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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

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

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