Search

Juyi Li,1,2 Yang Ge,3 Yuwei Chai,1 Chunjia Kou,1 Tian Tian Sun,4 Jia Liu,3,5– 7 Haiqing Zhang1,3,5– 7 1Department of Endocrinology, Shandong Provincial Hospital, Shandong University; Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Endocrinology, Geriatrics Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, People’s Republic of China; 3Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Infectious Diseases, Jinan People’s Hospital, Jinan, Shandong, 271100, People’s Republic of China; 5Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021, People’s Republic of China; 6Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, People’s Republic of China; 7Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Jia Liu; Haiqing Zhang, Department of Endocrinology, Shandong Provincial Hospital, 324 Jingwu Road, Jinan, Shandong Province, 250021, People’s Republic of China, Tel +86 18653155865 ; Tel +86 15168888303, Email liujia_625@163.com; zhanghq@sdu.edu.cnPurpose: Thyroid-stimulating hormone (TSH) has been identified as an independent risk factor for non-alcoholic fatty liver disease (NAFLD), TSH binds to the TSH receptor (TSHR) to exert its function. However, the underlying mechanisms by which TSHR influences NAFLD development remain unclear. This study investigates the role of miR374b in NAFLD progression.Methods: Firstly, a rat model of non-alcoholic fatty liver was constructed and divided into a normal group and a model group. The liver tissue pathology and fat accumulation were detected by Oil Red O staining and hematoxylin-eosin staining. Western blot and Real time PCR were used to detect for the impact of TSHR/miR-374b/C/EBP β/ FoxO1 pathway in the NAFLD model, and the expression of relevant inflammatory factors in each group was detected by ELISA assay. A NAFLD cell model was constructed using HepG2 cells, TSHR overexpression and interference, combined with miR-374b inhibitor and mimics, were transfected simultaneously to demonstrate TSHR/miR-374b/C/EBP β/ The mechanism of FoxO1 adipogenesis in vitro.Results: TSHR stimulates miR374b secretion in human liver cancer cells (HepG2) and promotes lipid accumulation in the liver. Deficiency of miR374b in HepG2 cells attenuated NAFLD progression. Mechanistically, TSH increases miR374b expression, which then suppresses the transcription of its target genes, CCAAT/enhancer binding protein-b (C/EBP β) and Forkhead Box Protein O1 (FOXO1). This suppression influences the expression of downstream lipid metabolism proteins, including PPARγ, SREBP2, and SREBP1c. Additionally, miR374b directly targets the 3′UTR of C/EBP β and FOXO1, establishing a negative feedback loop in lipid metabolism.Conclusion: These findings suggest that TSHR-induced upregulation of miR374b accelerates NAFLD progression by modulating lipid metabolism pathways through C/EBP β and FOXO1. Keywords: NAFLD, miR374b, TSHR

Changjian Liu, Yongpeng Ge Department of Rheumatology, the Key Laboratory of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, The Key Laboratory of Myositis, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Email gyp2016@163.comBackground: Interstitial lung disease (ILD) is one of the significant complications of dermatomyositis (DM), but the mechanisms by which it occurs remain incompletely elucidated. This study aimed to explore further the possible genetic mechanisms by which this complication occurs.Methods: Gene expression profiles for DM (GSE39454, GSE46239, GSE143323) and ILD (GSE32537, GSE110147, GSE150910) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying common differentially expressed genes (DEGs) to DM and ILD using the “limma” R package and the “VennDiagram” R package, functional annotation, relationship to immune cell infiltration, identification of transcription factors (TFs), we also collected clinical cases of DM-associated ILD (DM-ILD), including 3 cases of rapidly progressive ILD (RP-ILD) and 3 cases of none-RP-ILD, and explored whether there were differences in serum lymphocyte subpopulations.Results: A total of 4 common DEGs (SLAMF7, SPP1, TDO2, and VCAM1) were screened and Gene Ontology (GO) enrichment analysis showed that these genes were mainly enriched in T cell activation, regulation of lymphocyte activation, lymphocyte differentiation, leukocyte proliferation and regulation of T cell activation. In terms of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the three significantly enriched pathways were the PI3K-Akt signaling pathway, MAPK signaling pathway, and Cytokine-cytokine receptor interaction. In lung and muscle tissues, 21 and 3 TFs may regulate the expression of these genes, respectively. Finally, by analysing the serum lymphocyte subpopulations, we also found a decrease in the absolute number of CD8+ T cells and an increase in the CD4+ /CD8+ T cell ratio in DM combined with RP-ILD.Conclusion: These common pathways and key genes may provide new ideas for further research into DM-ILD.Keywords: dermatomyositis, interstitial lung disease, differentially expressed genes, immune cells

Xiaotong Tian,1,2 Jing Lin,1,2 Menglan Zhou,3,4 Ying Ge,1 Taisheng Li,1 Li Zhang,1 Zhengyin Liu1 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of ChinaCorrespondence: Zhengyin Liu; Li Zhang, Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China, Email liuzhy@pumch.cn; zhangli36@pumch.cnPurpose: To evaluate the clinical outcomes and safety of tigecycline (TGC) plus cefoperazone/sulbactam (CPS) or TGC monotherapy in patients with hospital-acquired pneumonia (HAP) caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB).Methods: This was a retrospective analysis of multicenter data from 62 Chinese hospitals with CRAB HAP. Risk factors for receiving TGC with CPS therapy and predictors of mortality were assessed using multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacy and safety of antimicrobial regimens.Results: A total of the 180 patients were included, with 95 receiving TGC monotherapy and 85 receiving combination therapy. Multivariate logistic regression analysis revealed that older age (P = 0.011), and intensive care unit (ICU) admission (P = 0.007) were significant risk factors for combination therapy. Multivariate Cox regression demonstrated that combination therapy was associated with a significantly higher risk of 90-day mortality (P = 0.031). Patients in the standard-dose TGC (SDT) plus CPS subgroup had significantly higher rates of SOFA scores ≥ 7 (P = 0.009) and MV used (P = 0.028), as well as higher 30-/90-day mortality compared to high-dose TGC (HDT) plus CPS group. TGC plus CPS significantly reduced CRP levels (P = 0.009), while the variations in ALT, TBIL, Cr, Hb, and PLT levels did not differ between different antimicrobial regimens after PSM.Conclusion: HDT and CPS combination therapy was more effective in patients with advanced age and more severe condition. Safety profiles of different antimicrobial regimens were similar with liver, kidneys, and coagulation functions.Keywords: carbapenem-resistant Acinetobacter baumannii, hospital acquired pneumonia, tigecycline, cefoperazone/sulbactam, risk factors

Yuying Ge,1,* Yuepeng Xie,2,* Junlei Chai,3,* Weifeng Ji,4,* Xiulong Lou,1 Kun Tian,2 Ronghua Bao,3 Chengliang Wu,1 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, People’s Republic of China; 4Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: Intervertebral disc (IVD) degeneration (IVDD) is highly prevalent among the elderly population and stands as a leading cause of low back pain. Our prior studies have highlighted the therapeutic potential of Liuwei Dihuang decoction (LWDHD) and its component Cornus officinalis (CO)-derived compounds in alleviating IVDD and osteoarthritis, suggesting beneficial effects of CO in treating degenerative osteoarthropathies. However, uncertainty remains regarding the optimal CO dosage within LWDHD and its potential mechanism for effectively treating IVDD.Objective: To ascertain the optimal dosage of CO within LWDHD for enhancing its therapeutic efficacy in treating IVDD, through a comparison of its effects across varied dosages using a mouse IVDD model.Methods: Eight-week-old male C57BL/6J mice were subjected to a lumbar spine instability surgery to induce an IVDD model and received a modified LWDHD formulation containing varied dosages of CO (original dose of CO, or 5- or 10-time dose of CO (referred to as 1 × CO, 5 × CO, and 10 × CO)) for 8 weeks. The therapeutic efficacy on IVDD was evaluated through changes in lumbar spine function, histopathological morphology, extracellular matrix metabolism, nucleus pulposus cell viability, sensory nerve ingrowth, and nucleus pulposus (NP) cell pyroptosis.Results: Augmenting CO levels in LWDHD led to a dose-dependent increase in the levels of CO-sourced active compounds in the plasma of mice. The modified LWDHD formulations, particularly the 5 × CO, exhibited a favorable pharmacological effect on lumbar function, structural integrity, ECM composition, NP cell viability, and sensory nerve ingrowth. Importantly, all 3 formulations notably mitigated NP cell pyroptosis by activating NRF2/KEAP1 pathway, with the 5 × CO formulation exhibiting superior efficacy. Additionally, a comprehensive score analysis indicated that 5 × CO formulation achieved the highest score.Conclusion: These data underscore that elevating the dosage of CO to a specific threshold can enhance the effectiveness of LWDHD in treating IVDD.Keywords: intervertebral disc degeneration, liuwei dihuang decoction, nucleus pulposus cell, pyroptosis, Cornus officinalis

Kunhui Sun,1,2,* Bing Wang,2,* Mengnan Li,2 Yanli Ge,1 Lijun An,2 Duanna Zeng,2 Yuhan Shen,1 Ping Wang,2 Meifang Li,2 Xuelei Hu,1 Xie-An Yu1,2 1Key Laboratory for Green Chemical Engineering Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, People’s Republic of China; 2NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanli Ge; Xie-An Yu, Email geyanli@wit.edu.cn; yuxieanalj@126.comBackground: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors.Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT).Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer.Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy. Keywords: multimodality imaging guided synergistic cancer phototherapy, FL/PA/IR multimodal imaging, PDT/PTT dual synergistic therapy pathway, Zn phthalocyanine derivant

Li Zhang,1,* Menglan Zhou,2,3,* Ziran Wang,2,3,* Hongqiong Zhu,4 Jing Lin,1,5 Minya Lu,2,3 Ying Ge,1 Yingchun Xu,2,3 Taisheng Li,1 Zhengyin Liu1 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 5Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengyin Liu, Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Number 1, Shuaifuyuan Road, Dongcheng District, Beijing, People’s Republic of China, Email zhengyinl@hotmail.comBackground: In China, due to the large population, infections caused by Nocardia may not be as rare. Unfortunately, there is still inadequate knowledge of the clinical impact caused by Nocardia. This study aimed to compare the clinical characteristics and treatment of localized and disseminated nocardiosis.Methods: The clinical and microbiological data of patients diagnosed with nocardiosis in a tertiary hospital in Beijing from July 2011 to July 2021 were collected and retrospectively analyzed.Results: Among the 54 nocardiosis cases, 34 cases were in the localized infection group, while 20 cases in the disseminated infection group. The proportion of patients with chronic structural lung disease was higher in the localized group (P=0.010). In contrast, patients with disseminated infections were more prone to receive long-term glucocorticoids and/or immunosuppressants (P=0.027). Pulmonary nodules were prominent features of imaging changes in patients with disseminated infections (P=0.027) whereas bronchial dilatation was more common in patients with localized infections (P=0.025). In addition, the disseminated group had longer average hospitalization days relative to the localized group (P=0.016), but there was no significant difference in mortality between them (P=0.942).Conclusion: There were differences in the clinical profiles between patients with localized and disseminated nocardiosis in terms of clinical presentation, infection site, radiological features, treatment, and prognosis. These findings may provide references for the management and treatment of patients with nocardiosis.Keywords: Nocardia, disseminated nocardiosis, immunosuppressive population

Xixia Chen,1 Sang Lin,2 Qiwen Jin,1 Lu Zhang,3 Wei Jiang,3 Xin Lu,3 Guochun Wang,1,3 Yongpeng Ge3 1Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13716106183, Email gyp2016@163.comObjective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM).Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared.Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P> 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05).Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.Keywords: invasive pulmonary aspergillosis, opportunistic infection, anti-MDA5+ dermatomyositis, prevalence, risk factors, prognosis

