.01). The expression level of miR-34c in DFU patients was positively correlated with the amputation rate of foot ulcers (P=0.030) and was negatively correlated with the healing rate of foot ulcers after eight weeks (P=0.025). Multifactorial logistic regression analysis showed that increased expression of miR-34c was an independent risk factor for DFU and DFO (ORDFU=3.47, ORDFO=4.25, P < 0.01). Meanwhile, the ROC curve analysis indicated that the AUC of miR-34c for the diagnosis of DFU and DFO was 0.803 and 0.904, the optimum sensitivity being was 100% and 98.7%, the optimum specificity was 98.4% and 98.4%, respectively.Conclusion: The increased expression of miR-34c in peripheral blood of T2DM patients is closely related to the occurrence, development and prognosis of DFU and DFO.Keywords: type 2 diabetes, diabetic foot, diabetic foot osteomyelitis, miRNAs

Dongli Xie,1,&ast; Jianchen Hu,1,&ast; Tong Wu,2 Kangli Cao,3 Xiaogang Luo1 1College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China; 2Shanghai LEVSON Nanotechnology Co., Ltd, Shanghai, 200444, People’s Republic of China; 3Shanghai Institute of Spacecraft Equipment, Shanghai, 200240, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Luo Tel +86 512-67162531Email xgluo@suda.edu.cnBackground: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.Methods: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein–protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.Results: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥ 4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of > 0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).Conclusion: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.Keywords: carbon nanotubes, malignant transformation, malignant pleural mesothelioma, tumor-infiltrating immune cells, prognosis, diagnosis

Wenjun Zhao,1 Gang Wang,2 Ping Xu,3 Tingting Wu,3 Binjuan Chen,3 Haijun Ren,2 Xingjie Li1 1Department of Ultrasound, Imaging, Healthy Management Centre, The Second Hospital of Lanzhou University, Lanzhou City, 730000, Gansu Province, People’s Republic of China; 2Department of Neurosurgeon, Neurology, Neurologist, The Second Hospital of Lanzhou University, Lanzhou City, 730000, Gansu Province, People’s Republic of China; 3Department of Ultrasound, Imaging, Ultrasound Centre, The Second Hospital of Lanzhou University, Lanzhou City, 730000, Gansu Province, People’s Republic of ChinaCorrespondence: Xingjie LiDepartment of Ultrasound, Imaging, Healthy Management Centre, The Second Hospital of Lanzhou University, Landa 2 Yard, No. 82, Cuiying Gate, Chengguan District, Lanzhou City, 730000, Gansu Province, People’s Republic of ChinaTel +86-9318942555; +86-13609337887Email LiXingjie723723@163.comObjective: To determine the risk factors associated with the progress of subaneurysmal aorta (SAA) to abdominal aortic aneurysm (AAA) and provide a reference for the prevention of AAA in rural areas.Methods: A total of 747 SAA patients screened by the Health Management Center of the Second Hospital of Lanzhou University from January 2015 to January 2016 were recruited. The ratio of SAA progressing to AAA was observed through 5 years of follow-up. Logistic stepwise regression analysis was performed to analyze the high-risk factors. The relevant clinical prediction model score table (Nom) was made and the C-index and calibration chart were used to verify the prediction ability of the model.Results: Of the 747 patients diagnosed with SAA, 260 developed to AAA, with an incidence of 34.8%. Univariate analysis showed that age (62– 65 years old), abdominal aorta diameter greater than 2.7 cm, smoking after 30 years old, moderate to severe hypertension, and blood pressure variability were the important high-risk factors of SAA progressing to AAA. Logistic regression analysis showed that these factors were statistically significant. The nomogram of clinical prediction model score showed that when 50– 60% of SAA developed to AAA, the score was 189– 201 and the C-index was 0.883, verifying the moderate predictive ability of this model.Conclusion: Age, smoking habit, degree of hypertension, and control situation were high-risk factors associated with the progression of SAA to AAA. The control of the above high-risk factors was imperative for the prevention of AAA in rural areas without sufficient medical resources.Keywords: abdominal aortic aneurysm, high-risk factors, abdominal aorta dilation, rural areas

