Search

Wenguang Lai,1,&ast; Xiaoli Zhao,2,&ast; Zhiyong Gao,1 Haozhang Huang,3,4 Donghui Huang,1 Yang Zhou,3,4 Guoxiao Liang,3,4 Shiqun Chen,3,4 Jin Liu,3 Yong Liu3 1Department of Pharmacy, Heyuan People’s Hospital; Guangdong Provincial People’s Hospital, Heyuan Hospital, Heyuan, 517001, People’s Republic of China; 2Department of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Tel +86 02083827812-10528, Fax +86 02083851483, Email liuyong@gdph.org.cn; ljaw397017568@163.comPurpose: Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF.Patients and Methods: Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular‑specific mortality, respectively.Results: 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01– 1.35], 1.31[1.13– 1.52], 1.51[1.30– 1.76], respectively; P for trend < 0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99– 1.51], 1.50[1.20– 1.86], 1.73[1.37– 2.18], respectively; P for trend < 0.001).Conclusion: Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.Keywords: heart failure with preserved ejection fraction, systemic inflammatory response index, all-cause death, cardiovascular death

Jun Ma,1 Yongkang Shi,1 Qiliang Lu,1 Dongsheng Huang2 1General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Dongsheng Huang, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, No. 158 Shangtang Road, Gongshu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel/Fax +86-571-88927749, Email dshuang126@163.comBackground: Gastric cancer (GC) is a malignant tumor originating from the gastric mucosa epithelium, and there is a low survival rate of GC patients after treatment, with a poor prognostic outcome. The inflammatory response within the tumor microenvironment plays an important role in GC progression.Methods: We downloaded GC-related datasets and inflammation-related genes from GEO, TCGA and MSigDB databases, performed differential analysis, protein-protein interaction analysis, immunoinfiltration analysis and Lasso analysis to screen inflammation-related hub genes affecting GC progression, and carried out qRT-PCR for validation. In order to explore the role of ADH1A, we constructed overexpressed plasmids, treated GC cells with cGMP/PKG pathway agonist 8-Br-cGMP, and tested cell functions with CCK8, EdU, Transwell, scratch assay and other experiments. On this basis, GC cells were co-cultured with monocyte THP-1 to explore the effect of ADH1A on the polarization of macrophages.Results: ADH1A was significantly decreased in GC cells, and its expression trend was consistent with the results of bioinformatics analysis. Therefore, we chose ADH1A for subsequent functional validation. Overexpression of ADH1A in GC cells revealed ADH1A’s role in inhibiting the activity, proliferation, migration and invasion of GC cells, promoting apoptosis and secretion of IL-6, IFN-γ, CCL5 and CSF2, and facilitating the transformation of macrophages to a pro-inflammatory M1 phenotype. ssGSEA results demonstrated the potential involvement of ADH1A in the cGMP/PKG signaling pathway, and significant changes in the expression of proteins related to the cGMP/PKG signaling pathway. The use of the cGMP/PKG signaling pathway agonist 8-Br-cGMP in ADH1A-overexpressing GC cells substantiated ADH1A’s capacity to inhibit the cGMP/PKG signaling pathway, thereby suppressing the malignant progression of GC and promoting the transformation of macrophages to a pro-inflammatory M1 phenotype.Conclusion: ADH1A is able to influence the malignant progression of GC and the transformation of macrophages to the pro-inflammatory M1 phenotype through the cGMP/PKG signaling pathway.Keywords: gastric cancer, inflammation, immune infiltration analysis, ADH1A, cGMP/PKG signaling pathway

Mingming Li,1,2,&ast; Xin Zhou,1,&ast; Doudou Huang,1,&ast; Yingkui Zhao,2 Jiani Chen,2 Zhiying Dong,1 Wansheng Chen,1,2 Feng Zhang,2 Lianna Sun1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianna Sun; Wansheng Chen, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Tel +86-13818946096 ; +86-15901818646, Email sssnmr@163.com; chenwansheng@shutcm.edu.cnBackground: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties.Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS.Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins.Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin’s action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.Keywords: diabetes mellitus, streptozotocin, metformin, davidiin, metabolomics

Jiayun Zhong,1 Yu Liu,2 Qian Fu,1 Dan Huang,2 Wenjun Gong,2 Jian Zou2 1Department of Pharmaceutical, the People’s Hospital of Pengzhou, Chengdu, Sichuan, 611930, People’s Republic of China; 2Department of Clinical Pharmacy, the People’s Hospital of Pengzhou, Chengdu, Sichuan, 611930, People’s Republic of ChinaCorrespondence: Jian Zou, Department of clinical pharmacy, the People’s Hospital of Pengzhou, Chengdu, Sichuan, 611930, People’s Republic of China, Tel +86 28 86239898, Email 70336641@qq.comBackground: Regorafenib, a novel multikinase inhibitor, has been approved by the US Food and Drug Administration as a standard treatment choice for metastatic colorectal cancer (mCRC). Nonetheless, its substantial cost places a significant burden on social health resources and patients. However, the cost-effectiveness (CE) of regorafenib compared to other third-line therapies is still undetermined.Objective: This study aims to assess the CE of regorafenib compared to other third-line therapies for the treatment of mCRC.Methods: We conducted a comprehensive literature search in PubMed, Medline, Scopus, Embase, Cochrane Library, as well as nine other databases to identify relevant studies published up to October 2023, focusing on patients with mCRC and examining the cost-effectiveness of regorafenib. Following the screening and extraction of pertinent data, the study quality was assessed using the Quality of Health Economic Studies (QHES) checklist.Results: The literature search yielded 751 records, and after applying the inclusion criteria, 13 studies from 7 different countries were included. Of these, 7 studies evaluated the cost-effectiveness of regorafenib compared to trifluridine/tipiracil (TAS-102), 3 studies compared regorafenib with best supportive care (BSC), and 3 studies compared regorafenib with fruquintinib, serplulimab, and regorafenib dose optimization (ReDo).The quality of the included studies was high with an average QHES scores of 85.62. Regorafenib standard dose proves to be less cost-effective than alternative third-line therapies. Implementing a dose optimization strategy could potentially rectify this disparity and enhance the cost-effectiveness of regorafenib.Conclusion: The use of the standard dose of regorafenib is generally regarded as not cost-effective when compared to other third-line therapies for patients with mCRC. However, implementing a dose-escalation strategy may enhance regorafenib’s cost-effectiveness. Consequently, significant price reductions or optimizing the dose of regorafenib are required to achieve cost-effectiveness.Keywords: regorafenib, metastatic colorectal cancer, cost-effectiveness, incremental cost-effectiveness ratios

Deyi Huang,1 Xingan Yang,2 Hongbiao Ruan,3 Yushui Zhuo,1 Kai Yuan,4 Bowen Ruan,1 Fang Li1 1Department of Ultrasound, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province, Linhai City, Zhejiang Province, People’s Republic of China; 3Department of Cardiology, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fang Li, Department of Ultrasound, The People’s Hospital of Yuhuan, No. 18, Changle Road, Yuhuan City, Zhejiang Province, 317600, People’s Republic of China, Tel +8613967672898, Email 3260772796@qq.comIntroduction: Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations.Methods: This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥ 2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥ 1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- “flash” impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction.Results: Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility.Conclusion: The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.Keywords: coronary artery disease, myocardial contrast echocardiography, radiomics, machine learning, myocardial recovery prediction, random forest

Yiyang Gong,1,2,&ast; Minqin Zhou,2,&ast; Yanting Zhu,2,&ast; Jingying Pan,2 Xuanrui Zhou,2 Yike Jiang,2 Hong Zeng,2 Hao Zheng,2 Xitong Geng,2 Da Huang1 1Department of Thyroid Surgery; Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Tel +13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma is the most common primary liver cancer, with poor prognosis. Complex immune microenvironment of the liver is linked to the development of HCC. PVALB is a calcium-binding protein which has been described as a cancer suppressor gene in thyroid cancer and glioma. Nevertheless, the role of PVALB in HCC is unknown.Materials and Methods: We obtained data from TCGA and GSE54236 datasets. MCP-counter, WGCNA and LASSO model were applied to identify PVALB. With UALCAN, MethSurv, and other websites, we probed the expression, methylation and survival of PVALB. LinkedOmics and GSEA were adopted for functional analysis, while TIMER, TISIDB, Kaplan-Meier plotter, TIDE databases were utilized to evaluate the relevance of PVALB to the tumor immune microenvironment and predict immunotherapy efficacy. TargetScan, DIANA, LncRNASNP2 databases and relevant experiments were employed to construct ceRNA network. Finally, molecular docking and drug sensitivity of PVALB were characterized by GeneMANIA, CTD, and so on.Results: PVALB was recognized as a gene associated with HCC and NK cell. Its expression was down-regulated in HCC tissue, which lead to adverse prognosis. Besides, the hypomethylation of PVALB was related to its reduced expression. Notably, PVALB was tightly linked to immune, and its reduced expression attenuated the anticancer effect of NK cells via the Fas/FasL pathway, leading to a adverse outcome. The lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB axis may regulate the PVALB expression. Finally, we found immunotherapy might be a viable treatment option.Conclusion: In a word, PVALB is a prognostic indicator, whose low expression facilitates HCC progression by impacting NK cell infiltration.Keywords: PVALB, hepatocellular carcinoma, immune, ceRNA, bioinformatics, prognostic factor

Dongfang Huang,1– 3 Jianhuai Zhang,3 Jianbo Xu,3 Qiang Niu,2 Dinghua Zhou2 1Department of Hepatobiliary Surgery, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, People’s Republic of ChinaCorrespondence: Dinghua Zhou, Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, No. 16 Xinjiekou Outer Street, Xicheng District, Beijing, 100088, People’s Republic of China, Tel +86 010-66343003, Fax +86 010-66343055, Email zhoudinghua3528@126.comObjective: To investigate the utility of alpha-fetoprotein (AFP) and ultrasound in the diagnosis and prognosis of patients with hepatocellular liver cancer (HCC).Methods: Using retrospective convenience sampling, 401 patients with HCC who underwent transarterial chemoembolisation at the Department of Oncology of The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University between June 2015 and January 2020 were recruited and assigned to the case group. Simultaneously, patients matched to the case group in terms of gender and age but excluded for HCC were enrolled at a 1:1 ratio and classified as the control group. Relevant parameters were collected from both groups for comparison.Results: Both AFP levels and ultrasound results demonstrated diagnostic value for patients with HCC (P < 0.05). Their combined use exhibited the highest diagnostic accuracy for the cancer, with an area under the curve of 0.896 (95% confidence interval [CI]: 0.876, 0.923), a sensitivity of 67.65% and a specificity of 91.22%. In terms of overall survival (OS), statistically significant differences in the OS rates were observed between the low-AFP (L-AFP) group and high-AFP (H-AFP) group as well as between the low-tumour-diameter (LTD) group and high-tumour-diameter (HTD) group (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Regarding the progression-free survival (PFS), significant differences in the PFS rates were also noted between the L-AFP and H-AFP groups and between the LTD and HTD groups (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05).Conclusion: Ultrasound and AFP display notable distinctions when used in the diagnosis of HCC. The sensitivity of ultrasound as a standalone diagnostic tool surpasses that of AFP alone. However, their combined use results in much higher specificity than the use of either test individually. In addition, both techniques hold predictive value for patients’ OS and PFS, enabling timely prognostic assessment.Keywords: alpha-fetoprotein, hepatocellular liver cancer, ultrasound, survival analysis, prognosis