Meiping Chen,1,2 Yijun Ge,1,3 Wen Zhang,1 Ping Wu,4 Chao Cao1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Ninghai First Hospital, Ningbo, 315600, People’s Republic of China; 4National Facility for Protein in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, CAS, Shanghai, 201210, People’s Republic of ChinaCorrespondence: Chao Cao, The First Affiliated Hospital of Ningbo University, 59 Liuting Road, Ningbo, 315010, People’s Republic of China, Tel +86-574-87089878, Fax +86-0574-8729-1583, Email caocdoctor@163.comPurpose: Little research has explored the proteomic characteristics of nasal lavage fluid from asthmatic patients. This study aims to investigate whether differentially expressed proteins (DEPs) in nasal lavage fluid can serve as a biomarker to differentiate asthma patients from healthy controls (HCs) and to discern between individuals with well controlled and poorly controlled asthma.Patients and Methods: We enrolled patients with allergic rhinitis (AR), asthma, or both conditions, and HCs in this study. We recorded patients’ demographic and medical history data and administered asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ). Nasal fluid samples were collected, followed by protein measurements, and proteomic analysis utilizing the data-independent acquisition (DIA) method.Results: Twenty-four with asthma, 27 with combined asthma+ AR, 25 with AR, and 12 HCs were enrolled. Four proteins, superoxide dismutase 2 (SOD2), serpin B7 (SERPINB7), kallikrein-13 (KLK13), and bleomycin hydrolase (BLMH) were significantly upregulated in nasal lavage fluid samples of asthma without AR, compared to HCs (Fold change ≥ 2.0, false-discovery rate [FDR] < 0.05). Conversely, 56 proteins including secretoglobin family 2A member 1 (SCGB2A1) were significantly downregulated (fold change ≥ 2.0, FDR < 0.05). Furthermore, 96.49% of DEPs including peptidase inhibitor 3 (PI3) and C-X-C motif chemokine 17 (CXCL17) were upregulated in poorly controlled asthma patients without AR relative those with well- or partly controlled asthma (fold change ≥ 1.5, FDR < 0.05). Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that PI3, with 18 connections, may be pivotal in asthma control.Conclusion: The study revealed significant alteration in the nasal lavage proteome in asthma without AR patients. Moreover, our results indicated a potential association between the expression of proteome in the upper airway and the level of asthma control. Specifically, PI3 appears to be a key role in the regulation of asthma without AR. Keywords: allergy, proteomic analysis, nasal lavage fluid, asthma control

Xueyan Shan,1,2 Yongpeng Ge3 1Department of Rheumatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Postgraduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Rheumatology, The Key Laboratory of Myositis, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, The Key Laboratory of Myositis, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Email gyp2016@163.comObjective: To investigate the clinical features, severity and prognosis of interstitial lung disease (ILD) in patients with mixed connective tissue disease (MCTD).Methods: We performed a retrospective study on clinical data of MCTD patients admitted to China-Japan Friendship Hospital between October 2012 and October 2022. Data including long-term follow-up were retrieved from medical records. We compared MCTD patients with and without ILD in terms of clinical features, laboratory and imaging findings, severity and treatment response.Results: A total of 59 patients were included, with a mean age of 46 years, among which 91.5% (n = 54) were females. Symptoms of pulmonary involvement were present in 44 patients (74.6%, 95% CI: 62.3– 84.9%). Based on lung high-resolution computed tomography (HRCT), ILD was diagnosed in 39 (66.1%) patients, among which 31 (79.5%) showed nonspecific interstitial pneumonia (NSIP) as the radiological pattern, 21 (53.9%) showed a reticulation pattern, while 24 (61.5%) showed ground glass opacity (GGO). Eight (13.6%) patients had pulmonary arterial hypertension (PAH), and 7 (11.9%) had pleural effusions. Based on pulmonary function tests (PFTs), 27 patients were divided into the mild 13 (48.1%) and moderate 14 (51.9%) groups. Multivariate analysis showed that gastroesophageal reflux (GER; OR=5.28, p=0.010) and cough (OR=4.61, p=0.043) were the predictive factors for ILD. With a median follow-up of 50 months, the mortality rate was 2.38%.Conclusion: ILD is common in MCTD patients, with NSIP as the common imaging pattern. Patients with GER and cough are relevant factors in the development of ILD. The majority of MCTD patients with ILD are mild to moderate in severity.Keywords: mixed connective tissue disease, interstitial lung disease, gastroesophageal reflux

Rui Zhang,1,2,&ast; Yingying Ge,3,&ast; Lu Xia,4 Yun Cheng5 1Department of Nursing, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Nursing, Fudan University, Shanghai, 200433, People’s Republic of China; 3Yijiangmen Community Health Service Center, Nanjing, 210009, People’s Republic of China; 4Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Xia, Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, 221 of Yanan West Road, Jingan District, Shanghai, 200040, People’s Republic of China, Tel +86 21-62483180-530401, Email yihaibeilu@126.com Yun Cheng, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of China, Tel +86 755-23516157, Email cloud2011930@qq.comBackgrounds: With the advent of the big data era, hospital information systems and mobile care systems, among others, generate massive amounts of medical data. Data mining, as a powerful information processing technology, can discover non-obvious information by processing large-scale data and analyzing them in multiple dimensions. How to find the effective information hidden in the database and apply it to nursing clinical practice has received more and more attention from nursing researchers.Aim: To look over the articles on data mining in nursing, compiled research status, identified hotspots, highlighted research trends, and offer recommendations for how data mining technology might be used in the nursing area going forward.Methods: Data mining in nursing publications published between 2002 and 2023 were taken from the Web of Science Core Collection. CiteSpace was utilized for reviewing the number of articles, countries/regions, institutions, journals, authors, and keywords.Results: According to the findings, the pace of data mining in nursing progress is not encouraging. Nursing data mining research is dominated by the United States and China. However, no consistent core group of writers or organizations has emerged in the field of nursing data mining. Studies on data mining in nursing have been increasingly gradually conducted in the 21st century, but the overall number is not large. Institution of Columbia University, journal of Cin-computers Informatics Nursing, author Diana J Wilkie, Muhammad Kamran Lodhi, Yingwei Yao are most influential in nursing data mining research. Nursing data mining researchers are currently focusing on electronic health records, text mining, machine learning, and natural language processing. Future research themes in data mining in nursing most include nursing informatics and clinical care quality enhancement.Conclusion: Research data shows that data mining gives more perspectives for the growth of the nursing discipline and encourages the discipline’s development, but it also introduces a slew of new issues that need researchers to address.Keywords: data mining, nursing, bibliometric analysis, global trends, hotspots

Qiu Huang,&ast; Yue Ge,&ast; Yu He, Jian Wu, Yonghua Tong, Haojie Shang, Xiao Liu, Xiaozhuo Ba, Ding Xia, Ejun Peng, Zhiqiang Chen, Kun Tang Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Chen; Kun Tang, Email zhqchen8366@163.com; tangsk1990@163.comAbstract: Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.Keywords: nanoparticles, cancer therapy, cancer-associated fibroblasts, drug delivery, cancer, nanomedicine

Tianyu Shi,&ast; Yitian Liu,&ast; Bo Ji, Jiajia Wang, Yunpeng Ge, Yang Fang, Yana Xie, Hongli Xiao, Le Wu, Yifei Wang School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Ji, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11 North Third Ring East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 139 1180 6678, Email jibo678@163.comPurpose: Local acupuncture has been found to have a good analgesic effect in rats with cervical spondylosis radiculopathy (CSR), but it lacks a regulatory effect on traditional Chinese medicine syndrome types of CSR. We proposed “Invigorating Qi and activating Blood” (IQAB) acupuncture, compared with Fenbid, and local electroacupuncture (LEA), to observe whether it has advantages in the protection of the CSR rat model and to elucidate its mechanism through the MAPK (mitogen-activated protein kinase) signaling pathway.Materials and Methods: Male Sprague-Dawley rats were randomly divided into six groups: control, sham, model, Fenbid, LEA, and IQAB. The CSR model was induced by inserting nylon sutures to compress the C4-T1 nerve root. The Fenbid group was treated with ibuprofen sustained-release capsules (15 mg/kg·d, ig). The LEA group received electroacupuncture at both C5 and C7 EX-B2 once a day. The IQAB group received acupuncture at both ST36 and BL17 based on the LEA group’s intervention. Mechanical allodynia and gait, morphological changes in the spinal cord, IL-6 and TNF-α levels, MAPKs phosphorylation ratio, monocyte chemoattractant protein-1 (MCP-1) levels in the spinal cord, and the expression of p-p38 in the spinal cord and its colocalization with neurons and glial cell activation markers were detected.Results: Mechanical allodynia, gait disorder, edema, reduced Nissl-positive cell numbers, and increased IL-6 and TNF-α levels in the spinal cord were observed in CSR rats. IQAB significantly alleviated these changes, and the effects were generally comparable to those of Fenbid. Meanwhile, the phosphorylation ratios of p38 and extracellular regulated protein kinase (ERK), co-expression of p-p38 with neuron/microglia, and MCP-1 levels in the spinal cord were markedly down-regulated by IQAB compared with those in CSR model rats.Conclusion: IQAB reduced p38-activation-related microglia activation and MCP-1 levels, thus alleviating pathological changes, inflammation levels in the local spinal cord, and pain behavior of CSR. Keywords: analgesia, mitogen activated protein kinases, inflammatory cytokine, chemokine, MCP-1

Lin Xia,1,&ast; Yu Liu,1,&ast; Zhonglu Yang,1 Yuguang Ge,1 Lu Wang,1 Yejun Du,1 Yinan Dong,2 Hui Jiang1 1Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, 110016, People’s Republic of China; 2Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, 110016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Jiang, Department of Cardiovascular Surgery, General Hospital of Northern Theater, Command, 83 Wenhua Road, Shenyang, Liaoning Province, 110016, People’s Republic of China, Tel +86-024-2889-7390, Fax +86-024-2889-7391, Email jianghsyzy@163.comPurpose: Upper hemisternotomy (UHS) has benefits over conventional full sternotomy because it ameliorates trauma during cardiac surgery. Owing to its challenging and technically demanding nature, this incision in acute type A aortic dissection (ATAAD) has rarely been reported. This study aimed to analyze the learning curve of total arch replacement (TAR) with moderate hypothermic circulatory arrest via a single UHS approach, which is necessary to guide the training of surgeons in adopting minimally invasive procedures.Patients and Methods: A total of 202 consecutive patients who were definitively diagnosed with ATAAD between July 2016 and June 2021 were enrolled in this retrospective analysis. Patients were divided into three groups based on cumulative sum plots for circulatory arrest time in chronological order. Perioperative characteristics were compared between the groups.Results: There was significant difference in the circulatory arrest time and cross-clamp time respectively among three groups (39.0 min vs 28.0 min vs 15.0 min, P < 0.001; 104.5 min vs 106.2 min vs 84.1 min, P < 0.001). The ventilation time and first 24-h chest tube drainage were statistically different among groups (35.5 h vs 24.0 h vs 19.0 h, P = 0.031; 220.0 mL vs 192.5 mL vs 125.5 mL, P = 0.043). No other clinical outcome was observed as significant difference.Conclusion: A cardiac surgeon can convert a conventional full sternotomy to a single UHS for TAR after experiencing a learning curve, to ensure patient safety. The mastery of this minimally invasive surgical technique may be beneficial for the prognosis of patients with ATAAD.Keywords: aneurysm, dissecting, cardiac surgical procedures, sternotomy, circulatory arrest, deep hypothermia induced, learning curve