Tong Yu,1,2,* Jinglue Song,1,2,* Hui Zhou,1,2 Tingyu Wu,1,2 Zhonglin Liang,1,2 Peng Du,1,2 Chen-Ying Liu,1,2 Guanghui Wang,3 Long Cui,1,2 Yun Liu1,2 1Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Colorectal Cancer Research Center, Shanghai, People’s Republic of China; 3Guizhou Provincial People’s Hospital, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Liu Tel + 86-021-25078825Email liuyun@xinhuamed.com.cnGuanghui Wang Email wangguanghui0625@163.comIntroduction: Stage I–III colorectal cancer patients are under risk of tumor recurrence and metachronous metastasis after radical surgery. An increased expression of transcription factor TEAD4 is associated with epithelial-mesenchymal transition, metastasis and poor prognosis in colorectal cancer. However, the mechanistic role of TEAD4 in driving colon cancer progression and its prognostic value in early stage of CRC remains unclear.Methods: In this study, the regulation, function and prognostic significance of TEAD4 and its new direct target gene SIX1 in CRC progression were evaluated using human tissues, molecular and cell biology.Results: We show that TEAD4 directly upregulates the expression of SIX1 at transcriptional level in CRC cells, establishing that SIX1 is a new direct target gene of TEAD4. TEAD4 promotes EMT and cell migration of CRC cells, while SIX1 knockdown attenuates this effect and SIX1 overexpression enhances this effect, indicating that SIX1 mediates the function of TEAD4 in promoting cell migration in CRC cells. Clinically, nuclear TEAD4, overexpression of SIX1 and nuclear TEAD4 with SIX1 overexpression predict poor prognosis in CRC patients.Discussion: Our study identifies TEAD4-SIX1-CDH1 form a novel signaling axis, which contributes to CRC progression, and its aberrant expression and activation predicts poor prognostic for CRC patients in stage I–III.Keywords: colorectal cancer, TEAD4, SIX1, hippo pathway

Gaoying Hong,1 Jiaxue Yang,1 Xin Jin,2 Tong Wu,1 Shiqi Dai,1 Haifeng Xie,1 Chen Chen2 1Jiangsu Key Laboratory of Oral Diseases, Department of Prosthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China; 2Jiangsu Key Laboratory of Oral Diseases, Department of Endodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Chen Chen; Haifeng Xie Han-Zhong Road 136thAffiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, People’s Republic of ChinaTel +86 25 6959 3031; +86 25 6959 3081Fax +86 25 8651 6414Email ccchicy@njmu.edu.cn; xhf-1980@126.comPurpose: The aim of this study was to investigate the effect of various mass fractions of 10-methacry-loyloxydecyl dihydrogen phosphate (MDP)-conditioned or unconditioned zirconia nano- or micro-particles with different initiator systems on the mechanical properties of nanohybrid resin composites.Methods: Both light-cured (L) and dual-cured (D) resin composites were prepared. When the mass fraction of the nano- or micro-zirconia fillers reached 55 wt%, resin composites were equipped with dual-cured initiator systems. We measured the three-point bending-strength, elastic modulus, Weibull modulus and translucency parameter of the nanohybrid resin composites containing various mass fractions of MDP-conditioned or unconditioned zirconia nano- or micro-particles (0%, 5 wt%, 10 wt%, 20 wt%, 30 wt% and 55 wt%). A Cell Counting Kit (CCK)-8 was used to test the cell cytotoxicity of the experimental resin composites. The zirconia nano- or micro-particles with MDP-conditioning or not were characterized by transmission electron microscopy (TEM), Fourier infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS).Results: Resin composites containing 5– 20 wt% MDP-conditioned or unconditioned nano-zirconia fillers exhibited better three-point bending-strength than the control group without zirconia fillers. Nano- or micro-zirconia fillers decreased the translucence of the nanohybrid resin composites. According to the cytotoxicity classification, all of the nano- or micro-zirconia fillers containing experimental resin composites were considered to have no significant cell cytotoxicity. The FTIR spectra of the conditioned nano- or micro-fillers showed new absorption bands at 1719 cm− 1 and 1637 cm− 1, indicating the successful combination of MDP and zirconia particles. The XPS analysis measured Zr–O–P peak area on MDP-conditioned nano- and micro-zirconia fillers at 39.91% and 34.89%, respectively.Conclusion: Nano-zirconia filler improved the mechanical properties of nanohybrid resin composites, but cannot be the main filler to replace silica filler. The experimental dual-cured composites can be resin cements with better opacity effects and a low viscosity.Keywords: resin composite, nano-zirconia filler, MDP, initiator system, mechanical property, translucence