Dong Huang,1,&ast; Dingxiu He,2,&ast; Linjing Gong,1,&ast; Wei Jiang,2,&ast; Rong Yao,3 Zongan Liang1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The People’s Hospital of Deyang, Deyang, Sichuan, People’s Republic of China; 3Department of Emergency Medicine, Emergency Medical Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongan Liang, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, People’s Republic of China, Email liangza@scu.edu.cnBackground: There is no predictive tool developed for pneumonia-associated acute respiratory distress syndrome (ARDS) specifically so far, and the clinical risk classification of these patients is not well defined. Our study aims to construct an early prediction model for hospital mortality in patients with pneumonia-associated ARDS.Methods: In this single-center retrospective study, consecutive patients with pneumonia-associated ARDS admitted into intensive care units (ICUs) in West China Hospital of Sichuan University in China between January 2012 and December 2018 were enrolled. The least absolute shrinkage and selection operator (LASSO) regression and then multivariate logistic regression analysis were used to identify independent predictors which were used to develop a nomogram. We evaluated the performance of differentiation, calibration, and clinical utility of the nomogram.Results: The included patients were divided into the training cohort (442 patients) and the testing cohort (190 patients) with comparable baseline characteristics. The independent predictors for hospital mortality included age (OR: 1.04; 95% CI: 1.02, 1.05), chronic cardiovascular diseases (OR: 2.62; 95% CI: 1.54, 4.45), chronic respiratory diseases (OR: 1.87; 95% CI: 1.02, 3.43), lymphocytes (OR: 0.56; 95% CI: 0.39, 0.81), albumin (OR: 0.94; 95% CI: 0.90, 1.00), creatinine (OR: 1.00; 95% CI: 1.00, 1.01), D-dimer (OR: 1.06; 95% CI: 1.03, 1.09) and procalcitonin (OR: 1.14; 95% CI: 1.07, 1.22). A web-based dynamic nomogram (https://h1234.shinyapps.io/dynnomapp/) was constructed based on these factors. The concordance index (C index) of the nomogram was 0.798 (95% CI: 0.756, 0.840) in the training cohort and 0.808 (95% CI: 0.747, 0.870) in testing cohort. The precision–recall (PR) curves, calibration curves, decision curve analyses (DCA) and clinical impact curves showed that the nomogram has good predictive value and clinical utility.Conclusion: We developed and evaluated a convenient nomogram consisting of 8 clinical characteristics for predicting mortality in patients with pneumonia-associated ARDS.Keywords: pneumonia, acute respiratory distress syndrome, mortality, risk factors, nomogram

Dan Yu, Wenhan Huang, Min Sheng, Shan Zhang, Hang Pan, Feifeng Ren, Lei Luo, Jun Zhou, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin Tang, Department of Rheumatology and Immunology, Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, People’s Republic of China, Tel +86 23 63693878, Fax +86 23 62888265, Email hopetang@hospital.cqmu.edu.cnPurpose: Inflammation triggers a metabolic shift in macrophages from oxidative phosphorylation to glycolysis, a phenomenon known as the Warburg effect. This metabolic reprogramming worsens inflammation and cascades into organ damage. Angiotensin-(1-7) [Ang-(1-7)], a small molecule, has demonstrated anti-inflammatory properties. This study investigates whether Ang-(1-7) mitigates inflammation in LPS-induced macrophages and septic mice by regulating the Warburg effect in immune metabolism.Methods: The study induced macrophages with LPS in vitro and measured inflammatory factors using ELISA and Western blot. Key enzymes in glycolysis, mitochondrial respiratory complexes, and citrate pathway key molecules were assessed using Western blot and qRT-PCR. Mitochondrial membrane potential (MMP), lactate, and ATP were measured using assay kits. In vivo, a mouse model of sepsis induced by LPS was used. Kidney tissues were examined for pathological and mitochondrial ultrastructural alterations. The levels of inflammatory factors in mouse serum, glycolysis and citrate pathway-related molecules in the kidney were assessed using qRT-PCR, Western blot, and immunofluorescence techniques. Additionally, MMP, lactate, and ATP in the kidney were measured using assay kits.Results: In vitro experiments demonstrated that Ang-(1-7) inhibited the levels of inflammatory factors in LPS-treated RAW264.7 cells. It also reduced the expression of key glycolytic enzymes HK2, PFKFB3, and PKM2, as well as lactate levels. Additionally, it decreased intracellular citrate accumulation, enhanced mitochondrial respiratory complexes I and III, and ATP levels. Ang-(1-7) alleviated MMP damage, modulated citrate pathway-related molecules, including SLC25A1, ACLY, and HIF-1α. In vivo experiments showed that Ang-(1-7) lowered glycolysis levels in septic mice, improved mitochondrial ultrastructure and function, mitigated inflammation and renal tissues damage in septic mice, and suppressed the expression of key molecules in the citrate pathway.Conclusion: In conclusion, Ang-(1-7) can regulate the Warburg effect through the citrate pathway, thereby alleviating inflammation in LPS-induced macrophages and septic mice.Keywords: Ang-(1-7), macrophage, sepsis, Warburg effect, glycolysis, citrate

Xingrui Li,1,&ast; Yue Wang,1,&ast; Denghao Huang,1 Zhonghao Jiang,1 Zhiyu He,1 Maoxuan Luo,2 Jie Lei,1,2 Yao Xiao1– 3 1Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Chengbei Outpatient, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Xiao; Jie Lei, Email orthoxiaoyao@outlook.com; 1067233579@qq.comAbstract: The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as “mesenchymal stem cells”, “nanotechnology”, “biomaterials”, “dentistry” and “tissue regeneration”. From 2013 to 2023, we selected approximately 150 articles that align with our philosophy.Keywords: nano-material, stem cell, tissue reconstruction, cell differentiation

Chongmei Tian,1,&ast; Jianqin Song,2,&ast; Delian Huang,3 Siwei Wang,4 Yaping Zhao,1 Liping Fu,1 Xueyu Fan,5 Tianhong Ma,6 Yongfeng Bai5 1Department of Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Shaoxing, Zhejiang, 312000, People’s Republic of China; 2Department of Traditional Chinese Medicine, Hangzhou Linping District Hospital of Integrated Chinese and Western Medicine, Hangzhou, People’s Republic of China; 3School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Core Facility, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, 324000, People’s Republic of China; 5Department of Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, 324000, People’s Republic of China; 6Department of Pharmacy, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, 314001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongfeng Bai; Tianhong Ma, Email bai.yongfeng@163.com; 15990312207@163.com

Yuncheng Ni,1 Fang Deng,1 Shanzi Yu,1 Jianping Zhang,1 Xiaoxue Zhang,1 Dong Huang,1,2 Haocheng Zhou1,2 1Department of Pain, the Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Brain Homeostasis, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Haocheng Zhou, Department of Pain, the Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, People’s Republic of China, Email Haocheng.Zhou@csu.edu.cnPurpose: Post-mastectomy pain syndrome is a common yet debilitating neuropathic complication after breast cancer procedures, resulting in significantly reduced quality of life. Recently, emerging evidence has supported the therapeutic effect of magnesium administration in chronic pain. However, the role of magnesium supplementation in development of chronic pain after breast cancer surgery remains less known. The aim of this study was to evaluate therapeutic effect of magnesium supplementation on persistent pain after breast cancer procedure.Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. A total of 109 patients who underwent breast cancer procedure received magnesium-L-threonate (n = 48) or placebo (n = 61) for 12 weeks. Chronic pain incidence, short form of the McGill Pain Questionnaire (SF-MPQ), Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Telephone Interview for Cognitive Status (TICS) were evaluated at 3- and 6-month follow-up.Results: About 31% (15 out of 48) of patients reported chronic pain after magnesium supplementation, and 26% (16 out of 61) of the control group at 6-month follow-up respectively. Total scores of SF-MPQ were significantly increased in the control group 6 months after surgical intervention (mean difference, 1.475; 95% CI, − 2.730 to − 0.2211), but NOT in the magnesium treated group (mean difference, 1.250; 95% CI, − 2.775 to 0.2748). No significant differences were found between two cohorts on SF-MPQ, GAD-7, PHQ-9, PSQI, or TICS at each timepoint.Conclusion: Oral supplementation of magnesium-L-threonate did not effectively prevent the development of persistent pain in breast cancer survivors, nor provide sufficient pain relief over placebo. We did not observe improvement of pain, mood, sleep disorder, or cognitive function after 12-week magnesium supplementation. Future study may focus on magnesium combined with other effective anti-neuropathic pain treatment.Keywords: breast cancer surgery, chronic pain, magnesium-l-threonate, neuropathic pain, pain management

Hua Wu,1 Xiaojun Zhou,1 Fan Zhou,2 Dongliang Huang,3 Tao Huang1 1Department of Laboratory Medicine, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College, Haikou, People’s Republic of China; 2International School of Public Health and One Health, Hainan Medical University, Haikou, People’s Republic of China; 3Emergency Department, Armed Police Hospital of Hainan, Haikou, People’s Republic of ChinaCorrespondence: Tao Huang, Department of Laboratory Medicine, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College, No. 19, Xiuhua Road, Xiuying District, Haikou, 570311, People’s Republic of China, Tel +868986842560, Email 13005080993@163.comAbstract: DL96 Microbial Identification/Antimicrobial Susceptibility Testing (ID/AST) System (Zhuhai DL, Guangdong, China) is one of the most commonly used commercial ID/AST System in China. This study aims to evaluate the performance of DL 96E for Antimicrobial Susceptibility Testing (AST) of 270 Enterobacterales isolates from Hainan general hospital using the broth microdilution method (BMD) as reference method. CLSI M52 criteria was followed when analyzing the evaluation results. Twenty antimicrobial agents were evaluated, and categorical agreement (CA) ranged from 62.8% to 96.5%. Imipenem had the lowest CA (63.9%) and highest very major errors (VME) (52.8%). A total of 103 carbapenem-resistant Enterobacterales were evaluated; DL 96E miss identified 22 isolates, including six carbapenemase-producing Enterobacteriaceae. DL 96E must adjust the Minimum Inhibitory Concentration (MIC) ranges of ciprofloxacin, levofloxacin, and piperacillin-tazobactam to cover Clinical and Laboratory Standards Institute (CLSI) breakpoints, adjust the formulation of some antimicrobial, such as imipenem, and increase the MIC detection range to cover the Quality control (QC) strains’ MIC range.Keywords: antimicrobial susceptibility testing, broth microdilution method, minimum inhibitory concentration, categorical agreement

