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Yinshuang Zou,1– 3,&ast; Yaji Yang,1,3,&ast; Jianye Yang,1,3 Yanhao Zhang,4 Chen Zhao,1,3 Leilei Qin,1,3 Ning Hu1,3 1Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Orthopedics, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434000, People’s Republic of China; 3Laboratory of Orthopedics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leilei Qin; Ning Hu, Email qinleilei@stu.cqmu.edu.cn; huning@cqmu.edu.cnBackground: Diagnosing chronic periprosthetic joint infection (PJI) is challenging. Synovial fluid interleukin-10 (SF IL-10), an anti-inflammatory cytokine produced by leukocytes, plays a pivotal role in inflammation and infection regulation. However, limited research has explored the diagnostic potential of SF IL-10 in chronic PJI patients.Objective: The study aimed to investigate the relationship between SF IL-10 and incidence of chronic PIJ, and to evaluate its diagnostic reliability.Design and Methods: We analyzed data from 137 patients who underwent revision surgery for aseptic loosening or chronic PJI between 2017 and 2019 in our hospital. PJI diagnoses followed the 2013 International Consensus Meeting criteria. We measured serum ESR, serum CRP, SF PMN%, SF WBC and SF IL-10 levels, using logistic regression and receiver operating characteristic (ROC) curves to evaluate associations and diagnostic accuracy.Results: Demographic data showed no significant differences. However, SF IL-10 levels differed significantly between groups. Logistic regression indicated a strong association between SF IL-10 and chronic PJI (OR = 1.11, 95% CI 1.05~1.17, p < 0.001). At a cut-off of 10.305 pg/mL, SF IL-10 had an area under the ROC curve (AUC) of 0.891, with 92.16% sensitivity and 77.91% specificity. Adding SF IL-10 to traditional models improved risk prediction for chronic PJI (net reclassification improvement [NRI]: 0.167 [0.023 ~ 0.312]; integrated discrimination improvement [IDI]: 0.160 [0.096 ~ 0.224]).Conclusion: Higher SF IL-10 levels were significantly associated with chronic PJI in revision surgery patients, and incorporating SF IL-10 into the traditional risk model enhanced its predictive value for chronic PJI in these patients.Keywords: periprosthetic infection, synovial fluid, interleukin-10, C-reactive protein, erythrocyte sedimentation rate

Zechuan Liu,1,&ast; Tianshi Lyu,1,&ast; Jinming Yang,2 Yong Xie,1 Siyuan Fan,1 Li Song,1 Yinghua Zou,1 Jian Wang1 1Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Vascular Interventional, Aerospace Central Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wang; Yinghua Zou, Department of Interventional and Vascular Surgery, Peking University First Hospital, Beijing, People’s Republic of China, Email wangjianbdyy@126.com; Dr_zouyinghua@126.comPurpose: Portal vein tumor thrombus (PVTT)–related severe symptomatic portal hypertension (SPH) leads to a poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Traditional transjugular intrahepatic portosystemic shunt (TIPS) using covered plus bare stent can effectively relieve SPH, however, the bare segment is susceptible to obstruction due to PVTT invasion. This study aimed to evaluate the safety and efficacy of fully covered stent-TIPS (FCS-TIPS) for treatment of PVTT-related SPH in advanced HCC patients.Patients and Methods: This retrospective study enrolled 25 patients with advanced HCC who underwent FCS-TIPS for PVTT-related severe SPH from June 2018 to January 2024. The evaluated outcomes included overall survival (OS), technical success rate, reduction in portal venous pressure gradient (PPG), stent patency rate, SPH control rate, liver function and complications.Results: The technical success rate was 100% without perioperative deaths or severe procedure-related adverse events. The average PPG decreased by 13.4± 4.6 mmHg. The overall symptom control rate of SPH was 96.0%. Variceal bleeding, ascites/hydrothorax, and enteropathy control rates were 100%, 95.0%, and 100%, respectively. Liver function showed mild improvement one month after TIPS. One patient (4.0%) experienced overt hepatic encephalopathy (OHE) and three (12.0%) patients developed shunt dysfunction during the follow-up period. None of the patients experienced shunt-induced extrahepatic metastasis. The median OS was 6.0 months and the cumulative survival rates at 3, 6, 12 months were 80.0%, 52.0% and 21.3%.Conclusion: FCS-TIPS is safe and effective for treating PVTT-related severe SPH and can serve as a bridging therapy for advanced HCC.Keywords: fully covered stent, transjugular intrahepatic portosystemic shunt, hepatocellular carcinoma, portal vein tumor thrombus, symptomatic portal hypertension

Jing Zhu,1 Yiming Huang,1,2 Chao Ye,3 Xiaoxia Deng,1,2 Yuxuan Zou,1,2 En Yuan,2 Qi Chen2 1Research Center for Chinese Medicine Resources and Ethnic Minority Medicine, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China; 2School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China; 3The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of ChinaCorrespondence: Jing Zhu, Research Center for Chinese Medicine Resources and Ethnic Minority Medicine, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China, Tel +86-13755654318, Email 277836041@qq.comObjective: The main objective of this study was to elucidate the effector material basis of Cimicifugae Rhizoma (CR) for the treatment of acute pneumonia (AP) and to explore the potential mechanisms underlying the anti-AP effects of these active components in a lipopolysaccharide (LPS)-induced inflammation model of lung epithelial cells.Methods: Chemical components were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-TOF-MS), and a CR component library was subsequently established based on a combination of databases and available literature. Bioinformatics techniques were used to construct “component-target” and “protein-protein interaction (PPI)” networks, and the potential active components and core targets screened according to degree value, followed by molecular docking and in vitro experiments for verification. Inflammation was induced in normal human lung epithelial cells using lipopolysaccharide (LPS) to mimic the occurrence of AP.Results: In total, 122 CR components were identified. The therapeutic effects of potential active components against AP were associated with 147 targets involving 165 signaling pathways. Molecular docking experiments revealed the strong affinity of N-cis- feruloyltyramine, ferulic acid, cimifugin, and isoferulic acid for core AP-associated targets. In vitro cellular experiments showed that the above compounds and CR alcoholic extracts inhibited the expression of inflammatory factors in the following order: isoferulic acid > cimifugin > CR alcoholic extract > N-cis-feruloyltyramine > ferulic acid.Conclusion: N-cis- feruloyltyramine, ferulic acid, cimifugin, and isoferulic acid were the effector components of CR with activity against AP. These compounds potentially co-regulate the IL-6/JAK/STAT3 and TLR4/IL-1β-IRAK pathways through the inhibition of cytokines such as IL-6, TNF-α, and IL-1β, and downregulation of P-STAT3, TLR4, PIK3CA, and NF-κB involved in TLR4/IL-1β-IRAK/NF-κB and PI3K-Akt signaling pathways to exert therapeutic effects on AP.Keywords: acute pneumonia, molecule docking, lung epithelial cells, LPS, signaling pathway

Minna Han,1,2,&ast; Zhikuan Xia,2,&ast; Yuekun Zou,3 Ping Hu,4 Mingwang Zhang,5 Xin Yang,3 Ming-Guo Ma,6 Rongya Yang2 1Chinese PLA Medical School, Beijing, 100072, People’s Republic of China; 2Department of Dermatology, The Seventh Medical Center of PLA General Hospital, Beijing, 100072, People’s Republic of China; 3Department of Geriatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100072, People’s Republic of China; 4Department of Dermatology, Southern Medical Branch of PLA General Hospital, Beijing, 100072, People’s Republic of China; 5Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 6College of Materials Science and Technology, Beijing Forestry University, Beijing, 100083, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming-Guo Ma; Rongya Yang, Email mg_ma@bjfu.edu.cn; yangrya@sina.comBackground: Silver nanomaterials have been widely proven to have antifungal effects against Trichosporon asahii. However, the antifungal mechanism of silver nanomaterials with different morphologies still needs to be explored.Methods: Herein, the antifungal effect of silver nanomaterials against fungus was comparative investigated via silver nanowires and silver nanoparticles with a similar size (30 nm).Results: The optimal antifungal concentration of silver nanowires is 6.24 μg/mL, meanwhile the antifungal concentration of silver nanoparticles is 100 μg/mL. The silver nanowires are significantly superior to the silver nanoparticles. SEM and TEM results indicated that both silver nanoparticles and silver nanowires showed significant morphological changes in the mycelium of the strain, compared with the control. The lower MFC value of silver nanowires indicates good sterilization effect and suitability for eradication treatment, which is slower than that of silver nanoparticles. Moreover, we also investigated the toxicological effects of silver nanoparticles and silver nanowires.Conclusion: We comparative studied and transcriptomic analyzed the antifungal mechanism of Ag nanoparticles and nanowires against Trichosporon asahii. The antifungal effects of silver nanowires were better than the silver nanoparticles, especially in the metabolic processes and oxidative phosphorylation. RNA sequencing results indicated that 15 key targets were selected for experimental verification to interpret the potential antifungal mechanism of Ag nanomaterials against fungus. This work proves that silver nanomaterials with different morphologies have potential applications in fungus therapy such as T. asahii.Keywords: Ag, nanoparticles, nanowires, fungus, antifungal mechanism, Trichosporon asahii, transcriptomics

Cailing E,1,&ast; Rongying Wang,1,&ast; Zudong Meng,1 Yulin Zou1,2 1Department of Dermatology, Renmin Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany&ast;These authors contributed equally to this workCorrespondence: Yulin Zou, Email zouyl1007@qq.comBackground: Psoriasis, a chronic and recurrent inflammatory skin disease, current treatments can only alleviate its symptoms. There is still no complete cure. Although increasing research supports the therapeutics to be better, the common mechanism of its occurrence is still not fully elucidated. Our study is about further explore the molecular mechanism of the occurrence of this disease.Methods: The gene expression profiles of psoriasis (GSE151177, GSE41664, GSE30999) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis using R software, three kinds of analyses were performed, namely WGCNA, GWAS Analysis, Drug Target Prediction.Results: A total of 14 common DEGs was selected for subsequent analyses. Our Drug Target Prediction analysis revealed that the expression profiles influenced by certain drugs, including methotrexate, budesonide, amino purvalanol-a, and selumetinib, exhibited negative correlations with the disease-perturbed expression profiles. Finally, It was found that S100A4, JAML, TRAF3IP3, MIAT, IL7R, and KLRB1 were prominently expressed in the immune pathway related to allograft rejection. In the metabolic pathway, oxidative phosphorylation showed high expression levels, while the reactive oxygen species pathway was notably expressed in the signaling pathways domain.Conclusion: Our study reveals the potential drugs and pathogenesis of psoriasis. These potential pathway and hub genes may provide new ideas for further mechanism research.Keywords: psoriasis, hub genes, bioinformatics, PPI, inflammation

