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Jingxia Mao,1,2,&ast; Guibo Yang,1,3,&ast; Qin Su,1,4,&ast; Zhonghong Zeng,1 Jueying Lin,2 Lin Kong,3 Lidun Zhang,4 Lidan Liu,1 Yihua Yang,1 Hongbo Wu1 1Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Obstetrics, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Obstetrics, The Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Obstetrics, The First People’s Hospital of Yulin, Yulin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo Wu; Yihua Yang, Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email 19587200@qq.com; workyyh@163.comObjective: To assess the safety and efficiency of in vitro fertilization/ intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) on maternal and neonatal perinatal outcomes in women (≥ 40y) with singleton pregnancies.Methods: This multi-center retrospective cohort study, carried out from January 2018 to June 2023, enrolled 1762 women (≥ 40y) with singleton pregnancies of at least 28 weeks. Participants were divided into two groups: the IVF/ICSI-ET group (204 cases) and the spontaneous conception (SC) group (1558 cases). After 1:2 propensity score matching (PSM), the two groups were compared for maternal and neonatal outcomes. The SC group (1558 cases) was further divided by age into the < 43 years group (1195 cases) and the ≥ 43 years group (363 cases) for subgroup analysis.Results: Adverse maternal and neonatal outcomes were comparable between the IVF/ICSI-ET group and the SC group, with a higher cesarean section rate (78% vs 67.5%, P =0.013), an increased maternal ICU admissions rate (5.5% vs 1.3%, P =0.008), and a lower birth defects rate (1.1% vs 4.6%, P =0.037) in the IVF/ICSI-ET group. Subgroup analysis showed that women aged ≥ 43 years had higher incidences of gestational diabetes, gestational hypertension, cesarean section, and neonatal asphyxia compared to women aged < 43 years.Conclusion: This study indicated IVF/ICSI-ET is relatively safe for women ≥ 40 years with singleton pregnancies. However, advanced maternal age deteriorated maternal and neonatal outcomes, and IVF/ICSI-ET further heightened the risk of cesarean section and maternal ICU admissions. Therefore, enhanced care and vigilance are crucial for women over 40 undergoing IVF/ICSI-ET.Keywords: in-vitro fertilization, intracytoplasmic sperm injection, advanced maternal age, maternal outcomes, neonatal outcomes

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

Xiaolan Guo,1 Dansen Wu,1 Xiaoping Chen,2 Jing Lin,1 Jialong Chen,1 Liming Wang,1 Songjing Shi,1 Huobao Yang,1 Ziyi Liu,3 Donghuang Hong1,4 1Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 2Computer Science and Mathematics, Fujian University of Technology, Fuzhou, Fujian, People’s Republic of China; 3Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Ziyi Liu, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai, 200127, People’s Republic of China, Email liu-ziyi@sjtu.edu.cn Donghuang Hong, Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134, Dongjie Street, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email hongdh2003@fjmu.edu.cnPurpose: The objective of this study was to identify the risk factors associated with Carbapenem-resistant Enterobacteriaceae (CRE) colonization in intensive care unit (ICU) patients and to develop a predictive risk model for CRE colonization.Patients and Methods: In this study, 121 ICU patients from Fujian Provincial Hospital were enrolled between January 2021 and July 2022. Based on bacterial culture results from rectal and throat swabs, patients were categorized into two groups: CRE-colonized (n = 18) and non-CRE-colonized (n = 103). To address class imbalance, Synthetic Minority Over-sampling Technique (SMOTE) was applied. Statistical analyses including T-tests, Chi-square tests, and Mann–Whitney U-tests were employed to compare differences between the groups. Feature selection was performed using Lasso regression and Random Forest algorithms. A Logistic regression model was then developed to predict CRE colonization risk, and the results were presented in a nomogram.Results: After applying SMOTE, the dataset included 198 CRE-colonized patients and 180 non-CRE-colonized patients, ensuring balanced groups. The two groups were comparable in most clinical characteristics except for diabetes, previous emergency department admission, and abdominal infection. Eight independent risk factors for CRE colonization were identified through Random Forest, Lasso regression, and Logistic regression, including Acute Physiology and Chronic Health Evaluation (APACHE) II score > 16, length of hospital stay > 31 days, female gender, previous carbapenem antibiotic exposure, skin infection, multi-site infection, immunosuppressant exposure, and tracheal intubation. The risk prediction model for CRE colonization demonstrated high accuracy (87.83%), recall rate (89.9%), precision (85.6%), and an AUC value of 0.877. Patients were categorized into low-risk (0– 90 points), medium-risk (91– 160 points), and high-risk (161– 381 points) groups, with corresponding CRE colonization rates of 1.82%, 7.14%, and 58.33%, respectively.Conclusion: This study identified independent risk factors for CRE colonization and developed a predictive model for assessing the risk of CRE colonization.Keywords: carbapenem-resistant Enterobacteriaceae, intensive care unit, colonization, risk factors, risk prediction model

Jingyu Zhang,1,&ast; Shenhua Qu,2,&ast; Yuting Huang,1,&ast; Xia Zhang,1 Xiubing Tong,1 Yanping Fang,1 Tianyu Rao,1 Kezhi Liu,1 Jia Lin,1 Yuye Lin,1 Chufan Zeng,1 Guojun Zhang,1 Xianghong Jing,3 Jun Liao,1 Yu Kan1 1College of Acupuncture and Tuina, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 2Guangzhou Traditional Chinese Medicine Hospital, Guangzhou, 510000, People’s Republic of China; 3Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Liao; Yu Kan, Email 2007065@fjtcm.edu.cn; 2019035@fjtcm.edu.cnPurpose: Chronic cervical muscle injury is the first common cause of the development of cervical spondylosis, and Tuina can effectively promote the repair of chronic cervical muscle injury and alleviate neck pain, but the mechanism behind its efficacy is still unknown. The proliferation and differentiation of muscle satellite cells and the apoptosis of cervical myocytes play important roles in the repair of chronic cervical muscle injuries; therefore, this study aimed to explore the potential mechanisms of Tuina to promote the repair of cervical muscle injuries in terms of the proliferation and differentiation of satellite cells and the apoptosis of myocytes.Patients and Methods: Twenty-eight Wistar rats were randomly divided into control group, model group, Tuina group, and meloxicam group, with 7 rats in each group. Except for the control group, each group were establish a chronic cervical muscle injury model (CCMI). Meloxicam (0.79 mg/kg) was administered by gavage, and in the Tuina group, pressure was applied to the Fengchi acupoint on the affected side once a day. Morphological changes of cervical muscle tissues were detected by ultrasonic diagnostic instrument and HE staining, electrophysiological recordings of electromyographic changes, apoptosis rate was detected by TUNEL staining, and positive expression of Bax, Bcl-2, IGF-1, MyoD, and Pax-7 were detected by Immunohistochemistry and Western blot.Results: In CCMI model rats, we observed that the cervical muscle fibers were disorganized, with irregular morphology, and the amplitude of electromyography was significantly weakened, while Tuina could significantly improve these symptoms and effectively promote the repair of chronic cervical muscle injury. Meanwhile, compared with the model group, Tuina could significantly increase the expression levels of IGF-1 (P< 0.01) and MyoD (P< 0.05) and decrease the expression level of Pax7 (P< 0.05). In addition, we found that the number of apoptotic cells in cervical myocytes was reduced after Tuina intervention (P< 0.05), and Tuina inhibited the expression of pro-apoptotic factor Bax (P< 0.01) and promoted the expression of anti-apoptotic factor Bcl-2 (P< 0.05).Conclusion: Tuina can promote the proliferation and differentiation of satellite cells to repair chronic cervical muscle injury by regulating the expression of Pax7, MyoD, and IGF-1, as well as inhibiting the expression of Bax and promoting the expression of Bcl-2 to ameliorate the apoptosis of cervical myocytes in CCMI model rats.Keywords: Tuina, cervical spondylosis, neck pain, satellite cell

Jing Li,1,2,&ast; Ganxiao Chen,1,&ast; Zhanxiong Xie,1 Jiayi Lin,1 Shunxiang Luo,1 Shanghua Xu1 1Department of Cardiology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, Fujian, People’s Republic of China; 2Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanghua Xu; Shunxiang Luo, Department of Cardiology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, People’s Republic of China, Email xushanghua@fjmu.edu.cn; luoshunxiang@fjmu.edu.cnPurpose: Flavonoids are naturally occurring compounds with diverse health-promoting properties. The purpose of this study was to explore the associations between dietary flavonoid intake and cardiovascular health in cancer survivors.Patients and Methods: We obtained data from the National Health and Nutrition Examination Survey (NHANES) 2007– 2008, 2009– 2010, and 2017– 2018 cycles. Weighted linear regression and restricted cubic spline (RCS) were used to explore the correlation between dietary flavonoid intake and cardiovascular health (Life’s Essential 8 (LE8) score) in cancer survivors. Then, weighted quantile sum (WQS) regression and quantile-based g-computation (qgcomp) models were performed to assess the mixed effects of the six flavonoid subclasses and to determine the major flavonoid types. Additionally, the protective effect of high flavonoid intake on cardiovascular health was further evaluated in different subgroups, and mediation analysis was used to explore mediating factors.Results: After adjusting for all covariates, compared to those in the first quartile, participants in the fourth quartile of total flavonoids, anthocyanidins, flavonols, flavanones, and flavones intake exhibited increases in LE8 scores of 3.24% (95% CI: 0.45– 6.03, P for trend=0.030), 6.25% (95% CI: 3.14– 9.36, P for trend< 0.001), 3.01% (95% CI: 1.33– 4.69, P for trend= 0.003), 3.23% (95% CI: 0.18– 6.27, P for trend=0.030), and 5.01% (95% CI: 2.42– 7.61, P for trend< 0.001), respectively. Meanwhile, significant non-linear relationships were supported by the RCS models. However, the weighted linear regression and RCS models did not reveal any clear correlations between isoflavone or flavan-3-ol intake and the LE8 score. Regarding mixed effects, anthocyanidin, flavonol, flavanone, and flavone intake were positively related to the LE8 score according to both the WQS and qgcomp models, and anthocyanidin intake was the major contributor.Conclusion: Our study indicated that dietary flavonoid intake is positively associated with cardiovascular health in cancer survivors, among which anthocyanidin intake might provide the most benefit. Keywords: weighted quantile sum, life’s essential 8 score, restricted cubic spline, NHANES