Jian Zou,&ast; Jia-Yun Zhong,&ast; Yan-Xin Liu, Yu Liu, Dan Huang, Bian-Tiao Xu, Xi-Wen Li, Wen-Jun Gong, Jia Tao Department of Clinical Pharmacy, The People’s Hospital of Pengzhou, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zou, The People’s Hospital of Pengzhou, No. 255 Second Section of South Third Ring Road, Chengdu, People’s Republic of China, Tel +86 28 86239898, Email 70336641@qq.comPurpose: Quality control circle (QCC) has acquired success in many fields in healthcare industry as a process management tool, whereas its efficacy in surgical antimicrobial prophylaxis (SAP) remains unknown. This study aimed to implement QCC interventions to improve the appropriateness of SAP.Methods: A QCC activity team was established to grasp the current situation of SAP in clean surgery procedure, set target, formulate corresponding countermeasures and implement and review them in stages. The plan-do-check-act (PDCA) method was cyclically applied.Results: The appropriateness of antibiotic prophylaxis before (January to December 2020) and after (January to December 2021) the implementation of QCC activities were evaluated based on relevant international and Chinese SAP guidelines. The overall SAP appropriateness was significantly improved from 68.72% before QCC to 93.7% post QCC implementation (P< 0.01). A significant improvement (P< 0.05) was also determined for each category: selection (from 78.82% to 96.06%), duration (from 90.15% to 96.46%), indication (from 94.09% to 97.64%), timing of first dose (from 96.55% to 99.21%), antimicrobial usage (from 96.8% to 99.41%), re-dosing of antimicrobial (from 96.55% to 99.21%).Conclusion: Implementation of a QCC program can optimize the use of antibiotics and improve the appropriateness of SAP and is of practical importance to their standardization.Keywords: surgical antimicrobial prophylaxis, quality control circle, appropriateness

Kongbo Zhu,1 Shaolei Ma,2 Hui Chen,3 Jianfeng Xie,3 Dan Huang,1 Cuiping Fu,4 Genshan Ma,1 Yingzi Huang3 1Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Emergency and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 4Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Yingzi Huang, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Email yz_huang@126.comBackground: The pathogenicity of Omicron is different from that of the previous strains. The value of hematological indicators in patients at high risk of Omicron infection remains unclear. We need rapid, inexpensive and widely available biomarkers to guide the early detection of people at risk of pneumonia and to provide early intervention. We aimed to assess the value of hematological indicators as risk factors for pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.Patients and Methods: The study enrolled 144 symptomatic COVID-19 patients with Omicron infection. We collected available clinical details, including laboratory tests and CT examinations. Univariate and multivariate logistic analyses and receiver operating characteristic (ROC) curve analyses were used to assess the value of laboratory markers in predicting the development of pneumonia.Results: Among the 144 patients, 50 (34.7%) had pneumonia. The ROC analysis revealed that the areas under the ROC curve (AUC) for leukocytes, lymphocytes, neutrophils, and fibrinogen were 0.603 (95% confidence interval (CI): 0.501– 0.704, P=0.043), 0.615 (95% CI: 0.517– 0.712, P=0.024), 0.632 (95% CI: 0.534– 0.730, P=0.009) and 0.635 (95% CI: 0.539– 0.730, P=0.008), respectively. The AUC for neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), fibrinogen to lymphocyte ratio (FLR), and fibrinogen to D-dimer ratio (FDR) were 0.670 (95% CI: 0.580– 0.760, P=0.001), 0.632 (95% CI: 0.535– 0.728, P=0.009), 0.669 (95% CI: 0.575– 0.763, P=0.001) and 0.615 (95% CI: 0.510– 0.721, P=0.023), respectively. Univariate analysis showed that elevated levels of NLR (odds ratio (OR): 1.219, 95% CI: 1.046– 1.421, P=0.011), FLR (OR: 1.170, 95% CI: 1.014– 1.349, P=0.031) and FDR (OR: 1.131, 95% CI: 1.039– 1.231, P=0.005) were significantly correlated with the presence of pneumonia. Multivariate analysis indicated elevated NLR (OR: 1.248, 95% CI: 1.068– 1.459, P=0.005) and FDR (OR: 1.160, 95% CI: 1.054– 1.276, P=0.002) levels were associated with the existence of pneumonia. The AUC for the combination of NLR and FDR was 0.701 (95% CI: 0.606– 0.796, P< 0.001, sensitivity 56.0%, specificity 83.0%).Conclusion: NLR and FDR can predict the presence of pneumonia in symptomatic COVID-19 patients infected with the SARS-CoV-2 Omicron variant.Keywords: COVID-19, Omicron, pneumonia, neutrophil to lymphocyte ratio, fibrinogen, D-dimer

Dujuan Huang,1 Tongqing Zhu,1 Yingyu Wu,2 Tao Sun1 1College of Business Administration, Anhui University of Finance and Economics, Bengbu, Anhui, People’s Republic of China; 2School of Business, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Yingyu Wu, Zhongkai University of Agriculture and Engineering, 501 Zhongkai Road, Haizhu District, Guangzhou, 510225, People’s Republic of China, Tel +86 18666080221, Email wuyingy3@qq.comPurpose: Based on the social cognitive theory and cognitive-affective system theory, the purpose of this study is to explore how and when paradoxical leadership enhances employees’ bootlegging innovation. To achieve this purpose, the authors proposed a double-chain mediation model in this study.Methods: Data with 342 questionnaires were collected for effective matching between employees and leaders at two time nodes. The hypotheses were validated by structural equation modeling and bootstrap approaches.Results: Results indicate that paradoxical leadership has a significant and positive impact on employees’ bootleg innovation. In addition, psychological capital and thriving at work play a partial mediating role between paradoxical leadership and employees’ bootlegging behaviors respectively and a chain mediating role between the two together. Moreover, there is no significant difference among the three mediating paths.Conclusion: The present research advances our understanding of bootleg innovation with a focus on the specific role of paradoxical leadership. Our findings, and especially those related to the role of psychological capital and thriving at work, reveal the influence mechanisms of paradoxical leadership on employees’ bootleg innovation. At the same time, it is useful for understanding what leadership style can effectively stimulate employees’ bootleg innovation.Keywords: paradoxical leadership, bootleg innovation, psychological capital, thriving at work

Huiqing Zhu,1,&ast; Zhifeng Huang,1,&ast; Tingting Liu,1 Nairui An,1 Hui Gan,1 Dongming Huang,2 Chuangli Hao,3 Wenting Luo,1 Baoqing Sun1 1Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Pediatrics, Boai Hospital of Zhongshan City, Zhongshan, 528400, People’s Republic of China; 3Department of Respirology, Children’s Hospital, Soochow University, Suzhou, 215025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Wenting Luo, Department of Allergy and Clinical Immunology, Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, Guangdong, People’s Republic of China, Tel +86 20 8306 2865, Fax +86 20 8306 2729, Email sunbaoqing@vip.163.com; 348307379@qq.comPurpose: An objective of this study was to investigate the allergen sensitization characteristics of cat, dog and horse dander in patients with suspected allergic diseases in different geographical regions of Chinese mainland.Patients and Methods: We invited 2377 patients aged 0– 86 years with suspected allergic diseases to participate in a cross-sectional survey in 11 provinces in China. Combined with the questionnaires and animal-specific IgE levels, we analyzed the epidemiological characteristics and risk factors of furry animal sensitization in different regions and populations of Chinese Mainland.Results: Among the 2377 patients with suspected allergic diseases, 14.9% were sensitized to cat dander, 9.3% to dog dander and 5.5% to horse dander. Animal allergens mainly cause low-level sensitization (class 1– 3). There was a significant correlation between cat, dog and horse dander allergen sIgE, with correlation coefficients (rs) all greater than 0.750. The majority (46.5%) of sIgE-positive patients were sensitized to at least two animal allergens simultaneously. The prevalence of these animals all showed a trend of increasing first and then decreasing with age, and all reached the peak in young adolescence. As for the geographical factors, the sensitization rate of cats and dogs in Western was significantly higher than that in Eastern (cat: 18.4% vs 9.2%, dog: 11.6% vs 5.5%, all P < 0.001), however, no significant differences were found in horses. Aged ≤ 6 years, living in Western, and high animal allergen exposure elevated the risk of cat or dog sensitization. Living on a lower floor (aOR: 0.56) was a protective factor for horse sensitization.Conclusion: In this representative sample of Chinese patients with suspected allergic diseases, there was an apparent geographic variation in sensitization to cats and dogs. Age factor and living in Western also had a significant impact on animal allergen sensitization rate.Keywords: animal allergen, specific immunoglobulin E, cross-sectional survey, suspected allergic patient

Dujuan Huang,1 Tongqing Zhu,1 Xue Ding,2 Xiaoliang Bi,3 Tao Sun1 1College of Business Administration, Anhui University of Finance and Economics, Bengbu, Anhui, People’s Republic of China; 2School of Financial Technology, Shanghai Lixin University of Accounting and Finance, Shanghai, People’s Republic of China; 3School of Economics and Management, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Xiaoliang Bi, School of Economics and Management, Tongji University, 1239 Siping Road, Yangpu District, Shanghai, 200092, People’s Republic of China, Tel +86 19512345360, Email tobxl@tongji.edu.cnPurpose: Bootleg Innovation helps enterprises create unconventional innovation achievements, and has gradually become an important approach for radical innovation under the background of open innovation. Through the integration of the cognitive-affective processing system and conservation of resources (COR) theory, the present study takes integrative complexity as a moderator, and explores the mechanism of LMX ambivalence on employees’ bootleg innovation.Participants and Methods: A total of 387 employees and 110 supervising managers participated in the two-wave dyadic survey. To test our hypotheses, we performed the hierarchical regression and conducted bootstrapping analyses to test our hypotheses.Results: Findings indicated that LMX ambivalence not only improves employees’ cognitive flexibility and promotes bootleg innovation, but also aggravates employees’ job anxiety and hinders bootleg innovation. In addition, integrative complexity significantly moderates the above two mediating paths. Specifically, when integrative complexity was higher, the negative mediating effect of job anxiety was attenuated, and the positive mediating effect of cognitive flexibility was enhanced.Conclusion: Contrasting with previous research, this research analyzed the triggering mechanism of bootleg innovation combined with the dynamic interaction of environmental stimulus, emotion and cognition. The findings provide novel insight into how to achieve bootleg innovation.Keywords: LMX ambivalence, bootleg innovation, cognitive flexibility, job anxiety, integrative complexity

