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Liyan Wu,1 Zhenyan Yuan,1 Min Wang,1 Xiaomeng Fu,1 Xiaohui Liu,1 Bing Wei,2 Yugeng Liu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China; 2Emergency Medicine Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, 100043, People’s Republic of ChinaCorrespondence: Bing Wei; Yugeng Liu, Email dr_weibing@126.com; yugeng_liu@126.comPurpose: Sepsis is a life-threatening condition associated with acute organ dysfunction. Iron is an essential trace element for multicellular organisms and almost all microorganisms, and its role in sepsis has been increasingly recognized. The aim of this study was to investigate the changes in iron metabolism in caecal ligation and puncture solution (CLP) -induced septic mice and the effects of hepcidin pretreatment on serum inflammatory marker levels and liver iron metabolism in CLP-induced septic mice.Methods: C57BL/6 mice were given normal saline, CLP (peritonitis model) or 100 μg of hepcidin via intraperitoneal injection. The experimental animals were divided into 4 groups: the control group, model group (CLP), hepcidin pretreatment Groups CLP+hepcidin-2h and CLP+hepcidin-24 h. Blood samples were collected at 6, 12 and 24 hours after CLP surgery, and the mice were euthanized and livers were obtained.Results: ELISA revealed that hepcidin pretreatment, especially 2 hours in advance (p< 0.01), increased the serum hepcidin, TNF-a and IL-6 in CLP-induced septic mice; the serum iron content of CLP-related septic mice decreased (P< 0.01), while the liver iron content increased (P< 0.01); Hepcidin pretreatment reduced the serum iron (P< 0.05) at 6 h and 12 h and liver iron concentrations (P< 0.01) at 6 h, 12 h and 24 h in CLP-related septic mice. Western blotting revealed that the hepatic iron absorption-related proteins transferrin receptor-2 (TFR2), ZRT/IRT-like protein 14 (ZIP14) and divalent meta lion transporter-1 (DMT1) were elevated (P< 0.01); The iron-exporting protein ferroportin (SLC40A1) was decreased (P< 0.01) throughout CLP and CLP+hepcidin sepsis. Compared with CLP group, the protein expressions in the CLP+ hepcidin-2 h group were more obvious than that in the CLP+ hepcidin-24 h group.Conclusion: Hepcidin has proinflammatory effect. Hepcidin exacerbates iron metabolism imbalances in sepsis by influencing the expression of iron absorption-related proteins and iron export-related proteins.Keywords: hepcidin, sepsis, iron metabolism, SLC40A1, liver

Xueyun Fu,&ast; Xue Tian,&ast; Jing Lin, Qian Wang, Lingwen Gu, Ziyi Wang, Menghui Chi, Bing Yu, Zhuhui Feng, Wenyao Liu, Lina Zhang, Cui Li, Guiqiu Zhao Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cui Li; Guiqiu Zhao, Department of Ophthalmology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Email yankelicui@126.com; zhaoguiqiu_good@126.comBackground: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability.Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability.Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis.Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro.Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.Keywords: fungal keratitis, MOFs, antifungal, anti-inflammatory, ZIF-8

Leilei Zhao,1 Xinmeng Fu,2 Hongbin Cheng3 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Traditional Chinese Medicine Department, Boao Yiling Life Care Center, Qionghai, Hainan Province, People’s Republic of China; 3Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Hongbin Cheng, Email chenghongbin@cdutcm.edu.cnAbstract: Melasma is a benign but emotionally distressing skin condition that reduces patients’ quality of life, with prevalence rates during pregnancy ranging from 36.4% to 75%. Troublingly, up to 30% of cases are reported to persist after delivery, even ten years later. And recurrence and aggravation are common in subsequent pregnancies. This review examines the risk factors and mechanisms associated with melasma during pregnancy and summarized corresponding preventive strategies. We emphasize the critical role of photoprotection, including the use of sunscreens from the first trimester, in reducing the incidence of melasma.Keywords: melasma, pregnancy, risk factors, prevention, photoprotection