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

Xiaoyan Hong,1 Yangrong Huang,1 Wei Lin,1 Yi Zhang,1 Jianyun Lin,1 Shengguo Zhang,2 Fengquan Cai,1 Jie Chen1 1Department of Emergency, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), Wenzhou, Zhejiang, People’s Republic of China; 2Department of Infection, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Fengquan Cai; Jie Chen, Department of Emergency, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), 108 Wansong Road, Wenzhou, 325200, Zhejiang, People’s Republic of China, Tel +86-13967723666 ; +86-13587409966, Email cfqruiyi@163.com; woshichenjie@wmu.edu.cnAbstract: Staphylococcus aureus (S. aureus) infection is readily disseminated, yet the multiple septic arthritis and extensive migratory skin and soft tissue infections it causes are uncommon and challenging to treat. The infection can be life-threatening, with a mortality rate of 15– 31%. Early, targeted antibiotic therapy is critical to improve prognosis. However, routine cultures are time-consuming and have low positivity rates, which may lead to errors in antibiotic regimen selection, depriving patients of optimal treatment. Genetic testing technologies, such as macrogenomic next-generation sequencing (mNGS) and digital polymerase chain reaction (dPCR), are now emerging as powerful tools for early pathogen diagnosis as well as pathogen diagnosis of target detectors with low microbial loads. In this study, we report a 53-year-old man who was admitted to the ICU for treatment of septic shock. The causative agent was targeted earlier as S. aureus by mNGS, and the shock was corrected more quickly with targeted antibiotic medication. However, he later developed multiple septic arthritis and an extensive migratory skin soft tissue infection with persistent fever, and at one point a gram-negative bacterial infection was suspected, and the antibiotic regimen was incorrectly changed. Blood dPCR suggested that the causative organism was still methicillin-sensitive S. aureus (MSSA), with no drug resistance gene detected, and the anti-infective regimen was readjusted, and the patient eventually recovered and was discharged from the hospital. We present this rare case and review related studies to validate the superiority of genetic testing technology in pathogen diagnosis, which deserves further application.Keywords: disseminated Staphylococcus aureus disease, multiple suppurative arthritis, extensive migratory skin and soft tissue infections, digital polymerase chain reaction, next-generation sequencing

Chen Wang, Jinping Yuan, Huiwen Yu, Jiaying Lin, Bingxue Bai Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Bingxue Bai, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email baibingxue@hrbmu.edu.cnBackground: Psoriasis and vitiligo are two common autoimmune skin diseases with increased risk of comorbidities, but the common molecular mechanism about the occurrence of these two diseases is still unknown.Objective: This study aimed to identify the combined genetic profiles and evaluate the potential mechanism underlying the occurrence of this complication.Methods: The Gene Expression Omnibus (GEO) database was used to obtain the gene expression profiles of psoriasis (GSE30999) and vitiligo (GSE75819), and common differentially expressed genes (DEGs) were identified using GEO2R. DEGs were analyzed using functional enrichment analysis, protein-protein interaction (PPI) network and module construction, hub gene identification, and co-expression analysis. And hub genes were identified using Cytoscape software, and the gene expression of hub genes were validated in psoriasis (GSE13355) and vitiligo (GSE65127) datasets and immunohistochemistry at the clinical sample.Results: A total of 164 common DEGs with the same trend (137 upregulated and 27 downregulated) were selected for subsequent analysis. Functional analysis emphasized the important roles of the cell cycle and mitotic cell division, cytoskeletal reorganization, and chromatin remodeling in the complications of these two diseases. Fourteen important hub genes were identified, including BUB1, CEP55, CDK1, TOP2A, CENPF, PBK, MELK, CCNB2, MAD2L1, NUSAP1, TTK, NEK2, CDKN3, and PTTG1. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) may be an important immune checkpoint in the pathogenesis of the comorbidities.Conclusion: Our study identified hub genes and potential mechanisms underlying psoriasis and vitiligo complications. And we proposed a new spatio-temporal theory and the probable immune checkpoint for the pathogenesis of the comorbidity which may provide new ideas for the further research.Keywords: psoriasis, vitiligo, comorbidity, differentially expressed genes, bioinformatics, mitotic cell division, cell cycle, cytoskeleton, immune checkpoint

Zhuajin Bi,1,2 Huajie Gao,1,2 Jing Lin,1,2 Mengcui Gui,1,2 Yue Li,1,2 Zhijun Li,1,2 Bitao Bu1,2 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhijun Li, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, Email lizhijun@tjh.tjmu.edu.cn Bitao Bu, Email bubitao@tjh.tjmu.edu.cnPurpose: To investigate the predictors for poor outcomes (including disease exacerbation, hospitalization and myasthenic crisis) in patients with pre-existing myasthenia gravis (MG) following Coronavirus disease 2019 (COVID-19), and to explore the potential effects of COVID-19 on inflammatory and immune responses in MG patients.Patients and Methods: This retrospective cohort study analyzed medical records of 845 MG patients who were diagnosed with COVID-19 between January 2020 to March 2023 at a single medical center.Results: Generalized MG at onset and comorbidities (chronic kidney disease and malignancy) were independent risk factors of poor outcomes. Patients achieving minimal manifestation or better status before COVID-19 had a significantly reduced risk for poor outcomes. Furthermore, patients with older onset age or anti-acetylcholine receptor antibody had a higher risk of exacerbation and hospitalization than those without. Prednisone or immunosuppressant treatment had the potential to reduce the occurrence of poor outcomes, while the duration of prednisone or immunosuppressant usage was associated with a higher risk of poor outcomes. Of the 376 MG patients with blood results available, patients with COVID-19 tended to have higher levels of leukocyte counts, neutrophil-lymphocyte-ratio, hypersensitive C-reactive protein, and Interleukin-6, as well as lower percentages of lymphocytes and regulatory T cells compared to patients without COVID-19.Conclusion: Disease severity at onset, comorbidities, and unsatisfactory control of myasthenic symptoms predicted the occurrence of poor outcomes in MG patients following COVID-19. The risk of poor outcomes was reduced in patients controlled by short-term immunosuppressive therapy. Novel coronavirus might affect inflammatory and immune responses in MG patients, particularly in altering interleukin-6 and regulatory T cell levels.Keywords: myasthenia gravis, COVID‐19, poor outcomes, immunosuppressive treatment, immune responses

Yucheng Wu,1,&ast; Jie Qiu,1,&ast; Xiang Sha,1,&ast; Benbingdi Gong,1 Jian Wang,1 Wei Yuan,1 Jie Lin,1 Lichun Wang,1 Qingqing Zhang2 1Department of Cardiology, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 2Panvascular Management Center, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lichun Wang, Department of Cardiology, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366 Taihu Road, Taizhou, 225300, Jiangsu Province, People’s Republic of China, Email 18652711566@163.com Qingqing Zhang, Panvascular Management Center, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366 Taihu Road, Taizhou, 225300, Jiangsu Province, People’s Republic of China, Email 18061986120@189.cnBackground: Management strategies for stable angina include pharmacotherapy, revascularization, and exercise-based cardiac rehabilitation (CR). The optimal treatment for stable angina patients with severe coronary artery stenosis remains unclear. This study aimed to compare interventional therapy with exercise rehabilitation in this population.Methods: Fifty stable angina patients with severe coronary stenosis who underwent stent implantation were included in the optimal medical therapy (OMT) plus percutaneous coronary intervention (PCI) group, and 50 patients who did not undergo interventional treatment were included in OMT plus CR group receiving exercise rehabilitation guidance for one year. Cardiovascular composite endpoint events, cardiopulmonary fitness, and quality of life scale scores were assessed after one year.Results: No significant difference in incidence of cardiovascular composite endpoint events was observed between OMT plus PCI group with OMT plus CR group (20.0% vs 14.6%) after one year. Cardiopulmonary fitness represented as peak VO2 (19.2± 3.5 vs 17.6± 3.2 mL/kg/min), peak load (120± 19 vs 108± 20 W), and AT (13.5± 1.5 vs 12.1± 1.3 mL/kg/min) were significantly higher in the rehabilitation group than the intervention group after one year. Both groups showed improvement in their quality of life, but the rehabilitation group improved in more scales.Conclusion: Interventional therapy did not reduce cardiovascular events compared to exercise-based rehabilitation in stable angina patients with severe coronary artery stenosis, but the rehabilitation can improve cardiovascular fitness and quality of life more.Keywords: cardiac rehabilitation, stable angina, percutaneous coronary intervention, cardiopulmonary fitness

Ying Zhu,1 Tao Zeng,1 Hongbo Huai,2 Tong Zhu,3 Ying Huang,3 Jing Li,3 Jian Lin3 1Department of Pain Medicine, Kunshan Integrated TCM and Western Medicine Hospital, Kunshan, 215332, People’s Republic of China; 2Rehabilitation Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Department of Pain Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Hongbo Huai; Tong Zhu, Email Huaihongbo@njglyy.com; 1911033561@qq.comPurpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia.Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data.Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000).Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches.Clinical Trial Registration: ChiCTR2300073281.Keywords: ophthalmic, herpetic neuralgia, pulsed radiofrequency, Gasserian ganglion, opioids

Dongzhu Lu,1,&ast; Huapeng Yu,2,&ast; Lichang Chen,3 Jinlan Lin,1 Shijie Chen,1 Yunjian Huang1 1Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 2Department of Respiratory Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjian Huang, Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People’s Republic of China, Tel +86 13805099580, Email yunjian13@126.comPurpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma–COPD overlap (ACO) and explored their relationships with airflow limitation.Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of − 860 HU to − 950 HU (RVC− 860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships.Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC− 860 to − 950 levels decreased in the following order: ACO, COPD, and asthma. RVC− 860 to − 950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC− 860 to − 950 in ACO patients.Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.Keywords: asthma, COPD, asthma-COPD overlap, quantitative HRCT, structure-function relationship