Yanyan Li,1,2 Junda Wang,2 Dan Huang,2 Chao Yu1 1College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Chao Yu, College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 23-68485589, Fax +86 23-68486294, Email yuchao@cqmu.edu.cnPurpose: To investigate the effect of baicalin on the reactive oxygen species (ROS)/ NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin-D (GSDMD) inflammasome pathway and its related mechanism in regulating pyroptosis of human renal tubular epithelial cells (HK-2) induced by contrast media.Methods: Iohexol was used to act on HK-2 cells to establish a renal tubular cell pyroptosis model; and the signal pathway genes were silenced, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and cell viability, gene expression, and protein expression were evaluated by double fluorescence staining and flow cytometry. To assess the cytotoxicity caused by the contrast agent; cells were pretreated with different concentrations of baicalin; and then the cells were exposed to iohexol again, and the relevant indicators were tested again.Results: After HK-2 cells were exposed to iohexol, the NLRP3 inflammasome pathway markers NLRP3, interleukin (IL)-1β, and IL-18 mRNA levels as well as the protein expression levels of NLRP3, ASC, Caspase-1, and GSDMD were up-regulated. In addition, the effect also significantly increased the IL-18, IL-1β, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) release, and cellular ROS levels. The results of Annexin V-FITC/PI flow cytometry showed that the level of apoptosis was increased. However, after the intervention of baicalin, the changes in the above indexes caused by iohexol stimulation of HK-2 cells were inhibited.Conclusion: Exposure to iohexol can induce pyroptosis of HK-2 cells through the ROS/NLRP3/Caspase-1/GSDMD signaling pathway. Baicalin ameliorated iohexol-induced pyroptosis in HK-2 cells by regulating the NLRP3 inflammasome pathway.Keywords: pyroptosis, baicalin, iohexol, ROS/NLRP3/Caspase-1/GSDMD pathway, kidney injury

Siwei Xing,1,&ast; Xiaohao Ruan,1,&ast; Jingyi Huang,1,&ast; Jiaqi Yan,1 Wenhao Lin,1 Jinlun Huang,1 Jiacheng Liu,1 Da Huang,1 Rong Na,2 Danfeng Xu1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Division of Urology, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Na, Division of Urology, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, People’s Republic of China, Email narong.hs@gmail.com Da Huang, Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China, Email huangdasjtu@gmail.comPurpose: To explore the impact of family history (FH) on renal cell carcinoma (RCC) and its pathological subtype clear cell RCC (ccRCC) in a Chinese population; a significant association has previously been determined not only in familial cancer syndrome but also in sporadic cases in western populations.Methods: Consecutive patients with kidney tumors from October 2017 to May 2021 at a tertiary hospital in Shanghai were enrolled in the study. Demographic and clinical information was collected, including age, gender, FH (positive or negative, types of cancers, degree of relatives, etc.), pathological diagnosis, and Fuhrman grades.Results: A positive FH of any cancer was observed in 26.5% of the RCC patients, while only 16.8% patients with benign kidney tumor were found to have a positive FH. A strong correlation was observed between FH of any cancers in first-degree relatives and RCC (odds ratio [OR]=4.60, 95% confidence interval [CI]: 1.95– 10.85, P=5.50× 10− 5) or ccRCC (OR=4.63, 95% CI: 1.95– 11.02, P=9.63× 10− 5). In subgroup analysis, FH of digestive cancers was significantly associated with RCC (OR=4.42, 95% CI: 1.35– 14.51, P=0.005) or ccRCC (OR=4.14, 95% CI: 1.25– 13.75, P=6.84× 10− 4). Similar results were found in multivariate analyses. However, no significant association was observed between FH and age at onset.Conclusion: FH was an independent risk factor for RCC and ccRCC in this Chinese population. FH of any cancer in first-degree relatives and FH of digestive cancers were found to be the most significant risk factors for kidney cancers.Keywords: Chinese population, family history, renal cell carcinoma, risk factor, multivariate regression analysis

Yue Liu,1,2 Bidong Fu,2 Zichuan Yu,2 Gelin Song,2 Hong Zeng,2 Yiyang Gong,2 Yongqi Ding,2 Da Huang3 1Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 3Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.Patients and Methods: In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.Results: The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.Conclusion: KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.Keywords: KRBA1, prognosis, biomarker, immune infiltration, hepatocellular carcinoma, m6A modification

Huali Gu,1 Yizhuo Wang,1 Dongsheng Huang,1 Xunda Ji,2 Yi Zhang,1 Jianmin Ma,3 Mei Li,4 Weiling Zhang,1 Huimin Hu,1 Jing Li,1 Pinwei Zhang1 1Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Ophthalmic Oncology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Nuclear Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Dongsheng Huang, Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, West South Road 2, Yizhuang Economic and Technological Development Zone, Daxing District, Beijing, 100176, People’s Republic of China, Tel +86 01058266032, Email hds5180@sina.com Xunda Ji, Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Kong Jiang Road 1665, Shanghai, 200092, People’s Republic of China, Tel +86 15921670980, Email jixunda@xinhuamed.com.cnPurpose: Retinoblastoma (RB) is the most common intraocular malignancy in infancy and childhood. This study evaluated the clinical and imaging features, treatment, and prognosis of patients with recurrent RB with limb bone metastases and without central nervous system involvement.Patients and Methods: The clinical data of five patients with RB with limb bone metastases who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital between January 2015 and January 2021 were analyzed retrospectively.Results: Three males and two females were included (seven eyes: four group E and one each of group D, C, and B). The most common symptom was pain. Three patients had bone marrow and lymph node metastases. Three patients had single and two had multiple skeletal lesions. The main bones that were involved were the femur, humerus, talus, and ulna. The simultaneous involvement of the bone marrow and cortex was also observed. Serum neuron-specific enolase (NSE) levels were significantly elevated in four cases and slightly elevated in one case; primary intravenous chemotherapy resulted in a decrease in NSE levels and the gradual resolution of the bone lesions. Two patients died at the time of follow-up and three were in complete remission. The results of the statistical analysis showed that anterior chamber invasion was correlated with prognosis, and there was significant difference in the decrease in the serum NSE levels after intravenous chemotherapy.Conclusion: Regular lifelong follow-up of patients with RB is warranted to identify bone metastases earlier. Anterior chamber invasion may be a risk factor. The simultaneous involvement of the bone marrow and cortex is characteristic manifestations in images of RB with bone metastases. Multidisciplinary treatment especially intravenous chemotherapy is useful, at least at the beginning.Keywords: recurrent, NSE, SRE, pathological fracture, pamidronate, osteoclast inhibitors

Chaowen He, Dongxuan Huang, Fan Yang, Dongsheng Huang, Yahui Cao, Jianfeng Peng, Xiaohua Luo Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, Guangdong, People’s Republic of ChinaCorrespondence: Chaowen He, Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital, No. 187 Guanlan Avenue, Longhua District, Shenzhen, 518110, Guangdong, People’s Republic of China, Tel +86-18123964996, Email chaowh0331@163.comBackground: This study aims to investigate the expression and clinical value of long non-coding RNA (lncRNA) HEIH in peripheral blood of patients with non-small cell lung cancer (NSCLC).Methods: Healthy subjects (N=70), patients with lung squamous cell carcinoma (LUSC, N=70) and patients with lung adenocarcinoma (LUAD, N=80) were included. LncRNA HEIH expression in peripheral blood of included subjects was detected using RT-qPCR. According to the median expression of lncRNA HEIH, LUSC and LUAD patients were allocated into lncRNA HEIH high/low expression groups. The correlation between lncRNA HEIH and clinical indicators of patients was analyzed; Logistic multifactor regression was used to analyze the independent risk factors influencing lncRNA HEIH level. Receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of lncRNA HEIH and carcinoembryonic antigen (CEA) in LUSC/LUAD patients. MedCalc-Comparison of ROC curves was used to compare the area under ROC curve. The cumulative survival rates of lncRNA HEIH high/low expression group were analyzed by Kaplan–Meier curve. COX multivariate analysis was used to assess the independent factors affecting prognosis of NSCLC.Results: LncRNA HEIH in peripheral blood of LUSC/LUAD patients was higher than that in healthy controls, with no evident difference between LUSC and LUAD groups. In LUSC/LUAD patients, TNM stage, lymph node metastasis, distal metastasis, and CEA were independent risk factors affecting lncRNA HEIH; patients with high lncRNA HEIH expression had larger pack-years and tumor size, higher CEA level and tumor stage, and higher risk of lymph node metastasis and distal metastasis. LncRNA HEIH had higher diagnostic efficiency than CEA in NSCLC patients. High expression of lncRNA HEIH predicted poor prognosis in patients with NSCLC and was an independent risk factor for prognosis of NSCLC.Conclusion: High expression of lncRNA HEIH is helpful in the diagnosis of NSCLC and predicts poor prognosis.Keywords: non-small cell lung cancer, long non-coding RNA HEIH, prognosis, carcinoembryonic antigen, lung squamous cell carcinoma, lung adenocarcinoma, peripheral blood

Xuebin Yan,1 Yi Liu,2 Shanzi Yu,1 Dong Huang,1 Rong Hu1 1Department of Pain, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Department of Anesthesia, The First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Rong Hu, Department of Pain, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86 18973162969, Email vroro@126.comObjective: The current study investigated the effects of bone marrow mesenchymal stem cells (BMSCs) on pain behavior in rats with trigeminal neuralgia induced by infraorbital nerve chronic constriction injury (ION-CCI), and the repair effects of BMSCs on pathological changes in trigeminal ganglion demyelination.Methods: BMSCs or phosphate-buffered saline (PBS) alone were injected around trigeminal ganglion in ION-CCI rats via a rat brain stereotaxic apparatus. Mechanical pain threshold (von Frey test) and face grooming behavior were measured in each group. Recovery of demyelination of trigeminal ganglion was observed via electron microscopy 2 weeks later, and BMSC differentiation was observed via immunofluorescence.Results: Rats in the BMSC group exhibited significant improvements in mechanical pain threshold and face grooming behavior compared with the PBS group. BMSCs could repair demyelinating changes in trigeminal ganglion in ION-CCI rats. Only cells expressing GFAP, S-100, and p75 were observed via immunofluorescence, and no PKH67-labeled BMSCs were observed in the trigeminal ganglion. No BMSC differentiation was observed in the trigeminal ganglion.Conclusion: Injection of BMSCs around the trigeminal ganglion could relieve trigeminal neuralgia effectively and repair trigeminal ganglion demyelination. No differentiation of BMSCs injected around the trigeminal ganglion into Schwann cells was observed. The mechanism of trigeminal neuralgia demyelination repair requires further investigation.Keywords: bone marrow mesenchymal stem cells, demyelination, trigeminal neuralgia, treatment