Jiale Xu,&ast; Musen Xu,&ast; Xin Gao, Jiahang Liu, Jingchao Sun, Ruiqi Ling, Xuchen Zhao, Xifeng Fu, Shaojian Mo, Yanzhang Tian Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanzhang Tian, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99, Longcheng Street, Xiaodian District, Taiyuan, Shanxi Province, People’s Republic of China, Phone/Fax +86-13903512030, Email tyz2030@163.comObjective: To analyze the influence of diabetes mellitus on the clinical outcomes of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP).Methods: This retrospective study included patients diagnosed with MSAP and SAP at Shanxi Bethune Hospital from January 1, 2017, to December 31, 2021. Clinical data were collected, including patient demographics, 24-hour laboratory indicators, and inflammation indices. Propensity score matching (PSM) was used to compare outcomes before and after matching. Patients were randomized into training and validation sets (7:3) to develop and validate a clinical prediction model for infected pancreatic necrosis (IPN).Results: Among 421 patients, 79 had diabetes at admission. Before PSM, diabetic patients had higher incidences of peripancreatic fluid (71% vs 47%, p< 0.001) and IPN (48% vs 10%, p< 0.001), higher surgical intervention rates (24% vs 12%, p=0.008), and significant differences in abdominocentesis (22% vs 11%, p=0.014). After PSM, 174 patients were matched, and the diabetes group still showed higher incidences of peripancreatic fluid (69% vs 47%, p=0.008), IPN (48% vs 11%, p< 0.001), and surgical intervention rates (27% vs 13%, p=0.037). Diabetes, modified CT severity index (MCTSI), serum calcium, and HDL-c were identified as independent risk factors for IPN. The prediction model demonstrated good predictive value.Conclusion: In MSAP and SAP patients, diabetes mellitus can exert an influence on their clinical outcome and is an independent risk factor for IPN. The alignment diagram and web calculator constructed on the basis of diabetes mellitus, modified CT severity index (MCTSI), serum calcium and high-density lipoprotein cholesterol (HDL-c) have good predictive value and clinical guidance for the occurrence of IPN in MSAP and SAP.Keywords: acute pancreatitis, diabetes, propensity score matching, predictive model

Mingtao Liu,1,&ast; Zhangkai J Cheng,1,&ast; Jiaxi Chen,2,&ast; Haiyang Li,1,3 Mingshan Xue,4,5 Xing Fu,1 Yanjun Li,2 Jiaxin Wang,2 Chenwei You,2 Haisheng Hu,1 Haojie Wu,1 Huimin Huang,1 Baoqing Sun1,4 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 511495, People’s Republic of China; 3MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK; 4Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of China; 5Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Huimin Huang, Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China, Tel +86 13824124015 ; +86 13631496651, Email sunbaoqing@vip.163.com; huanghuimin311@126.comBackground: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored.Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients.Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (&ast;p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin’s potential as a reliable biomarker for assessing IPF severity and therapeutic response.Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.Keywords: periostin, Krebs von den Lungen-6, idiopathic pulmonary fibrosis, HRCT fibrosis score, diagnostic hematology

Menghan Yu,1 Xiaoshu Fu,1 Yanli Zhu,2 Miao Li,3 Min Wu,1 Entong Zhou,1 Hanwen Dong,1 Likun Wang,1 Ruoxi Wang,4 Fang Liu,2 Chunlai Jiang,1 Xiangwei Kong,5 Weiheng Su1,6 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2People’s Hospital of Jiangyuan District, Baishan, Jilin Province, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China; 4School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Changchun University of Science and Technology, Changchun, People’s Republic of China; 6Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Weiheng Su, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China, Email suweiheng@jlu.edu.cn Xiangwei Kong, Changchun University of Science and Technology, Changchun, People’s Republic of China, Email tenbpro@163.comPurpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study.Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics.Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients.Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.Keywords: tick-borne encephalitis, TBE, tick-borne encephalitis virus, TBEV, TaqMan qPCR, IgM

Xiaoming Fu,1 Fuhai Zeng,2 Linling Li,1 Guoquan Liu,1 Qing Zhong,3 Shouwan Chen1 1Department of Burn and Plastic Surgery, The People’s Hospital of Jianyang City, Jianyang, Sichuan, People’s Republic of China; 2Department of Plastic and Maxillofacial Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Science and Technology, The People’s Hospital of Jianyang City, Jianyang, Sichuan, People’s Republic of ChinaCorrespondence: Shouwan Chen, Department of Burn and Plastic Surgery, The People’s Hospital of Jianyang City, No. 180 Hospital Road, Jianyang, Sichuan, 641400, People’s Republic of China, Email drshouwang@163.comBackground: The existing observational research on the relationship between physical activity (PA) and skin cancer (SC) is contentious, which points to the intricate nature of their association and underscores the imperative for more nuanced research to untangle the causal dynamics at play. The aim of this article is to delve deeper into this complex relationship, seeking to clarify whether PA serves as a protective factor against SC, or contributes to its risk.Methods: We utilized data from the genome-wide association study (GWAS) of PA from GWAS Catalog (include self-reported moderate to vigorous PA (MVPA), self-reported vigorous PA (VPA), and accelerometer-based average-accelerated PA). The data of SC is from FinnGen. All of the participants are of European ancestry. We used two-sample Mendelian Randomization (TSMR) to analyze the causal relationship between PA and SC.The research was conducted using inverse variance weighted (IVW) method as the primary approach, and MR Egger regression as supplementary analytical method. To ensure the robustness of the results, Cochran’s Q-test and MR pleiotropy residual sum and outlier (MR-PRESSO) global tests were used to measure sensitivity.Results: Our analysis indicated that average-accelerated PA was associated with an increased risk of SC (ORIVW = 0.94, 95% CI 0.93– 0.96, P