Rui Yuan,1,&ast; Yuwen Zhang,1,&ast; Liqiong Liao,2 Yige Ge,1 Weichang Li,1 Qinghui Zhi1 1Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510030, People’s Republic of China; 2Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghui Zhi, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People’s Republic of China, Email zhiqingh@mail.sysu.edu.cn Weichang Li, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People’s Republic of China, Email liwch57@mail.sysu.edu.cnBackground: Dentin caries remains a significant public concern, with no clinically viable material that effectively combines remineralization and antimicrobial properties. To address this issue, this study focused on the development of a bio-inspired multifunctional nanogel with both antibacterial and biomineralization properties.Methods: First, p(NIPAm-co-DMC) (PNPDC) copolymers were synthesized from N-isopropylacrylamide (NIPAm) and 2-methacryloyloxyethyl-trimethyl ammonium chloride (DMC). Subsequently, PNPDC was combined with γ-polyglutamic acid (γ-PGA) through physical cross-linking to form nanogels. These nanogels served as templates for the mineralization of calcium phosphate (Cap), resulting in Cap-loaded PNPDC/PGA nanogels. The nanogels were characterized using various techniques, including TEM, particle tracking analysis, XRD, and FTIR. The release properties of ions were also assessed. In addition, the antibacterial properties of the Cap-loaded PNPDC/PGA nanogels were evaluated using the broth microdilution method and a biofilm formation assay. The remineralization effects were examined on both demineralized dentin and type I collagen in vitro.Results: PNPDC/PGA nanogels were successfully synthesized and loaded with Cap. The diameter of the Cap-loaded PNPDC/PGA nanogels was measured as 196.5 nm at 25°C and 162.3 nm at 37°C. These Cap-loaded nanogels released Ca2+ and PO43- ions quickly, effectively blocking dental tubules with a depth of 10 μm and promoting the remineralization of demineralized dentin within 7 days. Additionally, they facilitated the heavy intrafibrillar mineralization of type I collagen within 3 days. Moreover, the Cap-loaded nanogels exhibited MIC50 and MIC90 values of 12.5 and 50 mg/mL against Streptococcus mutans, respectively, with an MBC value of 100 mg/mL. At a concentration of 50 mg/mL, the Cap-loaded nanogels also demonstrated potent inhibitory effects on biofilm formation by Streptococcus mutans while maintaining good biocompatibility.Conclusion: Cap-loaded PNPDC/PGA nanogels are a multifunctional biomimetic system with antibacterial and dentin remineralization effects. This strategy of using antibacterial nanogels as mineral feedstock carriers offered fresh insight into the clinical management of caries.Graphical Abstract: Keywords: nanomaterial, mineralization, antibacterial materials, dentinal tubule occlusion, caries

Yang Zhou, Yongxiang Ge, Jian Liu, Weijian Shen, Hailiang Gu, Guochang Cheng Department of Hernia and Pediatric Surgery, Taizhou People’s Hospital, Taizhou Clinical Medical School of Nanjing Medical University, Taizhou City, Jiangsu Province, 225300, People’s Republic of ChinaCorrespondence: Guochang Cheng, Email chengguochang@hotmail.comBackground: Postoperative seroma is the most common minor complication after inguinal hernia repair surgery and can have negative consequences. The objective of this study was to identify potential risk factors for postoperative seroma.Methods: This study consecutively included 354 elderly patients with inguinal hernia who underwent laparoscopic Transabdominal preperitoneal Patch Plasty (TAPP). Seroma diagnosis was conducted by the same experienced surgeon based on the physical examinations combined with ultrasound. Risk factors for seroma were identified through univariate analysis and subsequently included in the binary multivariate logistic regression model.Results: A total of 40 patients experienced postoperative complications of seroma, with an incidence rate of 11.3% (40/354). The binary logistic regression analysis revealed that obesity (OR: 2.98, 95% CI: 1.20– 7.41, P = 0.018), disease duration ≥ 4.5 years (OR: 4.88, 95% CI: 2.14– 11.18, P < 0.001), albumin-fibrinogen ratio (AFR) level < 9.25 (OR: 6.13, 95% CI: 2.00– 18.76, P = 0.001), and modified frailty index (mFI) score ≥ 0.225 (OR: 6.38, 95% CI: 2.69– 15.10, P < 0.001) were four independent risk factors for postoperative seroma.Conclusion: Obesity, prolonged disease duration, decreased AFR level, and increased mFI score independently predict postoperative seroma after laparoscopic TAPP.Keywords: inguinal hernia, Transabdominal preperitoneal Patch Plasty, modified frailty index, albumin-fibrinogen ratio, risk factor

Aihua Sun,1,2,&ast; Xiaoyu Gou,1,2,&ast; Yongze Zhu,1 Huoyang Lv,1 Yumei Ge1– 3 1Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, 310059, People’s Republic of China; 3Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Ge, Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China, Email 11218070@zju.edu.cnAbstract: Disseminated ankle mycosis is a life-threatening systemic infection caused by the emerging opportunistic and lethal fungal pathogen Talaromyces marneffei which is more common in HIV-positive patients. However, an increasing number of infections are occurring in HIV-negative patients. Here, we report a case of Talaromyces marneffei infection in HIV-negative patient. A 50s HIV-negative male patient with fever, cough, bloody sputum expectoration, pulmonary sarcoidosis and body rashes was hospitalized at Zhejiang Provincial People’s Hospital. CT scanning showed pulmonary multiple nodules with apical bronchial occlusion, patchy infiltration and pathological biopsy demonstrated bronchiolitis obliterans with organized pneumonia and chronic active inflammation of lung tissue with infiltration of numerous lymphocytes, plasma cells, phagocytes and neutrophils. Laboratory tests revealed significantly increased white blood cells count 18.3 × 109/L, neutrophil count 15.34 × 109/L, monocyte count 0.66 × 109/L, platelet count 517 × 109/L, C-reactive protein 116 mg/L, erythrocyte sedimentation rate 112mm/h. The β-D-glucan test was negative (33.06 pg/mL) while fungal culture of broncho alveolar lavage fluid revealed colonies with temperature-dependent dimorphic growth character and Talaromyces marneffei was confirmed by ITS sequencing of the colonies. The patient exhibited radiological improvement and clinical recuperation after intravenously guttae of voriconazole. Talaromycosis in immunocompetent and HIV-negative individuals is relatively rare and is characterized by an insidious onset, various clinical manifestations, and is clinically challenging. Fungal culture and ITS sequencing are warranted for diagnosis Talaromyces marneffei infection. This is the first report on identification of Talaromyces marneffei infection in an HIV-negative patient with skin involvement by ITS sequencing in Zhejiang.Keywords: Talaromyces marneffei, pulmonary sarcoidosis, HIV-negative, voriconazole, ITS sequencing

Xin Zhao,1,2,&ast; Yue Ge,1,3,&ast; Yuan Zhang,1 WenJie Zhang,1 HongBin Hu,1 LuLan Li,1 Tong Sha,1 ZhenHua Zeng,1 Feng Wu,1 ZhongQing Chen1 1Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The First Clinical Medical School, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of School of Nursing, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ZhongQing Chen; Feng Wu, Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Tel +86 13503049103 ; +86 15915751705, Email zhongqingchen2008@163.com; wishuhappy@126.comBackground: Next-generation sequencing of the metagenome (mNGS) is increasingly used in pathogen diagnosis for infectious diseases due to its short detection time. The time for Oxford Nanopore Technologies (ONT) sequencing-based etiology detection is further shortened compared with that of mNGS, but only a few studies have verified the time advantage and accuracy of ONT sequencing for etiology diagnosis. In 2022, a study confirmed that there was no significant difference in sensitivity and specificity between ONT and mNGS in suspected community-acquired pneumonia patients, which there was no clinical study verified in patients with SHAP.Methods: From October 24 to November 20, 2022, 10 patients with severe hospital-acquired pneumonia (SHAP) in the Nanfang Hospital intensive care unit (ICU) were prospectively enrolled. Bronchoalveolar lavage fluid (BALF) was collected for ONT sequencing, mNGS, and traditional culture. The differences in pathogen detection time and diagnostic agreement among ONT sequencing, mNGS, traditional culture method, and clinical composite diagnosis were compared.Results: Compared with mNGS and the traditional culture method, ONT sequencing had a significant advantage in pathogen detection time (9.6± 0.7 h versus 24.7± 2.7 h versus 132± 58 h, P < 0.05). The agreement rate between ONT sequencing and the clinical composite diagnosis was 73.3% (kappa value=0.737, P < 0.05).Conclusion: ONT sequencing has a potential advantage for rapidly identifying pathogens.Keywords: Oxford Nanopore Technologies, Nanopore sequencing, metagenomic next-generation sequencing, severe hospital-acquired pneumonia, pathogen

Zhisheng Liu,1,&ast; Junling Zhang,2,&ast; Yunjie Ge,3 Mengli Huang,2 Ye Wang1 1Department of General Surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong People’s Republic of China; 2Medical Department, 3D Medicines Inc, Shanghai, People’s Republic of China; 3Department of Healthcare Internal Medicine, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Wang, Department of General Surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, 266033, People’s Republic of China, Email qdwangye@163.comBackground: Combined small cell lung cancer (c-SCLC) is a relatively rare subtype of SCLC, especially when SCLC is initially diagnosed and recurrent lesions are non-small cell lung cancer (NSCLC). Moreover, SCLC combined lung squamous cell carcinoma (LUSC) has few been reported.Case Presentation: Here, we report a 68-year-old man pathologically diagnosed as stage IV SCLC of right lung. With cisplatin and etoposide, the lesions were significantly reduced. It was not until three years later that a new lesion was found in his left lung, pathologically confirmed as LUSC. The patient was initiated with sintilimab based on high tumor mutational burden (TMB-H). Both lung tumors were stable, and PFS was 9.7 months.Conclusion: This case provides a meaningful reference for the third-line treatment of SCLC combined LUCS patients. This case also provides valuable information on the response to PD-1 inhibition of patients with c-SCLC based on TMB-H and better understanding of PD-1 therapy applications in the future.Keywords: c-SCLC, LUSC, PD-1 inhibitor, high tumor mutational burden

Fangyan Chen,1 Yabo Ge,1,2 Wenjun Xu,1 Junshuai Yu,1 Yiwen Zhang,1 Xingjian Xu,1 Shuqiong Zhang1 1Institute of Child Development, Jinhua Polytechnic, Jinhua, People’s Republic of China; 2College of Teacher Education, Zhejiang Normal University, Jinhua, People’s Republic of ChinaCorrespondence: Shuqiong Zhang, Institute of Child Development, Jinhua Polytechnic, 1188 Wuzhou Road, Jinhua, Zhejiang Province, 321007, People’s Republic of China, Email 20050507@jhc.edu.cnIntroduction: Kindergarten teachers who empathize with toddlers experience a great risk of burnout and emotional disturbance. This is referred to as compassion fatigue, in which teachers’ empathy experience is reduced. This study proposed a moderated mediation model to identify the risks of compassion fatigue and its protective factors for developing evidence-based clinical interventions.Methods: In this cross-sectional study, self-report measures were administered to 1049 kindergarten teachers to observe their mindsets toward children, motivation for teacher empathy, job stress, social support, and compassion fatigue. The PROCESS macro (SPSS 23.0) was used to assess the moderated mediation model.Results: The results demonstrated that motivation for teacher empathy mediated the negative relationship between kindergarten teachers’ mindsets toward children and compassion fatigue. Moreover, job stress and social support moderated the relationship between kindergarten teachers’ mindsets toward children and motivation for teacher empathy. However, this effect was not observed in the negative relationship between kindergarten teachers’ mindsets toward children and compassion fatigue.Conclusion: The proposed moderated mediation model was found to be valid. Furthermore, the study findings have practical implications for developing evidence-based interventions for addressing kindergarten teachers’ compassion fatigue.Keywords: compassion fatigue, mindsets toward children, empathic motivation, kindergarten teachers