Ziwei Jiang,&ast; Lianglong Chen,&ast; Lei Huang, Shengxiang Yu, Jiabao Lin, Mengyao Li, Yanbin Gao, Lei Yang Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang, Department of Burns, Nanfang Hospital, Southern Medical University, Jingxi Street, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1841, Email yuanyang@smu.edu.cnAbstract: Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.Keywords: endogenous stem cell homing, in situ tissue regeneration, biomimetic design, wound healing, bioactive materials

Jiaqiong Lin,1,2 Yan Lin,3 Xiaoyong Li,4 Fei He,5 Qinyuan Gao,3 Yuanjun Wang,3 Zena Huang,3 Fu Xiong5,6 1Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 2Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, People’s Republic of China; 3Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 4General Surgery Department; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 6Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Fu Xiong, Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email xiongfu@smu.edu.cn Zena Huang, Yunkang School of Medicine and Health, Nanfang College, Guangzhou, 510970, People’s Republic of China, Email 506647168@qq.comBackground: Diabetic kidney disease (DKD) is an intricate complication of diabetes with limited treatment options. Anoikis, a programmed cell death activated by loss of cell anchorage to the extracellular matrix, participated in various physiological and pathological processes. Our study aimed to elucidate the role of anoikis-related genes in DKD pathogenesis.Methods: Differentially expressed genes (DEGs) associated with anoikis in DKD were identified. Weighted gene co-expression network analysis (WGCNA) was conducted to identify DKD-correlated modules and assess their functional implications. A diagnostic model for DKD was developed using LASSO regression and Gene set variation analysis (GSVA) was performed for enrichment analysis. Experimental validation was employed to validate the significance of selected genes in the progression of DKD.Results: We identified 10 anoikis-related DEGs involved in key signaling pathways impacting DKD progression. WGCNA highlighted the yellow module’s significant enrichment in immune response and regulatory pathways. Correlation analysis further revealed the association between immune infiltration and anoikis-related DEGs. Our LASSO regression-based diagnostic model demonstrated a well-predictive efficacy with seven identified genes. GSVA indicated that gene function in the high-risk group was primarily associated with immune regulation. Further experimental validation using diabetic mouse models and data analysis in the single-cell dataset confirmed the significance of PYCARD and SFN in DKD progression. High glucose stimulation in RAW264.7 and TCMK-1 cells showed significantly increased expression levels of both Pycard and Sfn. Co-expression analysis demonstrated distinct functions of PYCARD and SFN, with KEGG pathway analysis showing significant enrichment in immune regulation and cell proliferation pathway.Conclusion: In conclusion, our study provides valuable insights into the molecular mechanisms involved in DKD pathogenesis, specifically highlighting the role of anoikis-related genes in modulating immune infiltration. These findings suggest that targeting these genes may hold promise for future diagnostic and therapeutic approaches in DKD management.Keywords: diabetic kidney disease, anoikis, immune infiltration, biomarker, PYCARD, SFN

Huishan Zhang,1,2,&ast; Jing Lin,3,4,&ast; Yufang Huang,3,4 Yu Chen3,4 1Department of Phase I Clinical Trial Ward, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 2Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 3Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 4Cancer Bio-Immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Chen, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Tel +86-62752224 Ext 0596, Email chenyu1980@fjmu.edu.cnPurpose: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT).Materials and Methods: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates.Results: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤ 916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035).Conclusion: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS.Keywords: ESCC, NCRT, SII, resectable

Jing Lin,1 Fenglu Wu,2 Yanwen Zhu,2 Qianqian Zhu,2 Tong Du,2 Jiaying Lin2 1Center for Reproductive Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jiaying Lin; Tong Du, Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No. 639, Shanghai, People’s Republic of China, Email lemon_1114@126.com; ocyte@qq.comObjective: Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS).Patients and Methods: This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007– 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications.Results: Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (P < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (P > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, P > 0.05; double embryo transfer: 37.3% vs 45.6%, P > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (P > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (P > 0.05).Conclusion: The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.Keywords: letrozole, antagonist protocol, polycystic ovary syndrome, follicle, in vitro fertilization

Yanxia Guo,&ast; Zhihua Yao,&ast; Yan Feng, Dan Wang, Yizheng Wang, Jingyan Lin Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyan Lin, Email linjingyan@nsmc.edu.cnBackground: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy.Methods: Seventy-five patients aged ≥ 65 years and American Society of Anesthesiologists (ASA) class I–III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate.Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088– 0.108] mg/kg vs 0.162 [0.153– 0.171] mg/kg; 0.258 [0.249– 0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264– 0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167– 0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101– 0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups.Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.Keywords: painless gastroscopy, elderly patients, median effective dose, fentanyl, remimazolam tosilate

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

Huaqiao Tang,1,&ast; Liying Dong,1,&ast; Xue Xia,1,&ast; Xinling Chen,1 Meichen Ren,1 Gang Shu,1 Hualin Fu,1 Juchun Lin,1 Ling Zhao,1 Li Zhang,2 Guoqiang Cheng,2 Xianxiang Wang,3 Wei Zhang1 1College of Veterinary, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China; 2Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, People’s Republic of China; 3College of Science, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Email Zhangwei26510c@126.comIntroduction: Chrysin has a wide range of biological activities, but its poor bioavailability greatly limits its use. Here, we attempted to prepare casein (cas)-based nanoparticles to promote the biotransfer of chrysin, which demonstrated better bioavailability and anti-infection activity compared to free chrysin.Methods: Cas-based chrysin nanoparticles were prepared and characterized, and most of the preparation process was optimized. Then, the in vitro and in vivo release characteristics were studied, and anti-pulmonary infection activity was evaluated.Results: The constructed chrysin-cas nanoparticles exhibited nearly spherical morphology with particle size and ζ potential of 225.3 nm and − 33 mV, respectively. These nanoparticles showed high encapsulation efficiency and drug-loading capacity of 79.84% ± 1.81% and 11.56% ± 0.28%, respectively. In vitro release studies highlighted a significant improvement in the release profile of the chrysin-cas nanoparticles (CCPs). In vivo experiments revealed that the relative oral bioavailability of CCPs was approximately 2.01 times higher than that of the free chrysin suspension. Further investigations indicated that CCPs effectively attenuated pulmonary infections caused by Acinetobacter baumannii by mitigating oxidative stress and reducing pro-inflammatory cytokines levels, and the efficacy was better than that of the free chrysin suspension.Conclusion: The findings underscore the advantageous bioavailability of CCPs and their protective effects against pulmonary infections. Such advancements position CCPs as a promising pharmaceutical agent and candidate for future therapeutic drug innovations.Keywords: chrysin, nanoparticles, Acinetobacter baumannii, casein

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Guixing Zeng,1 Yujie Lin,2 Peirui Xie,3 Jiarong Lin,4 Yaxing He,5 Junping Wei1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 5School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, People’s Republic of ChinaCorrespondence: Junping Wei, Email weijunping@126.comBackground: To investigate the association between the NLR and the risk of all-cause and cardiovascular mortality in US adults with diabetic kidney disease (DKD).Methods: The data utilized for this analysis were sourced from ten National Health and Nutrition Examination Survey cycles (1999– 2018) with mortality data (up to 31 December 2019) via linkage to the National Death Index. The optimum NLR threshold for predicting survival outcomes was determined through the maximally selected rank statistics. Restricted cubic spline (RCS), weighted Cox proportional hazard regression, stratified analyses, and time-dependent receiver-operating characteristic curve (ROC) were employed to delineate the prospective correlations of the NLR with both all-cause and cardiovascular mortality.Results: In this investigation, a cohort comprising 2581 patients diagnosed with DKD was examined, encompassing 624 individuals with a higher NLR (≥ 3.07) and 1957 subjects with a lower NLR (< 3.07). Over a median follow-up of 79 months (interquartile range, 44– 128 months), 1103 deaths occurred, including 397 from cardiovascular causes and 706 from non-cardiovascular causes. The RCS analysis elucidated the positive linear correlation (both nonlinear P > 0.05). In the multivariable analyses, each one-unit increase in the NLR value was correlated with a 51% increased risk of all-cause mortality (1.51(1.28, 1.77)) and a 71% increased risk of cardiovascular mortality (1.71(1.32, 2.21)). The results were largely consistent across stratified analyses encompassing variables such as age, sex, race/ethnicity, marital status, family income, education levels, BMI, drinking status, smoking status, hypertension, CVD, and anti-infective drugs (P for interaction > 0.05 for all). Time-dependent ROC analyses underscored the NLR’s credible predictive efficacy for both short-term and extended durations in forecasting both all-cause and cardiovascular mortality.Conclusion: The findings emphasize the promising use of the NLR in stratifying and prognosticating the risk of mortality in DKD in clinical practice.Keywords: neutrophil–lymphocyte ratio, diabetic kidney disease, predictor, mortality, cohort study

Wenjie Xie,1,2,&ast; Yixun Zhang,1,2,&ast; Qianfeng Xu,1,2,&ast; Guowei Zhong,1,2 Jundong Lin,2,3 Huichan He,3 Qiuling Du,2 Huijing Tan,1,2 Muqi Chen,1,2 Zhenjie Wu,1– 3 Yulin Deng,1,2 Zhaodong Han,1– 3 Jianming Lu,1,2,4 Jianheng Ye,1,2,4 Fen Zou,1,2 Yangjia Zhuo,1,2 Weide Zhong1– 4 1Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 2Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China; 4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Zhuo; WeideZhong, Email eyyangjiazhuo@scut.edu.cn; zhongwd2009@live.cnPurpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment. Keywords: graphdiyne, biomimetic nanoplatform, cuproptosis, chemotherapy, prostate cancer

Jincheng Ma,1– 3,&ast; Jiansong Lin,4,&ast; Xite Lin,1– 3 Yuan Ren,1– 3 Dabin Liu,5 Shuting Tang,1– 3 Leyi Huang,1– 3 Shuxia Xu,4 Xiaodan Mao,1– 3 Pengming Sun1– 3,5 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian Province, People’s Republic of China; 4Department of Pathology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Gynecology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Mao; PengMing Sun, Email maodan1985@fjmu.edu.cn; sunfemy@hotmail.comObjective: This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation.Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann–Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC.Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d.Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.Keywords: endometrial cancer, mismatch repair-deficiency, immune, molecular classification, MutL, MutS