Xiujing Lu,&ast; Xi Lan,&ast; Xiaoqian Fu, Jing Li, Min Wu, Lu Xiao, Yachang Zeng Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yachang Zeng, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email zengyachang@163.comPurpose: Preeclampsia (PE) is a serious complication of obstetrics and represents a significant challenge in terms of understanding its underlying mechanism. It has been shown that a number of disorders involve dysregulation of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2). However, the relationship between PE and CITED2 is still mostly unclear. This work aimed to confirm the hub genes linked to PE and explore the roles of CITED2 in trophoblast using experimental and bioinformatic methods.Methods: To determine the hub genes, bioinformatics research was performed on two datasets from the Gene Expression Omnibus (GEO) public database. Immune infiltration analysis and enrichment analysis were also used to identify the related pathways and immune cells. PCR and WB were then used to validate the mRNA and protein levels of CITED2 in the PE samples. Finally, the expression of CITED2 was knocked down using siRNA to investigate the function of CITED2 in trophoblast development in vitro.Results: The study’s findings showed that the NOTCH signaling pathways, glycolysis, and hypoxia were the main areas of enrichment for the six PE-related genes that were tested. The results of immune infiltration suggest that activated NK cells and regulatory T cells may play an important role in this process. CITED2 was significantly upregulated in the PE placenta. In functional tests, the knockdown of CITED2 may enhance apoptosis while suppressing migration, invasion, and proliferation of cells.Conclusion: This study offers important proof that CITED2 influences trophoblast cell function and may one day be a therapeutic target for PE.Keywords: preeclampsia, CITED2, placenta, cell function, bioinformatics

Yang Li,1 Xue Yan,2 Zhen Luo,1 Xianxian Fu,1 Zhongju Li,1 Qiuzhu Xu,3 Juanjuan Chen,1 Jingmin Yang,2,4,5 Daru Lu4,5 1Department of Nephropathy, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Hainan, People’s Republic of China; 2Department of Medicine, Shanghai WeHealth Biomedical Technology Co., Ltd., Shanghai, People’s Republic of China; 3Department of Central Supply Service Department, Haikou Orthopedic and Diabetes Hospital, Hainan, People’s Republic of China; 4NHC Key Laboratory of Birth Defects and Reproductive Health (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning, Science and Technology Research Institute), Chongqing, People’s Republic of China; 5State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jingmin Yang; Daru Lu, Email jingmin.yang@we-health.vip; Email drlu@fudan.edu.cnIntroduction: X-linked Alport syndrome (XLAS) is caused by pathogenic variants in COL4A5 which lead to abnormalities of the glomerular basement membrane (GBM) structural and is characterized by progressive kidney disease, hearing loss, and ocular abnormalities. The aim of this study was to identify gene mutations in a Chinese family with XLAS by whole-exome sequencing (WES) and verified the pathogenicity of the mutation in vitro experiments.Case Presentation: A five-generation pedigree with a total of 49 family members originating from Hainan province of China was investigated in this study. The proband was a 23-year-old male who developed microscopic hematuria, proteinuria and end-stage kidney disease (ESKD) at age 17. WES identified a novel splicing mutation c.321+5G>A of COL4A5, which cause exon skip. Further co-segregation analysis confirmed that this mutation exists in relatives who had renal abnormalities using Sanger sequencing. According to American College of Medical Genetics and Genomics guidelines (ACMG), the mutation was determined to be of uncertain significance (VUS). In vitro splicing experiments have shown that the COL4A5 variant induces aberrant mRNA splicing and transcript deletion.Conclusion: We identified a novel intronic COL4A5 pathogenic mutation (c.321+5G>A) in a Chinese XLAS family and described the phenotypes of affected relatives. This study expands the mutation spectrum of COL4A5 gene in XLAS and demonstrates the importance of gene screening for AS.Keywords: Alport syndrome, COL4A5, whole exome sequencing, mRNA splicing, case series

Kaiyu Wang,1,&ast; Yan Gao,1,&ast; Shan Wu,1,&ast; Jin Zhang,1 Manfang Zhu,2 Xiayu Chen,1 Xizi Fu,1 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.comBackground: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (&epsiv;-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.Keywords: mRNA gene therapy, dual-mRNA delivery, tumor cell lysates, Bim and IL-23A mRNAs, immune response