Wanyuan Chen,1,2 Youqi Ji,2 Xin Hong,2 Yongze Zhu,2 Xiaoyu Gou,2 Mengyuan Chen,2 Huoyang Lv,2 Yumei Ge1– 3 1Department of Pathology, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, 310063, People’s Republic of ChinaCorrespondence: Yumei Ge, Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, No. 158, Shang-Tang Road, Gong-Shu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-0571-85893264, Email 11218070@zju.edu.cnAbstract: Aspergillus endocarditis (AE) is a highly fatal infection that can occur in heart valve replacement, pacemaker implantation and other heart surgeries, and early recognition and sufficient diagnosis are challenging. Here, we report the case of a 68-year-old male with a history of dilated cardiomyopathy and pacemaker implantation who had a repeated fever with failed antibacterial treatment and sterile blood culture. He developed endocarditis, and the culture and biopsy of vegetation tissue showed the abundant presence of septate hyphae, which was subsequently identified as Aspergillus fumigatus by internal transcribed spacer (ITS) sequencing. Although the patient had serious side effects from voriconazole, he had a good prognosis following surgery and prolonged caspofungin antifungal therapy of 42 consecutive days. We discuss the diagnosis and treatment strategy of AE, and recommend galactomannan assays and next-generation sequencing for a timely diagnosis. Early surgical intervention combined with prompt antifungal therapy appears significant for survival.Keywords: Aspergillus endocarditis, AE, Aspergillus fumigatus, vegetation, culture, fever

Huoyang Lv,1,&ast; Mengyuan Chen,1,2,&ast; Youqi Ji,1,3,&ast; Liya Pan,4 Xin Hong,1,5 Yumei Ge1– 6 1Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 4Center for Rehabilitation Medicine, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 5Department of Green Pharmaceutical Collaborative Innovation Center, School of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China; 6Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Ge, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China, Email 11218070@zju.edu.cnBackground: Nocardia cyriacigeorgica, which mainly causes pleuropulmonary and disseminated nocardiosis, has been proved to be one of the most common opportunistic pathogens in patients with immunodeficiency, but the cases that cause subcutaneous abscesses in normal individuals are rare and should be paid attention to.Methods: The clinical data of a patient with cutaneous nocardiosis caused by Nocardia cyriacigeorgica in Zhejiang Provincial People’s Hospital were retrospectively analyzed, including clinical manifestations, laboratory examinations, imaging examinations, medication and prognosis.Results: Magnetic resonance imaging (MRI) showed that there was a 26 mm × 73 mm abscess under the skin. The pus in the abscess was green. Gram staining showed positive branched rod-shaped and undivided hyphae. After culture, small wrinkle dry white small colonies were observed, and it was identified as Nocardia cyriacigeorgica by MALDI-TOF MS.Conclusion: We report the first case of a subcutaneous abscess caused by Nocardia cyriacigeorgica in an immunocompetent patient. Compared with cutaneous nocardiosis of which approximately 80% caused by Nocardia brasiliensis invasion, infection of Nocardia cyriacigeorgica is more insidious and latent, the features of the lesions are also unique. For this Nocardia cyriacigeorgica clinical isolate, the tested antibacterial drugs are generally sensitive and have an ideal prognosis after treatment with linezolid and timely debridement.Keywords: Nocardia cyriacigeorgica, subcutaneous abscess, nocardiosis, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, MALDI-TOF MS, debridement

Ting Yan,1,&ast; Chengming Shao,1,&ast; Minjie Zhang,1 Yongxing Ge,1 Tingting Chen,1 Dayang Chai2 1Department of Dermatology, The First People’s Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dayang Chai, Department of Cardiology, The First People’s Hospital of Taicang, The Affiliated Taicang Hospital of Suzhou University, No. 58 Changsheng Road, Taicang, 215400, People’s Republic of China, Tel/Fax +86-512-53101356, Email dayangchai@outlook.comBackground: The COVID-19 pandemic has considerable impact on health care system in the world directly. Although the pandemic has been effectively controlled, people’s lifestyle, stress of job, economic status and health conditions have all changed. Therefore, it is unclear whether the COVID-19 pandemic has affected the distribution of diseases in dermatology outpatient department, especially in the post-pandemic era and how we should respond to these changes.Objective: We aimed to assess the impact of the COVID-19 pandemic on diagnosis of dermatology outpatient department in eastern China.Methods: A pre-post study design was a retrospective study to assess the changes of diseases diagnoses from the outpatient department of Dermatology, Taicang first people’s hospital, Suzhou University, Suzhou, China in the 2021 (Post-COVID-19 pandemic) compared to the 2019 (Pre-COVID-19 pandemic). Statistical analysis was performed using the SPSS 23.0 and Excel 2010. The data were analysed by methods independent t-test and Pearson’s chi-square test. A two-sided p-value of < 0.05 was considered statistically significant.Results: A total of 67,994 patients in 2019 and 67,288 patients in 2021 were included in the study. During the pre-pandemic year, the most common diagnoses in the outpatient department were urticaria, fungal dermatitis, acne, herpes zoster, seborrheic dermatitis. Urticaria, acne, allergic dermatitis, fungal dermatitis, herpes zoster, were statistically more common in the post-pandemic period. Acne, animal-related diseases, allergic dermatitis, insect dermatitis, alopecia, and verruca vulgaris diagnoses were found to increase statistically during the post-pandemic period when compared with the pre-pandemic period.Conclusion: The COVID-19 pandemic had a minimal effect on the average yearly dermatology outpatients department visits, but the distribution of dermatology diagnoses was affected. As a result, governments and health departments may introduce innovative ways and training of medical teams according to the impact of the pandemic to ensure normal medical care.Keywords: COVID-19 pandemic, dermatology outpatient, dermatologic diseases, diagnostic distribution, pre-post study

Zhiguo Zhang,1,2,&ast; Fangda Fu,1,2,&ast; Yishan Bian,1,2,&ast; Huihao Zhang,1,2 Sai Yao,1,2 Chengcong Zhou,1,2 Yuying Ge,2 Huan Luo,3 Yuying Chen,4 Weifeng Ji,1 Kun Tian,1 Ming Yue,5 Weibin Du,6 Hongting Jin,1 Peijian Tong,1 Chengliang Wu,1,2 Hongfeng Ruan1,2 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 6Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure.Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression.Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence.Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation.Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.Graphical Abstract: Keywords: α-Chaconine, osteoarthritis, pyroptosis, nerve ingrowth, NF-κB signaling

Yuying Ge,1,&ast; Yuying Chen,2,&ast; Chijiao Guo,1,&ast; Huan Luo,3 Fangda Fu,1,4 Weifeng Ji,1,4 Chengliang Wu,1,4 Hongfeng Ruan1,4 1The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email wcl@zcmu.edu.cn Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnAbstract: Low back pain (LBP) is a common problem worldwide, resulting in great patient suffering and great challenges for the social health system. Intervertebral disc (IVD) degeneration (IVDD) is widely acknowledged as one of the key causes of LBP. Accumulating evidence suggests that aberrant pyroptosis of IVD cells is involved in the pathogenesis of IVDD progression, however, the comprehensive roles of pyroptosis in IVDD have not been fully established, leaving attempts to treat IVDD with anti-pyroptosis approaches questionable. In this review, we summarize the characteristics of pyroptosis and emphasize the effects of IVD cell pyroptosis on the pathological progression of IVDD, including secretion of cytokines, nucleus pulposus cell apoptosis and autophagy, accelerated extracellular matrix degradation, annulus fibrosus rupture, cartilage endplate calcification, vascularization, sensory and sympathetic fiber neoinnervation, and infiltrating lymphatic vessels. Finally, we discuss several interventions used to treat IVDD by targeting pyroptosis. This review provides novel insights into the crucial role of IVD cell pyroptosis in IVDD pathogenesis, and could be informative for developing novel therapeutic approaches for IVDD and LBP.Keywords: low back pain, intervertebral disc degeneration, pyroptosis, inflammasome, anti-pyroptotic approach

Yuan Ge1 &ast;, Gufeng Xu1 &ast;, Zhi Ruan,2 Yue Wang1 1Department of Ambulatory Surgery, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Wang, Women’s hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Email misswangyue@zju.edu.cn Zhi Ruan, Sir Run Run Shaw hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, People’s Republic of China, Email r_z@zju.edu.cnBackground: Listeria monocytogenes is a foodborne gram-positive bacterium which causes adverse pregnancy outcomes. Here, the genomic and phylogenetic characteristics of a L. monocytogenes isolate obtained from blood sample of a third trimester pregnant woman with stillbirth are investigated.Methods: Whole genome DNA of L. monocytogenes ST1 was sequenced with HiSeq X Ten platform. The NCBI Prokaryotic Genome Annotation Pipeline was used to annotate the genome sequence. The sequence type (ST) and antimicrobial resistance genes were then identified. The core genome multilocus sequence typing (cgMLST) analysis with other closely related L. monocytogenes stored in the NCBI GenBank database was performed using BacWGSTdb 2.0.Results: The complete genome sequence of L. monocytogenes ST1 is made up of 20 contigs totaling 2,914,725 bp, with 2886 protein-coding sequences and a GC content of 37.9%. Fosfomycin [fosX], Lincosamide antibiotic [lin] and peptide antibiotic [mprF] were discovered as antimicrobial resistance genes. In silico serogroup typing prediction revealed that L. monocytogenes ST1 belonged to serotype IVb. The closest relative of L. monocytogenes ST1, obtained from Poland in 2015, differs by only 15 cgMLST alleles.Conclusion: We identified a L. monocytogenes ST1 strain from blood sample of a woman with third trimester stillbirth in China. These discoveries would aid in our understanding of the genomic characteristics, mechanisms of antimicrobial resistance, and epidemiological features of this pathogen.Keywords: whole genome sequencing, Listeria monocytogenes, stillbirth

Yumei Ge,1,&ast; Xiaoyu Gou,1,&ast; Xiaoyan Dong,1,2 Yumeng Peng,1,3 Fangfang Yang4 1Department of Laboratory Medicine Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2The Second Medical College, Zhejiang Chinese Medical University, Hangzhou, 310014, People’s Republic of China; 3Department of Clinical Laboratory Diagnostics, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 4Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, 621000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangfang Yang, Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan mental health center), Mianyang, Sichuan, 621000, People’s Republic of China, Email yhge2159@163.comPurpose: At present, there is no gold standard or unified standard for the diagnosis of neurosyphilis, and the rate of misdiagnosis is high. The diagnosis of neurosyphilis is still challenging. This study compared the clinical indicators between neurosyphilis and latent syphilis infection in the central nervous system. The purpose of this study was to provide evidence for the differential diagnosis and prognosis of patients with neurosyphilis and latent syphilis infection of the central nervous system.Methods: The clinical data of 59 patients with neurosyphilis and 30 patients with latent syphilis infection in the nervous system from 2008 to 2021 were analyzed. The cerebrospinal fluid and serum biochemical markers were evaluated for all patients.Results: CSF-nucleated cells, CSF-TRUST, CSF-totalprotein and CSF-IgG (P< 0.001) were significantly different between neurosyphilis and latent syphilis infection in the central nervous system. CSF-TRUST titer was positively correlated with D-D concentration (r = 0.274, P < 0.05), sodion (r =0.251, P < 0.05), respectively. Glucose concentration is the most unreliable in the diagnosis of neurosyphilis (AUC=0.445, P=0.395), and TRUST combined with nucleated cells and total protein is the most accurate in the diagnosis of neurosyphilis (AUC=0.989, P< 0.001).Conclusion: The combination of TRUST, nucleated cell count and totalprotein detection in CSF can distinguish the patients with neurosyphilis and latent syphilis infection in the central nervous system, which has a significant diagnostic value.Keywords: neurosyphilis, latent syphilis infection, diagnosis, detection index