Cheng Chen, Yong Zou, Xiangbing Zheng, Taotao Hu, Jie Ni, Daohong Kan, Zongyin Yin, Lingxiao Ye, Bing Liu Department of Burn and Plastic Surgery, The Second People’s Hospital of Yibin (West China Yibin Hospital, Sichuan University), Yibin, Sichuan, People’s Republic of ChinaCorrespondence: Bing Liu, Email 4444093330@qq.comObjective: To investigate the role of the TopBP1 interacting checkpoint and replication regulator (TICRR) in cutaneous melanoma (CM) as a prognostic biomarker and therapeutic target.Methods: TICRR expression in tumour samples was explored using the TCGA and the GTEx database. The Kaplan-Meier survival curve, nomogram model and risk score curve were established to evaluate the prognostic role of TICRR in CM. Tissue samples of CM patients were obtained to validate the TICRR expression further. Several experiments in vitro were conducted to investigate the effect of TICRR upon CM aggressiveness and to explore underlying mechanisms.Results: TICRR was overexpressed in CM tissue and was correlated with poor prognosis of CM patients. The knockdown of TICRR decreased the proliferation, migration, and invasion of CM cells, whereas overexpression produced the opposite effect. Furthermore, TICRR suppression substantially attenuated the activation of PI3K/AKT/mTOR signalling, while the PI3K/AKT inhibitor LY294002 could partially reverse the aggressiveness-enhancing effect induced by TICRR overexpression. It was further confirmed that TICRR was closely related to immune cell infiltration activities by using immune infiltration and immunofluorescence analysis.Conclusion: TICRR overexpression may enhance CM aggressiveness by activating the PI3K/Akt/mTOR pathway and promoting immune infiltration. TICRR was verified as a potential prognostic biomarker and therapeutic target for CM.Keywords: cutaneous melanoma, TICRR, immune infiltration, invasion, prognosis

Longqing Xia,1 Mengmeng Yang,1 Nan Zang,1– 4 Jia Song,1– 4 Jun Chen,1– 4 Huiqing Hu,1 Kewei Wang,1 Yingyue Xiang,1 Jingwen Yang,1 Liming Wang,1 Ying Zou,1 Xiaoyu Lv,1 Xinguo Hou,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, 250012, People’s Republic of ChinaCorrespondence: Li Chen, Department of Endocrinology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Email chenli3@email.sdu.edu.cnBackground: The depletion of β cell mass is widely recognized as a significant contributor to the progression of type 2 diabetes mellitus (T2DM). Exosomes derived from mesenchymal stem cells (MSC-EXOs) hold promise as cell-free therapies for treating T2DM. However, the precise effects and mechanisms through which MSC-EXO affects β cell function remain incompletely understood, and the limited ability of MSC-EXO to target β cells and the short blood circulation time hampers its therapeutic effectiveness.Methods: The effects of MSC-EXO were investigated in T2DM mice induced by a high-fat diet combined with STZ. Additionally, the high glucose-stimulated INS-1 cell line was used to investigate the potential mechanism of MSC-EXO. Michael addition reaction-mediated chemical coupling was used to modify the surface of the exosome membrane with a β-cell-targeting aptamer and polyethylene glycol (PEG). The β-cell targeting and blood circulation time were evaluated, and whether this modification enhanced the islet-protective effect of MSC-EXO was further analyzed.Results: We observed that the therapeutic effects of MSC-EXO on T2DM manifested through the reduction of random blood glucose levels, enhancement of glucose and insulin tolerance, and increased insulin secretion. These effects were achieved by augmenting β cell mass via inhibiting nuclear factor erythroid 2–related factor 2 (NRF2)-mediated ferroptosis. Mechanistically, MSC-EXOs play a role in the NRF2-mediated anti-ferroptosis mechanism by transporting active proteins that are abundant in the AKT and ERK pathways. Moreover, compared to MSC-EXOs, aptamer- and PEG-modified exosomes (Apt-EXOs) were more effective in islet protection through PEG-mediated cycle prolongation and aptamer-mediated β-cell targeting.Conclusion: MSC-EXO suppresses NRF2-mediated ferroptosis by delivering bioactive proteins to regulate the AKT/ERK signaling pathway, thereby improving the function and quantity of β cells. Additionally, Apt-EXO may serve as a novel drug carrier for islet-targeted therapy.Keywords: exosome, type 2 diabetes mellitus, β-cell-targeting, polyethylene glycol modification, ferroptosis

Xiangan Gong,1,2 Qian Zhao,1,2 Huimin Zhang,1,2 Rui Liu,1,2 Jie Wu,1,2 Nanxin Zhang,3 Yuanxian Zou,1,2 Wen Zhao,1,2 Ran Huo,1,2,4 Rongtao Cui1– 4 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.Keywords: mesenchymal stem cells-derived exosomes, metabolic reprogramming, scar, wound healing, fibroblast

Qinchuan Li,1 Wenju Guan,2 Jian Zhang,2 Min Chen,3 Ya Zou1 1Department of Clinical Pharmacology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China; 2Department of Oncology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China; 3Sichuan Academy of Medical Sciences. Department of Pharmacy, Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Ya Zou, Department of Clinical Pharmacology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China, Email zouya_1214@163.comBackground: Patients with nasopharyngeal carcinoma (NPC) combined with non-tuberculous Mycobacteria-pulmonary disease (NTM-PD) are very rare in the clinic, and our case is the first patient with NPC combined with NTM-PD. For oncologists, rapid control of the symptoms of infection is essential to the treatment of the primary disease.Case Presentation: A 58-year-old man who developed a NTM-PD after chemotherapy for nasopharyngeal carcinoma. Granulocytosis after chemotherapy is a major factor in the development of various infectious diseases. Nasopharyngeal tumor was found on MRI of the patient’s head, and nasopharyngeal malignant tumor was considered after pathological examination after endoscopic resection of intranasal lesion, and then nasopharyngeal non-keratonic carcinoma (T4N1M0, stage IV) was confirmed in the department of oncology. The patient developed bone marrow suppression after chemotherapy and was admitted to hospital due to septic shock. Chest CT examination indicated pulmonary infection, and empirical antibiotic treatment was not effective. The NGS results showed that the patient was infected with Mycobacterium abscess. We treated with cefoxitin followed by moxifloxacin to reduce the lung lesions significantly.Conclusion: NPC with NTM-PD is very rare, and the treatment of NTM-PD is very important for the prognosis of the patient’s primary disease. Our study provides experience for anti-infection treatment of patients with immunosuppression.Keywords: nasopharyngeal carcinoma, immunosuppressed, NTM, anti-infection, cefoxitin, moxifloxacin

Yuhai Zou,1,&ast; Dongdong Li,1,&ast; Ge Guan,1 Wenting Liu2 1Department of Cardiology, General Hospital of Southern Theatre Command of PLA, Guangzhou, 510010, People’s Republic of China; 2Department of Otorhinolaryngology, Guangzhou First People’s Hospital, Guangzhou, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenting Liu, Department of Otorhinolaryngology, Guangzhou First People’s Hospital, Guangzhou, 510180, People’s Republic of China, Tel +86-13533976302, Email liuwt2023@126.comBackground: Coronary artery calcification (CAC) is in almost all patients with coronary artery disease and requires more effective therapies. We aim to explore the effects of phosphoglycerate dehydrogenase (PHGDH) on CAC.Methods: We identified the differentially expressed genes through bioinformatic analysis and selected PHGDH for further verification. Human coronary artery smooth muscle cells (HCASMCs) cultured with calcifying medium were used as models of CAC in vitro. Erastin was administered to induce ferroptosis. We determined the cell viability by the cell count kit-8 assay. The alkaline phosphatase activity, calcium content, and the expression of glutathione were evaluated by the corresponding detection kits. The calcification level was detected by alizarin red staining. Then we performed Western blot to examine the expression of runt-related transcription factor 2, bone morphogenetic protein 2, cyclooxygenase 2, glutathione peroxidase 4, P53, and solute carrier family 7a member 11 (SLC7A11).Results: We acquired 201 differentially expressed genes and selected PHGDH to verify. In calcifying medium-induced HCASMCs, PHGDH overexpression increased the cell viability and decreased the alkaline phosphatase activity, calcium content, calcification level, and the expression of bone morphogenetic protein 2 and runt-related transcription factor 2. Additionally, we found higher levels of glutathione, glutathione peroxidase 4, and SLC7A11 and lower levels of cyclooxygenase 2 and P53 after up-regulating PHGDH. Erastin reversed the effects of PHGDH on calcification of HCASMCs.Conclusion: PHGDH overexpression suppresses the calcification level of HCASMCs by inhibiting ferroptosis through the P53/SLC7A11 signaling pathway, suggesting PHGDH as a promising therapeutic target of CAC.Keywords: coronary artery calcification, PHGDH, the P53/SLC7A11 signaling pathway

Yang Zou, Yuting Peng, Jing Xu, Aijun Chen, Kun Huang, Ping Wang Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Ping Wang, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Email wang_ping@hospital.cqmu.edu.cn

Bin Hu,1 Jingchun Pei,1 Cheng Wan,1,2 Shuangshuang Liu,1 Zhe Xu,3,4 Yongwei Zou,1 Zhigao Li,1 Zhiwei Tang1 1Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Medical Imaging, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China; 4School of Basic Medical Sciences, Qujing Medical College, Qujing, People’s Republic of ChinaCorrespondence: Zhiwei Tang, Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People’s Republic of China, Email tangzhiwei7755@hotmail.comAbstract: Ischemic stroke constitutes a significant global health care challenge, and a comprehensive understanding of its recovery mechanisms is imperative for the development of innovative therapeutic strategies. Angiogenesis, a pivotal element of ischemic tissue repair, facilitates the restoration of blood flow to damaged regions, thereby promoting neuronal regeneration and functional recovery. Nevertheless, the mechanisms underlying postischemic stroke angiogenesis remain incompletely elucidated. This review meticulously examines the constituents of the neurovascular unit, ion channels, molecular mediators, and signaling pathways implicated in angiogenesis following stroke. Furthermore, it delves into prospective therapeutic strategies informed by these factors. Our objective is to provide detailed and exhaustive information on the intricate mechanisms governing postischemic stroke angiogenesis, thus providing a robust scientific foundation for the advancement of novel neurorepair therapies.Keywords: ischemic stroke, angiogenesis, signaling pathways