Linqi Zhou,1 Changyuan Qiao,1 Jialing Huang,2 Jian Lin,2 Haisheng Zhang,2 Jian Xie,2 Yonggui Yuan,3 Changchun Hu2 1School of the Fourth Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Psychosomatics and Psychiatry, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Changchun Hu, Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310002, People’s Republic of China, Tel +86-571-56006902, Email chuntianjs@163.comBackground: Previous studies have demonstrated a strong association between recent stressful life events and non-suicidal self-injury (NSSI) among adolescents. Internalizing symptoms and difficulty in emotion regulation (DER) may mediate this relationship. This study aimed to investigate the relationship between recent stressful life events and NSSI severity in adolescents and the potential moderating role of internalizing symptoms and DER.Methods: A total of 224 adolescent inpatients (78.6% female) participated in the study, with an age range of 12– 18 years old. Data on recent stressful life events, internalizing symptoms, DER, and NSSI behaviors were collected using a clinician-rated questionnaire. A structural equation model was used to test the hypothesized model.Results: The rate of NSSI reporting among adolescents in the past 12 months was 65.18%. Recent stressful life events were found to be directly associated with NSSI severity (β = 0.128, P = 0.023). A chain-mediating effect between recent stressful life events and NSSI was also confirmed (β = 0.034, P = 0.023), with DER and internalizing symptoms playing a chain-mediating role and DER having a significantly indirect association with NSSI through internalizing symptoms.Conclusion: Recent stressful life events appear to play a role in the etiology of NSSI, particularly punishment and interpersonal relationship events that warrant special attention. DER and internalizing symptoms play a chain-mediating role in the relationship between life events and NSSI. Reducing recent stressful life events, screening for internalizing symptoms, and improving emotion regulation may decrease NSSI behavior among adolescents.Keywords: non-suicidal self-injury, adolescents, recent stressful life events, internalizing symptoms, difficulty in emotion regulation, structural equation model

Xinchao Liu,1,&ast; Hao Xing,2,3,&ast; Jing Lin,1,3,&ast; Jian Sun,4 Yu Wang,3 Yaxu Liu,5 Wei Cao,1,6 Zhengyin Liu,1 Taisheng Li1,6,7 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 6State 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; 7Tsinghua-Peking Center for Life Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taisheng Li, Email litsh@263.netBackground: Talaromyces marneffei is prevalent in South Asia. Latent Talaromyces marneffei infection of travellers make the diagnosis difficult. There are similarities in clinical manifestations between Talaromyces marneffei infection and lymphoma. Brain abscess is a rare form of Talaromyces marneffei infection.Case Presentation: We reported a very rare case of a 19-year-old man with HIV infection who suffered from a brain mass and lymphadenopathy. His blood culture, bone marrow culture and sputum culture all grew Talaromyces marneffei. One month after treatment with voriconazole, the symptoms improved except brain mass. Surgical incision of the brain mass showed a compact mass, and pathological analysis showed the coexisting Talaromyces marneffei abscess and lymphoma. The patient is currently in a stable condition after receiving antifungal therapy and chemotherapy.Conclusion: Based on a case report of a traveller who suffered from a brain mass of Talaromyces marneffei abscess and lymphoma after a visit to an endemic area, this review summarized the cases where there was confusion between lymphoma and the brain abscess of Talaromyces marneffei. Talaromyces marneffei infection can be found globally due to the increasing number of international travels. Talaromyces marneffei infection and lymphoma had similar characteristics which is easy to misdiagnose in clinic. Infection may also be accompanied by tumors, especially in patients infected with HIV. The manifestations and imaging of brain abscess of Talaromyces marneffei were not characteristic in different patients.Keywords: Talaromyces marneffei, lymphoma, misdiagnose, HIV, travel

Jia Yan,1– 3,&ast; Ke xin Li,2,&ast; Lei Yu,2 Heng ye Yuan,2 Zhi min Zhao,2 Jing Lin,2,4 Chang Shan Wang2 1School of Basic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, People’s Republic of China; 3Medical Experimental Center of Basic Medical School, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 4Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chang Shan Wang; Jing Lin, Email changshanwang@imu.edu.cn; summerjia0627@163.comBackground: Protein arginine methyltransferase (PRMT) family members have important roles in cancer processes. However, its functions in the regulation of cancer immunotherapy of hepatocellular carcinoma (HCC) are incompletely understood. This study aimed to investigate the roles of PRMT1 in HCC.Methods: Single-cell RNA sequencing (scRNA-seq) and clinicopathological data were obtained and used to explore the diagnostic and prognostic value, cellular functions and roles in immune microenvironment regulation of PRMT1 in HCC. The functions of PRMT1 were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), as well as gene set enrichment analysis (GSEA). TIMER and CIBERSORT were used to analyze the relationships between PRMT1 expression and immune cell infiltration. The STRING database was used to construct a protein–protein interaction (PPI) network.Results: PRMT1 was aberrantly expressed in HCC, which high expression was associated with tumor progression, worse overall survival (OS) and disease-free survival (DFS) of patients with HCC. PRMT1 was also associated with immune cell infiltration. Moreover, it was specifically expressed in immune cells, including exhausted CD8 T cells, B cells, and mono/macro cells in patients with immunotherapy. The expression of immune checkpoints was significantly increased in the high-PRMT1 expression groups of HCC patients. Regarding biological mechanisms, cell viability, migration and invasion, and the expression of genes related to fatty acid metabolism were suppressed in PRMT1 knockdown HCC cells. Moreover, genes co-expressed with PRMT1 were involved in the fatty acid metabolic process and enriched in fatty and drug-induced liver disease.Conclusion: Taken together, these results indicate that PRMT1 might exert its oncogenic effects via immune microenvironment regulation and fatty acid metabolism in HCC. Our finding will provide a foundation for further studies and indicate a potential clinical therapeutic target for liver cancer.Keywords: protein arginine methyltransferase, PRMT1, prognosis, tumor-infiltrating, fatty acid metabolism

Xudong Zhu,1,2 Jiahui Yu,3 Fulu Ai,1 Yue Wang,1 Wu Lv,1 Guilin Yu,1 Xiankui Cao,1 Jie Lin1 1Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of ChinaCorrespondence: Jie Lin; Xudong Zhu, Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China, Tel +86 13940081800 ; +86 13354204706, Email linxiran0221@126.com; xdzhu@cmu.edu.cnPurpose: CD24 mediates a “don’t eat me” signal to escape the immune environment. However, the correlation between CD24 and PD-L1 is unclear. This study aimed to assess if CD24 can serve as a target for immunotherapy of triple-negative breast cancer (TNBC).Methods: Data on CD24 expression in breast cancer were acquired using the Oncomine and UALCAN tools. The role of CD24 expression on the prognosis of patients with TNBC was assessed using Kaplan–Meier analyses. Subsequently, STRING and TISIDB databases were used to construct protein–protein interaction networks and to explore immune-related molecules regulated by CD24. Immunofluorescence and immunohistochemistry assays were conducted to validate CD24 and PD-L1 expression and tumor infiltration lymphocyte (TIL) level. Survival analysis was also performed to explore the effect of CD24 and PD-L1 expression and TIL level in patients with TNBC. ShRNA was also used to explore the regulation role of CD24 on PD-L1 expression.Results: CD24 expression was significantly higher in breast cancer than in normal tissues, with high expression being significantly associated with a worse prognosis. CD24 was found to be significantly regulated by chemokines, immunoinhibitors, immunostimulators and TILs. Furthermore, CD24 expression showed a significant positive correlation with PD-L1 expression and a negative correlation with TIL level. In association with PD-L1, CD24 was found to positively regulate lymphocyte costimulation, T cell costimulation, and leukocyte activation. Furthermore, CD24 and PD-L1 co-expression contributed to worse survival outcomes. In addition, CD24 expression was found to attenuate the positive effects of high-level TILs on the prognosis of patients with TNBC. CD24 can also regulate the expression of PD-L1 in TNBC cells.Conclusion: CD24 may attenuate the positive effects of high TIL levels on survival and may facilitate the immune escape of TNBC by regulating PD-L1 expression. Thus, it is a potential target for immunotherapy in TNBC.Keywords: triple negative breast cancer, CD24, PD-L1, prognosis, immunotherapy

Jiaqiong Lin,1 Xiaoyong Li,2 Yan Lin,3 Zena Huang,3 Fei He,4 Fu Xiong4,5 1Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, People’s Republic of China; 2General Surgery Department; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 4Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Fu Xiong, Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email xiongfu@smu.edu.cnBackground: Diabetic nephropathy (DN) is one of the primary causes of end-stage renal disease, yet effective therapeutic targets remain elusive. This study aims to identify novel diagnostic biomarkers and potential therapeutic candidates for DN.Methods: Differentially expressed genes (DEGs) in GSE96804 and GSE142025 were identified and functional enrichment analysis was performed. Diagnostic biomarkers were selected using machine learning algorithms and evaluated by Receiver Operating Characteristic analysis. c-Fos expression was validated in an established DN mouse model. Immune infiltration levels were assessed with Single-Sample Gene Set Enrichment Analysis. Co-expression analysis revealed regulatory relationships involving FOS. cMAP predicted potential therapeutic candidates. Transcriptome sequencing and experiments in RAW264.7 cells was performed to investigate molecular mechanisms of emetine.Results: In both datasets, we identified 44 upregulated and 74 downregulated DEGs involved in focal adhesion, ECM-receptor interaction, and the PI3K-Akt signaling pathway. FOS emerged as a robust diagnostic marker with decreased expression in DN patients and DN mouse. Co-expression analysis revealed potential regulatory mechanisms of FOS, implicating the MAPK signaling pathway, regulation of cell proliferation and apoptotic signaling pathways. Immune dysregulation was observed in DN patients. Notably, emetine was identified as a potential therapeutic candidate. Transcriptome sequencing and experimental validation demonstrated emetine suppressed M1 macrophage polarization by inhibiting the activation of NF-κB signaling pathway, as well as reducing the expression of Il-18 and Ccl5.Conclusion: In conclusion, our study identified FOS as a promising diagnostic biomarker and emetine as a potential therapeutic candidate for DN. These findings enhance our understanding of DN pathogenesis and present novel prospects for therapeutic strategies.Keywords: diabetic nephropathy, diagnostic markers, FOS, emetine, immune infiltration, inflammation