Yanjun Ge,1,&ast; Yuchen Zhang,1,&ast; Kong-Nan Zhao,2,3 Haiyan Zhu1,2 1Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2School of Basic Medical Science, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland, Australia&ast;These authors contributed equally to this workCorrespondence: Haiyan Zhu, Shanghai First Maternity and Infant Hospital, No. 2699 Gaokexi Road, Shanghai, 200092, People’s Republic of China, Tel +86 13758465255, Email zhuhaiyandoc@sina.comAbstract: Currently, therapeutic methods for advanced and recurrent cervical cancer patients are limited and unsatisfactory. Immunotherapy is a promising approach for cancer treatment. However, its investigation and application in cervical cancer remain slow. Although pembrolizumab is a remarkable milestone as the first anti-PD-1 mAb approved by the FDA for treating cervical cancer, it shows relatively low response rate. It is noticed that multiple novel immune checkpoints have emerged in recent years, such as CTLA-4, TIGIT, LAG-3, TIM-3, and A2AR. Accumulated studies have suggested that strategies combining the PD-1/PD-L1 inhibitors and different immunotherapies or biotherapies could enhance the antitumor efficacy in human cancers. In this review article, we provide an overview of anti-PD-1/PD-L1-based immunotherapy in cervical cancer treatment. We further summarize the developmental strategies of different immunotherapies or biotherapies combined with PD-1/PD-L1 blockade for treating cervical cancer. We also discuss how these new combined therapies increase the therapeutic benefit gained from experimental evidence in cervical cancer.Keywords: cervical cancer, immunotherapy, PD-1/PD-L1, combinatorial strategy, mechanism, clinical practice

Ke Zhang,&ast; Songwei Feng,&ast; Yu Ge, Bo Ding, Yang Shen Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen, Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China, Email shenyang@seu.edu.cnPurpose: Mucinous ovarian cancer (MOC) is a rare histological type of EOC. In order to guide the clinical diagnosis and management of MOC patients, we constructed and verified a nomogram for the estimation of overall survival in patients with MOC.Patients and Methods: We collected 494 patients with MOC diagnosed from 2010 to 2015 in SEER database, and the following main inclusion criteria were used: (1) patients whose MOC was confirmed by pathology; (2) patients without a history of primary other cancer. Subsequently, we performed randomized grouping (6:4) and Cox hazard regression analysis in the training group. Subsequently, the nomogram was established. A variety of indicators were used to validate the prognosis value of nomogram, including the C-index, area under the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Moreover, Kaplan–Meier analysis was used to compare the survival results among different risk subgroups.Results: Cox hazard regression analysis revealed that age, grade, FIGO stage and log odds of positive lymph nodes stage were independent risk factors for patients with MOC. In the training group, the C-index of the nomogram was 0.827 (95% CI: 0.791– 0.863) and the areas under the curve (AUC) predicting the 1-, 3- and 5-year survival rate were 0.853 (95% CI: 0.791– 0.915), 0.886 (95% CI: 0.852– 0.920) and 0.815 (95% CI: 0.766– 0.864), respectively. The calibration curve revealed that the nomogram of the 1-, 3- and 5-year survival rate was consistent with the actual fact. Patients with high risk had a poorer prognosis than those with low risk (P < 0.001). DCA revealed that the nomogram had the best clinical value than other classical prognostic markers. Similarly, nomogram had excellent prognostic ability in the testing group.Conclusion: The nomogram was constructed to predict overall survival in patients with MOC, which had the significance for clinical evaluation.Keywords: mucinous ovarian cancer, SEER database, nomogram, prognosis, log odds of positive lymph nodes (LODDS) stage

Yuhuan Shen,1,&ast; Xiaoyan Dong,2,&ast; Jinlin Liu,1 Huoyang Lv,1 Yumei Ge1,3 1Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Laboratory, Ningbo Blood Centers, Ningbo, Zhejiang, People’s Republic of China; 3Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Ge, Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158, Shang-Tang Road, Gong-Shu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-0571-85893264, Email 11218070@zju.edu.cnBackground: Interleukin-26 (IL-26) is an atypical proinflammatory cytokine due to its binding to circulating double-stranded DNA and direct antibacterial activity. Although IL-26 has been confirmed to be involved in the pathophysiology of cancer, chronic inflammatory diseases and infections, the diagnostic and prognostic values of IL-26 levels in syphilis patients are not clear. This study aimed to investigate IL-26 levels in different stages of syphilis progression.Methods: A total of 30 healthy controls and 166 patients with syphilis at different stages of disease progression were enrolled. Serum IL-26 levels were quantified in accordance with the protocols of RayBio® Human Interleukin-26 Enzyme Linked Immunosorbent Assay (ELISA) kits. Clinical laboratory diagnostic parameters and blood analysis data were detected and collected according to clinical medical laboratory standards.Results: The levels of serum IL-26 were significantly higher in neurosyphilis patients than in healthy subjects (6.87 (4.36, 12.14) and 1.67 (0.09, 4.89) pg/μL, respectively; &ast;&ast;&ast;&ast;p < 0.0001), latent syphilis (1.48 (0.40, 2.05) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001), seroresistant syphilis (0.81 (0.20, 2.91) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) and secondary syphilis (1.66 (0.41, 4.25) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) with data presented as the median with interquartile range. The concentration of serum IL-26 was most sensitive to serum low-density lipoprotein concentration (r = − 0.438, &ast;&ast;p = 0.004) in latent syphilis, urine epithelial cells (r = 0.459, &ast;&ast;p = 0.003) in seroresistant syphilis, and serum creatinine levels (r = 0.463, &ast;&ast;p = 0.004) and urea creatinine ratio levels (r = 0.500, &ast;&ast;p = 0.008) in secondary syphilis patients. There was no significant correlation with the concentration of IL-26 and toluidine red unheated serum test (TRUST) titers in each type of syphilis patient.Conclusion: Circulating IL-26 in serum displays diagnostic potential in the progression of neurosyphilis and warrants further evaluation in clinical trials.Keywords: neurosyphilis, interleukin-26, IL-26, disease progression, biomarker, diagnosis

Ming Yang,1– 3 Qi Zhang,1– 3 Yizhong Ge,1– 4 Meng Tang,1– 3 Chunlei Hu,1– 3 Ziwen Wang,1– 3 Xi Zhang,1– 3 Mengmeng Song,1– 3 Guotian Ruan,1– 3 Xiaowei Zhang,1– 3 Tong Liu,1– 3 Hailun Xie,1– 3 Heyang Zhang,1– 3 Kangping Zhang,1– 3 Qinqin Li,1– 3 Xiangrui Li,1– 3 Xiaoyue Liu,1– 3 Shiqi Lin,1– 4 Hanping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, People’s Republic of China; 4The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Hanping Shi, Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China, Tel/Fax +86 10 6392 6983, Email shihp@ccmu.edu.cnPurpose: The incidence, progression, and prognosis of cancer could be affected by inflammation and nutrition. Female patients have different inflammatory and nutritional states depending on their age and tumor types. It is important to screen for suitable prognostic indicators in female patients with cancer of different ages and tumor types.Patients and Methods: Baseline clinicopathologic and laboratory characteristics of 1502 female patients with cancer were obtained from a multicenter cohort study. Concordance indices (C-indices) were used to evaluate the prediction accuracy of following inflammation- and nutrition-based indicators: advanced lung cancer inflammation index (ALI), systemic immune inflammation index (SII), modified geriatric nutritional risk index (mGNRI), albumin-to-globulin ratio (AGR), prognostic nutritional index (PNI), lymphocyte-to-C-reactive protein ratio (LCR), controlling nutritional status score (CONUT), modified Glasgow prognostic score (mGPS), and lymphocyte-to-C-reactive protein score (LCS).Results: The most suitable indicators in different female populations with cancer had C-indices as follows: LCR (0.668; 95% CI, 0.644– 0.693) for all females; AGR (0.681; 95% CI, 0.619– 0.743) for young females; LCR (0.667; 95% CI, 0.628– 0.706) for middle-aged females; ALI (0.597; 95% CI, 0.574– 0.620) for elderly females; LCR (0.684; 95% CI, 0.621– 0.747) for females with reproductive system cancer; and ALI (0.652; 95% CI, 0.624– 0.680) for females with non-reproductive system cancer.Conclusion: The most suitable indicators for the different female populations with cancer are summarized as follows: LCR for all females, AGR for young females, LCR for middle-aged females, ALI for elderly females, LCR for females with reproductive system cancer, and ALI for females with non-reproductive system cancer.Keywords: female, cancer, prognosis, inflammation, nutrition

Wei Cheng, Fen Li, Jing Tian, Xi Xie, Jin-Wei Chen, Xiao-Fei Peng, Qi Tang, Yan Ge Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaCorrespondence: Yan Ge, Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China, Email geyan2003@csu.edu.cnAbstract: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by dermatological disorders and osteoarticular inflammatory lesions. This article reviews the application of biologics and other treatments based on the therapeutic target and the size of molecules in SAPHO syndrome. We found that drugs, especially biologics, have different effects on bone, joint, and skin damage. This may relate to the different inflammatory pathways involved in the osteoarticular and cutaneous symptoms in SAPHO patients. In this study, we provide stratified medication recommendations for SAPHO syndrome. Patients with osteoarticular symptoms can consider tumor necrosis factor blockers, JAK inhibitor, interleukin (IL)-1 inhibitor, and IL-17 inhibitor. Patients with cutaneous symptoms should consider IL-17 and JAK inhibitors. Apremilast, Tripterygium wilfordii Hook F, and bisphosphonates are other effective treatments.Keywords: SAPHO, osteoarticular symptoms, cutaneous symptoms, immune pathway pathways, biologics, targeted small molecule compounds

Shudong Hu,1,2,&ast; Heng Zhang,1,2,&ast; Yanqi Zhong,3,&ast; Enock Adjei Agyekum,2,&ast; Zongqiong Sun,1 Yuxi Ge,1 Jie Li,4 Weiqiang Dou,5 Junlin He,6 Hong Xiang,7 Yuandong Wang,8 Xiaoqin Qian,2 Xian Wang2 1Department of Radiology, Affiliated Hospital, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Ultrasound, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 4Department of Interventional Radiology, Affiliated Hospital, Jiangnan University, Wuxi, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of China; 6Department of Radiology, Tinglin Hospital of Jinshan District, Shanghai, People’s Republic of China; 7Department of Pediatric, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 8Department of Radiotherapy, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Wang; Xiaoqin Qian, Tel +86 13952808812 ; +86 13813186750, Email wangxian8812@126.com; yz_tyz1030@126.comPurpose: To explore the separate diagnostic value of preoperative ultrasound (US), magnetic resonance imaging (MRI), and the combination of US and MRI in extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC).Materials and Methods: This retrospective study was approved by the Affiliated People’s Hospital of Jiangsu University review board. A total of 158 PTC patients with ETE received preoperative US and MRI examination and underwent surgery between May 2014 and December 2018 in Affiliated People’s Hospital of Jiangsu University. For each case, the US and MRI features of ETE were retrospectively and independently investigated by two radiologists. The clinical assessment for each case was implemented, respectively, using US imaging only, MRI only, and a combination of both modalities at three different time points with one-month intervals.Results: The diagnostic accuracies of US, MRI, and the combined set for T3 (minimal ETE) were 91.7% (88/96), 74.0% (71/96), and 97.9% (94/96), respectively, indicating a significantly different performance (P < 0.001). The diagnostic accuracies for T4 (extensive ETE) were 62.9% (39/62), 87.1% (54/62), and 93.5% (58/62), respectively. The difference between the three methods for T4 was statistically significant (P = 0.000). The diagnostic accuracies for overall ETE were 80.4% (127/158), 79.1% (125/158), and 96.2% (152/158), respectively. The difference between the three methods for ETE was statistically significant (P = 0.001).Conclusion: This study suggests that ETE can be predicted most accurately by the combination of preoperative US and MRI.Keywords: thyroid cancer, ultrasonography, magnetic resonance imaging, neoplasm staging