Jianbao Zheng,1,2,&ast; Zepeng Dong,1,&ast; Xianzhen Jin,1 Jing Li,2 Yuanwu Zou,2 Guanghong Bai,2 Qianhong Wu,2 Shenghang Xu,3 Zifeng Wang,3 Xuejun Sun,1 Dingxin Liu,3 Li Guo3 1Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Tuberculosis Prevention and Treatment Hospital in Shaanxi Province, Xi’an, 710100, People’s Republic of China; 3Center for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianhong Wu; Li Guo, Email 15902969531@126.com; guoli35@mail.xjtu.edu.cnPurpose: This study aimed to investigate the antibacterial effects of plasma-activated saline (PAS) on My-cobacterium tuberculosis (Mtb).Methods: We conducted a growth assay on 3 strains of Mtb and an antibiotic sensitivity test on 4 strains of Mtb. Both tests included groups treated with normal saline (NS), PAS, and hydrochloric acid (HCl). The test of antibiotic sensitivity consisted of parallel tests with two concentrations of bacteria suspension: 10− 2 and 10− 4. The selected antibiotics were rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and streptomycin (SM). The number of bacteria was determined after one month of culture under different conditions. The Kruskal–Wallis test was used to analyze the differences in grouping factors at representative time points.Results: The growth assay indicated that PAS significantly inhibited the growth of 3 strains of Mtb compared with NS and HCl treatment groups. Furthermore, except for the initial observation time point, the remaining three observation time points consistently demonstrate no significant differences between the NS group and the HCl group. The antibiotic sensitivity test of INH, SM, and RIF indicated that PAS could inhibit the growth of antibiotic-resistant Mtb, and the antibiotic sensitivity test of INH and SM with bacterial suspension concentration of 10− 2 and SM with bacterial suspension concentration of 10− 4 showed statistically different results. The antibiotic sensitivity test of EMB indicated that the growth of Mtb in PAS was slower than that in NS and HCl in both antibiotic-resistant and sensitive Mtb, but there was no statistical difference.Conclusion: The study indicates that PAS contains a significant amount of active substances and exhibits high oxidizability and an acidic pH state. The unique physicochemical properties of PAS significantly delayed the growth of Mtb, compared to the NS and the HCl. PAS not only inhibited the growth of drug-sensitive strains but also significantly enhanced the sensitivity of drug-resistant strains to anti-tuberculosis drugs, which may provide a new therapeutic strategy for the treatment of tuberculosis.Keywords: plasma-activated saline, mycobacterium tuberculosis, antibacterial effect, antibiotic sensitivity

Yuan Xu, Jing-Yan Wang, Yang Zou, Xue-Wei Ma, Tian Meng College of Health Industry, Sichuan Tourism University, Chengdu, Sichuan, 610100, People’s Republic of ChinaCorrespondence: Yuan Xu, Email 230973159@qq.comAbstract: Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.Keywords: IL-36, IL-37, IL-38, osteoarthritis, rheumatoid arthritis

Jiajun Qiu,1– 3,&ast; Xin Huang,1– 3,&ast; Maobin Kuang,1– 3,&ast; Ruijuan Yang,1,4 Jiachong Li,1 Guotai Sheng,5,6 Yang Zou2,3 1Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 3Jiangxi Cardiovascular Research Institute, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, People’s Republic of China; 4Department of Endocrinology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 5Jiangxi Provincial Geriatric Hospital, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 6Jiangxi Provincial Geriatric Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guotai Sheng, Jiangxi Provincial Geriatric Hospital, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Email tgs200509@163.com Yang Zou, Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Email jxyxyzy@163.comPurpose: The association between traditional lipid parameters and non-alcoholic fatty liver disease (NAFLD) has been extensively discussed. This study aims to evaluate and compare the lipoprotein combine index (LCI) and traditional lipid parameters [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] to identify NAFLD.Patients and Methods: The analysis included 14,251 participants from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA). Logistic regression models were employed to calculate standardized odds ratios (ORs) and 95% confidence intervals (CIs) for assessing and comparing the association of LCI and traditional lipid parameters with NAFLD. Additionally, receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) for LCI and traditional lipid parameters in identifying NAFLD.Results: After adjusting for various confounders, we found that LCI was positively associated with NAFLD (OR=2.25, 95% CI 1.92– 2.63), and this association was stronger than that of traditional lipid parameters [OR: TC1.23, TG1.73 LDL-C1.10]. Further subgroup analyses revealed that the association of LCI with NAFLD was stronger than other traditional lipid parameters in all subgroups, including men and women, overweight/obese [body mass index (BMI)≥ 25 kg/m2] and non-obese (BMI< 25 kg/m2), and older (age≥ 45 years) and younger (age< 45 years) participants. Additionally, ROC analysis indicated that LCI (AUC=0.8118) had significantly higher accuracy (All DeLong P< 0.05) in identifying NAFLD compared to traditional lipid parameters (AUC: TC0.6309; TG0.7969; LDL-C0.6941); HDL-C0.7587). Sensitivity analysis further confirmed the robustness of the study findings.Conclusion: This study revealed for the first time a positive correlation between LCI and NAFLD. Compared to traditional lipid parameters, LCI has a higher correlation with NAFLD. Additionally, further ROC analysis demonstrated that LCI had higher accuracy in identifying NAFLD compared to traditional lipid parameters, suggesting that LCI may be a better marker for NAFLD identification than traditional lipid parameters.Keywords: non-alcoholic fatty liver disease, lipoprotein combine index, NAFLD, traditional lipid parameters, LCI

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

Guofei Feng, Pan Zhuge, Yaping Zou, Zhifeng Zhang, Jiandong Guo, Junxiang Ma Department of ENT, Jinhua Central Hospital, Jinhua, Zhejiang, 321000, People’s Republic of ChinaCorrespondence: Guofei Feng, Department of ENT, Jinhua Central Hospital, No. 365, East Renmin Road, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel/Fax +86 579 82552620, Email guofeifeng1781f@163.comObjective: To investigate the correlation between the levels of serum lipopolysaccharide (LPS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cognitive impairment in patients with obstructive sleep apnoea (OSA).Methods: Serum LPS, Nrf2, HO-1 levels and cognitive impairment were measured using the Montreal Cognitive Assessment (MoCA) score in 56 patients in the “severe” group, 67 patients in the “mild-to-moderate” group and 100 healthy people in the “control” group. The differences in general conditions and serological indexes between the three groups were compared, the correlation between the MoCA scores and the serological indexes was explored and the independent predictors of the MoCA scores were analysed.Results: Serum LPS, Nrf2 and HO-1 levels were higher in the severe group than in the mild-to-moderate group and the control group (p < 0.05). A total of 71 patients with OSA had combined cognitive impairment, accounting for 57.7%, and the MoCA scores were lower in the severe group than in the mild-to-moderate group and the control group (p = 0.018). Serum LPS, Nrf2 and HO-1 levels were significantly higher in the severe group and mild-to-moderate group than in the control group (p < 0.05) and were negatively correlated with the MoCA scores. Lipopolysaccharide (p < 0.001) and HO-1 (p = 0.002) could be considered independent predictors of the MoCA score.Conclusion: Serum LPS and HO-1 levels are closely related to cognitive impairment in patients with OSA and have potential clinical value in the diagnosis.Keywords: obstructive sleep apnoea, cognitive impairment, lipopolysaccharide, nuclear factor erythroid 2-related factor 2, haem oxygenase 1

Longmin Chen,1 Qing Zhou,2 Xun Fang,1 Qianqian Xu,2 Yuan Zou,2 Jing Zhang2 1Department of Rheumatology and Immunology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Jing Zhang, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Caidian, 430100, People’s Republic of China, Email jingzhang@tjh.tjmu.edu.cnBackground: Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease characterized by synovial inflammation and joint destruction. Despite progress in RA therapy, it remains difficult to achieve long-term remission in RA patients. Phosphodiesterase 3B (Pde3b) is a member of the phosphohydrolyase family that are involved in many signal transduction pathways. However, its role in RA is yet to be fully addressed.Methods: Studies were conducted in arthritic DBA/1 mice, a suitable mouse strain for collagen-induced rheumatoid arthritis (CIA), to dissect the role of Pde3b in RA pathogenesis. Next, RNAi-based therapy with Pde3b siRNA-loaded liposomes was assessed in a CIA model. To study the mechanism involved, we investigated the effect of Pde3b knockdown on macrophage polarization and related signaling pathway.Results: We demonstrated that mice with CIA exhibited upregulated Pde3b expression in macrophages. Notably, intravenous administration of liposomes loaded with Pde3b siRNA promoted the macrophage anti-inflammatory program and alleviated CIA in mice, as indicated by the reduced inflammatory response, synoviocyte infiltration, and bone and cartilage erosion. Mechanistic study revealed that depletion of Pde3b increased cAMP levels, by which it enhanced PKA-CREB-C/EBPβ pathway to transcribe the expression of anti-inflammatory program-related genes.Conclusion: Our results support that Pde3b is involved in the pathogenesis of RA, and Pde3b siRNA-loaded liposomes might serve as a promising therapeutic approach against RA.Keywords: rheumatoid arthritis, Pde3b, liposomes, macrophages