Yingying Lin,1,&ast; Xiaoyan Xiu,2,&ast; Juan Lin,3 Zhiwei Chen,3 Cui Xian Zheng,3 Xuehong Pan,2 Lihua Lin,1 Jianying Yan3 1Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Health Education, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianying Yan, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China, Tel +86591-86329270, Email fjsfyyan@126.comBackground: The goal is to evaluate the effects of a flipped class strategy on knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes in primiparas undergoing antenatal education.Methods: A random sampling method was adopted. A total of 600 primiparas who were diagnosed with early pregnancy in a first-class hospital in southeast China and received continuous prenatal health education from May to July 2020 were selected as the research subjects. In order to make the baseline of the two groups of primipara comparable, we divided the two groups in the antenatal education centre according to the odd-even number of the lesson card number. The odd-numbered group was the experimental group, who used the prenatal health education model based on blended learning; the even-numbered group was the control group, who used the traditional mode of prenatal health education. The two groups were compared on the following outcomes: knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes.Results: Compared with traditional learning, the blended learning approach can effectively controlled the gestational weight gain (GWG), alleviated the anxiety and depression during pregnancy, improved the natural delivery rate of the primipara, shortened the delivery process and reduced the risk of gestational diabetes mellitus (GDM), the difference was statistically significant (all P< 0.05).Conclusion: Blended learning may be an effective strategy because of its validity and practicality in antenatal education.Keywords: health education, flipped classroom, team-based learning, primipara, pregnancy outcomes, blended learning

Shiyu Lin,&ast; Xiaojuan Li,&ast; Yuning Zhang,&ast; Wei Zhang, Gang Shu, Haohuan Li, Funeng Xu, Juchun Lin, Hualin Fu Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hualin Fu, Tel +86 28 82691162, Fax +86 28 82652669, Email fuhl2005@sohu.comIntroduction: Biofilm is highly resistant to antibiotics due to its heterogeneity and is implicated in over 80% of chronic infections; these refractory and relapse-prone infections pose a huge medical burden.Methods: In this study, rhamnolipid (RHL), a biosurfactant with antibiofilm activity, was loaded with the antibiotic azithromycin (AZI) to construct a stable nanomicelle (AZI@RHL) that promotes Staphylococcus aureus (S. aureus) biofilm disruption.Results: AZI@RHL micelles made a destruction in biofilms. The biofilm biomasses were reduced significantly by 48.2% (P< 0.05), and the main components polysaccharides and proteins were reduced by 47.5% and 36.8%, respectively. These decreases were about 3.1 (15.9%), 7.3 (6.5%), and 1.9 (19.5%) times higher compared with those reported for free AZI. The disruption of biofilm structure was observed under a confocal microscope with fluorescent labeling, and 48.2% of the cells in the biofilm were killed. By contrast, the clearance rates of cells were only 20% and 17% when treated alone with blank micelles or free AZI. Biofilm formation was inhibited up to 92% in the AZI@RHL group due to effects on cell auto-aggregation and eDNA release. The rates for the other groups were significantly lower, with only 27.7% for the RHL group and 12% for the AZI group (P< 0.05). The low cell survival and great formation inhibition could reduce biofilm recolonization and re-formation.Conclusion: The antibiofilm efficacy of rhamnolipid was improved through micellar nanoparticle effects when loading azithromycin. AZI@RHL provides a one-step solution that covers biofilm disruption, bacteria inactivation, recolonization avoidance, and biofilm re-formation inhibition. Keywords: Staphylococcus aureus, antibiofilm, rhamnolipid, biosurfactant, nanomicelle

Zhe Zhao,1,&ast; Yinghui Gao,2,&ast; Junling Lin,3,&ast; Ruyi Xu,4 Zijun He,5 Libo Zhao,1 Fengfeng Fang,5 Weimeng Cai,6 Kaibin Chen,7 Li Fan,1 Lin Liu6 1Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2PKU-Upenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China; 4Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Medical College, Yan’an University, Yan’an, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 7Sleep Center, The Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan, Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13301100573, Email fl6698@163.com Lin Liu, Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13263189578, Email liulin715@qq.comIntroduction: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Depression is a crucial factor among the various factors that are associated with OSA and CVD.Purpose: This study was conducted with an aim to assess the prognostic significance of depression on the MACE in older patients with OSA.Patients and Methods: 1106 older patients with OSA, without myocardial infarction (MI), history of hospitalization for unstable angina, or heart failure at baseline were enrolled and followed up prospectively. Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were major adverse cardiovascular events (MACE). Each patient underwent polysomnography (PSG) and GDS-12 scale assessment. Those with an apnea-hypopnea index (AHI) greater than 5 were diagnosed with OSA, while those with a scale score greater than 3 were diagnosed with depression.Results: Among the 1106 older patients with OSA, depression was found in 133(12.0%) patients, 96(8.7%) patients experienced MACE during the follow-up. Depression was associated with a higher cumulative incidence of MACE in older patients with OSA. Multivariate analysis revealed that depression independently increased the risk of MACE (adjusted hazard ratio [aHR] = 2.29; 95% confidence interval [CI]: 1.34– 3.90; P = 0.002). Subgroup analyses showed that male patients (aHR = 2.96; 95% CI: 1.52– 5.77; P = 0.001), overweight-obese individuals (aHR = 2.98; 95% CI: 1.49– 6.00; P = 0.002), and those with moderate-severe OSA (aHR = 2.82; 95% CI: 1.55– 5.14; P = 0.001) and concurrent depression were at a higher risk for MACE.Conclusion: Depression is common in older patients with OSA in the absence of MI, hospitalization for unstable angina, or heart failure, and confers an independent, increased risk of MACE.Keywords: obstructive sleep apnea, OSA, depression, major adverse cardiovascular events, MACE, older adults

Lihua Lin,1,&ast; Juan Lin,2,&ast; Fang Yang,2 Shouzhen Chen,2 Zhaozhen Liu2 1Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaozhen Liu, Department of Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13515001752, Email fjsfcliuzz@163.comBackground: To evaluate the association of the baseline triglyceride-glucose (TyG) index in the first trimester of pregnancy with the risk of large for gestational age (LGA) in Southeast Chinese pregnant women.Methods: A prospective birth cohort study recruiting 12,108 pregnant women at their first prenatal visit before 13 gestation weeks was conducted in 2019– 2022. Baseline characteristics were collected from medical records or using questionnaires and blood samples were collected in the first trimester. The TyG index was obtained through the formula: ln[triglyceride (mg/dl)×fasting plasma glucose (mg/dl)/2]. The binary logistic regression model was performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) to reveal the relationship between TyG index and LGA. Receiver-operating characteristic curve analysis was conducted to evaluate the ability of the TyG index to predict the risks of LGA.Results: The overall incidence of LGA in the current study was 11.4% and the incidence of LGA increased with the baseline TyG index increasing. The risk of LGA was 2.05 (1.64, 2.57) for per unit increase in baseline TyG index. The increasing trend was found across the TyG index quartiles and the highest TyG quartiles raised the risk of LGA to 1.86 (95% CI: 1.51, 2.27) compared to the bottom TyG quartiles after full adjustment. The risk of LGA remained positive after stratification analysis. The AUC was 0.584 (95% CI: 0.569~0.600) in the entire subject, and the threshold was 8.34, with a sensitivity of 0.74 and specificity of 0.38.Conclusion: The findings suggested that a higher TyG index in the first trimester was independently associated with higher risk of LGA and high TyG index in the first trimester may play as a early predictor for LGA.Keywords: triglyceride-glucose index, large for gestational age, first trimester

Wenqian Lin,1– 3 Yongyong Yang,1– 3 Jun Lin,1– 3 Jianxing Chen,1– 3 Qun Lin1– 3 1Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 3Anesthesiology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Qun Lin, Department of Anesthesiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Email linqun008@163.comPurpose: To compare the effect of Dural puncture epidural (DPE) and conventional epidural (EP), in conjunction with programmed intermittent epidural bolus (PIEB) and low-concentration ropivacaine strategy.Methods: After written informed consent was obtained, healthy nulliparous women with singleton pregnancies, vertex presentation at 38– 42 weeks’ gestation, cervical dilation of 3– 5 cm, and a desire for pain relief were randomly assigned to DPE or EP group. Dural matter was puncture with 25G Whitacre needle in DPE group. Analgesia was initiated with 15 mL of 0.1% ropivacaine over 5 minutes and was maintained by PIEB (8 mL of 0.08% ropivacaine with 2 μg/mL fentanyl every 40 min). Primary outcome was the percentage of adequate analgesia, defined as NRPS ≤ 1, at 30 minutes after the initiation of the epidural bolus.Results: Out of 130 enrolled parturients, 127 were included in final analysis (64 in DPE group, 63 in EP group). No significant difference was found in percentage of adequate analgesia at 30 minutes (risk ratio: 1.09; 95% confidence interval: 0.90– 1.31; P = 0.366). At 8, 12, 14, and 16 minutes, percentage of adequate analgesia was higher in DPE group (P = 0.023, 0.027, 0.016 and 0.033, respectively). NPRS scores in DPE group decreased more dramatically within the first 30 min. The incidence of S2 sensory blocks at 20 and 30 min in DPE group was higher (P = 0.010 and 0.006, respectively). There were no differences in patient satisfaction, delivery mode, adverse effects, fetal bradycardia, and Apgar scores at 1 and 5 minutes.Conclusion: The combination of the use of DPE technique with 25G spinal needle and PIEB technique for labor analgesia appears to enhance the quality of labor analgesia by accelerating onset and providing improved sacral blockade, without increasing adverse effects.Keywords: dural puncture epidural, labor analgesia, programmed intermittent bolus, ropivacaine