Hongmei Hu,1– 4,* Tingting Wu,3,* Luying Fan,5 Keying Zuo,5 Ling Chen,5 Jiaqiong Zhang,1,3 Xin Zhao2 1College of Pre-School Education, Chongqing University of Education, Chongqing 400067, People’s Republic of China; 2Children’s Research Institute, Chongqing University of Education, Chongqing 400067, People’s Republic of China; 3Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, People’s Republic of China; 4Family Education Guidance Center for 0– 6 Years Old, Chongqing University of Education, Chongqing 400067, People’s Republic of China; 5School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaqiong Zhang; Xin Zhao Tel +86-23-6163-8842; +86-23-6265-3650Email cque@foxmail.com; zhaoxin@cque.edu.cnAim: This research aims to explore the health knowledge mastery of preschool teachers in Chongqing.Methods: A cross-sectional questionnaire survey of preschool teachers in Chongqing was conducted by random sampling. A total of 399 preschool teachers were included in this research. Multiple linear regression analysis was conducted to explore the influencing factors on preschool teachers’ mastery of preschool child health knowledge.Results: This research found that the average score of preschool teacher’s knowledge of preschool children was only 34.01± 0.78, and the accuracy of the knowledge points of continuous short-distance eye use time was the lowest, at less than 5%. The conducting of eye exercises by the kindergarten and the scores of preschool teachers were negatively correlated (β=− 0.257, p< 0.001); the score of health knowledge of preschool teachers of the kindergarten whose screen time met the standard was lower (β=− 0.113, p=0.017); whether the time and frequency for outdoor activities of the kindergarten met the standards and the health knowledge score of preschool teachers was positively correlated (β=0.130, p< 0.001 vs β=0.163, p< 0.001). Male preschool teachers and teachers overweight according to BMI had higher scores for preschool health knowledge (β=− 0.114, p=0.016 vs β=0.099, p=0.034).Conclusion: Preschool teachers in Chongqing had a poor grasp of knowledge regarding preschool children’s health, and in particular, knowledge of children’s exercise and eye use. Educational background and work experience may no longer indicate preparedness for teaching these topics, and suggests that supportive measures can also be directly provided at the kindergarten level in the future to increase the health knowledge of preschool teachers.Keywords: preschool teachers, preschool children, health knowledge, supportive measures

Fanqin Bu,1,2,* Xiaojian Zhu,3,* Jinfeng Zhu,1,2,* Zitao Liu,1,2 Ting Wu,4 Chen Luo,1,2 Kang Lin,1,2 Jun Huang1 1Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of China; 2Jiangxi Medical College of Nanchang University, Nanchang, People’s Republic of China; 3Research Center of The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 4Department of Infectious Diseases of Guixi Traditional Chinese Medicine Hospital, Yingtan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Huang Email huangjun0727@163.comBackground: Colorectal cancer (CRC) is one of the most lethal malignancies and the incidence of CRC has been on the rise. Herein, we aimed to identify effective biomarkers for early diagnosis and treatment of colorectal cancer via bioinformatic tools.Methods: To identify differentially expressed genes (DEGs) in CRC, we downloaded CRC gene expression data from GSE24514 and GSE110223 datasets in Gene Expression Omnibus (GEO) and employed R to analyze the data. We further performed functional enrichment analysis of the DEGs on the DAVID gene ontology analysis tool. STRING database and Cytoscape visualization tool were employed to construct a PPI (protein–protein interaction) network and establish intensive intervals in the network. Immunohistochemistry, qRT-PCR and Western blotting were performed to identify the expression level of GINS1 in CRC. In vitro and in vivo experiments were performed to assess the impact of GINS1 in the pathogenesis of CRC in terms of proliferation, migration and metastasis.Results: Among the two datasets, 389 DEGs were identified and used to construct a PPI network. These genes were mainly involved in cell proliferation and cell cycle. Among them, 15 genes including GINS1 were found to be strongly associated with the PPI network. We further performed immunohistochemistry, qRT-PCR and Western blotting to identify that GINS1 expression was higher in CRC than in paired normal tissues. Moreover, in vitro and in vivo experiments demonstrated GINS1 could promote the proliferation, invasion and migration of colorectal cancer cells.Conclusions: GINS1 could be considered as a potential biomarker for CRC patients.Keywords: GINS1, colorectal cancer, bioinformatics screening