Hailun Xie,1– 3,&ast; Guotian Ruan,1– 3,&ast; Qi Zhang,1– 3,&ast; Yizhong Ge,1– 3 Mengmeng Song,1– 3 Xi Zhang,1– 3 Xiaoyue Liu,1– 3 Shiqi Lin,1– 3 Xiaowei Zhang,1– 3 Xiangrui Li,1– 3 Kangping Zhang,1– 3 Ming Yang,1– 3 Meng Tang,1– 3 Minghua Cong,4 Hanping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, People’s Republic of China; 4Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanping Shi, Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China, Email shihp@ccmu.edu.cnPurpose: The nutritional risk index (NRI) and handgrip strength (HGS) are useful indicators of nutritional and physical status, respectively, both of them can predict the prognosis of many cancers; however, the predictive accuracy of a single indicator is unsatisfactory. Whether the combination of NRI and HGS could enhance the stratification of the prognosis of patients with cancer cachexia.Patients and Methods: The study population was randomly divided into training and validation cohorts. We combined NRI and HGS and constructed the NRI–HGS score. Restricted cubic splines were used to assess the associations between NRI, HGS, and all-cause mortality. The Kaplan–Meier method was used to calculate the survival probability of the patients. The Cox proportional hazards risk model was used to analyze survival and prognostic factors.Results: Low NRI and low HGS were independent predictors of poor prognosis in patients with cancer cachexia. The NRI–HGS score showed a better prognostic stratification than either NRI or HGS. The co-occurrence of low NRI and low HGS was associated with an approximately 1.8-fold increased risk of mortality. The NRI–HGS score could effectively distinguish patients with a poor prognosis at different pathological stages. Furthermore, we constructed a novel prognostic nomogram based on NRI and HGS. The concordance index and calibration plot confirmed that the nomogram had good prognostic accuracy. The area under the receiver operating characteristic curve of the nomogram reached > 0.8, which was much higher than that of the traditional tumor–node–metastasis staging system. The nomogram provided better prognostic stratification for patients with cancer cachexia.Conclusion: Low NRI and low HGS are independent prognostic indicators in cancer cachexia. The combination of NRI and HGS improve prognostic stratification for patients with cancer cachexia. Our study suggests combining nutritional and physical status in future cachexia research.Keywords: nutritional risk index, handgrip strength, cancer cachexia, prognostic

Wenpeng You,1,2 Renata Henneberg,1 Arthur Saniotis,1,3 Yanfei Ge,4,5 Maciej Henneberg1,6 1Biological Anthropology and Comparative Anatomy Research Unit (BACARU), Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; 2FAPAB Research Center, Avola SR, 96012, Sicily, Italy; 3Department of Anthropology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; 4Australian Graduate School of Management (Executive MBA Candidate), University of New South Wales, Sydney, New South Wales, Australia; 5Community Services, Health & Lifestyle, Technical and Further Education, Adelaide, South Australia, 5000, Australia; 6Institute of Evolutionary Medicine, University of Zürich, Zurich, SwitzerlandCorrespondence: Wenpeng You, Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia, Email wenpeng.you@adelaide.edu.auBackground: The association between a plant-based diet (vegetarianism) and extended life span is increasingly criticised since it may be based on the lack of representative data and insufficient removal of confounders such as lifestyles.Aim: We examined the association between meat intake and life expectancy at a population level based on ecological data published by the United Nations agencies.Methods: Population-specific data were obtained from 175 countries/territories. Scatter plots, bivariate, partial correlation and linear regression models were used with SPSS 25 to explore and compare the correlations between newborn life expectancy (e(0)), life expectancy at 5 years of life (e(5)) and intakes of meat, and carbohydrate crops, respectively. The established risk factors to life expectancy – caloric intake, urbanization, obesity and education levels – were included as the potential confounders.Results: Worldwide, bivariate correlation analyses revealed that meat intake is positively correlated with life expectancies. This relationship remained significant when influences of caloric intake, urbanization, obesity, education and carbohydrate crops were statistically controlled. Stepwise linear regression selected meat intake, not carbohydrate crops, as one of the significant predictors of life expectancy. In contrast, carbohydrate crops showed weak and negative correlation with life expectancy.Conclusion: If meat intake is not incorporated into nutrition science for predicting human life expectancy, results could prove inaccurate.Keywords: meat intake, ecological study, life expectancy, vegetarian, evolution, agriculture

Younian Xu,1 Yangyang Ge,1 Miaomiao Zhou,2 Zongze Zhang2 1Anesthesiology Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Anesthesiology Department, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Miaomiao ZhouAnesthesiology Department, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, People’s Republic of ChinaTel/Fax +86 027-67812903Email 879475227@qq.comBackground: Large ischemic stroke provokes an inflammatory response, promoting the release of norepinephrine (NE) by intensifying the sympathetic nervous system. This augmented sympathetic outflow was deemed to act on β 2-adrenergic receptors (β 2-ARs) expressed by immune cells, rendering organisms to post-stroke infections, like pneumonia. To clarify this issue, we introduced selective β 2-ARs agonist clenbuterol (CLEN) to stroke mice to investigate how β 2-adrenergic signaling augmentation after stroke affects immune response and post-stroke outcomes, including central and peripheral.Methods: We developed a middle cerebral artery occlusion (MCAO) stroke model in mice to induce large ischemic stroke and administered CLEN 24 h after the onset of MCAO stroke. First, we assessed infarct volume and NE levels in plasma and spleen 3ds later. Next, the immune state was identified by analyzing the spleen index, immune cell populations, and immune cytokines. Finally, peripheral outcomes were assessed by measuring signs of pneumonia, such as pathology, bacterial burden, and lung cytokines.Results: We report that CLEN treatment 24 h after MCAO stroke causes an enlarged infarct volume and a decrease in NE levels at 3ds after stroke. Consistent with a reduction of total T cells, T helper cells, and increase of cytotoxic T cells, the immune milieu after CLEN treatment presents an anti-inflammatory landscape, showing raised expression of anti-inflammatory cytokines: IL-4, IL-10, and TGF-β 1, and decreased expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IFN-γ, with a dramatically reduced percentage of Gr-1+ neutrophils and B cells but an increased percentage of NK cells. In our study, CLEN treatment results in no higher risk of pneumonia but relieves bacterial burden, inhibits or limits pneumonia, and diminishes TNF-α expression in lung tissues after MCAO.Conclusion: We identified increased β 2-adrenergic signaling after MCAO stroke, inhibits or limits post-stroke pneumonia but enlarges stroke volume in MCAO mice. Thus, careful consideration must be taken to improve post-stroke outcomes by manipulation over β 2-adrenergic receptors.Keywords: ischemic stroke, β 2-adrenergic receptor, infarct, pneumonia, immunity, sympathetic

Chao Zhu,1 Yongmei Yu,2 Shihui Wang,2 Xia Wang,1 Yankun Gao,1 Cuiping Li,1 Jianying Li,3 Yaqiong Ge,3 Xingwang Wu1 1Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China; 3GE Healthcare China, Shanghai, 210000, People’s Republic of ChinaCorrespondence: Xingwang WuDepartment of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, Anhui Province, 230022, People’s Republic of ChinaTel +86 138 56919001Email duobi2004@126.comPurpose: To establish a clinical radiomics nomogram to differentiate Crohn’s disease (CD) from intestinal tuberculosis (ITB).Patients and Methods: Ninety-three patients with CD and 67 patients with ITB were recruited (111 in training cohort and 49 in test cohort). The region of interest (ROI) for the lesions in the ileocecal region was delineated on computed tomography enterography and radiomics features extracted. Radiomics features were filtered by the gradient boosting decision tree (GBDT), and a radiomics score was calculated by using the radiomics signature-based formula. We constructed a clinical radiomics model and nomogram combining clinical factors and radiomics score through multivariate logistic regression analysis, and the internal validation was undertaken by ten-fold cross validation. Analyses of receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the prediction performance. DeLong test was applied to evaluate the performance of the clinical, radiomics and combined model.Results: The clinical radiomics nomogram, which was based on the 9 radiomics signature and two clinical factors, indicated that the clinical radiomics model had an area under the ROC curve (AUC) value of 0.96 (95% confidence interval [CI]: 0.93– 0.99) in the training cohort and 0.93 (95% CI: 0.86– 1.00) in validation cohort. The clinical radiomics model was superior to the clinical model and radiomics model, and the difference was significant (P = 0.006, 0.004) in the training cohort. DCA confirmed the clinical utility of clinical radiomics nomogram.Conclusion: CTE-based radiomics model has a good performance in distinguishing CD from ITB. A nomogram constructed by combining radiomics and clinical factors can help clinicians accurately diagnose and select appropriate treatment strategies between CD and ITB.Keywords: Crohn’s disease, intestinal tuberculosis, computed tomography, radiomics, nomogram

Huihao Zhang,1,&ast; Sai Yao,1,&ast; Zhiguo Zhang,1,&ast; Chengcong Zhou,1 Fangda Fu,1 Yishan Bian,1 Huan Luo,2 Yan Li,1 Shuxin Yan,1 Yuying Ge,1 Yuying Chen,3 Kunyu Zhan,4 Yanzhi Ge,1 Zuxiang Chen,1 Ming Yue,5 Xiaofeng Li,6 Weibin Du,1,7 Hongting Jin,1 Peijian Tong,1 Hongfeng Ruan,1,8 Chengliang Wu1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopedics and Traumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Research Institute of Orthopedics, The Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 8Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Peijian TongInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail rhf@zcmu.edu.cn; peijiantongzjtcm@163.comPurpose: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation.Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology.Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD.Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.Keywords: intervertebral disc degeneration, Liuwei Dihuang decoction, network pharmacology, pharmacological mechanisms, apoptosis

Jian Chen, Shu Li, Yan Ge, Jin Kang, Jia-fen Liao, Jin-feng Du, Jing Tian, Xi Xie, Fen Li Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Fen LiDepartment of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, No. 139 Ren Min Middle Road, Changsha, 410011, People’s Republic of ChinaEmail lifen0731@csu.edu.cnBackground: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study.Methods: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥ 1.2 folds change or ≤ 0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs.Results: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis.Conclusion: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.Keywords: rheumatoid arthritis, proteomics, effectiveness, disease modifying antirheumatic drugs, serotransferrin