Renchuan Jia, Sushupti Kayastha, Jingrong Lin Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Jingrong Lin, Email amy4963@163.comAbstract: Acne is a chronic inflammatory disease of pilosebaceous glands. Microsurgical acupuncture and debridement technique is one of the most precise and effective external treatment for acne. We introduce successful treatment of two cases of moderate to severe acne with this technique and describe the characteristics and mechanism of the technique in detail. We innovatively put forward a series of technical schemes including minimally invasive debridement, key points in operation and combined medication in the microsurgical therapeutic technique of acupuncture and debridement. It provides a practical reference for the simple and effective therapeutic technique to be applied to the clinical treatment of acne.Keywords: acne, acupuncture, debridement

Qingsen Ran,1 He Tian,1 Jian Lin,1 Han Wang,2 Bo Wang,1 Zhixin Chen,1 Da Song,1 Chunzhu Gong1 1Department of Science and Education, Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital), Shenzhen, Guangzhou Province, 518118, People’s Republic of China; 2Department of Gastroenterology, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin Province, 130021, People’s Republic of ChinaCorrespondence: Chunzhu Gong, Email gczq_82@126.comAbstract: The progression of diabetes frequently results in a myriad of neurological disorders, including ischemic stroke, depression, blood-brain barrier impairment, and cognitive dysfunction. Notably, diabetes-associated cognitive impairment, a prevalent comorbidity during the course of diabetes, progressively affects patients’ cognitive abilities and may reciprocally influence diabetes management, thereby severely impacting patients’ quality of life. Extracellular vesicles, particularly nanoscale exosomes, have garnered considerable attention in recent years. These exosomes carry and transfer various functional molecules, such as proteins, lipids, and diverse non-coding RNAs, serving as novel regulators and communicators in intercellular interactions. Of particular interest, mesenchymal stem cell-derived exosomes (MSC-Exos) have been reported to traverse the blood-brain barrier and ameliorate intracerebral pathologies. This review elucidates the role of MSC-Exos in diabetes-related cognitive impairment, with a focus on their applications as biomarkers, modulation of neuronal regeneration and synaptic plasticity, anti-inflammatory properties, antioxidative effects, and their involvement in regulating the functionality of β-amyloid proteins during the course of cognitive impairment. The immense therapeutic potential of MSC-Exos in the treatment of diabetes-induced cognitive dysfunction is emphasized.Keywords: diabetes-associated cognitive impairment, mesenchymal stem cell-derived exosomes, blood-brain barrier, neuronal regeneration, synaptic plasticity

Guanglan Li,1,2 Jing Yu,1,2 Simin Jiang,1,2 Kefei Wu,1,2 Yiping Xu,1,2 Xiaohui Lu,1,2 Yating Wang,1,2 Jianxiong Lin,1,2 Xiao Yang,1,2 Zhibin Li,3 Haiping Mao1,2 1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; 2NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China; 3Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, ChinaCorrespondence: Haiping Mao, Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China, Email maohp@mail.sysu.edu.cnPurpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD.Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan–Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities.Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088– 1.327, P< 0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126– 1.456, P< 0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066– 1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185– 2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only.Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.Keywords: all-cause mortality, cardiovascular mortality, peritoneal dialysis, systemic immune-inflammation index

Li Che,1,2 Zhefan Xie,2,3 Guangshu Chen,4 Wei Zhang,2 Tingting Xia,2,3 Jiaxin Lin,2 Wenzhi Luo,2 Li Chen,2 Wenguang Yin,1 Xingdong Cai,2 Shengming Liu2 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Affiliated Dongguan People’s Hospital, Southern Medical University, Donguan, People’s Republic of China; 4Department of Endocrinology, Guangzhou Red Cross Hospital, The Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Shengming Liu; Xingdong Cai, The First Affiliated Hospital of Jinan University, Guangdong, People’s Republic of China, Email tlsm@jnu.edu.cn; cxd19790920@sina.comBackground: The role of irreversible airway inflammatory damage in chronic obstructive pulmonary disease (COPD) progression is evident. Autophagy is an essential process in the cellular material metabolic cycle, and a family of resistant vegetative molecules may be involved in the COPD autophagic process. In this study, we investigated the mechanism of resistin-like molecule β (RELMβ) in COPD smoking-induced autophagy.Methods: Firstly, the expression differences of RELMβ and autophagy markers between COPD and control groups were analyzed in the Gene Expression Omnibus (GEO) datasets and clinical specimens. Secondly, in vitro and in vivo experiments were conducted using immunoblotting, immunofluorescence, immunohistochemistry, and other methods to investigate the mechanism by which RELMβ promotes airway inflammation through autophagy in a cigarette smoke extract-induced 16HBE cell inflammation model and a cigarette smoke-induced COPD-like mouse model. In addition, immunoprecipitation was used to analyze the binding of RELMβ to the membrane protein TLR4.Results: The expression of RELMβ and autophagy genes p62 and LC3B in lung tissue of COPD patients was significantly increased. RELMβ can mediate the activation of autophagy in 16HBE cells, and through autophagy, it increases the expression of inflammatory cytokines in a cigarette smoke extract-induced 16HBE cell inflammation model. RELMβ promotes cigarette smoke-induced COPD-like mouse airway inflammation through autophagy, and RELMβ can mediate signal transduction through the cell membrane receptor TLR4.Conclusion: The RELMβ binds to TLR4 to encourage signal transduction and that RELMβ can promote inflammation in smoky COPD lungs through autophagy.Keywords: autophagy, COPD, airway inflammation, cigarette smoke extract

Liyan Yuan,&ast; Yang Li,&ast; Junjie Lin, Xiuqiu Lin, Bin Yang, Mao-Qiang Man, Xiaohua Wang Dermatology Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Wang, Dermatology Hospital, Southern Medical University, No. 2 Lujing Road, Guangzhou, 510095, People’s Republic of China, Tel +86-20-87255286, Email Wxh_21773@163.com

Min Yang,1,2,&ast; Yaqin Yang,1,2,&ast; Yuntong Xu,1,2 Yuchi Wu,1,2 Jiarong Lin,1,2 Jianling Mai,1,2 Kunyang Fang,1,2 Xiangxia Ma,1,2 Chuan Zou,1,2 Qizhan Lin1,2 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Zou; Qizhan Lin, Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong, 510000, People’s Republic of China, Email doctorzc541888@126.com; linqizhan656635@163.comPurpose: This study aimed to develop two predictive nomograms for the assessment of long-term survival status in hemodialysis (HD) patients by examining the prognostic factors for all-cause mortality and cardiovascular (CVD) event mortality.Patients and methods: A total of 551 HD patients with an average age of over 60 were included in this study. The patients’ medical records were collected from our hospital and randomly allocated to two cohorts: the training cohort (n=385) and the validation cohort (n=166). We employed multivariate Cox assessments and fine-gray proportional hazards models to explore the predictive factors for both all-cause mortality and cardiovascular event mortality risk in HD patients. Two nomograms were established based on predictive factors to forecast patients’ likelihood of survival for 3, 5, and 8 years. The performance of both models was evaluated using the area under the curve (AUC), calibration plots, and decision curve analysis.Results: The nomogram for all-cause mortality prediction included seven factors: age ≥ 60, sex (male), history of diabetes and coronary artery disease, diastolic blood pressure, total triglycerides (TG), and total cholesterol (TC). The nomogram for cardiovascular event mortality prediction included three factors: history of diabetes and coronary artery disease, and total cholesterol (TC). Both models demonstrated good discrimination, with AUC values of 0.716, 0.722 and 0.725 for all-cause mortality at 3, 5, and 8 years, respectively, and 0.702, 0.695, and 0.677 for cardiovascular event mortality, respectively. The calibration plots indicated a good agreement between the predictions and the decision curve analysis demonstrated a favorable clinical utility of the nomograms.Conclusion: Our nomograms were well-calibrated and exhibited significant estimation efficiency, providing a valuable predictive tool to forecast prognosis in HD patients.Keywords: all-cause, cardiovascular, mortality, hemodialysis, model, nomogram

Jiecheng Lin,1,2,&ast; Na Huang,2,&ast; Mingjuan Li,2 Mengyuan Zheng,2 Zhuoxiang Wang,2 Xiaojuan Zhang,2 Huan Gao,2 Yunzhe Lao,2 Jie Zhang,2 Baoyue Ding2 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 214122, People’s Republic of China; 2Department of Pharmaceutics, Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, Jiaxing, 314001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoyue Ding; Jie Zhang, Department of Pharmaceutics, Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, No. 118 Jiahang Road, Jiaxing, Zhejiang Province, 314001, People’s Republic of China, Tel/Fax +86-0573-83643808, Email lena_310@163.com; zhangjiepharm@zjxu.edu.cnPurpose: Malignant melanoma (MM), the most lethal skin cancer, is highly invasive and metastatic. These qualities are related to not only genetic mutations in MM itself but also the interaction of MM cells with the immune system and microenvironment. This study aimed to construct a combined immunotherapy and gene therapy drug delivery system for the effective treatment of MM.Methods: Mature dendritic cell (mDC) exosomes (mDexos) with immune induction functions were used as carriers. BRAF siRNA (siBRAF) with the ability to silence mutated BRAF in MM was encapsulated in mDexos by electroporation to construct a biomimetic nanosystem for the codelivery of immunotherapy and gene therapy drugs (siBRAF-mDexos) to the MM microenvironment. Then, we investigated the nanosystem’s serum stability and biocompatibility, uptake efficiency in mouse melanoma cells (B16-F10 cells), cytotoxicity against B16-F10 cells and inhibitory effect on BRAF expression. Furthermore, we evaluated its antimelanoma activity and safety in vivo.Results: SiBRAF-mDexos were nanosized. Compared to siBRAF, siBRAF-mDexos displayed significantly increased serum stability, biocompatibility, uptake efficiency in B16-F10 cells, and cytotoxicity to B16-F10 melanoma cells; they also had a significantly greater inhibitory effect on BRAF expression and induced T-lymphocyte proliferation. Moreover, compared with siBRAF, siBRAF-mDexos showed significantly enhanced anti-MM activity and a high level of safety in vivo.Conclusion: The study suggests that the siBRAF-mDexo biomimetic drug codelivery system can be used to effectively treat MM, which provides a new strategy for combined gene therapy and immunotherapy for MM.Keywords: malignant melanoma, dendritic cell exosomes, BRAF siRNA, immunotherapy, gene therapy