Fan Li, Weiling Zhang, Huimin Hu, Yi Zhang, Jing Li, Dongsheng Huang Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of ChinaCorrespondence: Dongsheng HuangDepartment of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of ChinaTel +86 10-58266032Email hdsmed@126.comBackground: It is not clear which known adverse prognostic factors of neuroblastoma are closely associated with tumor recurrence after complete response. We analyzed the factors for post-remission recurrence in children with neuroblastoma through a retrospective study.Methods: A total of 179 children with neuroblastoma who achieved initial complete response were included in this study. Kaplan–Meier method and multivariate Cox regression model were used to assess the factors that may have impact on tumor recurrence after complete response.Results: The 5-year overall survival rates of the entire cohort (n = 179), recurrence group (n = 86) and non-recurrence group (n = 93) were 81.9%, 66.2%, and 98.7%, respectively. The 5-year recurrence-free survival (RFS) rates of the entire cohort and the high-risk cohort were 47.3% and 31.2%, respectively. RFSs were significantly reduced in children with age ≥ 18 months, INSS stage 4, unfavorable histology, bone marrow metastasis, osseous metastasis, serum NSE level ≥ 100 ng/mL, and serum LDH level ≥ 1400 U/L (P < 0.05). The independent risk factors for post-remission recurrence in the entire cohort were age ≥ 18 months, unfavorable histology, and serum LDH level ≥ 1400 U/L (P < 0.05). In the high-risk cohort, the independent risk factor for recurrence was serum LDH ≥ 1400 U/L (P < 0.05). Based on a new recurrence risk stratification, the 5-year RFSs of the children were 93.5%, 66.4%, and 22.5% in the low-risk, intermediate-risk, and high-risk groups, respectively. The area under the ROC curve of the new stratification was 0.773 (95% CI: 0.704− 0.842).Conclusion: Age ≥ 18 months, unfavorable histology, and serum LDH level ≥ 1400 U/L are independent risk factors for post-remission recurrence in children with neuroblastoma. A newly established recurrence risk stratification has diagnostic advantages in predicting risk of recurrence, which is especially suitable for low- and middle-income countries or regions.Keywords: age, MYCN amplification, histology, recurrence-free survival, serum lactate dehydrogenase, serum neuron-specific enolase

Lei Yang,1,&ast; Dingxiu He,2,&ast; Dong Huang,1,&ast; Zhongwei Zhang,3 Zongan Liang1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The People’s Hospital of Deyang, Deyang, Sichuan, People’s Republic of China; 3Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongan Liang Tel +8618980601259Email liangza@scu.edu.cnPurpose: Risk factors and prognostic model of fatal outcomes need to be investigated for the increasing number of immunocompromised hosts (ICHs) who are hospitalized for severe pneumonia with high hospital mortality.Patients and Methods: In this single-center, retrospective study, we recruited 1,933 ICHs with severe pneumonia who were admitted to the intensive care unit (ICU) in West China hospital, Sichuan university, China between January, 2012 and December, 2018. Clinical features, laboratory findings, and fatal outcomes were collected from electronic medical records. Patients were randomly separated into a 70% training set (n=1,353) and a 30% testing set (n=580) for the development and validation of a prediction model. All data within 24 hours of ICU admission were compared between survivors and non-survivors. The risk factors were identified through LASSO and multivariate logistic regression analysis, and then used to develop a predicting nomogram. The nomogram for predicting hospital mortality of ICHs with severe pneumonia in the ICU was validated by C-index, AUC (area under the curve), calibration curve, and Decision Curve Analysis (DCA).Results: Eight risk factors, including age, fever, dyspnea, chronic renal disease, platelet counts, neutrophil counts, PaO2/FiO2 ratio, and the requirement for vasopressors, were adopted in a nomogram for predicting hospital mortality. The nomogram had great predicting accuracy with a C-index of 0.819 (95% CI=0.795– 0.842) in the training set, and a C-index of 0.819 (95% CI=0.783– 0.855) in the testing set for hospital mortality. Additionally, the nomogram had well-fitted calibration curves. DCA demonstrated that the nomogram was clinically beneficial.Conclusion: This study developed a novel nomogram for predicting hospital mortality of ICHs with severe pneumonia in the ICU. Validation showed good discriminatory ability and calibration, indicating that the nomogram was expected to be a superior predictive tool for doctors to identify risk factors and predict mortality, and might be generally applied in clinical practice after more external validations.Keywords: immunocompromised, severe pneumonia, ICU, risk factors, nomogram

Xiao-kun Liu,1 Shan-lin Chen,1 Dan-ling Huang,1 Zi-shang Jiang,1 Yu-ting Jiang,1 Li-juan Liang,1 Lu-lu Qin2 1The First Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 2Department of Social Medicine and Health Management, School of Medicine, Hunan Normal University, Changsha, People’s Republic of ChinaCorrespondence: Xiao-kun LiuThe First Affiliated Hospital of Hainan Medical University, 3 Xueyuan Road, Haikou, 571199, Hainan, People’s Republic of ChinaEmail lacyfairy@qq.comPurpose: Road safety research is important due to the large number of road traffic fatalities globally. This study investigated the influences of age, driving experience and other covariates on aggressive driving behavior.Methods: A cross-sectional survey was conducted in Yixing City, Wuxi City, Jiangsu Province, China. Regression analysis was applied to explore the influences of age and driving experience and their interactions with other covariates on aggressive driving behavior. Two analyses methodologies were used to assess the simple effect of the interactions. Firstly, the Jamovi automatic analysis classification program was used to calculate the simple slope test. Second, the SPSS macro program was also used to calculate the simple slope test also.Results: A total of 570 drivers (247 males, 282 females) participated in the survey. A negative correlation was found between age and aggressive driving behaviors, and a positive correlation was found between neuroticism and aggressive driving behaviors in the multiple regression analysis. Significant associations were also found between age, driving experience, and depression, as well as age, driving experience, and neuroticism. Simple slope tests showed that depressive symptoms could increase aggressive behaviors in the elderly and experienced drivers. When experiencing neuroticism, individuals with higher driving experience were more aggressive in driving than shorter experienced drivers.Conclusion: Age and neuroticism influenced aggressive driving behaviors. Veteran drivers could be aggressive drivers when experiencing depressive symptoms or neuroticism. Mobile intervention could be sent to the potentially risky drivers, which would be safe and broadly feasible to prevent aggressive driving behavior in the background of COVID-19.Keywords: aggressive driving behavior, age, driving experience, depressive symptoms, neuroticism

Liting Wu,1,&ast; Wenting Luo,1,&ast; Haisheng Hu,1 Xianhui Zheng,1 Zhangkai J Cheng,1 Dongming Huang,2 Xiaowen Huang,2 Hong Zhang,3 Yang Liu,3 Rongfang Zhang,4 Hui Yang,4 Yun Sun,5 Yi Wang,5 JinHai Ma,6 Jing Liu,6 Xin Sun,7 Huajie Wu,7 Chunhua Wei,8 Shuping Zhang,8 Xiaoluan Li,9 Shuang Ren,9 Chuangli Hao,10 Baoqing Sun1 1Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 2Department of Pediatrics, Boai Hospital of Zhongshan City, Zhongshan, 528400, People’s Republic of China; 3Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China; 4Gansu Provincial Maternity and Child Care Hospital, Lanzhou, 730000, People’s Republic of China; 5Yinchuan Maternal and Child Health Care Hospital, Yinchuan, 750000, People’s Republic of China; 6Ningxia Medical University General Hospital, Yinchuan, 750000, People’s Republic of China; 7Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, Xian, 710032, People’s Republic of China; 8Weifang Weien Hospital, Weifang, 261000, People’s Republic of China; 9The First Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 10Department of Respirology, Children’s Hospital, Soochow University, Suzhou, 215025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing SunFirst Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, Guangdong, People’s Republic of ChinaTel +86 20 8306 2865Fax +86 20 8306 2729Email sunbaoqing@vip.163.comChuangli HaoDepartment of Respirology, Children’s Hospital, Soochow University, Suzhou, 215025, Jiangsu, People’s Republic of ChinaTel +86-51280693588Fax +86-512-80696309Email hcl_md@163.comBackground: Up to now, epidemiological studies on allergy rhinitis (AR) have primarily focused on determining the risk of disease in Chinese adults, with the majority of them designed by single centers, while cross-sectional and epidemiological data describing allergic sensitization in children with self-reported AR are scarce.Objective: This study was estimating of the latest information about the sensitization patterns and risk factors of clinical AR to develop effective strategies for the prevention and treatment of AR.Methods: We conducted a cross-sectional survey between January 2020 and June 2021 involving children from seven cities in China who reported AR. A total of 762 children participated in this survey. To evaluate the risk factors and specific sensitization patterns of clinical AR through questionnaires and specific immunoglobulin E to 11 aeroallergens.Results: Of the 762 patients, 593 (77.8%) had at least one positive IgE level. Aged 7– 14 years (OR 1.503, (95% CI 1.058– 2.136), P = 0.023); With allergic conjunctivitis (OR 1.843, (95% CI 1.297– 2.620), P = 0.001) and living in the Eastern (OR 1.802, (95% CI 1.263– 2.573), P = 0.001) all elevated the risk of clinical AR associated with aeroallergens. The sensitization rates of D. pteronyssinus and D. farinae were higher than those of other allergens in the 0– 6 and 7– 14 years old age groups. The most common aeroallergens among self-reported children with AR in the eastern were D. farinae (74.9%) and D. pteronyssinus (74.3%), while in the western were mugwort (60.0%) and marguerite (56.6%). Majority of sIgE-positive subjects were sensitized to three or more of the tested pollen allergens in the Western (52.1%), compared with 5.7% in the Eastern.Conclusion: There was an apparent geographic variation in childhood allergies in China. Age factors also had strong impacts on the allergen sensitization rate of children, but these impacts differed across regions.Keywords: allergic rhinitis, specific immunoglobulin E, cross-sectional survey, aeroallergen, children

Doudou Huang,1,2,&ast; Zenan Du,1,2,&ast; Yanhong Chen,3,&ast; Zhiying Dong,1 Xiujuan Wang,1 Mengshuang Li,1 Feng Zhang,3,&ast; Wansheng Chen,2,3 Lianna Sun1 1Department of TCM Processing, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianna Sun; Wansheng Chen Tel/Fax +86-21-51322211Email sssnmr@163.com; chenwansheng@smmu.edu.cnPurpose: Diabetes is a common disease caused by a combination of genetic and environmental factors, which was the top three diseases threatening human health. Therefore, it is necessary to seek more efficient hypoglycemic drugs. The main objective of this study was to investigate the potential hypoglycemic effects of compounds from Polygonum capitatum.Materials and Methods: Our experiments were divided into three steps: (1) α-amylase test and oral starch tolerance test (OSTT) for screening the biological extract part of P. capitatum; (2) chemical isolation and identification using various separation techniques, and spectrum methods; and (3) evaluation of α-amylase inhibitory activity of isolates and in silico analysis for mechanism investigation.Results: The n-butanol fractioned part of P. capitatum was confirmed to be the biological part according to α-amylase test. Then, two new triterpenoid saponins were isolated from the n-butanol part, which were also the first isolated triterpenoid saponins from P. capitatum. The activities of compounds 1 and 2 against α-amylase were 51.9± 2.8% and 38.1± 2.2%, respectively, which was consistent with the molecular docking analysis. In which, 1 and 2 showed the binding affinity energy for α-amylase was − 9.4 kcal/mol and − 7.8 kcal/mol, respectively.Conclusion: Two new triterpenoid saponins were firstly isolated from P. capitatum, and displays potency as a hypoglycemic agent through blocking α-amylase.Keywords: α-amylase, Polygonum capitatum, triterpene saponins, hypoglycemic