Chenxi Zeng,1,&ast; Qi Wang,2,&ast; Xuhan Liu,3,&ast; Kai Wang,1 Congjian Wang,1 Xuetao Ju,1 Tianlai Wang,1 Qing Zhou,4 Xiangning Fu,1 Jun Yu,1 Yi Wang4 1Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 3Department of Emergency Medicine, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Wang, Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, People’s Republic of China, Email wangyi@tjh.tjmu.edu.cn Jun Yu, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, People’s Republic of China, Email junyu2018@hotmail.comBackground: Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by chronic lung injury leading to macrophage infiltration and fibroblast activation. However, there is no effective therapeutic strategy targeting the crucial crosstalk between macrophages and fibroblasts to halt IPF progression.Methods: Studies were conducted in IPF patients and fibrotic mice models to elucidate the role of Bcar3 in the pathogenesis of pulmonary fibrosis. The effect of Bcar3 on macrophage polarization, fibroblast activation, and related signaling pathways were next investigated to unravel the underlying mechanisms.Results: Our study elucidates a marked increase in Bcar3 expression in lung tissues from IPF patients and fibrotic mice, recording 1.7 and 7.8-fold increases compared to control subjects, respectively. Additionally, Bcar3 was found to significantly enhance macrophage activation and fibroblast differentiation, observable in both in vivo and in vitro settings. Mechanistically, the upregulation of Bcar3 in macrophages was reliant on Stat6, while in fibroblasts, it depended on TGFβR1/Smad3. Furthermore, Bcar3 augmented IL-4/Stat6 pathway in macrophages and TGF-β/Smad3 pathway in fibroblasts, supporting a synergistic activation loop that expedited lung fibrogenesis. Notably, intratracheal injection of liposomes containing Bcar3 siRNA precisely delivered gene therapeutics to lung macrophages and fibroblasts, effectively reducing Bcar3 expression to 59% of baseline levels. Importantly, this intervention protected mice from lung fibrosis induced by either FITC or bleomycin, as well as human precision-cut lung slices against TGF-β 1 stimulation.Conclusion: Our study underscores the pivotal role of Bcar3 in orchestrating the macrophage-fibroblast crosstalk during pulmonary fibrosis progression. Targeting Bcar3 emerges as a novel therapeutic avenue to halt IPF progression and enhance patient prognosis.Keywords: idiopathic pulmonary fibrosis, Bcar3, liposomes, macrophages, fibroblasts

Yang Liu,1,2,&ast; Hui Yang,1,2,&ast; Xueshu Fu,1,2 Luting Zhong,1,2 Ping Xu,1,2 Fang Fang,1,2 Ying Liu,1,2 Qing Li,1,2 Ya’nan Yan,1,2 Shanchuang Wei,1,2 Junqing Wang,1,2 Chunhua Zhang1– 3 1Department of Gynaecology, Affiliated Hospital of YangZhou University Huai ‘an Maternal and Child Health Care Center, Huai’an, Jiangsu, People’s Republic of China; 2Department of Gynaecology, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Department of Integrated Traditional Chinese & Western Clinical Medicine, Macau University of Science and Technology, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhua Zhang, Department of Gynaecology, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China, Tel +86-13952326117, Email hafyzch@126.comBackground: Multiple primary cancer (MPC) refers to the presence of more than one cancer in an individual. Triple primary malignancies are uncommon.Case: We report the case of a 50-year-old postmenopausal woman in our gynecology department, diagnosed with endometrial cancer, ovarian cancer, and unilateral breast cancer. She carried germline mutations in BRCA2, PALB2, and RECQL4, along with a somatic pathogenic variant in TP53. Endometrial cancer patients harboring germline pathogenic variants in BRCA2 exhibit a heightened risk of ovarian and breast cancer. BRCA2 is known to play a role in the development of ovarian and breast cancer, while PALB2 is identified as a gene associated with breast cancer susceptibility. RECQL4 has been linked to breast cancer, cervical cancer, and other tumors.Conclusion: Genetic testing may be imperative for identifying MPC in endometrial cancer patients. For individuals with BRCA2 and other gene pathogenic variants, routine examination and monitoring of the endometrium, ovaries, breasts, and other sites prone to polygenic cancer are recommended.Keywords: multiple primary cancer, endometrial cancer, ovarian cancer, breast cancer, genetic test