Amelia Nabatanzi,1 Magesa Mafuru,2 Musa Male,3 Chunxia Tian,4 Lingyun Zhang,1 Ting Wu,1 Shidi Wu,1 Changzheng Huang1 1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pharmacology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Changzheng HuangDepartment of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of ChinaTel +86-13971176116Fax +86-27-85768188Email hcz0501@126.comBackground: The available treatments for refractory hyperkeratotic eczema are inadequate with frustrating results. We, therefore, incorporated Calcipotriol and Betamethasone Dipropionate (Daivobet®), and Viaminate into the mainstay treatment to improve the clinical symptoms. The study aimed to evaluate the efficacy of Daivobet® and Viaminate as a potential treatment alternative for refractory hyperkeratotic eczema.Patients and Methods: Between 2013 and 2015, 61 patients diagnosed with refractory hyperkeratotic eczema (RHE) who had shown inadequate response to conventional therapies were pooled from a single center. Besides, they were all treated with Daivobet®, Viaminate, and an occlusive dressing mixture containing 5% salicylic acid ointment and 25% zinc oxide paste following inadequate response to conventional therapies (corticosteroids plus 25% zinc oxide paste and 5% salicylic acid ointment). Investigators Global Assessment (IGA) and Patient-Oriented Eczema Measure (POEM) assessed baseline and outcome measures for the degree of hyperkeratinization (0-clear; 3-moderate; 4-severe).Results: Of the 61 patients, 49 (80.3%) patients presented with moderate RHE and 12 (19.7%) with severe RHE. After 24 weeks of treatment, the period for loss of keratinization was significantly lower in patients with moderate RHE (3.9± 1.9 weeks) than those with severe RHE (10.8± 1.0 weeks) with a P-value < 0.01. Furthermore, they required a significantly shorter total treatment duration (10.6 ± 4.3 weeks) than those with severe RHE (20.3± 3.6 weeks) with a P-value of < 0.01. However, there were no significant differences in post hoc analysis at week 36 with P-values of 0.46 and 1.00 for IGA and POEM, respectively.Conclusion: Our results showed that the incorporation of Viaminate and Daivobet® into mainstay treatment was effective and safe for the long-term management of RHE.Keywords: refractory, hyperkeratosis, eczema, Viaminate, Daivobet®

Yuzheng Xue,1,* Yao Zhong,1,* Tielong Wu,1 Yingyue Sheng,1 Yuanyuan Dai,1 Lingling Xu,1 Chuanqing Bao2 1Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214041, Jiangsu, People’s Republic of China; 2Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214041, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuzheng XueDepartment of Gastroenterology, Affiliated Hospital of Jiangnan University, No. 585, Xingyuan North Road, Wuxi 214041, Jiangsu, People’s Republic of ChinaEmail xueyz001@163.comPurpose: The expression of microRNA-125b (miR-125b) is low in a variety of cancers, including gastric, lung, bladder, thyroid, and esophageal cancers. However, its specific mechanism in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study is aimed to explore the role of miR-125b in PDAC.Methods: PDAC tissues and adjacent tissues were collected for miR-125b analysis by qRT-PCR. Different PDAC cell lines were cultured for miR-125b detection by qRT-PCR, and CAPAN1 cells were selected for the downstream experiments. Cell proliferation was characterized by methyl thiazolyl tetrazolium (MTT) and 5-bromo-2-deoxyUridine (BrdU) staining. Flow cytometry was utilized for apoptosis and cell cycle changes. Cell invasion was determined by the Transwell assay and the dual-luciferase assay was utilized for validating the target gene. Western blotting was used to detect apoptosis related and PI3K/AKT signaling proteins.Results: miR-125b was significantly down-regulated in human PDAC tissues and cell lines (P < 0.05). miR-125b inhibited the growth and invasion of CAPAN1 cells, facilitated apoptosis, and blocked the cell cycle at the G0/G1 phase. Furthermore, miR-125 directly targeted NEDD9. The high expression of NEDD9 impaired the anti-proliferative and anti-apoptotic activity of miR-125b. miR-125b also inhibited apoptosis-related proteins and PI3K/AKT signaling pathways via NEDD9.Conclusion: miR-125b decreased cell growth and invasion, and facilitated apoptosis in CAPAN1 cells through PI3K/AKT inhibition via targeting NEDD9.Keywords: miR-125b, pancreatic ductal adenocarcinoma, apoptosis, NEDD9, PI3K/AKT