Dongdong Huang,1 Saibin Wang2 1Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua Municipal Central Hospital, Jinhua, 321000, Zhejiang, People’s Republic of ChinaCorrespondence: Saibin WangDepartment of Respiratory Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua Municipal Central Hospital, Jinhua, 321000, Zhejiang Province, People’s Republic of ChinaTel +86 579 82552278Fax +86 579 82325006Email saibinwang@hotmail.comPurpose: Sleep duration is associated with aging. However, the relationship between sleep duration and the concentration of the protein klotho in the serum remains unknown in the general population of the United States. Hence, this study aimed at exploring the association between them.Methods: Participants whose data included klotho protein and sleep duration variables in the National Health and Nutrition Examination Survey data from 2007 to 2016 were utilized for this analysis.Results: Sleep duration was non-linearly associated with the level of klotho protein in the serum, with a negative association between sleep duration and serum klotho concentration after adjusting for confounding variables (β = − 7.6; 95% CI: − 11.3, − 4.0; P < 0.001). The conversion of the sleep duration from a continuous variable to a categorical variable (tertile: T1: < 5.5 hours; T2: 5.5– 7.5 hours; T3: > 7.5 hours) revealed that the serum klotho of the participants in the highest tertile (> 7.5 hours) was 21.9 pg/mL lower (95% CI: − 38.6, − 5.2; P = 0.01) than those in the lowest tertile (< 5.5 hours).Conclusion: Our results revealed that people who sleep more than 7.5 hours per night have decreased levels of the anti-aging protein klotho in their serum, thus being more at risk of aging-related syndromes.Keywords: klotho protein, sleep duration, aging, NHANES

Qian Zhang,1,2,&ast; Jun Li,3,&ast; Minjie Bian,1,2 Qin He,1,2 Yuxian Shen,1,2 Yue Lan,4 Dongfeng Huang1,2 1Department of Rehabilitation Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 2Guangdong Engineering and Technology Research Center for Rehabilitation Medicine and Translation, Guangzhou, People’s Republic of China; 3Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 4Department of Rehabilitation Medicine, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue LanDepartment of Rehabilitation Medicine, Guangzhou First People’s Hospital, Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510030, People’s Republic of ChinaTel +86-18988991916Email sybluemoon@126.comDongfeng HuangDepartment of Rehabilitation Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518107, People’s Republic of ChinaTel +86-13322800919Fax +86-0755-81206511Email huangdf@mail.sysu.edu.cnBackground and Purpose: Mild Cognitive Impairment (MCI) is thought to be the signal of many progressive diseases but is easily ignored. Therefore, a simple and easy screening method for recognizing and predicting MCI is urgently needed. The study aimed to establish machine learning models of retinal vascular features to categorize and predict MCI.Patients and Methods: Subjects enrolled underwent cognitive function assessment and were divided into a normal group, an MCI group, and a dementia group, and fundus photography was performed. MATLAB 2019b was used for fundus image preprocessing and vascular segmentation. Via the Green channel, adaptive histogram equalization (AHE), image binarization, and median filtering, we obtained the original and segmentation retinal vessel images. Afterwards, the histogram of oriented gradient (HOG) was used for image feature extraction. Support vector machine (SVM) and extreme learning machine (ELM) were selected for training models in the fundus original images and fundus vascular segmentation images, respectively. Among the three cognitive groups, sensitivity, specificity, the receiver operating characteristic (ROC) curves, and the area under the curve (AUC) were used to evaluate and compare the predictive performance of the two models in the fundus original and vascular segmentation images, respectively.Results: A total of 86 eligible subjects were enrolled in the study. After a clinical cognitive assessment, the participants were divided into the normal group (N = 38), the MCI group (N = 26), and the dementia group (N = 22). A total of 332 qualified fundus images were adopted after screening. Comparing the models among the three groups showed that the SVM model had more advantages than the ELM model in the fundus original images and vascular segmentation images. Meanwhile, we found that the original images performed better than the segmentation images in the same prediction model. Among the three groups, the SVM model of the fundus original images had the best performance.Conclusion: The establishment of a predictive model based on vascular-related feature extraction from fundus images has high recognition and prediction abilities for cognitive function and can be used as a screening method for MCI.Clinical Trial Registration: ChiCTR.org.cn (ChiCTR1900027404), Registered on Nov 12, 2019.Keywords: retinal imaging techniques, mild cognitive impairment, machine learning, support vector machine, extreme learning machine

Yanni Yang,1– 3,&ast; Daning Li,1,&ast; Wentao Wu,1 Dingxing Huang,1 Haishi Zheng,3 Yirixiati Aihaiti3 1School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 2Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 3Department of Joint Surgery, Xi’an Jiaotong University Affiliated HongHui Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wentao WuSchool of Public Health, Xi’an Jiaotong University Health Science Center, 76 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel +86 156 80833716Email 15680833716@163.comBackground: Selenium (Se) exhibits its anti-carcinogenic properties by regulating the redox system. However, the relationship between selenoprotein P (SeP), mRNA (SELENOP mRNA) and tumorigenesis remains unclear. Plasma SeP transports Se to various target tissues and has antioxidant characteristics. The present study aimed to explore the multifaceted pan-cancer properties of SELENOP in terms of its tissue-specific expression, prognostic value, immune function, and signaling pathway enrichment.Patients and Methods: The expression profile of SELENOP was determined in 33 tumor types and survival, pathway enrichment, and correlation analyses were conducted based on TCGA database. The relationship between SELENOP expression and immune infiltration and macrophage subtype gene markers was investigated using the TIMER and GEPIA.Results: SELENOP gene expression was decreased in many cancer tissues, but was upregulated in brain lower grade glioma (LGG). Furthermore, SELENOP expression was associated with a better prognosis in most cancers, but a poorer prognosis in LGG and uterine corpus endometrioid carcinoma (UCEC). Our results showed that SELENOP was correlated with infiltration level of six immune cell types, where SELENOP also showed a strong correlation with macrophages in some cancer types. However, we failed to determine macrophage polarization in 33 tumor types. SELENOP negatively regulated vascular endothelial cell proliferation in LGG and UCEC and epidermal cell differentiation in six tumor types. In contrast, upregulation was related to immune function, including T cell activation, B cell-mediated immunity, adaptive immune response and immune response regulation cell surface receptor signaling pathways in another six tumor types.Conclusion: These findings highlighted the tissue-specific expression, prognostic value and immune characteristics of SELENOP in pan-cancer, and provided insights for illustrating the role of SELENOP in tumorigenesis.Keywords: selenoprotein P, pan-cancer, immune infiltration, prognosis, tissue-specific expression

Caixia Pei,&ast; Fei Wang,&ast; Demei Huang, Shihua Shi, Xiaomin Wang, Yilan Wang, Shuiqin Li, Yongcan Wu, Zhenxing Wang Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenxing Wang; Yongcan WuHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaEmail wangzhenxing@vip.tom.com; appleofcan@163.comIntroduction: Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells).Methods: The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells.Results: After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro.Conclusion: Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.Keywords: PM2.5, lung injury, astragaloside IV, autophagy, inflammation

Dong Huang,1 Huan Yang,1 He Yu,1 Ting Wang,1 Zhu Chen,2 Zongan Liang,1 Rong Yao3 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Infectional Inpatient Ward Two, Chengdu Public Health Clinical Medical Center, Chengdu, Sichuan, People’s Republic of China; 3Department of Emergency Medicine, Emergency Medical Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Zongan LiangDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86 028 8542 2377Email liangza@scu.edu.cnRong YaoDepartment of Emergency Medicine, Emergency Medical Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86 028 8542 2461Email yaorong@wchscu.cnPurpose: We sought to explore the prognostic value of blood urea nitrogen (BUN) to serum albumin ratio (BAR) and further develop a prediction model for critical illness in COVID-19 patients.Patients and Methods: This was a retrospective, multicenter, observational study on adult hospitalized COVID-19 patients from three provinces in China between January 14 and March 9, 2020. Primary outcome was critical illness, including admission to the intensive care unit (ICU), need for invasive mechanical ventilation (IMV), or death. Clinical data were collected within 24 hours after admission to hospitals. The predictive performance of BAR was tested by multivariate logistic regression analysis and receiver operating characteristic (ROC) curve and then a nomogram was developed.Results: A total of 1370 patients with COVID-19 were included and 113 (8.2%) patients eventually developed critical illness in the study. Baseline age (OR: 1.031, 95% CI: 1.014, 1.049), respiratory rate (OR: 1.063, 95% CI: 1.009, 1.120), unconsciousness (OR: 40.078, 95% CI: 5.992, 268.061), lymphocyte counts (OR: 0.352, 95% CI: 0.204, 0.607), total bilirubin (OR: 1.030, 95% CI: 1.001, 1.060) and BAR (OR: 1.319, 95% CI: 1.183, 1.471) were independent risk factors for critical illness. The predictive AUC of BAR was 0.821 (95% CI: 0.784, 0.858; P< 0.01) and the optimal cut-off value of BAR was 3.7887 mg/g (sensitivity: 0.690, specificity: 0.786; positive predictive value: 0.225, negative predictive value: 0.966; positive likelihood ratio: 3.226, negative likelihood ratio: 0.394). The C index of nomogram including above six predictors was 0.9031125 (95% CI: 0.8720542, 0.9341708).Conclusion: Elevated BAR at admission is an independent risk factor for critical illness of COVID-19. The novel predictive nomogram including BAR has superior predictive performance.Keywords: blood urea nitrogen, albumin, predictive performance, critical illness, COVID-19

Jun Zhou, Wenhan Huang, Feifeng Ren, Lei Luo, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, People’s Republic of ChinaEmail tanglin1217@163.comObjective: The aim of our study was to elucidate the potential prognostic factors in anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive patients.Methods: We divided anti-MDA5-positive patients into death and survival groups. The differences in clinical characteristics were analyzed.Results: A total of 56 cases were included. The death group comprised 10 (17.9%) cases, and the survival group comprised 46 (82.1%) cases. Median age of the death group was greater than the survival group, 59.50 years vs 39.25 years, p< 0.05. The death group had lower lymphocyte count and albumin and higher erythrocyte sedimentation rate, ferritin and lactate dehydrogenase initially (p< 0.05, respectively). Ground-glass opacity on chest computed tomography was found more often in the death group (p< 0.05), in which there was an absence of honey-combed shadow initially. The diagnosis of interstitial pneumonia with autoimmune features was higher in the death group than the survival group (70% vs 13%, p< 0.05). The median dose of maximum daily methylprednisolone in the death group (160 mg/d) was higher than that in the survival group (48 mg/d) (p< 0.05).Conclusion: Advanced age, low lymphocyte count and albumin, and increased levels of inflammatory markers may portend poor prognosis in anti-MDA5-positive patients. Extra-large doses of glucocorticoid may have no additional benefit in these patients.Keywords: anti-melanoma differentiation-associated gene 5 antibody, interstitial lung disease, clinical manifestation, prognosis