Yu Liu,&ast; Hongying Guo,&ast; Wei Yuan, Ying Zou, Zhiping Qian, Xue Mei, Liujuan Ji, Jiefei Wang, Yuyi Zhang Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuyi Zhang, Email zhangyuyi@shaphc.orgBackground: Talaromyces marneffei (TM) is the third most prevalent opportunistic infection in HIV-positive patients after tuberculosis and cryptococcosis. However, such infection of non-HIV individuals has rarely been reported.Case Presentation: We describe a very rare case of a 52-year-old male who presented with a single space-occupying lesion on the right lung and was eventually diagnosed with pulmonary TM infection. The patient was HIV-negative and had liver cirrhosis with portal vein thrombosis. Lung tissue next-generation sequencing (NGS) revealed TM infection. We successfully treated the patient with voriconazole for 8 weeks and observed lesion absorption via subsequent CT. The patient consumed wild bamboo rats two months before admission. Mutations related to congenital immune deficiency were not detected by whole-exome sequencing.Conclusion: Early and timely diagnosis is critical for improving patient prognosis. NGS plays a vital role in the diagnosis of pulmonary TM infection in patients. To our knowledge, this is the first published case of pulmonary TM infection in an HIV-negative patient with liver cirrhosis.Keywords: Talaromyces marneffei, pulmonary infection, HIV-negative, PVT

Guoqiang Yang,1– 3 Jiraporn Kantapan,3 Maryam Mazhar,4,5 Qiongdan Hu,1,5,6 Xue Bai,5,7 Yuanxia Zou,1,3 Honglian Wang,1 Sijin Yang,4,5 Li Wang,1,5 Nathupakorn Dechsupa3 1Research Center for Integrated Chinese and Western Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Acupuncture and Rehabilitation Department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 4National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 5Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 6Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 7Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Li Wang; Nathupakorn Dechsupa, Email wangli120@swmu.edu.cn; nathupakorn.d@cmu.ac.thBackground: Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms.Methods: The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed.Results: Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway.Conclusion: These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.Keywords: mesenchymal stem cells, IronQ, intracerebral hemorrhage, cGAS/STING/NFκB, inflammatory response

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Li Li,&ast; Run Guo,&ast; Yingxue Zou, Xu Wang, Yifan Wang, Shiying Zhang, Huihua Wang, Xingnan Jin, Ning Zhang Department of Pulmonology, Tianjin Children’s Hospital (Children’s Hospital, Tianjin University) Machang Compus, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingxue Zou, Department of Pulmonology, Tianjin Children’s Hospital (Children’s Hospital, Tianjin University) Machang Compus, Tianjin, People’s Republic of China, Email zouyingxue2015@126.comBackground: This study aimed to develop a nomogram model for early prediction of the severe Mycoplasma pneumoniae pneumonia (MPP) in children.Methods: A retrospective analysis was conducted on children with MPP, classifying them into severe and general MPP groups. The risk factors for severe MPP were identified using Logistic Stepwise Regression Analysis, followed by Multivariate Regression Analysis to construct the nomogram model. The model’s discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer–Lemeshow goodness-of-fit test.Results: Univariate analysis revealed that age, duration of fever, length of hospital-stay, decreased sounds of breathing, respiratory rate, hypokalemia, and incidence of co-infection were significantly different between severe and general MPP. Significant differences (p < 0.05) were also observed in C-reactive protein, procalcitonin, peripheral blood lymphocyte count, neutrophil-to-lymphocyte ratio, ferritin, lactate dehydrogenase, alanine aminotransferase, interleukin-6, immunoglobulin A, and CD4+ T cells between the two groups. Logistic Stepwise Regression Analysis showed that age, decreased sounds of breathing, respiratory rate, duration of fever (OR = 1.131; 95% CI: 1.060– 1.207), length of hospital-stay (OR = 1.415; 95% CI: 1.287– 1.555), incidence of co-infection (OR = 1.480; 95% CI: 1.001– 2.189), ferritin level (OR = 1.003; 95% CI: 1.001– 1.006), and LDH level (OR = 1.003; 95% CI: 1.001– 1.005) were identified as risk factors for the development of severe MPP (p < 0.05 in all). The above factors were applied in constructing a nomogram model that was subsequently tested with 0.862 of the area under the ROC curve.Conclusion: Age, decreased sound of breathing, respiratory rate, duration of fever, length of hospital-stay, co-infection with other pathogen(s), ferritin level, and LDH level were the significant contributors for the establishment of a nomogram model to predict the severity of MPP in children.Keywords: Mycoplasma pneumoniae pneumonia, nomogram, severity prediction

Xin Yang,1,2,&ast; Zhikuan Xia,1,&ast; Yunlong Fan,1 Yitong Xie,1 Ge Ge,1 Dexiu Lang,3 Junhong Ao,1 Danxia Yue,1 Jiamin Wu,1 Tong Chen,1 Yuekun Zou,1 Mingwang Zhang,4 Rongya Yang1,2 1Department of Dermatology, The Seventh Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Department of Dermatology, Yanbian University Hospital, Yanji, People’s Republic of China; 3Department of Dermatology, XingYi People’s Hospital, Xingyi, People’s Republic of China; 4Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwang Zhang; Rongya Yang, Email mingwangzhang2@163.com; yangrya@sina.comBackground: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers.Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features.Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model’s classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs.Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells.Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.Keywords: solar lentigines, photoaging, diagnostic biomarkers, immune infiltration, artificial neural network

Yue Wang,1,2 Jun Li,3 Jianming Wu,3 Shihong Gu,3 Huishu Hu,3 Rongjuan Cai,2 Man Wang,4 Yue Zou3 1Institute of Shanghai Oriental Beauty Valley, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 2School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 3R&D Center, JALA (Group) Co., Ltd, Shanghai, People’s Republic of China; 4Department of Nutrition, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, People’s Republic of ChinaCorrespondence: Yue Zou, R&D Center, JALA (Group) Co., Ltd, Building 2, No. 333, Guiping Road, Xuhui District, Shanghai, 200233, People’s Republic of China, Email zouyue3@jala.com.cnIntroduction: Sensitive scalp is one of the most frequent complaints related to sensitive skin syndrome, characterized by unpleasant sensory reactions in the absence of visible signs of inflammation. In this study, the effects of topical application of postbiotic Himalaya-derived Saccharomyces and Lactobacillus ferment complex (SLFC) on the bacterial and fungal scalp microbiome at the taxonomic level and alleviation of sensitive skin syndrome were investigated.Methods: Firstly, healthy female participants (aged 30– 45) were classified into a healthy scalp group and a sensitive scalp group based on the questionnaire. Thereafter, topical application of SLFC on sensitive scalp as well as scalp microbiome was evaluated, with the difference in the distribution of microbial taxa between healthy and sensitive scalp communities was assessed using 16S rRNA and ITS1 sequencing analysis. In addition, the effect of SLFC on scalp microbiome at the species level for Cutibacterium acnes, Staphylococcus epidermidis, and Malassezia restricta was evaluated by the qPCR assessment.Results: After treatment with SLFC for 28 days, the abundance of Staphylococcus, Lawsonella, and Fusarium in the sensitive scalp group was highly significantly increased (p < 0.001), while the abundance of Cutibacterium and Malassezia was highly significantly decreased (p < 0.001). Furthermore, the self-assessment questionnaire indicated a syndrome alleviation effect of 100% after 28 days with a twice-daily application of the SLFC.Discussion: The obtained results would help to better understand the microbial community of the sensitive scalp and provide useful information on utilization of SLFC for maintaining a healthy scalp and modulating the scalp microbiome.Keywords: sensitive scalp, scalp microbiome, postbiotics, microbial diversity, questionnaire analysis

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

Yi Liu,1– 3,&ast; Xu Yang,3,&ast; Huan Li,3,4 Dongfeng Li,1,2 Yuhao Zou,1,2 Bo Gong,4– 6 Man Yu1,2 1Department of Ophthalmology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Human Disease Genes Key Laboratory of Sichuan Province and Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 6Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Man Yu, Department of Ophthalmology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, People’s Republic of China, Tel/Fax +8617708130597, Email Yuman712@126.com Bo Gong, Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, People’s Republic of China, Tel/Fax +8617708131021, Email gongbo@med.uestc.edu.cnPurpose: Keratoconus (KTCN) is one of the most common degenerative keratopathies, significantly affecting vision and even leading to blindness. This study identifies potential biomarkers of KTCN based on the characterization of autophagy-related genes (ARGs) and the construction of a diagnostic model; and explores their relevance to immune infiltrating cells in KTCN.Methods: Gene Expression Omnibus (GEO) data were downloaded and ARGs were acquired from GeneCards and Molecular Signatures Database (MSigDB). Autophagy-related differential expression genes (ARDEGs) were discovered through the integration of differentially expressed genes (DEGs) with ARGs, while hub genes of KTCN were discovered by protein-protein interaction (PPI) network analysis. The probable biological roles of these hub ARDEGs were examined using functional enrichment analysis, and a KTCN diagnostic model was generated using the least absolute shrinkage and selection operator (LASSO) regression analysis. We also employed the CIBERSORTx and ssGSEA algorithms to identify potential regulatory pathways to compare the abundance of immune cell infiltrates and their association with hub genes. Finally, the hub gene expression levels were confirmed using validation datasets as well as blood samples from KTCN and healthy individuals.Results: In this study, we identified 12 hub ARDEGs, of which 9 genes were substantially distinct between KTCN patients and normal groups. The LASSO risk score was used to generate the nomogram, and the calibration curve evaluated the model’s effective diagnostic performance (C index of 0.961). Patients with KTCN had greater percentages of M2 Macrophages and Gamma delta T cells, according to CIBERSORTx and ssGSEA. The outcomes of the bioinformatics analysis were supported by the DDIT3 and BINP3 expression levels in KTCN patients and healthy controls, according to the qRT-PCR data.Conclusion: Five biomarkers (CFTR, PLIN2, DDIT3, BAG3, and BNIP3) and diagnostic models offer fresh perspectives on identifying and managing KTCN.Keywords: keratoconus, autophagy-related genes, diagnostic model, biomarker, immune infiltration, bioinformatics analysis