Jing Huang,1,&ast; Kaiyu Wang,1,&ast; Xizi Fu,1,&ast; Manfang Zhu,2 Xiaohua Chen,1 Yan Gao,1 Pingchuan Ma,3 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 3State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comBackground: Messenger ribonucleic acid (mRNA)-based gene therapy has great potential in cancer treatment. However, the application of mRNA-based cancer treatment could be further developed. Elevated delivery ability and enhanced immune response are advantages for expanding the application of mRNA-based cancer therapy. It is crucial that the prepared carrier can cause an immune reaction based on the efficient delivery of mRNA.Methods: We reported DMP nanoparticle previously, which was obtained by the self-assembly of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and (ethylene glycol)-b-poly (&epsiv;-caprolactone) (mPEG-PCL). Research demonstrated that DMP can deliver mRNA, siRNA, and plasmid. And it is applied to various tumor types. In our work, the tumor cell lysate was introduced to the internal DMP chain, fusing cell-penetrating peptides (CPPs) modification on the surface forming the CLSV system. And then mixed encoded IL-22BP (interleukin-22 binding protein) mRNA and CLSV to form CLSV/IL-22BP complex.Results: The size of the CLSV system was 213.2 nm, and the potential was 45.7 mV. The transfection efficiency of the CLSV system is up to 76.45% in C26 cells via the micropinocytosis pathway. The CLSV system also could induce an immune response and significantly elevate the expression of CD80, CD86, and MHC-II in vivo. Then, by binding with IL-22BP (Interleukin-22 binding protein) mRNA, the CLSV/IL-22BP complex inhibited tumor cell growth, with an inhibition rate of up to 82.3% in vitro. The CLSV/IL-22BP complex also inhibited tumor growth in vivo, the tumor cell growth inhibition up to 75.0% in the subcutaneous tumor model, and 84.9% in the abdominal cavity metastasis tumor model.Conclusion: Our work demonstrates that the CLSV system represents a potent potential for mRNA delivery.Keywords: mRNA, cell-penetrating peptide, gene therapy, tumor cell lysate, immune response

Yinshan Lin,1,2,&ast; Xiaoling Guan,1,2,&ast; Jianfen Su,1,2,&ast; Sheng Chen,2 Xihua Fu,1 Xiaowei Xu,2 Xiaohua Deng,2 Jishuo Chang,2 Aiping Qin,2,&ast; Ao Shen,2,&ast; Lingmin Zhang1,2,&ast; 1Pharmacy Department & Panyu Institute of Infectious Diseases, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, 511400, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingmin Zhang, Guangzhou Panyu Central Hospital, No. 8 Fuyu East Road, Guangzhou, Guangdong, 511400, People’s Republic of China, Email zhanglm@gzhmu.edu.cn Ao Shen; Aiping Qin, Guangzhou Medical University, No. 1 Xinzao Road, Guangzhou, Guangdong, 511426, People’s Republic of China, Email shenao@gzhmu.edu.cn; qinaiping_2008@163.comAbstract: Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery. Keywords: nucleic acids, bioinspired nanoparticles, non-viral vehicles, gene therapy, cell membranes

Songbai Xu,1 Guangxin Zhang,2 Jiaomei Zhang,1 Wei Liu,2 Yicun Wang,2 Xiying Fu2 1Department of Neurosurgery, Department of Obstetrics, Obstetrics and Gynaecology Center, the First Hospital Jilin University, Changchun, People’s Republic of China; 2Department of Endocrinology, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yicun Wang; Xiying Fu, Email wangyicun@jlu.edu.cn; fuxiying@jlu.edu.cnAbstract: Brain tumors, including primary gliomas and brain metastases, are one of the deadliest tumors because effective macromolecular antitumor drugs cannot easily penetrate the blood-brain barrier (BBB) and blood-brain tumor barrier (BTB). Magnetic nanoparticles (MNPs) are considered the most suitable nanocarriers for the delivery of brain tumor drugs because of their unique properties compared to other nanoparticles. Numerous preclinical and clinical studies have demonstrated the potential of these nanoparticles in magnetic targeting, nuclear magnetic resonance, magnetic thermal therapy, and ultrasonic hyperthermia. To further develop and optimize MNPs for the diagnosis and treatment of brain tumors, we attempt to outline recent advances in the use of MNPs to deliver drugs, with a particular focus on their efficacy in the delivery of anti-brain tumor drugs based on magnetic targeting and low-intensity focused ultrasound, magnetic resonance imaging for surgical real-time guidance, and magnetothermal and ultrasonic hyperthermia therapy. Furthermore, we summarize recent findings on the clinical application of MNPs and the research limitations that need to be addressed in clinical translation.Keywords: magnetic nanoparticles, blood-brain tumor barrier, tumor therapy, drug delivery, brain tumor