Li Song,1 Yan Ge,2 Xuyang Zhang3 1Institute of Arts and Humanities, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 3School of Humanities, Shanghai Institute of Technology, Shanghai, 201418, People’s Republic of ChinaCorrespondence: Li SongInstitute of Arts and Humanities, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of ChinaTel +86-18585059965Fax +86-21-62932801Email rediscovering@163.comPurpose: WeChat is China’ biggest social media platform. In addition to instant messaging, it has a great many useful functions that can help Chinese citizens adapt to an increasingly digitized society. This study aimed to examine the effect of WeChat use on the subjective well-being (SWB) of Chinese older adults living alone, and how the effect could occur.Participants and Methods: A total of 415 Chinese older adults living alone participated in the survey. Participants filled out questionnaires (scales) measuring their SWB, proficiency in WeChat use, social activity levels and self-esteem respectively. Mean scores of SWB were used to determine the difference in SWB between the users and non-users, and correlation test was performed to find out the association between proficiency in WeChat use and SWB among the users.Results: The mean score of WeChat users was 34.68 (SD = 7.301), significantly higher than that of the non-users, which was 32.73 (SD = 7.168) (t = 2.741, p = 0.006). Among the users, the more proficient in WeChat use one was, the higher their SWB score (r = 0.458, p < 0.01). The results combined to demonstrate that WeChat use has a positive effect on the SWB of Chinese older adults living alone. The findings also showed that the increase in SWB was obtained through the mediation of intergenerational support and social activities.Conclusion: This study suggests that WeChat use by Chinese older adults living alone could increase their intergenerational support and social activities; the increased intergenerational support and social activities then enhance the SWB of Chinese older adults living alone.Keywords: WeChat, older adults, subjective well-being, intergenerational support, social activity, self-esteem

Xijiao Yu,1,2,&ast; Yuxuan Wang,3,&ast; Xiaoliang Liu,3 Yuwei Ge,3,4 Shanyong Zhang1 1Department of Oral Surgery, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 2Central Laboratory, Department of Endodontics, Jinan Stomatological Hospital, Jinan, Shandong, People’s Republic of China; 3Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuwei Ge; Shanyong Zhang Email geyw2000@163.com; zhangshanyong@126.comPurpose: Mesoporous hydroxylapatite (MHAP) might be important for bone regeneration, and ursolic acid (UA) has anti-inflammatory effects. Accordingly, we developed, for the first time, ursolic acid-loaded MHAP-chitosan (MHAP-CS-UA) scaffolds to treat bone defects.Methods: In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, flow cytometry, immunofluorescence, alizarin red staining, and Western blotting, we test the anti-inflammatory and osteo-inductive properties of scaffolds. In vivo, we verify osseointegration ability and bone regeneration.Results: The MHAP is a rod-shaped structure with a length of 100∼ 300nm and a diameter of 40∼ 60nm. The critical structure gives the micro-scaffold a property of control release due to the pore sizes of 1.6∼ 4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably inhibit the polarization of macrophages to pro-inflammatory macrophages (M1 type) and promote the expression of osteogenic-related genes (COL1, ALP and OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1).Conclusion: The MHAP-CS-UA scaffolds have good anti-inflammatory, osseointegration, osteo-inductivity and bone regeneration. And they will be the novel and promising candidates to cure the bone disease.Keywords: mesoporous hydroxylapatite, polarization, bone regeneration, ursolic acid, drug delivery

Yuan Ge,1 Chunhong Shi,2 Bin Wu,1 Yannan Liu,3 Ling Chen,1 Yuegui Deng4 1School of Nursing, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of China; 2School of Nursing, Xiangnan University, Chenzhou, 423000, People’s Republic of China; 3Nursing School, Hunan University of Medicine, Huaihua, 418000, People’s Republic of China; 4Nursing Department, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530022, People’s Republic of ChinaCorrespondence: Chunhong ShiSchool of Nursing, Xiangnan University, 889 Chenzhou Avenue, Suxian District, Chenzhou, 423000, Hunan, People’s Republic of ChinaTel +86 15907354840Fax +86-735-2325007Email shichunhong@xnu.edu.cnPurpose: This study explored the impact of COVID-19 on the mental health and adaptation of behavior of Zhuang women in China to provide more specific guidance for the social and medical practice of pregnant women during public health emergencies.Participants and Methods: This cross-sectional study recruited 446 pregnant Zhuang women from obstetric outpatient clinics in four tertiary hospitals and online maternity schools in Nanning, Guangxi, between February 24 and March 1, 2020. Self-designed questionnaires and the Self-Rating Anxiety Scale were used.Results: During the COVID-19 pandemic, the prevalence rate of anxiety among women was 36.77%, and some adaptation of behavior was observed. Logistic regression analysis showed that pregnant women who had an annual household income of less than $7,000, were primiparous, went out for prenatal examination, wanted to self-monitor during pregnancy but did not know how to do it, believed that they should be strictly isolated at home and cancel prenatal examinations, and expected to receive pregnancy healthcare through teleconsultation services showed a higher risk of anxiety. Nevertheless, pregnant Zhuang women who were 22– 35 years old, undergraduate-educated, and in their second trimester were less likely to suffer from anxiety.Conclusion: The COVID-19 pandemic has a significant psychological impact on pregnant women from ethnic minorities. Factors related to quarantine and social isolation policies appear to drive changes in behaviors and anxiety disorders. Multidisciplinary mental health services and culturally sensitive interventions are necessary for minority pregnant women, especially for low-income primiparous women in the first or third trimester.Keywords: pregnant women, minority, psychological, behavior, coronavirus disease 2019

Xicheng Wang,1 Jianfeng Zhou,2 Yan Li,1 Yuping Ge,2 Yanping Zhou,2 Chunmei Bai,2 Lin Shen1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 2Department of Oncology, Peking Union Medical College Hospital, Beijing 100032, People’s Republic of ChinaCorrespondence: Lin ShenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, No. 52, Fu Cheng Road, Hai Dian District, Beijing, People’s Republic of ChinaTel +86-010-88156175Fax +86-010-88196561Email linshenpku@163.comChunmei BaiDepartment of Oncology, Peking Union Medical College Hospital, No. 41, Da Mu Cang Hutong, Xi Cheng District, Beijing, People’s Republic of ChinaTel/ Fax +86-010-69158315Email baichunmei1964@163.comPurpose: Trifluridine/tipiracil (FTD/TPI) is approved in Japan, the United States (US), and Europe for metastatic colorectal cancer (mCRC) refractory to standard therapies. This Phase 1b open-label study focused on the pharmacokinetic (PK) and toxicity profiles of FTD/TPI in Chinese patients with solid tumors.Methods: Patients with definitive histologically or cytologically confirmed advanced/metastatic solid tumors refractory to standard treatments were enrolled. FTD/TPI (35 mg/m2) was administered orally twice daily for five consecutive days, followed by a 2-day recovery. Treatment was repeated for five consecutive days, followed by a 16-day recovery. The primary objective was to assess PK characteristics of FTD, 5-trifluoromethyl-2,4 (1H,3H)-pyrimidinedione (FTY; an inactive form of FTD), and TPI, calculated from plasma concentrations. Additionally, these PK values were compared with those from similar Phase 1 studies in patients from Japan and the US, using Tukey–Kramer’s honestly significant difference (HSD) multiple comparison tests. Safety and preliminary efficacy of FTD/TPI were assessed.Results: Fifteen patients (12 males, three females) were enrolled, most with CRC (87%). Geometric mean analysis showed that maximum plasma concentration (Cmax) of FTD increased after multiple administration (from day 1 [3019.5 ng/mL] to day 12 [3693.1 ng/mL]), and the exposure (AUC0-t) increased 2.4-fold (day 1:7796.6 ng/mL•h; day 12:18,181.3 ng/mL•h). There was no meaningful change in the exposure to FTY and TPI throughout the study. HSD tests showed comparable PK for FTD, FTY, and TPI between Chinese and Japanese patients, and comparable exposure to FTD between Chinese and US patients. Eight patients (53.3%) experienced Grade 3 treatment-emergent adverse events, most frequently anemia and fatigue (13.3%, two events each). Median progression-free survival was 1.9 months.Conclusion: FTD/TPI had an acceptable safety and efficacy profile and PK characteristics were comparable between Chinese, Japanese, and US patients, suggesting that this treatment may be suitable for Chinese patients with refractory mCRC.Trial Registration: This trial was registered at clinicaltrials.gov as NCT02261532.Keywords: Chinese, colorectal cancer, pharmacokinetics, safety, trifluridine/tipiracil

Juan Xu, 1,* Zhao Zhao, 2,* Yumei Ge, 2 Fang He 2 1Institute of Hygiene, Zhejiang Academy of Medical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310013, People’s Republic of China; 2Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang He Tel/Fax +86-571-8821-5596Email hetrue@163.comPurpose: Pandrug-resistant K. pneumoniae is still rare in China, and the lack of studies limits our understanding of the emergence mechanism of pandrug-resistant K. pneumoniae. Here, we report the rapid emergence of a pandrug-resistant K. pneumoniae ST11 strain in an inpatient after treatment with multiple broad-spectrum antibiotics in China.Patients and Methods: K. pneumoniae strain KP65 was isolated from a 55-year-old male patient hospitalized in the Department of Intensive Care Unit (ICU) of a teaching hospital in China. Antimicrobial susceptibility testing was conducted according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). The complete genome sequence of the strain was determined using the Illumina NovaSeq 6000 platform and long-read MinION sequencer. Genomic features and resistance mechanisms of the strain were comprehensively analysed using various bioinformatics approaches.Results: K. pneumoniae strain KP65 was found to be resistant to all antibiotics tested, including beta-lactams, aminoglycosides, quinolones, tigecycline and colistin. Seven resistance genes were identified in the genome. The carbapenem-resistant gene blaKPC-2 and extended-spectrum β-lactamase (ESBL)-producing gene blaCTX-M-65 are located on the IncFII-type plasmid pKPC-2-KP65. No mcr genes were detected in the genome, but an IS 5 insertion element was found at position 117 of the mgrB gene. Regarding the rpsJ gene, single-base substitution, G169C, leading to the amino acid substitution V57L was also identified. According to in silico MLST analysis, K. pneumoniae KP65 belongs to sequence type ST11. The closest relative of K. pneumoniae KP65 is another ST11 K. pneumoniae strain, which was isolated from a bloodstream infection in Hangzhou, differing by only 53 cgMLST loci.Conclusion: Under the selective pressure of antibiotics, the KPC-2-producing K. pneumoniae ST11 strain can easily evolve pandrug resistance through chromosomal mutations. More attention is required to monitor the prevalence of the KPC-2-producing K. pneumoniae ST11 strain in China.Keywords: Klebsiella pneumoniae, mgrB, rpsJ, ST11, blaKPC-2

Feng Ye, Ronghua Xu, Yuanhong Ge, Yi Zheng, Xiaowei Liu, Pingfu Deng, Xuejun Xu Department of Neurosurgery, The Second People’s Hospital of Chengdu, Chengdu, Sichuan 610021, People’s Republic of ChinaCorrespondence: Xuejun XuDepartment of Neurosurgery, The Second People’s Hospital of Chengdu, 10 Qingyun South Street, Chengdu, Sichuan 610021, People’s Republic of ChinaEmail xuxejun@163.comBackground: Glioma is a prevalent disease of the central nervous system with a high incidence and mortality rate. Many long noncoding RNAs (lncRNAs) have been determined to be critical regulators of glioma oncogenesis. However, the function and mechanism of LINC00963 in glioma have not been fully elucidated.Methods: The expression level of RNA was determined by qRT-PCR, and the protein level was determined by Western blot analysis. A luciferase activity assay was conducted to verify the interaction between miRNA and lncRNA or the target gene. The proliferation, cell cycle distribution, invasion, and migration were evaluated by MTT, EdU, flow cytometry, wound-healing and Transwell invasion assays, respectively. In vivo tumor growth was evaluated in a xenograft nude mouse model.Results: We found that LINC00963 was upregulated in glioma cells and tissues and associated with the poor prognosis of patients with glioma. Ectopic expression of LINC00963 promoted cell proliferation, cell cycle progression, migration, and invasion in vitro and tumorigenesis in vivo. Mechanistically, the results of luciferase activity and RNA pulldown assays validated that LINC00963 could act as a molecular sponge of miR-506. Reciprocal repression was found between LINC00963 and miR-506. In addition, BCAT1 was identified as a target of miR-506, and both the mRNA and protein levels of BCAT1 were reduced by miR-506. In tumor tissues, the expression of BCAT1 was negatively and positively correlated with miR-506 and LINC00963 expression, respectively. The reintroduction of BCAT1 in glioma cells abolished the tumor suppressive function of miR-506 by promoting cell viability and motility. The upregulated LINC00963 and BCAT1 were associated with the aggressive phenotypes of tumors.Conclusion: Our data revealed that LINC00963 confers oncogenic function in the progression of glioma and that the LINC00963/miR-506/BCAT1 axis may be a novel mechanism and therapeutic strategy for this disease.Keywords: LINC00963, miR-506, BCAT1, glioma, ceRNA, invasion