Chunjiao Zheng, Ying Zou Skin and Cosmetic Research Department, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Ying Zou, Skin and Cosmetic Research Department, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Baode Road, Jingan District, Shanghai, 200443, People’s Republic of China, Tel +86-18017336869, Fax +86-21-36803062, Email zouyingsh@163.comIntroduction: Allergen distribution has obvious geographical characteristics. Understanding local epidemiological data may provide evidence-based strategies for the prevention and management of disease. We investigated the distribution of allergen sensitization in patients with skin diseases in Shanghai, China.Methods: Data from tests for serum-specific immunoglobulin E were collected from 714 patients with three skin diseases who visited the Shanghai Skin Disease Hospital from January 2020 to February 2022. The prevalence of 16 allergen species, as well as age, sex, and disease-group differences in allergen sensitization, were investigated.Results: Dermatophagoides farinae and Dermatophagoides pteronyssinus were the most common aeroallergen species to cause allergic sensitization in patients with skin diseases, whereas shrimp and crab were the most common food-allergen species. Children were more susceptible to various allergen species. With regard to sex differences, males were sensitized to more allergen species than females. Patients suffering from atopic dermatitis were sensitized to more allergenic species than patients with non-atopic eczema or urticaria.Conclusion: Allergen sensitization in patients with skin diseases in Shanghai differed by age, sex, and disease type. Knowing the prevalence of allergen sensitization across age, sex, and disease type may help facilitate diagnostic and intervention efforts, and guide the treatment and management of skin diseases in Shanghai.Keywords: atopic dermatitis, non-atopic eczema, urticaria, specific immunoglobulin E, sensitization

Ruipeng Zhong,1,2,&ast; Yun Zou,3,&ast; ShuZhen Bao,2 YiJian Chen,2 Guiming Huang,2 Lifeng Wang,3 Li Chen,3 Maolin Zhong,3 Weidong Liang3 1Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Anesthesiology,Ganzhou People’s Hospital, Ganzhou, People’s Republic of China; 3Anesthesia Surgery Center, the First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Liang, Anesthesia Surgery Center, the First Affiliated Hospital of Gannan Medical University, No. 128, Jinling West Road, Economic and Technological Development Zone, Ganzhou, Jiangxi Province, 341000, People’s Republic of China, Tel +86 15970122157, Email lwd0929@gmu.edu.cnPurpose: This study aimed to investigate the analgesic effect of ultrasound-guided transversus thoracis plane block (TTPB) combined with intermediate cervical plexus block (ICPB) in the early postoperative period after trans-areolar endoscopic thyroidectomy.Patients and Methods: A total of 62 female patients undergoing trans-areolar endoscopic thyroidectomy were randomly classified to the TTPB combined with ICPB group with ropivacaine (block group) or superficial cervical plexus block group (control group). The primary outcome measures were resting visual analogue scale (VAS) in the chest area at 6 h after surgery. The secondary outcome measures included chest resting and movement VAS score, neck resting and movement VAS score within 24 h after surgery, intraoperative remifentanil consumption, postoperative analgesia rate and analgesic requirements and patient satisfaction score for pain management at discharge.Results: Compared with the control group, the block group at rest showed consistently lower VAS scores in the chest area at 6 and 12 h after operation; the block group at rest showed lower VAS scores in the neck at 6, 12 and 24 h after operation. Regarding movement, the VAS scores of the chest and neck area at 2, 6, 12 and 24 h after the operation were lower in the block group than in the control group. The consumption of remifentanil, rate of postoperative analgesic requirements, and consumption of postoperative rescue analgesia in the block group were lower than those in the control group. Satisfaction with pain treatment at discharge was higher in the block group than in the control group.Conclusion: Ultrasound-guided TTPB combined with ICPB provides good analgesic effect in the early postoperative period after trans-areola endoscopic thyroidectomy.Keywords: regional anesthesia, nerve block, analgesia, trans-areolar endoscopic thyroidectomy

Qian Yang,1,&ast; Jing Wang,2,&ast; Ningyu Mi,2 Yulin Zou2,3 1Department of Obstetrics, Renmin Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Department of Dermatology, Renmin Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 3Department of Dermatology, Jinzhou Medical University Graduate Training Base, Renmin Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulin Zou, Email zouyl1007@qq.comAbstract: The most common type of dementia disease is Alzheimer, which placing a heavy burden on the healthcare system all over the world. At the same time, psoriasis is also one of the most common health problems, as a skin disease. Alzheimer’s disease (AD) is more often in patients with psoriasis than in the general people. Several evidence has proved the relation between AD and psoriasis through immune-mediated pathophysiologic processes. This review aims to summary the potential relation between AD and psoriasis, and provide suggestions based on the relationship at the same time. Neurologists, dermatologists should pay attention to the relationship between Alzheimer’s disease and psoriasis. Dermatology and neurology need referral each other when it is necessary.Keywords: psoriasis, Alzheimer, IL-17, relation, inflammation, genetic

Yaru Zou,1,2 Wei Gao,3 Huizhen Jin,2 Chenmei Mao,2 Yi Zhang,1 Xiaoling Wang,1 Dong Mei,1 Libo Zhao1,4 1Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Department of Pharmacy, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA; 4Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Dong Mei; Libo Zhao, Email meidong11290926@126.com; libozhao2011@163.comBackground: Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed.Methods: 6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter.Results: Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 μg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 μg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer’s patches (PPs) in rats.Conclusion: 6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.Keywords: nanomedicines, oral bioavailability, cellular uptake, transport mechanism

Jing Peng,1,* Jiaming Su,2,* Lei Song,1 Qiuyi Lv,1 Ying Gao,1 Jingling Chang,1 Hua Zhang,1 Yihuai Zou,1 Xing Chen3 1Department of Encephalopathy, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Brain Function Examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing Chen, Department of brain function examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, No. 05 Haiyuncang Road, Beijing, People’s Republic of China, Tel +86 18610044016, Email yeahchency@sina.comObjective: Limb numbness is a frequent symptom of post-stroke somatosensory dysfunction, which may be alleviated by non-invasive therapy such as acupuncture. However, the precise mechanism via acupuncture remains unknown. The goal of this study was to investigate how the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) changed between stroke patients with limb numbness and healthy people, as well as how acupuncture might work.Methods: 24 stroke sequelae patients with unilateral limb numbness and 14 matched healthy controls were enrolled in the study. The patients with limb numbness received acupuncture therapy three days a week for four weeks. We mainly assessed the clinical outcomes via the visual analogue scale (VAS). In addition, fMRI data from patients with unilateral limb numbness at baseline and after treatment (4th week) were collected, as well as data from healthy controls at baseline.Results: Compared with the healthy subjects, the patient group demonstrated significantly decreased ALFF in several brain regions, mainly associated with the sensorimotor network (SMN) and default mode network (DMN), including left superior frontal gyrus (SFG), right temporal fusiform cortex (TFC), right middle frontal gyrus (MFG), bilateral middle temporal gyrus (MTG), right putamen (PUT), right precentral gyrus (preCG), right planum polare (PP), and left supplementary motor area (SMA). These regions were chosen as the seeds for investigating the FC alteration induced by acupuncture. Several sensorimotor-related brain regions were activated by acupuncture, and the FC of the left supramarginal gyrus (SMG) with right MTG, as well as brain-stem, cerebellum vermis 9 with right MFG showed enhancement following acupuncture in the patient group, which had a significant correlation with clinical outcomes.Conclusion: Acupuncture treatment may be used to stimulate brain areas associated with somatosensory processing and to strengthen the FC of sensorimotor and cognitive brain networks in order to achieve therapeutic effect.Keywords: acupuncture, stroke, somatosensory dysfunction, functional magnetic resonance imaging, amplitude of low-frequency fluctuation, functional connectivity

Yanzheng Zou,1,* Ming Yue,2,* Linna Jia,1 Yidi Wang,1 Hongbo Chen,3 Yifan Wang,3 Meiling Zhang,3 Yue Feng,4 Rongbin Yu,1 Sheng Yang,5 Peng Huang1 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Infectious Disease, Jurong Hospital Affiliated to Jiangsu University, Jurong, People’s Republic of China; 4Faculty of Life Science and Technology, Kunming University of Science and Technology, Yunnan, People’s Republic of China; 5Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Huang, Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email huangpeng@njmu.edu.cn Sheng Yang, Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email yangsheng@njmu.edu.cnPurpose: It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes.Patients and Methods: A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years.Results: Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 > 3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 > 3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25.Conclusion: FIB-4 > 3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 > 3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.Keywords: chronic hepatitis C, sustained virologic response, direct-acting antivirals, serum biomarker, hepatocellular carcinoma

Qixian Sun,1 Xinrong Tao,1– 4 Bing Li,1 Hangbing Cao,1 Haoming Chen,1 Yuanjie Zou,1 Huihui Tao,1– 4 Min Mu,1– 4 Wenyang Wang,1 Keyi Xu1– 4 1Center for Medical Research, Medical School, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2Key Laboratory of Industrial Dust Control and Occupational Health, Ministry of Education, Anhui University of Science and Technology, Huainan, People’s Republic of China; 3Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety, Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan, People’s Republic of China; 4Engineering Laboratory of Occupational Safety and Health, Anhui Province, Anhui University of Science and Technology, Huainan, People’s Republic of ChinaCorrespondence: Xinrong Tao, Medical School, Anhui University of Science and Technology, Huainan, People’s Republic of China, Email xrtao1116@hotmail.comBackground: Silicosis is a severe pulmonary disease caused by inhaling dust containing crystalline silica. The progression of silicosis to pulmonary fibrosis is usually unavoidable. Recent studies have revealed positivity for the overexpression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary fibrosis and shown that the CXCR4 inhibitor AMD3100 attenuated pulmonary fibrosis after bleomycin challenge and paraquat exposure. However, it is unclear whether AMD3100 reduces crystalline silica-induced pulmonary fibrosis.Methods: C57BL/6 male mice were instilled intranasally with a single dose of crystalline silica (12 mg/60 μL) to establish an acute silicosis mouse model. Twelve hours later, the mice were injected intraperitoneally with 5 mg/kg AMD3100 or control solution. Then, the mice were weighed daily and sacrificed on day 7, 14, or 28 to collect lung tissue and peripheral blood. Western blotting was also applied to determine the level of CXCR4, while different histological techniques were used to assess pulmonary inflammation and fibrosis. In addition, the level of B cells in peripheral blood was measured by flow cytometry.Results: CXCR4 and its ligand CXCL12 were upregulated in the lung tissues of crystalline silica-exposed mice. Blocking CXCR4 with AMD3100 suppressed the upregulation of CXCR4/CXCL12, reduced the severity of lung injury, and prevented weight loss. It also inhibited neutrophil infiltration at inflammatory sites and neutrophil extracellular trap formation, as well as reduced B-lymphocyte aggregates in the lung. Additionally, it decreased the recruitment of circulating fibrocytes (CD45+collagen I+CXCR4+) to the lung and the deposition of collagen I and α-smooth muscle actin in lung tissue. AMD3100 also increased the level of B cells in peripheral blood, preventing circulating B cells from migrating to the injured lungs.Conclusion: Blocking CXCR4 with AMD3100 delays pulmonary inflammation and fibrosis in a silicosis mouse model, suggesting the potential of AMD3100 as a drug for treating silicosis.Keywords: CXCR4, silicosis, pulmonary fibrosis, inflammation, AMD3100, mice