Lietao Wang,1,&ast; Xin Fu,1,&ast; Min He,1,&ast; Lvyuan Shi,1 Dingyuan Wan,1 Yucong Wang,1 Qin Wu,1 Jing Yang,1 Bayuan Cai,2 Hongtao Xia,3 Hongxu Chen,4 Ge Zhang,5 Xianying Lei,6 Wei Zhang,7 Zhongxue Feng,7 Bo Wang,1 Zhongwei Zhang1 On behalf of Heat Stroke Research Group in Southwestern China1Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Critical Care Medicine, The People’s Hospital of Jiajiang, Leshan, People’s Republic of China; 3Department of Critical Care Medicine, Suining Central Hospital, Suining, People’s Republic of China; 4Department of Critical Care Medicine, The Hospital of Traditional Chinese Medicine of Leshan, Leshan, People’s Republic of China; 5Department of Critical Care Medicine, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 6Department of Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 7Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Wang; Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85422739, Email wchicu@126.com; 716461751@qq.comObjective: The aim of this nationwide multicenter study was to ascertain the risk factors associated with in-hospital mortality in patients with heat stroke admitted to intensive care units (ICUs) and to develop a nomogram for prognostic prediction.Methods: A retrospective analysis was conducted on clinical data collected from ICU patients diagnosed with heat stroke across multiple centers nationwide. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for in-hospital mortality. Based on the results of the multivariate analysis, a nomogram was constructed to estimate the individualized probability of mortality. Internal validation of the nomogram was performed, and its performance was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).Results: A total of 292 ICU patients with heat stroke were included in this study. Three risk factors, namely Cr (creatinine), AST (aspartate aminotransferase), and SBP (systolic blood pressure), were found to be significantly associated with in-hospital mortality. These risk factors were incorporated into the nomogram, which exhibited good discriminative ability (area under the ROC curve of the training and validation cohorts were 0.763 and 0.739, respectively) and calibration. Internal validation and decision curve analysis confirmed the stability and reliability of the nomogram.Conclusion: This nationwide multicenter study identified key risk factors for in-hospital mortality in ICU patients with heat stroke. The developed nomogram provides an individualized prediction of mortality risk and can serve as a valuable tool for clinicians in the assessment and management of ICU patients with heat stroke.Keywords: heat stroke, intensive care unit, in-hospital mortality, risk factors, nomogram

Wei Gan,1,&ast; Yan Bi,2,&ast; Xuwen Fu,1 Jialu Wei,1 Min Qi,1 Jintang He,3 Xiang Li1 1Department of Radiology, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, 650041, People’s Republic of China; 2Department of Radiology, The People’s Hospital of Lincang, Lincang, Yunnan, 677000, People’s Republic of China; 3Department of Surgery, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, 650041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Li, Department of Radiology, Kunming Third People’s Hospital /Yunnan Clinical Medical Center for Infectious Diseases, No. 319 of Wujing Street, Guandu District, Kunming, 650041, People’s Republic of China, Tel +86 871 6352 3507, Fax +86 871 6351 4717, Email li_xiang115@126.com Jintang He, Department of Surgery, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, No. 319 of Wujing Street, Guandu District, Kunming, 650041, People’s Republic of China, Tel +86 871 6842 3689, Fax +86 871 6351 4717, Email he_jintang06@21cn.comObjective: This study aimed to examine the radiographic manifestations of seminal vesicle tuberculosis (SVT) on magnetic resonance imaging to gain a deeper understanding of this disease.Methods: The clinical symptoms, general conditions, relevant laboratory tests and radiological data of 13 patients diagnosed with SVT were collected through bacteriological examination. A descriptive analysis was used to explore the composition ratio and rate values of the collected data.Results: All 13 cases (100.0%) showed isointense signals on T1WI and hypointense signals on T2WI in the affected seminal vesicles, with the disappearance of the multi-chambered high signal on T2WI in normal seminal vesicles. Eight cases (61.5%) showed diffusion restriction on DWI of the affected seminal vesicle and significant enhancement on the contrast scan, whereas five cases (38.5%) showed unrestricted diffusion and mild enhancement on the contrast scan. Patients with significant enhancements exhibited higher counts and neutrophil percentages than patients with mild enhancements, with statistically significant differences (Z = 2.196, P = 0.030; Z = 2.781, P = 0.003, respectively). The counts and percentage of lymphocytes, CD3+T cells and CD4+T cells were significantly lower in patients with significant enhancements than in those with mild enhancements, with statistically significant differences (Z = − 2.196, P = 0.030; Z = − 2.928, P = 0.002; Z = − 2.928, P = 0.002; Z = − 2.928, P = 0.002, respectively). Patients with significant enhancements were more likely to have active pulmonary tuberculosis than those with mild enhancements, with a statistically significant difference (P = 0.035).Conclusion: Magnetic resonance imaging reveals distinct radiographic features of SVT, and variations in imaging presentations can indicate a patient’s immune status.Keywords: seminal vesicle tuberculosis, magnetic resonance imaging, genitourinary tuberculosis