Yonghao Feng, 1,* Ying Ge, 2,* Men Wu, 1 Yangmei Xie, 3 Ming Wang, 3 Yinghui Chen, 3 Xiaohong Shi 1 1Department of Endocrinology, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China; 2Department of General Medicine, Community Health Service Center of Shanghai Jinshan Industrial Zone, Shanghai 201506, People’s Republic of China; 3Department of Neurology, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong ShiDepartment of Endocrinology, Jinshan Hospital, Fudan University, No. 1508 Longhang Road, Shanghai 201508, People’s Republic of ChinaTel +86 21-34189990Fax +86 21-57039502Email xiaohongshi@fudan.edu.cnYinghui ChenDepartment of Neurology, Jinshan Hospital, Fudan University, No. 1508, Longhang Road, Shanghai 201508, People’s Republic of ChinaTel +86 21-34189990Fax +86 21-57039502Email yinghuichen@fudan.edu.cnBackground: Long non-coding RNAs (lncRNAs), as competing endogenous RNAs (ceRNAs), can regulate various pathophysiological processes by binding competitively to microRNAs at the post-transcription level. Our previous work demonstrated that miR-146a-5p was lowly expressed in diabetic peripheral neuropathy (DPN) rats. However, the ceRNA network in DPN mediated by lncRNAs and miR-146a-5p remains to be explored.Methods: Two groups of rats (n=4 per group), a type 2 diabetes (T2DM) group and a DPN group, were used in this study. Sciatic nerve conduction velocity (NCV) of each rat was determined at the 6th and the 12th week. LncRNA microarray analysis was performed in the sciatic nerve of DPN and T2DM rats. Based on the TargetScan algorithm and the miRanda database, we determined the differentially expressed (DE) lncRNAs bound to miR-146a-5p. Furthermore, we verified the DE lncRNAs potentially bound to miR-146a-5p by qRT-PCR. The genes targeted by miR-146a-5p were identified by bioinformatics prediction and experimental techniques.Results: We found 413 DE lncRNAs between DPN and T2DM rats (|log2FC| ≥ 2 and adjust P ≤ 0.05). Eight DE lncRNAs were predicted to bind to miR-146a-5p by both algorithms, of which four were verified by qRT-PCR. TRAF6, IRAK1, and SMAD4 were identified as miR-146a-5p targeted genes and were predominantly enriched in the inflammatory signaling pathway.Conclusion: LncRNAs may contribute to the pathogenesis of DPN by regulating inflammation through functioning as ceRNAs of miR-146a-5p.Keywords: diabetic peripheral neuropathy, long non-coding RNA, MicroRNA, inflammation

Jian Rong,1,* Guimei Chen,1,* Xueqin Wang,2 Yanhong Ge,1 Nana Meng,1 Tingting Xie,1 Hong Ding1 1Department of Health Services Management, School of Health Management, Anhui Medical University, Hefei 230032, People’s Republic of China; 2Department of Medical Engineering, The Second Hospital of Anhui Medical University, Hefei 230601, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong DingSchool of Health Management, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, People’s Republic of ChinaTel +86 551 516 1220Fax +86 551 512 8754Email dinghong2003@126.comPurpose: We aimed to assess the current status of depressive symptoms and quality of life (QoL) among rural elderly in central China (Anhui Province) and explore their correlation and associated factors for depressive symptoms.Methods: A multi-stage random sampling method was used to obtain 3349 participants (aged ≥60): 1206 poor and 2143 non-poor. The 30-item Geriatric Depression Scale (GDS-30) and five-dimensional European quality of health scale (EQ-5D) were employed to evaluate depressive symptoms and QoL, respectively.Results: The prevalence of depressive symptoms was 52.9%, and that in the poor group (62.3%) was significantly higher than the non-poor group (47.6%). The GDS-30 score was 12.40 ± 7.089, and the poor group scored significantly higher (14.045 ± 6.929) than the non-poor group (11.472 ± 7.011). The EQ-5D score was 0.713 ± 0.186, and the poor group (0.668 ± 0.192) scored significantly lower than the non-poor group (0.738 ± 0.178). There was a significant negative correlation between depressive symptoms and QoL (r = −0.400, P-value

Lijun Zhang,1 Jianyang Liu,1 Yingbin Ge,2 Meiyan Liu1 1Department of Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, People’s Republic of China; 2Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, People’s Republic of ChinaCorrespondence: Meiyan LiuDepartment of Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, People’s Republic of ChinaEmail liumeiyanaz@163.comBackground: Depression has been shown to share an extremely high comorbidity with heart failure (HF). Ginkgo biloba extract (GBE) is a widely used traditional Chinese medicine in cardiac disease. However, its potential therapeutic effect on depressive symptoms following HF largely remains unknown. In this article, we aimed to investigate its effects in reducing depressive behaviors of a HF mouse model. Moreover, we also discussed whether its effects are associated with changes in neural inflammation and 5-hydroxytryptamine (5-HT) signaling.Methods: Mice were randomly divided into three groups: sham, HF+saline and HF+GBE (150 mg/kg/d) (n=10 per group). Systolic heart failure was induced by ligating the left anterior descending coronary artery. Cardiac functions together with depressive-like behaviors were measured after 4 weeks’ treatment. Levels of brain natriuretic peptide (BNP), 5-HT, 5-HT receptor 2A (5-HT2AR), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1), (cleaved) caspase-3, Bax and Bcl-2 were analyzed by Western blot, Elisa and immunohistochemistry at the end of the experiments.Results: GBE benefited antidepressant-like behaviors and improved cardiac functions in mice with heart failure. Levels of TNF-α, IL-1β and 5-HT were reduced in the hippocampus after the administration of GBE. Further experiments revealed that GBE also blocked the release of serotonin in the peripheral blood and triggered HIF-1 induced anti-apoptotic pathways.Conclusion: GBE has potential therapeutic effects in relieving depressive status of patients with HF.Keywords: heart failure, inflammation, 5-HT, apoptosis, depression

Yueping Ge,1 Thangavel Lakshmipriya,2 Subash CB Gopinath,2,3 Periasamy Anbu,4 Yeng Chen,5 Firdaus Hariri,6 Lu Li7 1Department of Gynaecology and Obstetrics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450003, People’s Republic of China; 2Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, Kangar, Perlis 01000, Malaysia; 3School of Bioprocess Engineering, Universiti Malaysia Perlis, Arau 02600, Perlis, Malaysia; 4Department of Biological Engineering, College of Engineering, Inha University, Incheon 402-751, Republic of Korea; 5Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia; 6Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia; 7Department of Obstetrics, Jinan Central Hospital Affiliated to Shandong University, Jinan City, Shandong Province 250013, People’s Republic of ChinaCorrespondence: Lu LiDepartment of Obstetrics, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Rd, Lixia Qu, Jinan City, Shandong Province 250013, People’s Republic of ChinaEmail lilu2019@sina.comBackground: Gestational diabetes mellitus is a commonly occurring metabolic disorder during pregnancy, affecting >4% of pregnant women. It is generally defined as the intolerance of glucose with the onset or initial diagnosis during pregnancy. This illness affects the placenta and poses a threat to the baby as it affects the supply of proper oxygen and nutrients.Purpose: Due to the high percentage of affected pregnant women, it should be mandatory to evaluate glucose levels during pregnancy and there is a need for a continuous monitoring system.Methods: Herein, the investigators modified the interdigitated (di)electrodes (IDE) sensing surface to detect the glucose on covalently immobilized glucose oxidase (GOx) with the graphene. The characterization of graphene and gold nanoparticle (GNP) was performed by high-resolution microscopy.Results: Sensitivity was found to be 0.06 mg/mL and to enhance the detection, GOx was complexed with GNP. GNP-GOx was improved the sensitive detection twofold from 0.06 to 0.03 mg/mL, and it also displayed higher levels of current changes at all the concentrations of glucose that were tested. High-performance of the above IDE sensing system was attested by the specificity, reproducibility and higher sensitivity detections. Further, the linear regression analysis indicated the limit of detection to be between 0.02 and 0.03 mg/mL.Conclusion: This study demonstrated the potential strategy with nanocomposite for diagnosing gestational diabetes mellitus.Keywords: gestational diabetes, glucose oxidase, graphene, interdigitated electrode, gold nanoparticle

Tristan Knight,1,2 Holly Edwards,3,4 Jeffrey W Taub,1–2,4 Yubin Ge2–41Division of Pediatric Hematology and Oncology, Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI, USA; 2Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA; 3Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA; 4Molecular Therapeutics Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USAAbstract: Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML) in adult patients aged 75 years or older, or otherwise unable to tolerate intensive induction chemotherapy, in combination with either hypomethylating agents or low-dose cytarabine. In this review article, we discuss venetoclax’s mechanism of action, in relation to both the BCL-2 protein family in general and BH3-mimetic activity in particular. We then outline the pharmacological advances that preceded and facilitated its development, as well as providing an overview of key preclinical and clinical studies which lead to its use first in chronic lymphoid leukemia (CLL), then in small lymphocytic leukemia (SLL), and subsequently in AML. Finally, we seek to offer an overview of the challenges and opportunities encountered as venetoclax moves into more widespread use, including its use and activity against leukemia initiating cells and oxidative phosphorylation.Keywords: ABT-199, acute myeloid leukemia, apoptosis, BCL-2 inhibitor, BH3-mimetic, venetoclax

Meina Li,1,* Wenya Yu,1,* Wei Tian,2,* Yang Ge,3 Yuan Liu,1 Tao Ding,1 Lulu Zhang1 1Department of Military Health Service Management, College of Military Health Service Management, Second Military Medical University, Shanghai, China; 2Medical Care Department, Dalian Rehabilitation Center of PLA, Dalian, China; 3School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China *These authors contributed equally to this work Background: Infectious and endemic diseases are a serious public health concern worldwide, and their prevention and treatment are globally controversial. This study aimed to establish an system dynamics (SD) model to analyze the factors influencing public health services provided by the Chinese Centers for Disease Control and Prevention (China CDC) to implement infectious and endemic disease control in China, by establishing more effective interventions to provide public health services and thus achieving the goal of controlling infectious and endemic diseases. Materials and methods: An SD model was constructed using the Vensim DSS program. Intervention experiments were performed using the SD model, which reflected the influences on disease control by adjusting the governmental investment and compensation level for public health products. Results: The experimental results showed that increasing the governmental investment in China CDC and compensation level for public health products will significantly increase the public health product rate provided by China CDC. Discussion: Problems with infectious and endemic disease prevention and treatment are the result of the system’s incomplete functioning and limited health resources. To address the current problems and improve the system, the government should increase its investment in the public health service system and improve the compensation system to ensure smooth implementation of infectious and endemic disease prevention and treatment and, ultimately, improve public health in China. Keywords: epidemic model, transmission, spread, epidemiology, public health, system dynamics, disease management