Hanbi Wang,1 Zhiyuan Zhang,2 Jie Chen,1 Han Dong,3 Ying Zou,4 Wei Wang,5 Qingmei Zheng,6 Ying Feng,7 Zhangyun Tan,8 Xiaoqin Zeng,9 Yinqing Zhao,8 Yanfang Wang,1 Aijun Sun1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of International Medical Service, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, People’s Republic of China; 4Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 5Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 6Department of Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 8Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, People’s Republic of China; 9Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnObjective: To explore the needs of obstetricians and gynecologists with different working years for the contents and forms of CME.Methods: The online questionnaire was distributed on the largest academic training platform for obstetrics and gynecology in China from April 2020 to May 2020. The survey contents mainly included the training forms and training contents of CME, as well as the mastery of diseases by doctors with different working years.Results: 4458 questionnaires were returned, of which 3954 questionnaires were included in the study. There was a significant (p < 0.001) positive correlation between the mastery of 19 diseases by obstetricians and gynecologists with different working years. After adjusting for specialist departments, hospital grades, nature of units and ages, it was found that there was no statistically significant difference between the groups in gynecological endocrine-related diseases, such as precocious puberty/delayed puberty, and there was also no statistically significant difference between the groups of shorter working years in infertility, menopausal syndrome, hyperprolactinemia and premature ovarian failure.Conclusion: The most popular training content for obstetricians and gynecologists with different working years is common gynecological endocrine diseases, of which abnormal uterine bleeding, menopausal syndrome, polycystic ovarian syndrome and cervical lesions are the most selected diseases, and the most popular form of training is online.Keywords: continuing medical education, working years, internet, obstetrics and gynecology

Zehao Zheng,1,2,&ast; Renguo Guan,3,4,&ast; Yiping Zou,1,2,&ast; Zhixiang Jian,2 Ye Lin,2 Rongping Guo,3,4 Haosheng Jin2 1Shantou University Medical College, Shantou, People’s Republic of China; 2Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 4State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongping Guo, Department of Liver Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People’s Republic of China, Email guorp@sysucc.org.cn Haosheng Jin, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510060, People’s Republic of China, Email kinghaos@126.comPurpose: Our study aimed to identify inflammatory biomarkers and develop a prediction model to stratify high-risk patients for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) recurrence after curative resection.Patients and Methods: A total of 583 eligible HBV-HCC patients with curative hepatectomy from Guangdong Provincial People’s Hospital (GDPH) and Sun Ya-sen University Cancer Centre (SYSUCC) were enrolled in our study. Cox proportional hazards regression was utilized to evaluate potential risk factors for disease-free survival (RFS). The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to assess the discrimination performance. Calibration plots and decision curve analyses (DCA) were used to evaluate the calibration of the nomogram and the net benefit, respectively.Results: Based on the systemic inflammation response index (SIRI), aspartate aminotransferase to neutrophil ratio index (ANRI), China Liver Cancer (CNLC) stage and microvascular invasion, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 2-, and 3-year RFS was 0.767, 0.726, and 0.708 in the training cohort and 0.761, 0.716, and 0.715 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability.Conclusion: The novel nomogram showed a higher prognostic power for the RFS of HCC patients with curative hepatectomy than the CNLC, AJCC 8th edition and BCLC staging systems and may help oncologists identify high-risk HCC patients.Keywords: hepatocellular carcinoma, inflammatory biomarkers, nomogram, recurrence-free survival

Yezi Chen,1,2,&ast; Xiaoqin Luo,2,3,&ast; Yun Liu,4 Yunlei Zou,1,2 Shiqi Yang,1,2 Chaoqi Liu,1,2 Yun Zhao1,2 1Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, People’s Republic of China; 2Medical College of China Three Gorges University, Yichang, People’s Republic of China; 3Department of Medical Imaging Center, Renmin Hospital Affiliated to Hubei University of Medicine, Shiyan, People’s Republic of China; 4Department of Ultrasonography, Yichang Central People’s Hospital, Yichang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Zhao; Chaoqi Liu, Medical College of China Three Gorges, University, Yichang, People’s Republic of China, Email zhaoyun@ctgu.edu.cn; ctgulcq@163.comPurpose: Ultrasound nanobubbles (NBs) can kill tumor cells, mediated by their effects of cavitation and acoustic perforation through ultrasound, while as novel drug carriers, biomaterial-modified NBs release drugs at a target region. In this work, the ultrasound NBs bridged by biotin-streptavidin were prepared simultaneously to be loaded with both programmed death ligand 1 monoclonal antibody (PD-L1 mAb) and doxorubicin (DOX), which are immune checkpoint inhibitors (ICIs) and chemotherapeutic agents, to synergize immunotherapy and chemotherapy combined with sonodynamic therapy (SDT).Methods: The PD-L1 mAb/DOX NBs, using bridging affinity biotin (BRAB) technology as a bridge, were prepared by thin-film hydration and mechanical oscillation for the targeted delivery of biotinylated PD-L1 mAb and DOX. Characterization and pharmacokinetic studies of PD-L1 mAb/DOX NBs were performed in vitro and in vivo. The antitumor effect of ultrasound-mediated PD-L1 mAb/DOX-NBs was studied in the subcutaneously transplanted tumor of the H22 hepatoma model, and the mechanism of synergistic tumor repression was investigated.Results: The data of in vitro targeting experiments, contrast-enhanced ultrasound imaging (CEUS), in vivo imaging of the small animals imaging system (IVIS), and frozen sections showed that PD-L1 mAb/DOX-NBs have well-targeted aggregation in the tumor. By observing tumor inhibition rate, tissue cell apoptosis, and apoptosis-related gene and protein expression, the PD-L1 mAb/DOX-NBs group showed the best immunotherapy effects, and its tumor volume and mass inhibition rates were about 69.64% and 75.97%, respectively (P < 0.01). Therefore, blocking the PD-1/PD-L1 pathway could improve immune cells’ tumor-killing ability. Antitumor immune cytokines were further enhanced when combined with DOX-induced tumor cell apoptosis and immunogenic cell death (ICD).Conclusion: In summary, ultrasound-mediated PD-L1 mAb/DOX-NBs showed significant synergistic antitumor effects, providing a potential combined immunotherapy strategy for HCC.Keywords: ultrasound targeted nanobubble destruction, tumor immune therapy, immune checkpoint inhibitors, immunogenic cell death, drug delivery

Ting Li,1,&ast; Ling Hu,1,&ast; Xiao-Ling Yin,1 Yi Zou,1 Hai-Yan Fu,1 Hong-Lin Li2 1Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, People’s Republic of China; 2Department of Biochemistry, Medical College of Georgia, Augusta, GA, USA&ast;These authors contributed equally to this workCorrespondence: Ling Hu, Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), No.128 of Xiangshan North Road, Donghu District, Nanchang, Jiangxi, 330008, People’s Republic of China, Tel +86 0791-88862350, Fax +86 0791-6782945, Email ythulingh@163.comObjective: To retrospectively review the clinical data of type 2 diabetes mellitus (T2DM) patients hospitalized in Nanchang, China, summarized the prevalence of osteoporosis (OP) in T2DM patients in this area, and analyzed related influencing factors.Methods: The clinical data of hospitalized patients with T2DM were collected retrospectively. According to the results of bone mineral density test, the subjects were divided into the normal bone mass group, the osteopenia group, and the OP group. Age, gender, educational background, body mass index (BMI), waist-to-hip ratio (WHR), duration of T2DM, glycosylated hemoglobin, serum lipids, and complications of T2DM in the three groups were analyzed and compared.Results: The prevalence of OP in patients with T2DM was 35.77%. There were statistically significant differences in age, gender, BMI, WHR, duration of T2DM, educational background, the level of high-density lipoprotein cholesterol (HDL-C), the prevalence of diabetic retinopathy (DR), and diabetic peripheral neuropathy among the three groups (P < 0.05). Logistic regression analysis showed that increasing age, prolonged duration of T2DM, low BMI, high levels of HDL-C, and complicated DR were risk factors for osteopenia and OP.Conclusion: The prevalence of OP in T2DM was high. Risk factors for abnormal bone mass in T2DM might be females, advanced age, long duration of T2DM, low BMI, high levels of HDL-C, and diabetic microangiopathy.Keywords: type 2 diabetes mellitus, osteoporosis, risk-factors, prevalence

Chunmei Qin,1– 3 Yiting Wang,1,2 Lijun Zhao,1,2 Junlin Zhang,1,2 Honghong Ren,1,2 Yutong Zou,1,2 Yucheng Wu,1,2 Tingli Wang,1,2 Yuancheng Zhao,1,2 Rui Zhang,1,2 Huan Xu,4 Jie Zhang,5 Mark E Cooper,6 Fang Liu1,2 1Division of Nephrology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Department of Nephrology, Luzhou People’s Hospital, Luzhou, People’s Republic of China; 4Division of Pathology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 5Key Laboratory of Transplant Engineering and Immunology, Chengdu, People’s Republic of China; 6Department of Diabetes, Central Clinical School, Monash University, Melbourne, AustraliaCorrespondence: Fang Liu, Division of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-18980601214, Fax +86-28-85422335, Email liufangfh@163.comObjective: The rate of kidney function decline in patients with diabetic kidney disease (DKD) is known to differ. This study analyzed the clinicopathologic features and related risk factors affecting long-term renal survival in Chinese type 2 diabetic patients with rapid estimated glomerular filtration rate (eGFR) decline.Methods: In this retrospective descriptive study, 191 DKD patients were first classified as rapid eGFR decliners and slow eGFR decliners on the basis of the median eGFR slope value (− 8.0 mL/min/1.73 m2/year). In total, 96 patients with rapid eGFR decline were included in the analyses and subsequently allocated to end-stage renal disease (ESRD) and non-ESRD groups. Baseline clinicopathological data of rapid eGFR decliners were collected. Cox proportional hazard analysis was performed to calculate the hazard ratios (HRs) for progression to ESRD.Results: During a median follow-up of 25 months, 52 (54.2%) rapid eGFR decliners progressed to ESRD. These 52 rapid eGFR decliners had poorer renal function, lower hemoglobin and albumin concentrations, higher total cholesterol and baseline proteinuria levels, and more severe interstitial inflammation than those who did not progress to ESRD. After adjustment for age, gender, baseline eGFR, proteinuria, hemoglobin level, serum albumin concentration, and histopathologic parameters, multivariate Cox proportional hazard analysis revealed that eGFR (HR 0.973, 95% CI 0.956– 0.989) and proteinuria (HR 1.125, 95% CI 1.030– 1.228) were associated with the increased risk of progression to ESRD.Conclusion: Higher proteinuria and lower eGFR were independent risk factors for renal progression in Chinese patients with type 2 diabetes and rapid eGFR decline.Keywords: diabetic kidney disease, rapid eGFR decline, clinical, pathological, type 2 diabetes