Limin Jia,1 Yanfeng Wang,2 Wenyuan Zhang,3 Yulian Lin,1 Fang Chen,1 Yixiao Wan,1 Xin Fu4,5 1Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, People’s Republic of China; 2Department of Geriatrics, Taizhou Central Hospital (Taizhou University Hospital) of Zhejiang, Taizhou, Zhejiang, 318000, People’s Republic of China; 3Department of ICU, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, People’s Republic of China; 4Department of Radiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, 317000, People’s Republic of China; 5Department of Radiology, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, Zhejiang, 318000, People’s Republic of ChinaCorrespondence: Xin Fu, Department of Radiology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, No. 150 Ximen Street, Linhai City, Taizhou, Zhejiang, 317000, People’s Republic of China, Tel + 86-0576-85120120, Email fux005ing@126.comBackground and Purpose: To explore the feasibility of the modified blood collection method in pre-deposit autotransfusion in patients undergoing thoracotomy surgery.Methods: This double-blinded randomised controlled trial enrolled 92 patients from the cardiothoracic surgery department from February 2019 to October 2020.Results: Compared with the conventional blood collection method, the modified blood collection method avoided blood overflow from the oblique plane of the needle (χ2 = 61.986, P < 0.01) and reduced the diameter of the bruising area after 24 hours (χ2 = 24.611, P < 0.01). Furthermore, due to optimising the blood collection method, diastolic blood pressure reduced slightly before and after blood collection (t = 2.036, P < 0.05), and patients in the test group had less pain (based on the numerical rating score) (t = 5.556, P < 0.01). Meanwhile, the time required to collect 400 mL of blood was shortened (t = 17.744, p < 0.01).Conclusion: An improved blood collection method can enhance the blood donation experience, avoid blood spillage, lessen pain and reduce adverse reactions. This may be of great significance in ensuring blood quality and the safety of subsequent transfusions.Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT05539846.Keywords: pre-deposit autotransfusion, extracorporeal circulation, open heart surgery

Xuzhe Fu,1 Zhi Liu,2 Yu Wang1 1Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Yu Wang, Email wangy8@sj-hospital.orgAbstract: Sepsis is a life-threatening disease caused by a systemic infection that triggers a dysregulated immune response. Sepsis is an important cause of death in intensive care units (ICUs), poses a major threat to human health, and is a common cause of death in ICUs worldwide. The pathogenesis of sepsis is intricate and involves a complex interplay of pro- and anti-inflammatory mechanisms that can lead to excessive inflammation, immunosuppression, and potentially long-term immune disorders. Recent evidence highlights the importance of immunosuppression in sepsis. Immunosuppression is recognized as a predisposing factor for increased susceptibility to secondary infections and mortality in patients. Immunosuppression due to sepsis increases a patient’s chance of re-infection and increases organ load. In addition, antibiotics, fluid resuscitation, and organ support therapy have limited impact on the prognosis of septic patients. Therapeutic approaches by suppressing excessive inflammation have not achieved the desired results in clinical trials. Research into immunosuppression has brought new hope for the treatment of sepsis, and a number of therapeutic approaches have demonstrated the potential of immunostimulatory therapies. In this article, we will focus on the mechanisms of immunosuppression and markers of immune monitoring in sepsis and describe various targets for immunostimulatory therapy in sepsis.Keywords: sepsis, hyperinflammation, immunosuppression, immune cell

Xiangjie Fu,1 Yaqiong Ni,2 Guanchen Wang,3 Runda Nie,3 Yang Wang,4 Run Yao,1 Danyang Yan,1 Mingming Guo,3 Ning Li1 1Department of Blood Transfusion, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Hunan Provincial Key Laboratory of Micro&Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, People’s Republic of China; 4Institute of Integrative Medicine, Key Laboratory of Hunan Province for Liver Manifestation of Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Ning Li, Tel +86 731 84327436, Email liningxy@csu.edu.cnBackground: Multidrug-resistant staphylococcus aureus infected wounds can lead to nonhealing, systemic infections, and even death. Although advanced dressings are effective in protecting, disinfecting, and maintaining moist microenvironments, they often have limitations such as single functionality, inadequate drug release, poor biosafety, or high rates of drug resistance.Methods: Here, a novel wound dressing comprising glycyrrhizic acid (GA) and tryptophan-sorbitol carbon quantum dots (WS-CQDs) was developed, which exhibit synergistic and long-lasting antibacterial and anti-inflammatory effects. We investigated the characterization, mechanical properties, synergistic antibacterial effects, sustained-release properties, and cytotoxicity of GA/WS-CQDs hydrogels in vitro. Additionally, we performed transcriptome sequence analysis to elucidate the antibacterial mechanism. Furthermore, we evaluated the biosafety, anti-inflammatory effects, and wound healing ability of GA/WS-CQDs dressings using an in vivo mouse model of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds.Results: The prepared GA/WS-CQDs hydrogels demonstrated superior anti-MRSA effects compared to common antibiotics in vitro. Furthermore, the sustained release of WS-CQDs from GA/WS-CQDs hydrogels lasted for up to 60 h, with a cumulative release of exceeding 90%. The sustained-released WS-CQDs exhibited excellent anti-MRSA effects, with low drug resistance attributed to DNA damage and inhibition of bacterial biofilm formation. Notably, in vivo experiments showed that GA/WS-CQDs dressings reduced the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and significantly promoted the healing of MRSA-infected wounds with almost no systemic toxicity. Importantly, the dressings did not require replacement during the treatment process.Conclusion: These findings emphasize the high suitability of GA/WS-CQDs dressings for MRSA-infected wound healing and their potential for clinical translation.Graphical Abstract: Keywords: tryptophan-sorbitol CQDs, glycyrrhizic acid, wound dressings, synergistic synergism, sustained release, methicillin-resistant staphylococcus aureus-infected wounds healing