Jiequn Huang,1 Changzhi Liu,1 Zhujiang Zhou,1 Han Xia,2 Zhensheng Zhu,2 Jianhai Lu,1 Jingcheng Lin,1 Zhen Chen,1 Qimei Ye,1 Liuer Zuo1 1Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, People’s Republic of China; 2Department of Scientific Affairs, Hugobiotech Co, Ltd, Beijing, People’s Republic of ChinaCorrespondence: Liuer Zuo, Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan), Foshan, Guangdong, People’s Republic of China, Email 13500276597@163.comBackground: Pneumonia infected by Chlamydia abortus (C. abortus) is rare, especially complicated with severe acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).Case Presentation: We presented the clinical details of a 44-year-old male who was diagnosed with C. abortus pneumonia, which rapidly progressed and ultimately led to ARDS, sepsis and MODS. Although he was initially diagnosed with pneumonia upon admission, no pathogenic bacteria were detected in sputum by conventional tests. Empirical intravenous infusion of meropenem and moxifloxacin was administered, but unfortunately, his condition deteriorated rapidly, especially respiratory status. On Day 2 after extracorporeal membrane oxygenation (ECMO) initiation, metagenomic next-generation sequencing (mNGS) was performed on the patient’s bronchoalveolar lavage fluid, which indicated an infection with C. abortus. The patient’s antimicrobial therapy was adjusted to oral doxycycline (0.1g every 12h), intravenous azithromycin (0.5g every day), and imipenem and cilastatin sodium (1g every 6h). The patient’s condition improved clinically and biologically. However, the patient was discharged due to financial reasons and unfortunately passed away eight hours later.Conclusion: Infections with C. abortus can result in severe ARDS and serious visceral complications which necessitate prompt diagnosis and active intervention by clinicians. The case highlights the significance of mNGS as an essential diagnostic tool for uncommon pathogens. Tetracyclines, macrolides or their combinations are effective choices for treatment of C. abortus pneumonia. Further study is needed to explore the transmission routes of C. abortus pneumonia and establish precise guidelines for antibiotic treatment.Keywords: Chlamydia abortus, ECMO, pneumonia, acute respiratory distress syndrome, metagenomic next-generation sequencing

Ji Cheng Zhang, Jin Hua Wang, Jia Lin, Guo Ming Su, Yi Lin Shen, Qi Wei Guo, Jia Jing Cai, Jun Yi Liu, Ke Xin Jia, Ding Zhi Fang Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ding Zhi Fang, Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China, Email dzfang@scu.edu.cnAim: To explore anthropometric, metabolic and dietary factors associated with and their interplays with the Val66Met polymorphism at brain-derived neurotrophic factor (BDNF) gene (Bdnf) on serum BDNF levels in adolescents.Methods: Serum BDNF levels were quantified using an enzyme-linked immunosorbent assay in 644 high school students (278 males/366 females). A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for Bdnf Val66Met genotyping followed by verification using DNA sequencing. Serum levels of metabolic characteristics were assayed by routine methods. The intake of macro and micronutrients was collected by a three-day food record.Results: Serum BDNF levels were found to be significantly different in the subjects with different genotypes of Bdnf Val66Met (Val/Val homozygotes, 60.05 ± 28.07 ng/mL vs Val/Met heterozygotes, 56.37 ± 29.34 ng/mL vs Met/Met homozygotes, 51.32 ± 24.54 ng/mL, p = 0.022). Among the 36 tested variables, waist–hip ratio (WHR) (β = − 0.163, p < 0.001), iodine intake (β = 0.132, p = 0.001), heart rate (β = 0.108, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (β = 0.098, p = 0.011) and dietary fiber intake (β = 0.082, p = 0.084) were the predictor of serum BDNF levels, while SBP (β = 0.097, p = 0.013) and WHR (β = 0.091, p = 0.021) were related with Bdnf Val66Met. Moreover, WHR was observed to play a partial mediating role in the relationship between Bdnf Val66Met and serum BDNF levels (95% CI [− 1.161, − 0.087]) and contribute 13.05% of its total effect on serum BDNF levels.Conclusion: There are interplays between WHR and Bdnf Val66Met on serum BDNF levels, which may be among the explanations for the previous heterogeneous reports and provide novel insights into the regulation of serum BDNF levels.Keywords: serum, brain-derived neurotrophic factor, Val66Met, waist–hip ratio, mediator, adolescent

Jisheng Lin,1,&ast; Sijia Guo,1,&ast; Weiyang Zuo,1,&ast; Hao Wu,2 Yongjin Li,3 Xiuquan Yang,4 Yong Yang,1 Qi Fei1,&ast; 1Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Fangzhuang Community Health Service Center, Beijing, People’s Republic of China; 3Tuanjiehu Community Health Service Center, Beijing, People’s Republic of China; 4Wangzuo Community Health Service Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Fei, Tel +86 10 6313 8353, Fax +86 10 8391 1029, Email spinefei@126.comPurpose: This cross-sectional study estimated three clinical tools including the Osteoporosis Self-Assessment Tool for Asians (OSTA), Body Mass Index (BMI), and Beijing Friendship Hospital Osteoporosis Self-assessment Tool for Elderly Male (BFH-OSTM) for identifying primary osteoporosis and found optimal cut-off values in an elderly Han Beijing male population.Materials and Methods: We conducted a cross-sectional study, enrolling 400 community-dwelling elderly Han Beijing males aged ≥ 50 from 8 medical institutions. Osteoporosis was diagnosed as a T-score of − 2.5 standard deviations or lower than that of the average young adult in different diagnostic criteria [lumbar spine (L1-L4), femoral neck, total hip, WHO]. BFH-OSTM, OSTA, and BMI were assessed for predicting OP by receiver operating characteristic (ROC) curves. Sensitivity, specificity, and areas under the ROC curves (AUC) were determined. Ideal thresholds for the omission of screening BMD were proposed.Results: The prevalence of osteoporosis ranged from 9.25% to 19.0% according to different diagnostic criteria. The present study indicated the highest discriminating ability was BFH-OSTM in different criteria. The AUCs of OSTA and BMI were 0.748 and 0.770 in WHO criteria, which suggested limiting predictive value for identifying OP in elderly Beijing males. The AUC of BFH-OSTM to predict OP based on WHO criteria was 0.827, yielding a sensitivity of 65.8% and specificity of 82.7%, respectively. With a cost of missing 6.5% of osteoporosis patients, BFH-OSTM could reduce 73.5% of participants in screening BMD tests.Conclusion: BFH-OSTM may be a simple and effective tool for identifying OP in the elderly male population in Beijing to omit BMD screening reasonably.Keywords: male, osteoporosis, osteoporosis self-assessment tool for Asians, OSTA, Beijing friendship hospital osteoporosis self-assessment tool for elderly male, BFH-OSTM, body mass index, BMI

JinJian Yao,1,2,&ast; Xiaochun Mao,3,&ast; Qigang Sun,4,&ast; Biao Wu,5 Weiling Yu,6 Yanjing Huang,7 Shuai Luo,1 Jia Zeng,1 Jusheng Lin2 1Department of Emergency, Hainan General Hospital, Haikou, Hainan, People’s Republic of China; 2Institute of Liver and Gastrointestinal Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Ophthalmology, Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Haikou, Hainan, People’s Republic of China; 5Infectious Disease, Hainan General Hospital, Haikou, Hainan, People’s Republic of China; 6Oncology Department, Haikou City People’s Hospital, Haikou, Hainan, People’s Republic of China; 7Oncology Department of Hainan General Hospital, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: JinJian Yao; Jusheng Lin, Email 114715854@qq.com; jslin2005@163.comPurpose: Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are progressions affected by genetic predispositions, and persistent hepatitis B virus infection also demonstrates genetic susceptibility. All HBV-related outcomes have been compared in parallel to identify risk polymorphism in HBV progression.Methods: The multiple-stage association study filtered and validated the risk SNPs for HBV progression and explored their association with persistent infection, with a total of 8906 subjects in China from three sites. Cox proportional hazards models and Kaplan–Meier Log rank tests were used to determine the time to the progressive event in relation to the risk SNPs.Results: Rs3825214 in TBX5 replicated a specific association with LC and HCC in 4 progression cohorts and was not related to persistent infection, naivety to HBV infection and natural clearance in 3 persistent cohorts. In combined samples, rs3825214 was associated with an increased risk of LC (P< 0.001; OR = 1.98) and HCC (P< 0.001; OR = 1.68). The results of bioinformatics analysis indicated that rs3825214 genotypes change RNA structure and intron excision ratio. In the follow-up of 571 hospital-based persistent HBV infection patients, ninety-three (16.29%) developed LC, and seventy-four (12.96%) progressed to HCC at a median follow-up of 5.1 years. Rs3825214 was associated with HCC and LC events in Cox proportional hazards models (P< 0.001).Conclusion: We identified and confirmed that genetic variants in TBX5 are significantly associated with susceptibility to and the incidence of LC and HCC.Keywords: TBX5, polymorphism, liver cirrhosis, hepatocellular carcinoma, follow-up, hepatitis B virus