Youqing Zou,1 Ping Sun,1 YanYan Zhang,2 Ying Li1 1Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 2Infection Intensive Care Unit, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of ChinaCorrespondence: Ying Li, Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China, Tel +86 135 0024 2293, Email playly_81@163.comPurpose: Regular physical activity is essential for maintaining health and improving people’s overall quality of life living with HIV; improving metabolic side effects associated with taking highly active antiretroviral therapy (HAART). This study investigated physical activity levels and associated factors among HIV/AIDS patients.Patients and Methods: A single-center, cross-sectional study was conducted from July to September 2021. A convenience sample of 377 HIV/AIDS patients was recruited from a medical center in Zhuhai, China. Data were collected through self-report questionnaires and patients’ medical records.Results: The average physical activity of HIV/AIDS patients was 1007.15± 868.63 met-min/w; 53.8% of patients expressed medium-level activity, and 46.2% in low-level activity. Log-link gamma generalized linear model results showed that gender, T-CD4+ at the latest visit, self-efficacy, and perceived barriers were significant predictors of assessing physical activity levels.Conclusion: Nearly half of HIV/AIDS patients have low levels of physical activity. In particular, women and patients with lower CD4 cells, lower self-efficacy, and more perceived barriers had lower levels of physical activity. More knowledge is needed on the causes of physical inactivity among people with HIV, and physical activity programs need to be developed for people living with HIV in developing countries.Keywords: acquired immune deficiency syndrome, AIDS, human immunodeficiency virus, HIV, physical activity, exercise

Guotai Sheng,1,&ast; Dingyang Liu,1,&ast; Maobin Kuang,1,&ast; Yanjia Zhong,2 Shuhua Zhang,3 Yang Zou3 1Cardiology Department, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, 330006, People’s Republic of China; 2Endocrinology Department, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 3Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Yang Zou, Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, People’s Republic of China, Email jxyxyzy@163.comPurpose: Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters.Patients and Methods: This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose–response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes.Results: Of the 15,464 people aged 18– 79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk.Conclusion: In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.Keywords: non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol, diabetes, longitudinal cohort, operator characteristic curve

Yiye Zhu,1,2 Guoshun Huang,1,2 Yang Yang,1,2 Chen Yong,1,2 Xiang Yu,1,2 Gang Wang,3 Lan Yi,1,4 Kun Gao,1,4 Fang Tian,2 Shushu Qian,2 Enchao Zhou,1,4 Yanqin Zou1,3,4 1Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Zou’s Nephrology Medicine Intangible Cultural Heritage Inheritance Studio, Nanjing Boda Nephrology Hospital, Nanjing, Jiangsu, People’s Republic of China; 4Inheritance Studio of Traditional Chinese Medicine Master Yanqin Zou, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Enchao Zhou; Yanqin Zou Tel +86-13851572603; +86-25-86538830Fax +86-25-86538830Email snk110@163.com; fsyy00650@njucm.edu.cnPurpose: Proteinuria is an independent risk factor of chronic kidney disease (CKD). Albumin-induced tubulointerstitial inflammation and epithelial-mesenchymal transition (EMT) via the activation of NLRP3 inflammasome is a potential therapeutic target for CKD. Suyin Detoxification Granule (SDG) improves proteinuria and postpones renal failure. However, the underlying mechanism is still unknown.Methods: Firstly, the rat model of renal failure was established using intragastric administration of adenine. Renal function, proteinuria, inflammatory indicators in serum, and renal pathology were assessed, and renal immunohistochemical staining of NLRP3 inflammasomes was performed after intervention with low and high concentrations of SDG. Secondly, the model of renal tubular epithelial HK-2 cells was established using albumin in vitro, and the cell viability, EMT phenotype, and the expression of proteins in the NLRP3 inflammasome signaling pathway were measured after the freeze-dried powder of Suyin Detoxification Prescription (SDP) and CY-09, which is a selective and direct NLRP3 inhibitor, were co-incubated with albumin. ATP, SOD, mitochondrial membrane potential, and ROS were further measured in vitro, and changes in the mitochondrial function after SDP intervention were observed. The mitochondrial antiviral signaling protein (MAVS) was knocked down using siRNA, and the interaction between MAVS and NLRP3 was verified using Western blotting, polymerase chain reaction (PCR), and immunofluorescence.Results: SDG improved renal function and proteinuria, alleviated renal fibrosis, and reduced serum inflammation and the expression of the components of the NLRP3 inflammasome in the kidney. In vitro, SDP and CY-09 enhanced cell viability after injury with albumin and inhibited pyroptosis induced by the NLRP3 inflammatory signaling pathway and expression of proteins involved in EMT. It was further found that SDP alleviated the mitochondrial dysfunction caused by albumin. The knockdown of MAVS reduced the expression of NLRP3 pathway proteins and their mRNA levels and also weakened the co-localization of NLRP3, thus, reducing cell pyroptosis.Conclusion: SDP protected renal tubular epithelial cells from cell pyroptosis and EMT by regulating the albumin-induced mitochondrial dysfunction/ MAVS/ NLRP3-ASC-caspase-1 inflammasome signaling pathway.Keywords: Suyin Detoxification Granule, renal tubular epithelial cells, mitochondrial dysfunction, MAVS, NLRP3 inflammasome, pyroptosis, EMT

Guobo Xie,1 Yanjia Zhong,2 Shuo Yang,3 Yang Zou4 1Cardiology Department, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Endocrinology Department, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Cardiology Department, Dean County People’s Hospital, Jiujiang, Jiangxi, People’s Republic of China; 4From the Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Yang Zou Email jxyxyzy@163.comPurpose: Remnant cholesterol (RC) is the cholesterol of triglyceride-rich lipoproteins, which has a high degree of atherogenic effect. To date, epidemiological evidence supports that higher RC levels lead to a greater risk of adverse cardiovascular events in patients with diabetes, but the nature of the association between RC levels and diabetes risk remains unclear. This study was designed to assess the association of RC with the risk of new-onset diabetes and to investigate whether there is a causal relationship between the two.Patients and Methods: The subjects included 15,464 individuals of the general population who participated in a health examination. Subjects were quartered according to the RC quartile, and the Cox proportional hazard model was used to assess the independent association between RC and new-onset diabetes.Results: During an average observation period of 6.13 years, 2.41% of the subjects were diagnosed with new-onset diabetes. Kaplan–Meier analysis showed that the 13-year cumulative diabetes rates corresponding to the RC quartile were 8.62%, 2.49%, 12.78%, and 17.91%. Multivariate Cox regression analysis indicated that higher RC levels were independently associated with an increased risk of new-onset diabetes (HR: 2.44, 95% CI: 1.50– 3.89). Additionally, according to the results of receiver operating characteristic curve analysis, RC had the largest area under the curve (0.7314) compared to traditional lipid parameters in predicting new-onset diabetes.Conclusion: These results indicated that RC is an important independent predictor of new-onset diabetes in the general population.Keywords: diabetes, remnant cholesterol, independent predictor, cohort study

Yulin Zou, Zudong Meng Department of Dermatology, Renmin Hospital, Hubei University of Medicine, Shiyan City, People’s Republic of ChinaCorrespondence: Zudong Meng Email zylmch1007@hbmu.edu.cnAbstract: The COVID-19 pandemic has posed a serious problem for drug anti-viral efficacy in combatting the cytokine storm triggered by SARS-CoV-2. From dermato-epidemiological studies conducted on psoriatic and other rheumatological patients, IL-17 inhibitors seem to attenuate or even prevent the cytokine storm and thus ICU referral. Furthermore, both in-vivo and in-vitro experiments suggest that IL-17 plays a key role in SARS-CoV-2 infection progression. Due to this evidence, we decided to summarize the literature findings on IL-17 inhibitors and COVID-19, maintaining psoriasis as the referral disease to better understand the extent of drug effects on the immune system.Keywords: biologics, COVID-19, psoriasis, therapy, IL-17