Zipeng Xu,1,&ast; Yong Zhao,2,&ast; Xu Fu,3,&ast; Weidong Hu,1 Chunlong Zhao,1 Chen Ge,1 Hui Ye,4,5 Chaobo Chen1,3,5 1Department of General Surgery, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of China; 2Department of General Surgery, Wuxi Rehabilitation Hospital, Wuxi, 214007, People’s Republic of China; 3Department of General Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical school, Nanjing, 210008, People’s Republic of China; 4Department of Anesthesiology, ZhongDa Hospital, Southeast University, Nanjing, 210009, People’s Republic of China; 5Department of Immunology, Ophthalmology & ORL, Complutense University School of Medicine, Madrid, 28040, Spain&ast;These authors contributed equally to this workCorrespondence: Chaobo Chen; Hui Ye, Email bobo19820106@gmail.com; carciapene@126.comObjective: Although laparoscopic repair has been widely carried out and promoted due to its minimally invasive advantages, open surgery is still popular compared to elderly patients. This study aims to compare the outcomes of laparoscopic (LIHR) vs open repair of inguinal hernias (OIHR) in elderly patients.Methods: A retrospective analysis of the database was performed to identify elderly patients, from January 2021 through December 2022, who underwent surgery for an inguinal hernia. After a 1:1 propensity score matching (PSM) with a caliper of 0.1 was conducted to balance potential bias, binary logistic regressions were used for categorical and continuous outcomes.Results: After PSM, 78 pairs of elderly patients were enrolled in this study, and there were no significant differences in baseline between LIHR and OIHR groups. Compared to OIHR, univariable and multivariable logistic regression analysis showed that LIHR was independently affected for reducing intraoperative hemorrhage (OR = 0.06, 95% CI: 0.02– 0.18, P < 0.001) and shortening postoperative hospitalization time (OR = 0.29, 95% CI: 0.15– 0.57, P < 0.001) in elderly patients. Furthermore, LIHR (OR = 0.28, 95% CI: 0.14– 0.57, P < 0.001) and age (OR = 0.89, 95% CI: 0.82– 0.96, P = 0.002) were independent affecting factors for relieving postoperative pain. Meanwhile, no obvious differences were detected in postoperative complications [LIHR 7.7% (6/78) vs OIHR 14.1% (11/78), P = 0.199].Conclusion: LIHR was closely associated with reducing intraoperative hemorrhage and shortening postoperative hospitalization time. Whilst LIHR and age were independently affecting factors for relieving postoperative pain.Keywords: inguinal hernia, propensity score matching, elderly patient, laparoscopy, retrospective study

Mengtong Chen,1,2,&ast; Yuting Zhang,1,2,&ast; Yuqiao Mao,1 Yunwen Lian,1 Peng Ye,1 Chunlong Liu,2 Zhijie Zhang,3 Xihua Fu1 1Department of Infectious Diseases Unit, Panyu Central Hospital, Guangzhou, People’s Republic of China; 2College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Rehabilitation, Luoyang Orthopedics Hospital of Henan Province, Luoyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xihua Fu, Email 455170667@qq.comBackground: Chronic Obstructive Pulmonary Disease (COPD) is the leading cause of death in the world. Pulmonary rehabilitation includes, but is not limited to, exercise training and education, which aim to improve the physical and psychological conditions of patients with chronic respiratory diseases through self-management interventions.Objective: The aim of this study was to perform a bibliometric analysis of studies on exercise and COPD published from 2000 to 2021 using VOSviewer and CiteSpace.Methods: All included literature was obtained from the Web of Science core collection. VOSviewer was used to analyze country or region, institution, major co-cited journals, and keywords. CiteSpace was used to analyze centrality, author and co-cited authors, journals, the strongest citation bursts of references, and keywords.Results: A total of 1889 articles meeting the criteria were obtained. The United States has the largest number of publications. The American Journal of Respiratory and Critical Care Medicine is the most influential in this field, and the most published research institution is Queen’s University. Denis E. O’Donnell has made significant contributions to exercise and COPD research. Association, impact, and statement are hot spots of research in this field.Conclusion: A bibliometric analysis of exercise interventions for COPD over the past 22 years provides direction for future research.Keywords: bibliometrics, visualization, exercise, COPD, research hotspots