Jiuling Deng,1,&ast; Ying Ma,2,&ast; Yuqiong He,1,&ast; Hong Yang,2 Yanhong Chen,2 Liang Wang,1 Doudou Huang,1 Shi Qiu,1,&ast; Xia Tao,2 Wansheng Chen1 1Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wansheng ChenInstitute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaTel +64 021 81886182Email chenwansheng@shutcm.edu.cnXia TaoDepartment of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of ChinaTel +64 021 81886182Email taoxia2003@126.comPurpose: Isatis indigotica (Ii) is a cruciferous herb that is widely distributed in China, and its roots and leaves have been used in two renowned antipyretic detoxicate crude drugs in Chinese Pharmacopoeia, Radix (R) and Folium (F) Isatidis. However, the pharmacodynamic material basis and underlying mechanisms of the herbal efficacy remained to be elucidated.Methods: Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was adopted for the chemical profiling of R and F Isatidis. The active ingredients were screened out through the prediction of gastrointestinal absorption and druglikeness analysis using SwissADME. A herb-ingredient-target network was constructed through target prediction of the herbal active ingredients and anti-inflammation or anti-viral properties, followed by protein–protein interaction analysis. Then, the potential relevant signaling pathways were predicted by pathway enrichment. Finally, for verification, RAW 264.7 cell line was adopted to examine the anti-inflammatory and anti-viral activities of 6 representative ingredients in Ii.Results: Seventy-three compounds have been identified from Ii through UPLC-Q-TOF-MS. A total of 17 potential active ingredients were screened through pharmacokinetics and drug-likeness evaluation using SwissADME. It was shown that key targets might include TNF, AKT1, SRC, IL2, CASP9, and CASP3 in our herb-ingredient-target network, and isovitexin, a flavonoid, tended to participate in the inflammatory response, indoles were more likely to affect the cell proliferation processes, and lignans might have a broader affinity to key targets than the other active ingredients, such as regulating immune system (targeting IL-2) and PI3K-Akt signaling pathway. In vitro, indigo and secoisolariciresinol diglucoside markedly reduced TNF-α expression in Poly (I: C)-incubated cells. Isovitexin significantly inhibited TNF-α expression, and isatin treatment markedly reduced IL-1β expression in LPS-incubated cells.Conclusion: As the pharmacodynamics material basis of Ii, indoles, lignans, and flavonoids are believed to confer beneficial properties through various cellular aspects with multiple signaling pathways involved.Keywords: Isatis indigotica, UPLC-Q-TOF-MS, network analysis, bioassay analysis

Yao Zou,1,2 Owais M Bhat,2 Xinxu Yuan,2 Guangbi Li,2 Dandan Huang,2 Yi Guo,1,3 Dan Zhou,1,3 Pin-Lan Li2 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; 3School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Pin-Lan LiDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, 1220 East Broad Street, Richmond, VA, 23298-0613, USATel +1 804-828-4793Fax +1 804-828-4794Email pin-lan.li@vcuhealth.orgDan ZhouResearch Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel/Fax +86 22-59596211Email acuzhoudan@163.comBackground: Exosomes have been reported to mediate activation of the inflammatory response by secretion of inflammasome products such as IL-1β or IL-18 and that changes in exosomes production or secretion may be a therapeutic target for treatment of a variety of different chronic diseases. The present study tested the hypothesis that exosome-mediated release of NLRP3 inflammasome products instigates the inflammatory response in the lung during emphysema, a type of chronic obstructive pulmonary disease (COPD) and that electroacupuncture (EA) may attenuate emphysema by inhibition of NLRP3 inflammasome activation and consequent inflammation.Methods: The COPD mice model was developed by injecting porcine pancreatic elastase (PPE) via puncture tracheotomy and instillation. EA (4 Hz/20 Hz, 1 to 3 mA) was applied to the bilateral BL13 and ST36 for 30 min, once every other day for 2 weeks. Micro computed tomography (micro-CT) was performed to measure lung function. Histopathological changes in the lungs were displayed by HE staining.Results: In a mouse model of porcine pancreatic elastase (PPE)-induced emphysema, the lung tissue was found to display several key features of emphysema, including alveolar septal thickening, enlarged alveoli, interstitial edema, and inflammatory cells infiltration. Lungs of mice receiving PPE exhibited substantially increased low attenuation area (LAA) in micro-CT images. The colocalization of NLRP3 vs ASC or caspase-1 detected by confocal microscopy was shown to increase in both bronchial and alveolar walls, indicating the increased formation of NLRP3 inflammasomes. IL-1β, a prototype NLRP3 inflammasome activating product, was also found to have increased in the lung during emphysema, which was colocalized with CD63 (an exosome marker), an indicative of inflammatory exosome formation. By nanoparticle tracking analysis (NTA), IL-1β-containing exosomes were shown to significantly increase in the bronchoalveolar lavage (BAL) from mice with emphysema. Therapeutically, IL-1β production in the lung during emphysema was significantly reduced by EA at the acupoint Feishu (BL13) and Zusanli (ST36), accompanied by decreased colocalization of NLRP3 vs ASC or caspase-1. Increased exosome release into BAL during emphysema was shown to be significantly attenuated in EA-treated mice compared to their controls. However, EA of non-specific BL23 together with ST36 acupoint had no effects on NLRP3 inflammasome activation, exosome release and associated lung pathology during emphysema.Conclusion: NLRP3 inflammasome activation in concert with increased release of exosomes containing IL-1β or other inflammasome products contributes to the development of lung inflammation and injury during PPE-induced emphysema and that EA of lung-specific acupoints attenuates inflammasome activation and exosome release, thereby reducing inflammatory response in the lung of mice with emphysema.Keywords: chronic lung disease, inflammation, acupoints, exosome

Wenhan Huang, Feifeng Ren, Lei Luo, Jun Zhou, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaEmail hopetang@163.comObjective: Clinical characterization of lipid metabolism in untreated patients with anti-melanoma differentiation-associated gene 5 antibodies-positive (anti-MDA5+).Methods: Body-mass index (BMI), autoantibodies, lipid levels, and serum ferritin levels in 57 anti-MDA5+ patients were determined in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University.Results: Plasma high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) levels were significantly lower in deceased group than in the survival group (P < 0.05). Plasma levels of HDL and ApoA1 were significantly lower in patients who were simultaneously anti-MDA5+ and anti-Ro-52+ than in patients who were anti-MDA5+ alone (P < 0.05). Plasma levels of total cholesterol, low-density lipoprotein, HDL, and ApoA1 were significantly decreased in patients with high levels of serum ferritin compared with patients with low levels (P < 0.05). There were no significant differences in blood lipid levels between patients grouped according to BMI.Conclusion: 1) HDL and ApoA1 levels are important indicators of poor prognosis in anti-MDA5+ patients; 2) Dysregulated lipid metabolism in anti-MDA5+ patients is closely associated with anti-Ro-52 antibody and ferritin levels but independent of BMI; 3) HDL involvement in inflammation and immune regulation merits close attention by rheumatologists.Keywords: anti-melanoma differentiation-associated gene 5 antibodies, anti-Ro-52 antibody, lipid, high-density lipoprotein, apolipoprotein A1

Jing Li,* Weiling Zhang,* Huimin Hu, Yi Zhang, Yizhuo Wang, Huali Gu, Dongsheng Huang Department of Pediatrics, Beijing Tongren Hospital of China Capital Medical University, Beijing, 100176, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongsheng HuangDepartment of Pediatrics, Beijing Tongren Hospital of China Capital Medical University, No. 1 Dongjiao Lane, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 10 5826 6032Email huamgdomgshemg@163.comObjective: This study aims to summarize the clinical features and prognoses of the malignant rhabdoid tumor of the kidney (MRTK) in children. It further aims to analyze the high-risk factors affecting MRTK prognosis.Methods: Clinical data from 14 children with MRTK treated in Paediatrics of Beijing Tongren Hospital from January 2010 to December 2019, along with the high-risk factors affecting prognosis, were retrospectively analyzed.Results: There were 14 children with MRTK included in the study, with a median onset age of 13 (3– 46) months. Thirteen patients had distant metastases, the most common site for metastases being inside the lung. A comprehensive treatment protocol combined with chemotherapy was mainly applied during the surgery. A surgical resection of primary tumors was performed on 13 (13/14) patients, and all 14 children received chemotherapy with ifosfamide + carboplatin + etoposide, ifosfamide + etoposide, and vincristine + pirarubicin + cyclophosphamide regimens, alternately. Three patients received radiotherapy and two received oral targeted drugs after partial response. The median follow-up was after 16.5 months (3– 53 months) and the four-year overall survival (OS) was 41.8%. In children aged ≤ 24 months and children aged > 24 months, the two-year OS was 67.2% and 100% (χ2 = 108.998, P< 0.05), respectively. In children with Ki 67 > 70% and children with Ki 67 < 70%, the two-year OS was 52.6% and 86.9% (χ2 = 8.544, P = 0.003), respectively. In children with distant metastases and children without distant metastasis, the two-year OS was 70% and 100% (χ2 = 14.239, P< 0.05), respectively.Conclusion: The most common MRTK distant metastasis site is the lung. Risk factors for poor MRTK prognoses include an age of < 24 months, Ki 67 > 70%, and distant metastases.Keywords: children, malignant rhabdoid tumor of the kidney, MRTK, treatment, prognosis

Jianyuan Song,1– 3 Zhuhong Chen,1 Daxin Huang,1 Benhua Xu1– 3 1Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Medical Imaging Technology, College of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Medical University Union Clinical Medicine College, Fuzhou, Fujian Province, People’s Republic of ChinaCorrespondence: Benhua XuDepartment of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of ChinaEmail benhuaxu@163.comPurpose: The prognostic significance of pretreatment elevated and normalized CEA after neoadjuvant chemoradiotherapy (nCRT) was evaluated.Materials and Methods: The characteristics of 951 locally advanced rectal cancer patients with nCRT were retrieved and were analyzed retrospectively. Pretreatment CEA levels were defined as CEA evaluated one week prior to the nCRT. CEA after nCRT was deemed as CEA measured one week before surgery. The normal CEA levels were set at < 5 ng/mL. The normal CEA group was defined as patients with normal pretreatment CEA levels. The normalized CEA group was defined as patients with elevated pretreatment CEA levels and normal CEA levels after nCRT. The elevated CEA group was defined as patients with elevated pretreatment CEA levels and elevated CEA levels after nCRT.Results: Compared with the elevated CEA group, the normalized CEA group was associated with better overall survival (OS) (HR: 0.625, 95%CI: 0.416– 0.938, P=0.022). There was no difference between the normalized CEA group and the normal CEA group (HR: 1.143, 95%CI: 0.84– 1.557, P=0.395).Conclusion: In conclusion, the study indicated that OS of the normalized CEA group and the normal CEA group was better than the elevated CEA group.Keywords: rectal cancer, locally advanced rectal cancer, LARC, carcinoembryonic antigen, CEA