Shunxin Zhu,1 Caixiu Zeng,2 Yan Zou,1 Yanjiao Hu,1 Canfang Tang,1 Chunmei Liu2 1Clinical Laboratory, The Maternity & Child Health Care Hospital of Xiangtan City, Xiangtan City, Hunan Province, 411100, People’s Republic of China; 2Department of Pediatrics, The Maternity & Child Health Care Hospital of Xiangtan City, Xiangtan City, Hunan Province, 411100, People’s Republic of ChinaCorrespondence: Shunxin ZhuClinical Laboratory, The Maternity & Child Health Care Hospital of Xiangtan City, Xiangtan City, Hunan Province, 411100, People’s Republic of ChinaTel +86- 18975221633Email zhushunxin349@126.comBackground: Bacterial, viral, and bacterial and viral co-infections generally lead to inflammatory-related diseases. The aim of this study is to assess the clinical diagnostic values of serum amyloid A (SAA), procalcitonin (PCT), C-reactive protein (CRP), and interleukin (IL)-6 in children with bacterial, viral, or co-infections.Methods: A total of 181 children with infection symptoms (bacterial infection (Bac group), n = 46; viral infection (Vir group), n = 7; co-infections (Bac + Vir group), n = 128) were enrolled in our hospital from December 2019 to April 2020. Meanwhile, 42 healthy children without any infections were used as the controls. Venous blood samples were collected and the levels of serum SAA, PCT, CRP, and IL-6 were determined by immunoluminometric assay under an IMMAGE® analyzer. The diagnostic values of these biomarkers were assessed using the receiver operating characteristic (ROC) curves.Results: The results indicated that IL-6 level was increased in three infection groups compared to the controls. Both SAA and CRP were significantly elevated in Vir and Bac + Vir groups. High level of PCT was observed in Bac and Bac + Vir goups. In addition, PCT (0.9281, 95% CI = 0.8645– 0.9916) alone is an effective method for identifying bacterial infections. SAA in combination with CRP may distinguish co-infection from bacterial infection. Simultaneous positive of SAA, PCT, IL-6, and CRP can discriminate co-infection from the healthy controls.Conclusion: In a word, the levels of serum SAA, PCT, CRP, and IL-6 are increased to varying degrees in different infection situations. Our findings may provide early diagnosis for patients with different infections.Keywords: bacterial infection, viral infection, co-infection, combined biomarkers, diagnostic accuracy

Chih-Jung Chang,1,2,&ast; Hai-Qing Wang,3,&ast; Jing Zhang,3 Ying Zou,3 Yi-Hua Zhang,3 Jia-Wen Chen,3 Chun-Bing Chen,2,4– 7 Wen-Hung Chung,1,2,4– 6,8,9 Chao Ji3 1Medical Research Center and Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, Fujian, People’s Republic of China; 2Department of Dermatology and Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan; 3Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5College of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; 7Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; 8Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, Fujian, People’s Republic of China; 9School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen-Hung ChungDepartment of Dermatology and Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, TaiwanTel +886-3-3281200 ext. 8494Email wenhungchung@yahoo.comChao JiDepartment of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaTel +86-18651619908Email jichaofy@fjmu.edu.cnBackground: Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disorder characterized by a T helper 2 (Th2) immune response phenotype. Extracellular vesicles (EVs) are a heterogeneous family of cell-derived membranous structures, which transport cellular components such as DNA and proteins, and are involved in multiple physiological and pathological processes. Increasing evidence has shown that EVs secretion took part in the pathogenesis of AD. However, the proteomic studies of plasma-derived EVs in AD patients have not been reported.Objective: In this study, we investigated the diversity of plasma EVs collected from AD patients and healthy individuals and suggested that the candidates for uniquely or differentially expressed proteins in plasma EVs could be a diagnostic marker in AD.Methods: The plasma EVs were collected from 12 patients with moderate-to-severe AD and 13 healthy subjects. Proteomic analysis was performed by using a comprehensive nanoLC‑MS/MS method.Results: Proteomic analysis revealed that a total of 1478 proteins in plasma EVs were found to be common proteins in AD, whereas a total of 1597 proteins in plasma EVs were found to be common proteins in HC. Eighty-six proteins in plasma EVs showed more than 2.5-fold up-regulation, while a total of 225 proteins in plasma EVs showed less than 1/2.5-fold down-regulation with a significant difference (p < 0.05) among AD compared with HC. The candidates for differentially expressed proteins in plasma EVs have been described as a connectivity PPI network related to several KEGG pathways, including pathways in platelet activation, complement, and so on.Conclusion: SLP-76 tyrosine phosphoprotein (SLP76) involved in platelet activation may significantly contribute to the pathogenesis of AD. We will further verify the role of SLP67 in AD via animal and cell experiments to provide a promising therapeutic or diagnostic target.Keywords: atopic dermatitis, extracellular vesicle, plasma, proteomic profiling

Zuyi Ma,1,2,&ast; Zhenchong Li,1,3,&ast; Shujie Wang,1,4,&ast; Qi Zhou,5,6,&ast; Zuguang Ma,7 Chunsheng Liu,1,2 Bowen Huang,8 Zehao Zheng,1,2 LinLing Yang,9 Yiping Zou,1,2 Chuanzhao Zhang,1,3,4 Shanzhou Huang,1,3,4 Baohua Hou1,3,4 1Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Shantou University of Medical College, Shantou, 515000, People’s Republic of China; 3South China University of Technology School of Medicine, Guangzhou, 51000, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Department of General Surgery, Hui Ya Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Huizhou, 516081, People’s Republic of China; 6Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510000, People’s Republic of China; 7Sanshui Disease Prevention Cure Station, Foshan, 528100, People’s Republic of China; 8Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 9Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanzhou Huang; Baohua Hou Tel +86 13928842869; +86 13609006510Email hshanzh@163.com; hbh1000@126.comBackground: Recent evidence has shown that Solute Carrier Family 39 Member 10 (SLC39A10) promoted tumor progression in several cancer types. The study intended to explore the expression and function of SLC39A10 in hepatocellular carcinoma (HCC).Methods: Multiple bioinformatics analyses were used to evaluate SLC39A10 expression and potential role in HCC. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to confirm SLC39A10 expression. Intro studies were performed to assess the effects of SLC39A10 on HCC cells proliferation and migration. Furthermore, flow cytometry was conducted to identify its specific function in apoptosis of HCC.Results: SLC39A10 was significantly over-expressed in HCC samples from both bioinformatic databases and our cohort. Survival analyses suggested patients with high expression of SLC39A10 had poor overall survival and disease-free survival (P-value < 0.01). Further, the expression of SLC39A10 was positively correlated with tumor-infiltrating lymphocytes and some immune checkpoints like CTLA4, TIM3 and TGFB1. In HCC cell lines, SLC39A10 knockdown inhibited cells proliferation and migration, but promoted apoptosis.Conclusion: An increased SLC39A10 expression was found and served as an unfavorable indicator of survival in HCC. Further studies suggested SLC39A10 promotes tumor aggressiveness and may provide a novel target for HCC therapy.Keywords: Solute Carrier Family 39 Member 10, hepatocellular carcinoma, immune infiltration, prognosis, cancer aggressiveness

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

Hongjie Qian,1,2 Qian Chen,1,2 Liyu Liang,1,2 Yang Zou,1,2 Huahua Pu,1,2 Liang Xin,1,2 Rong Song,1,2 Tingting Li,1,2 Huijuan Zhu,1,2 Yu Wang,3 Guanghui Tian,4 Jingshan Shen,2,3 Hualiang Jiang,2,3 Chen Yu,1,2 Zhen Wang,2,3 Jingying Jia1,2 1Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, 200031, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, 200031, People’s Republic of China; 3CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China; 4Vigonvita Life Science Co., Ltd., Suzhou, 215123, People’s Republic of ChinaCorrespondence: Jingying JiaShanghai Xuhui Central Hospital, No. 966, Huaihai Road(M), Shanghai, 200031, People’s Republic of ChinaTel/Fax +86 21 54030254Email jyjia@shxh-centerlab.comZhen WangShanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zu Chong Zhi Road, Pudong, Shanghai, 201203, People’s Republic of ChinaTel +86 21 20231000Fax +86 21 20231962Email wangzhen@simm.ac.cnPurpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H.Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: In Part I, AUC and Cmax were proved to be linear within the 5– 30 mg dose range. T1/2 of TPN171H was 8.02– 10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease Cmax, prolong Tmax, but had no effect on AUC. In Part III, the accumulation ratio at steady-state for AUC and Cmax indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination.Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.Keywords: TPN171H, PDE5 inhibitor, safety, pharmacokinetics, food effect, healthy subjects

Dingtao Hu,1,&ast; Nana Meng,2,&ast; Xiaoqi Lou,1 Zhen Li,3 Ying Teng,3 Bizhi Tu,4 Yanfeng Zou,3 Fang Wang1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Quality Management Office, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang WangDepartment of Oncology, The First Affiliated Hospital of Anhui Medical University, 218Jixi Road, Hefei, 230022, Anhui, People’s Republic of ChinaTel +86055162923615Fax +86055162923615Email wangfangahmu@163.comYanfeng ZouDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81, Meishan Road, Shushan District, Hefei, 230032, Anhui, People’s Republic of ChinaEmail zouyanfeng2015@163.comBackground: Numerous studies on the E2F transcription factors have led to increasing insights that E2Fs could be an important driver of the formation and progression of many human cancers. Little is known about the function of distinct E2Fs in chromophobe renal cell carcinoma (chRCC).Methods: We utilized the UALCAN, GEPIA, Cancer Genome Atlas (TCGA) database, cBioPortal, Metascape, STRING, Cytoscape, GeneMANIA, TIMER, TISIDB, GSCALite, and MEXPRESS databases to investigate the transcription level, genetic alteration, methylation, and biological function of E2Fs in chRCC patients, and its association with the occurrence, progress, prognosis, and immune cell infiltration in patients with chRCC.Results: We found that E2F1/2/4/7/8 were more expressed in chRCC tissues than in normal tissues, while the expression of E2F5/6 was lower in the former than in the latter, and the expression levels of E2F1/2/4/5/6//7/8 were also associated with the histological parameters of chRCC, including T-stage and N-stage. Higher expression of E2F1/2/7/8 was found to be significantly correlated with worse overall survival (OS) in chRCC patients. Cox regression and time-dependent ROC analysis further suggested that E2F1/2 could be the potential independent biomarkers for chRCC prognosis. Besides, a moderate mutation rate of E2Fs (34%) was noticed in chRCC, and the genetic mutations in E2Fs were associated with poor survival of chRCC patients. We noticed that the expression of E2Fs was statistically correlated with the immune cell infiltration in chRCC. Moreover, we also found that the expression of E2F1 was significantly correlated with tumor-infiltrating lymphocytes and immunomodulators, E2F7 expression was associated with MHC molecules, and the expression of E2F1/8 was correlated to their methylation levels.Conclusion: Our results provide novel insights for selecting the prognostic biomarkers for chRCC and suggest that E2F1/2 could act as potential prognostic biomarkers for the survival of chRCC patients. However, more in-depth experiments are required to identify the underlying mechanisms and verify the clinical value of E2F1/2 in the prognosis of chRCC.Keywords: chromophobe renal cell carcinoma, E2Fs, prognosis, UALCAN, GEPIA