Tianshu Wu,1 Xue Liang,1 Keyu He,2 Xi Liu,1 Yimeng Li,1 Yutong Wang,1 Lu Kong,1 Meng Tang1 1Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People’s Republic of China; 2Blood Transfusion Department, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Tianshu Wu Email ninatswu@126.comIntroduction: Since CdTe quantum dots (QDs) are still widely considered as advanced fluorescent probes because of their far superior optical performance and fluorescence efficiency over non-cadmium QDs, it is important to find ways to control their toxicity.Methods: In this study, the adverse effects of two cadmium-containing QDs, ie, CdTe QDs and CdTe@ZnS QDs, on the nervous system of nematode C. elegans, the hippocampus of mice, and cultured microglia were measured in order to evaluate the neuroinflammation caused by cadmium-containing QDs and the potential mechanisms.Results: Firstly, we observed that cadmium-containing QD exposure-induced immune responses and neurobehavioral deficit in nematode C. elegans. In the mice treated with QDs, neuroinflammatory responses to QDs in the hippocampus, including microglial activation and IL-1ß release, occurred as well. When investigating the mechanisms of cadmium-containing QDs causing IL-1ß-mediated inflammation, the findings suggested that cadmium-containing QDs activated the NLRP3 inflammasome by causing excessive ROS generation, and resulted in IL-1ß release.Discussion: Even though the milder immune responses and neurotoxicity of CdTe@ZnS QDs compared with CdTe QDs indicated the protective role of ZnS coating, the inhibitions of NLRP3 expression and ROS production completely reduced the IL-1ß-mediated inflammation. This provided valuable information that inhibiting target molecules is an effective and efficient way to alleviate the toxicity of cadmium-containing QDs, so it is important to evaluate QDs through a mechanism-based risk assessment.Keywords: quantum dot, Caenorhabditis elegans, hippocampus, BV2 cells, interleukin-1ß, NLRP3 inflammasome

Li-Hua Zhu,1,* Jun Yao,2,* Ting Wu,3 Yan Wang,1 Chen-Wei Wang,1 Chun-Quan Xue,1 Li-Guang Wu,1 Xing-Wen Fan,4 Chao-Yang Wu1 1Department of Radiation Oncology, The People’s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu Province 212003, People’s Republic of China; 2Department of Gastroenterology, The People’s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu Province 212003, People’s Republic of China; 3Department of Pathology, The People’s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu Province 212003, People’s Republic of China; 4Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao-Yang WuDepartment of Radiation Oncology, The People’s Hospital Affiliated to Jiangsu University, Dianli Road 8 In, Zhenjiang, Jiangsu Province 212003, People’s Republic of ChinaTel +86 511 88915041Email wuchaoyang9@163.comXing-Wen FanDepartment of Radiation Oncology, Shanghai Cancer Center, Fudan University, 270 Dong’an Road, Shanghai 200032, People’s Republic of ChinaTel +86 136 51669687Email wenxingfan@126.comPurpose: Endoscopic submucosal dissection (ESD) is a widely performed procedure for esophageal carcinoma when the depth of invasion reaches the epithelium and lamina propria. However, ESD for esophageal carcinoma with depth of invasion exceeding the muscularis mucosa is controversial. This study aimed to evaluate the long-term outcomes of ESD for T1N0M0 (tumor invading the mucosa and submucosa [T1], no regional lymph node metastasis [N0], no distant metastasis [M0]) esophageal cancer.Patients and Methods: Esophageal cancer was evaluated via pathology and computed tomography (CT) in consecutive patients with negative margin and without additional therapy. A total of 84 patients were included. The mean follow-up time was 42 (range, 9– 99) months.Results: No recurrence and metastasis were detected in the M1 and M2 group. The 5-year locoregional recurrence rate and distant metastasis rate were 4.2% and 5.6% for the M3 group and were 0% and 1.4% for the SM group, respectively. The 3- and 5-year overall survival were 94.4% (M1+M2 group, 95.0%; M3 group, 95.0%; SM group, 92.9%) and 80.9% (M1+M2 group, 95.0%; M3 group, 95.0%; SM group, 92.9%). Meanwhile, the 3- and 5-year disease-specific survival rates were 100% (M1+M2 group, 100%; M3 group, 100%; SM group, 100%) and 90.8% (M1+M2 group, 100%; M3 group, 90.0%; SM group, 85.7%). The major complications were postoperative strictures, most of which were grade 1– 2. In total, two (4.8%) and one (1.2%) patient developed grade 3 and 5 late esophageal strictures, respectively.Conclusion: ESD complete resection yields low recurrence and metastasis rates in early esophageal cancer (T1N0M0). Thus, additional treatment is not necessary, and a watch and wait strategy may be reasonable.Keywords: esophageal carcinoma, endoscopic therapy, endoscopic submucosal resection, recurrence and metastasis