Haochen Jiang,1,2,&ast; Zhi Shang,2,&ast; Liping You,1,2,&ast; Jinghao Zhang,1 Junzhe Jiao,2 Yihan Qian,2 Jiacheng Lin,2 Fang Wang,2 Yueqiu Gao,1 Xiaoni Kong,2 Xuehua Sun1 1Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuehua Sun, Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email susan_sxh@shutcm.edu.cn Xiaoni Kong, Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email xiaonikong@shutcm.edu.cnBackground and Purpose: Current pharmacological approaches to prevent hepatic ischemia/reperfusion injury (IRI) are limited. To mitigate hepatic injury, more research is needed to improve the understanding of hepatic IRI. Depending on traditional Chinese medicine (TCM) theory, acupuncture therapy has been used for the treatment of ischemic diseases with good efficacy. However, the efficacy and mechanism of acupuncture for hepatic IRI are still unclear.Methods: Blood provided to the left and middle lobe of mice livers was blocked with a non-invasive clamp and then the clamps were removed for reperfusion to establish a liver IRI model. Quantitative proteomics approach was used to evaluate the impact of EA pretreatment on liver tissue proteome in the IRI group. Serum biochemistry was used to detect liver injury, inflammation, and oxidative stress levels. H&E staining and TUNEL staining were used to detect hepatocyte injury and apoptosis. Immunohistochemistry and ELISA were used to detect the degree of inflammatory cell infiltration and the level of inflammation. The anti-inflammatory and antioxidant capacities were detected by Quantitative RT-PCR and Western blotting.Results: We found that EA at Zusanli (ST36) has a protective effect on hepatic IRI in mice by alleviating oxidative stress, hepatocyte death, and inflammation response. Nuclear factor E2-related factor 2 (Nrf2) as a crucial target was regulated by EA and was then successfully validated. The Nrf2 inhibitor ML385 and cervical vagotomy eliminated the protective effect in the EA treatment group.Conclusion: This study firstly demonstrated that EA pretreatment at ST36 significantly ameliorates hepatic IRI in mice by inhibiting oxidative stress via activating the Nrf2 signal pathway, which was vagus nerve-dependent.Keywords: inflammation, liver, proteomics

Jiding Fu,1,&ast; Jie Lin,2,&ast; Xiaohui Zeng,3 Guanger Li,3 Yier Wei,1 Lewu Xian1 1Department of Intensive Care Unit, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China; 2Department of Radiation oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China; 3Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lewu Xian, Department of Intensive Care Unit, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China, Email xianlewu0080@126.comBackground: GABRP has been reported to play an oncogenic role in various carcinomas. However, no report has been found for its involvement in lung squamous cell carcinoma (LUSC) development yet. We aimed to explore the expression and prognostic roles of GABRP and assessment of its association with tumor microenvironment in LUSC.Methods: The GABRP expression in LUSC was analyzed using TCGA, GEO, and HPA databases. The Kaplan-Meier, Cox regression analysis, and receiver operating characteristic (ROC) curve were applied to assess the prognostic and diagnostic values of GABRP in LUSC. We also performed ESTIMATE and ssGSEA to explore the association between GABRP expression and immune cell infiltrations. GABRP was highly expressed in LUSC patients, and up-regulation of GABRP was associated with shorter overall survival (OS). Cox regression analysis indicated that GABRP was an independent prognostic factor for LUSC patients. KEGG analysis revealed that GABRP may play an important role in starch and sucrose metabolism and nicotine addiction. Specifically, GABRP expression showed significant positive correlations with the infiltration levels of most types of immune cells, as well as immune checkpoint molecules expression.Conclusion: Up-regulation of GABRP in LUSC could be severed as a prognostic marker and a potential target for immunotherapy in LUSC.Keywords: lung cancer, immune infiltrates, TCGA, prognosis, bioinformatics

Minli Zhu,1 Leying Wang,1 Zhangming Zhuge,1 Wei Li,1,2 Yihui Zheng,1 Jingyun Mai,1 Zhenlang Lin,1 Jing Lin1,3 1Key Laboratory of Perinatal Medicine of Wenzhou, Department of Neonatology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2Zhijin People’s Hospital of Guizhou Province, Guizhou, 552100, People’s Republic of China; 3Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USACorrespondence: Jing Lin, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA, Tel +1-212-241-6186, Fax +1-212534-5207, Email jing.lin@mssm.edu Zhenlang Lin, Department of Neonatology, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86 13806689800, Email linzhenlang@hotmail.comBackground and Objective: An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics.Patients and Methods: All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis.Results: ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184– 199.326, P< 0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009– 10.055, P< 0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis.Conclusion: E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility.Keywords: infant, newborn, neonatal sepsis, Escherichia coli, drug resistance, extended-spectrum beta-lactamase

Rongxiu Huo,&ast; Xinxiang Huang,&ast; Yang Yang, Jinying Lin Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinying Lin, Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, 6 Taoyuan Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, 530016, People’s Republic of China, Email jinyinglin@sina.comAbstract: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with unclear pathogenesis. One characteristic of SLE is pro-inflammatory and anti-inflammatory cytokine imbalance. Janus kinase (JAK) is an intracellular non-receptor tyrosine kinase essential for many cytokine signaling pathways. Dysregulation of the JAK/signal transduction and transcriptional activator (STAT) pathway is an important process in SLE pathogenesis. Targeting JAK/STAT proteins can simultaneously block the functions of multiple cytokines. Current SLE treatment with non-specific corticosteroids and immunosuppressants can cause many adverse reactions. Therefore, treatments designed to control specific molecular targets for SLE are desirable. JAK inhibitors (JAKis) are a potential treatment for rheumatic diseases; however, the use of targeted signaling pathways to treat SLE remains a challenge, and its efficacy has not been determined. JAKis have shown positive results in reducing the use of glucocorticoids and/or non-specific immunosuppressants for SLE. JAKis are currently undergoing several clinical trials and expected to be the next stage in the treatment of SLE. Therefore, inhibition of the JAK/STAT pathway through JAKis may improve traditional treatment strategies for SLE.Keywords: systemic lupus erythematosus, Janus kinase, JAK/STAT pathway, JAK inhibitors

Jian Lin,1,&ast; Tianpeng Shi,2,&ast; Yi Wang,1 Zhiqi He,1 Zhixiang Mu,1 Xiaojun Cai,1 Hui Deng,1 Jianliang Shen,3– 5 Fen Liu6 1School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Stomatology, PLA Strategic Support Force Medical Center, Beijing, People’s Republic of China; 3State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, People’s Republic of China; 5Department of Regenerative Medicine, Vision, and Brain Health, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Wenzhou, People’s Republic of China; 6Department of Histology and Embryology, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Deng; Fen Liu, Email dh0726@gmail.com; liufen6459@163.comBackground: Much attention has been paid to sustained drug release and anti-infection in wound management. Hydrogels, which are biocompatible materials, are promising tools for controlled drug release and infective protection during wound healing. However, hydrogels also demonstrate limitations in the highly efficient treatment of wounds because of the diffusion rate. In this work, we explored pH-sensitive hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties.Methods: We constructed a hybrid gelatin methacrylate (GelMA) system with sustainable antibacterial properties combining hyaluronic acid (HA)-coated mesoporous silica nanoparticles (MSN), which loaded host-guest complexes of chlorhexidine (CHX) with β-cyclodextrins (β-CD) (CHX⊂CD-MSN@HA@GelMA). The release mechanism of CHX was explored using UV-vis spectra after intermittent diffusion of CHX. The hybrid hydrogels were characterized, and the drug content in terms of the release profile, bacterial inhibition, and in vivo experiments were investigated.Results: Except for dual protection from both hydrogels, MSN in the HA improved the drug loading efficiency to promote the local drug concentration. It showed that complicated CHX-loaded MSN releases CHX more gradually and over a longer duration than CHX-loaded MSNs. This demonstrated a 12-day CHX release time and antibacterial activity, primarily attributable to the capacity of β-CD to form an inclusion complex with CHX. Meanwhile, in vivo experiments revealed that the hydrogels safely promote skin wound healing and enhance therapeutic efficacy.Conclusion: We constructed pH-sensitive CHX⊂CD-MSN@HA@GelMA hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties. The combination of β-CD and MSN would be better suited to release a reduced rate of active molecules over time (slow delivery), making them great candidates for wound dressing anti-infection materials.Keywords: mesoporous silica, cyclodextrin, pH-responsive, antibacterial property, wound healing

Shunhang Feng,1,2,&ast; Jiansheng Lin,1,2,&ast; Xiaoyan Zhang,1,2 Xin Hong,1,2 Wanyin Xu,1,2 Yancheng Wen,1,2 Feifei She1,2 1Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feifei She, Fujian Medical University, Xueyuan Road 1, Minhou County, Fuzhou, Fujian Province, People’s Republic of China, Tel +86-135-1406-3583, Email Shefeifei@yeah.net Yancheng Wen, Fujian Medical University, Xueyuan Road 1, Minhou County, Fuzhou, Fujian Province, People’s Republic of China, Tel +86-157-0593-5209, Email hitwyc@qq.comPurpose: Helicobacter pylori is associated with the development of gastrointestinal diseases. However, its eradication is challenged by an increased rate of drug resistance. AlgC and GalU are important for the synthesis of UDP-glucose, which is a substrate for the synthesis of lipopolysaccharide (LPS) in H. pylori. In this study, we investigated the role of UDP-glucose in the intrinsic drug resistance in H. pylori.Methods: Gene knockout strains or complementation strains, including ΔalgC, ΔgalU, ΔgalE, Δhp0045, ΔalgC/algC&ast; and ΔgalU/galU&ast; were constructed in Hp26695; and ΔalgC and ΔgalU were also constructed in two clinical drug-resistant strains, Hp008 and Hp135. The minimum inhibitory concentrations (MIC) of H. pylori to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MNZ), levofloxacin (LEV), and rifampicin (RIF) were measured using MIC Test Strips. Silver staining was performed to examine the role of AlgC and GalU in LPS synthesis. Ethidium bromide (EB) accumulation assay was performed to assess the outer membrane permeability of H. pylori strains.Results: Knockout of algC and galU in H. pylori resulted in increased drug sensitivity to AMO, MNZ, CLA, LEV, and RIF; whereas knockout of hp0045 and galE, which are involved in GDP-fucose and UDP-galactose synthesis, respectively, did not significantly alter the drug sensitivity of H. pylori. Knockout of algC and galU in clinically drug-resistant strains resulted in significantly increased drug sensitivity to all the antibiotics, except MNZ. The lipid A-core structure was altered in ΔalgC and ΔgalU when their EB accumulation was higher than that in the wild type and complementation strains.Conclusion: UDP-glucose may play an important role in increasing drug resistance to AMO, MNZ, CLA, LEV, TET, and RIF by maintaining the lipid A-core structure and decreasing membrane permeability. AlgC and GalU may serve as potential drug targets for decreasing antibiotic resistance in clinical isolates.Keywords: H. pylori, UDP-glucose, algC, galU, intrinsic multidrug resistance