Rong Hu,1– 3 Jintao Zhang,1,2,4 Xuemei Liu,1,2 Dong Huang,3 Yu-Qing Cao1,2 1Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA; 2Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; 3Department of Pain Management, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Yu-Qing CaoDepartment of Anesthesiology, Washington University School of Medicine, 660 South Euclid, Box 8054, St. Louis, MO, 63110, USATel +1 314 362 8726Fax +1 314 362 8334Email caoy@anest.wustl.eduPurpose: Nerve injury-induced mechanical hyper-sensitivity, in particular stroking-induced dynamic allodynia, is highly debilitating and difficult to treat. Previous studies indicate that the immunosuppressive regulatory T (Treg) cells modulate the magnitude of punctate mechanical allodynia resulting from sciatic nerve injury. However, whether enhancing Treg-mediated suppression attenuates dynamic allodynia is not known. In the present study, we addressed this knowledge gap by treating mice with low-dose interleukin-2 (ld-IL2) injections or adoptive transfer of Treg cells.Methods: Female Swiss Webster mice received daily injections of ld-IL2 (1 μg/mouse, intraperitoneally) either before or after unilateral spared nerve injury (SNI). Male C57BL/6J mice received adoptive transfer of 1 x 106 Treg cells 3 weeks post-SNI. The responses to punctate and dynamic mechanical stimuli on the hindpaw were monitored before and up to 4– 6 weeks post-SNI. We also compared the distribution of Treg cells and CD3+ total T cells after SNI and/or ld-IL2 treatment.Results: Ld-IL2 pretreatment in female Swiss Webster mice completely blocked the development of SNI-induced dynamic mechanical allodynia and reduced the magnitude of punctate allodynia. Delayed ld-IL2 treatment in female mice significantly attenuated the morphine-resistant punctate and dynamic allodynia at 3– 5 weeks post-SNI. Adoptive transfer of Treg cells to male C57BL/6J mice 3 weeks post-SNI effectively reversed the persistent punctate and dynamic allodynia, supporting that the effect of ld-IL2 is mediated through endogenous Treg cells, and is likely independent of mouse strain and sex. Neither ld-IL2 treatment nor Treg transfer affected the basal responses to punctate or brush stimuli. Ld-IL2 significantly increased the frequency of Treg cells among total CD3+ T cells in the injured sciatic nerves but not in the uninjured nerves or the dorsal root ganglia, suggesting the injured nerve as ld-IL2’s site of action.Conclusion: Collectively, results from the present study supports Treg as a cellular target and ld-IL2 as a potential therapeutic option for nerve injury-induced persistent punctate and dynamic mechanical allodynia.Keywords: spared nerve injury, chronic pain, punctate allodynia, dynamic allodynia, low-dose interleukin-2, regulatory T cell

Tian Zhi, Weiling Zhang, Yi Zhang, Huimin Hu, Dongsheng Huang Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100176, People’s Republic of ChinaCorrespondence: Dongsheng HuangDepartment of Pediatrics, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 10 58266032Email huamgdomgshemg@163.comObjective: The present study aimed to summarize the clinical data of hepatoblastoma (HB) in infants under one year of age and to analyze the factors that affected the prognoses.Methods: The clinical data of 132 pediatric patients with a pathologically confirmed HB, aged less than one year and who had visited the Pediatric Single Center of Beijing Tongren Hospital from May 2005 to May 2019, were retrospectively analyzed to summarize the clinical outcomes and prognoses.Results: The male/female ratio was 1.27 and the median age was 8.40 months. The onset of HB was usually characterized by abdominal bulging (75.0%). The median level of AFP at the first visit was 154.7μg/mL, and the average platelet count was (405± 166)× 109/L. The epithelial type (57.6%) was the predominant pathological type, and stage III (54.5%) was the main PRETEXT staging. Distant metastases occurred in 45 cases, with pulmonary metastases (86.7%) being the most common site. At the time of visit, 24 cases (18.2%) had either portal vein, hepatic vein, or vena cava infiltration. Five cases (3.8%) had a hemorrhage of the ruptured tumor, and 26 cases (19.7%) had multiple intrahepatic foci. At the follow-up in May 2020, the overall survival (OS) rate at one, three, and five years of age was 94.3%, 88.8%, and 80.1%, respectively, and the event-free survival rate was 91.8%, 86.9%, and 77.5%, respectively, by the Kaplan–Meier survival analysis. According to the Log rank test, pediatric patients with an AFP < 100ng/mL, a PRETEXT stage IV, presence of distant metastases and multiple foci of the primary tumor at the initial diagnosis had poorer prognoses (P< 0.05).Conclusion: The prognosis of HB in infancy is relatively good, but is still vulnerable to multiple factors, such as tumor features leading to different AFP levels, PRETEXT stage, presence of distant metastases, and multiple intrahepatic foci.Keywords: hepatoblastoma, infant, AFP, chemotherapy, prognosis

Jing Li, Weiling Zhang, Huimin Hu, Yi Zhang, Yuan Wen, Dongsheng Huang Department of Pediatrics, Beijing Tongren Hospital of China Capital Medical University, Beijing, 100176, People’s Republic of ChinaCorrespondence: Dongsheng HuangDepartment of Pediatrics, Beijing Tongren Hospital of China Capital Medical University, No. 1 Dongjiao Lane, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 10 5826 6032Email dshuang588@163.comObjective: This study aimed to summarize the clinical characteristics, comprehensive treatment, and prognosis of adrenocortical carcinoma (ACC) in children.Methods: The clinical data of eight children with definite diagnoses of ACC were retrospectively analyzed, and statistical methods were used to analyze the clinical characteristics, comprehensive treatment mode, and prognosis of these patients.Results: (1) Clinical characteristics: two were males and six were females with the median age of onset was six-years old were involved. Four patients had a rash and precocious puberty as the symptoms of onset. European Network for the Study of Adrenal Tumors (ENSAT) staging: stage II, two patients; stage IV, six patients. (2) Comprehensive treatment: all eight patients underwent surgical treatment and received six cycles of chemotherapy: the regimen was “etoposide + pirarubicin + cisplatin + mitotane.” (3) Prognosis analysis: among these eight patients, two patients died, two patients achieved complete remission, the disease was stable in four patients, and the overall five-year survival rate was 75%. Prognosis analyzed according to ENSAT staging (stage II versus stage IV) revealed that two-year survival rates of the two groups were 100% versus 65%, respectively, without statistical significant (χ2 = 1.066, P = 0.302). Prognosis analyzed according to Weiss score (Weiss score was < 6, five patients;≥ 6, three patients) revealed That survival time of the two groups was 50± 9.52 months versus 6± 1.70 months, the two-year survival rates of the two groups were 100% versus 35%, and the difference in survival rates between these two groups was statistically significant (χ2 = 4.091, P = 0.043).Conclusion: The Weiss score is an important prognostic factor for ACC. The chemotherapy regimen “mitotane + etoposide + adriamycin + cisplatin” is recommended.Keywords: adrenocortical carcinoma, children, prognosis

Dan Huang, Dong Wu, Jinhong He, Min Chen, Xuanna Zhao, Dongming Li, Bin Wu Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of ChinaCorrespondence: Dongming Li; Bin WuDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, 57th South Renmin Road, Zhanjiang, Guangdong, 524001, People’s Republic of ChinaTel/Fax +867592387413Email 1335887835@qq.com; wubin621011@126.comPurpose: Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death in the world. Many studies have shown that COPD often exists with thyroid dysfunction; however, the relationship between thyroid function and COPD is often ignored in clinical. We retrospectively analyze the serum thyroid hormone levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and explore the association between thyroid function and AECOPD.Methods: The study included patients hospitalized for AECOPD in our institution between January 2018 and September 2020. Patients with AECOPD were divided into moderate-to-severe and very severe groups based on lung function, and into normal and abnormal thyroid function groups based on thyroid hormone levels. Collected data and compared data between groups to identify risk factors for thyroid dysfunction in patients with AECOPD.Results: The cohort included 97 in the moderate-to-severe group (72.39%) and 37 in the very severe group (27.61%). Compared with the very severe group, the moderate-to-severe group had higher triglyceride (P=0.017), high-density lipoprotein (P< 0.05), partial pressure of carbon dioxide (PaCO2; P< 0.05), and serum thyroid-stimulating hormone (TSH; P< 0.001). FEV1 as a percentage of the predicted value (FEV1%pred) was positively correlated with TSH and FT3 (r=0.329, r=0.192, respectively, both P< 0.05). Duration of hospitalization was negatively correlated with TSH (r=− 0.256, P=0.003). Among the 134 subjects, 98 (73.13%) had normal thyroid function and 36 (26.87%) had abnormal thyroid function. The two groups significantly differed regarding forced vital capacity (FVC), forced expiratory volume in 1 second, FEV1%pred, and albumin level. Logistic regression analysis showed that high FVC correlated with a low risk of thyroid dysfunction in AECOPD.Conclusion: In patients with AECOPD, TSH is related to lung function and duration of hospitalization, and high FVC reduces the risk of thyroid dysfunction.Keywords: AECOPD, thyroid hormone, retrospective cohort study, risk factor

Bingling Guo,1,* Chunyan Xiao,1,* Yumin Liu,2 Ning Zhang,3 Hao Bai,4 Tao Yang,1 Ying Xiang,1 Yingyu Nan,1 Qiying Li,1 Wenjun Zhang,1 Dehong Huang1 1Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 2Medical Records Management Division, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 3Intensive Care Unit, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 4Pharmacy Services, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehong HuangDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Chongqing, People’s Republic of ChinaTel +86 23-65311341Email dehong_h012436@163.comPurpose: This study investigated the function and molecular mechanisms of miR-744-5p in multiple myeloma (MM).Methods: miR-744-5p and SRY-related high-mobility-group box 12 (SOX12) expression in clinical tissues and MM cells was monitored by quantitative real-time polymerase chain reactions and Western blot. miR-744-5p expression in MM cells was regulated by transfection. Cell proliferation was researched by cell counting kit-8 assay and plate clone formation experiment. Transwell experiment was utilized for migration and invasion detection. Glycolysis test was conducted for the detection of glucose uptake and lactate production of MM cells. The relationship between miR-744-5p and SOX12 was determined by dual-luciferase reporter gene assay and RNA pull-down experiment. In vivo experiment was conducted using nude mice.Results: miR-744-5p expression was reduced in MM patients (P< 0.01). Low miR-744-5p expression was associated with lower 60-month survival in MM patients (P=0.0402). miR-744-5p overexpression inhibited MM cells proliferation, invasion, migration, glucose uptake, lactate production, and epithelial mesenchymal transformation (EMT) (P< 0.01). miR-744-5p directly inhibited SOX12 expression. miR-744-5p silencing promoted MM cells proliferation, invasion, migration, glucose uptake, lactate production, and EMT by elevating SOX12 (P< 0.01). miR-744-5p inhibited the growth of MM xenograft tumors in vivo (P< 0.001).Conclusion: miR-744-5p inhibits MM cells proliferation, invasion, migration, EMT, and glycolysis by targeting SOX12/Wnt/β-catenin.Keywords: MM, miR-744-5p, SOX12, EMT, glycolysis