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Mengdie Chen,1 Ping Feng,1 Yao Liang,2 Xun Ye,3 Yiyun Wang,2 Qiao Liu,1 Chaoyin Lu,1 Qidong Zheng,2 Lijing Wu2 1Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China; 2Department of Internal Medicine, Yuhuan Second People’s Hospital, Yuhuan, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lijing Wu, Department of Internal Medicine, Yuhuan Second People’s Hospital, No.77, Environmental Protection Middle Road, Chu Men Town, Yuhuan, Zhejiang, 317600, People’s Republic of China, Tel: +86-13777603508, Email 13777603508@163.comPurpose: This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC).Patients and Methods: From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses.Results: Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (− 28.49 (− 44.26, − 6.45)% vs − 13.70 (− 30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2.Conclusion: Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.Keywords: age of onset, disease management, type 2 diabetes

Yunxia Zhu,1 Deng Zhang,1 Liang Wu,1 Xiaoliang Ouyang,2 Shengcai Zhu,1 Xiuping Wang,1 Zhen Xiao,3 Yanping Tan,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of China; 4Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 79186278821, Email chunminglincu@163.comPurpose: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis. The gene responsible for DSH has been identified as adenosine deaminase acting on RNA1 (ADAR1). This study aimed to identify the causative variants in the ADAR1 gene in three Chinese families with DSH.Patients and Methods: Data and blood samples were collected from three Chinese families with DSH. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Bioinformatics tools were used to predict the pathogenicity of the variants.Results: Four heterozygous ADAR1 variants were identified, including two novel missense variants c.2369G>C (Arg790Pro), and 503C>T (Pro168Leu), and two previously reported variants: c.3232C>T(R1078C), and c.1472C>G (p.S491X). The novel c.503C>T variant was predicted as “deleterious” (score =− 2.704) by PROVEAN, and “probably damaging” (score = 1) by PolyPhen2. The other novel variant c.2369G>C was also predicted as “deleterious” (score =− 4.167) by PROVEAN, “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.Conclusion: Two novel ADAR1 variants were found in Chinese patients with DSH. This research has expanded the ADAR1 gene database for DSH, enhancing our comprehension of the underlying mechanisms.Keywords: dyschromatosis symmetrica hereditaria, adenosine deaminase acting on RNA1, mutation analysis, Chinese

Jing He,1,&ast; Nan Lin,2,&ast; Ting Jin,2 Ming Lin,1 Zuowei Huang,1 Shuxian Li,1 Jinling Liu,1 Lin Su,1 Xian Ye,2 Lei Wu,1 Zhenghong Song,2 Hongzhen Xu,2 Zhimin Chen1 1Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Nursing Department, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhimin Chen, Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, People’s Republic of China, Email zmchen@zju.edu.cn Hongzhen Xu, Master of nursing, Nursing Department, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, People’s Republic of China, Email 6184020@zju.edu.cnBackground: Allergic conditions, identified as a significant global health challenge, are profoundly influenced by indoor allergens, especially house dust mites (HDM). Yet the relationship between mite sensitized components and respiratory allergies and asthma control remains poorly understood.Methods: A cohort of 96 children, either with allergic rhinitis (AR) or rhinitis with asthma syndrome (ARAS), was assessed. Protein microarray technology was deployed to quantify sIgE responses to the allergenic components of Der p and Der f.Results: The study cohort comprised 18 AR and 78 ARAS patients; with 43 mild and 53 moderate-to-severe AR; with 28 uncontrolled, 21 partially controlled, and 29 well-controlled asthma. Sensitization prevalence for HDM components was highest with Der p (97.9%), Der f 2 (97.9%), Der p 2 (94.8%), Der f 1(94.8%), Der p 1 (93.8%), Der p 23 (57.3%). Notably, sIgE concentrations for Der f and Der f 2 were significantly greater in the ARAS compared to AR (P < 0.05). While sIgE levels varied between mild and moderate-to-severe AR, the differences were not statistically significant (P > 0.05). However, Der p 23 sIgE levels demonstrated a significant fluctuation across the asthma control strata (P < 0.05), with the well-controlled group exhibiting the lowest readings.Conclusion: The sIgE levels to HDM allergens were higher in ARAS group compared to AR group, especially Der f and Der f 2, indicating an association between sIgE reactivity and the diagnosis of asthma. Reduced Der p 23 sIgE levels were indicative of enhanced asthma control.Keywords: house dust mite, allergic rhinitis, asthma, molecular sensitization, children

Meixin Yu,1,&ast; Ling Pei,1,&ast; Han Liu,1 Jiaxin Wang,1 Yun Wen,1 Xian Yang,1 Caixia Ma,1 Xiaofang Zhang,2,3 Liangyan Wu,1 Lihong Wang1,2 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2The Academician Cooperative Laboratory of Basic and Translational Research on Chronic Diseases, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3The Guangzhou Key Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihong Wang, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, No. 613, Huang Pu Avenue West, Guangzhou, Guangdong, People’s Republic of China, Email nd6688@163.comPurpose: To explore the relationship between Red cell distribution width/albumin ratio (RAR) and vascular complications, including atherosclerosis of the lower limbs, diabetic nephropathy(DN), and diabetic retinopathy(DR), in patients with type 2 diabetes mellitus(T2DM).Patients and Methods: The study included 427 patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Jinan University (Guangzhou, China) between April 1, 2022 and May 31, 2023. Baseline characteristics were displayed according to the quartiles of the RAR. Logistic regression analysis and receiver operating characteristic curves (ROC) were used to analyze the data.Results: After adjusting for confounders, a higher RAR quartile(the fourth quartile) was associated with an increased risk of atherosclerosis of the lower limbs(OR: 2.973, 95% CI 1.281– 6.906, p = 0.011), and diabetic nephropathy(OR: 2.876, 95% CI 1.315– 6.287, p = 0.008) compared to the lowest RAR quartile. The patients were further divided into two groups according to urinary albumin to creatinine ratio (UACR≥ 30mg/g and UACR < 30mg/g) and Glomerular Filtration Rate (eGFR< 60 mL·min⁻¹ (1.73 m²) ⁻¹ and eGFR≥ 60 mL·min⁻¹ (1.73 m²) ⁻¹). Similar results were observed. However, We found that RAR quartile did not significantly increase the likelihood of developing diabetic retinopathy(OR: 1.183, 95% CI 0.633– 2.211, p = 0.598).Conclusion: The RAR ratio is associated with an increased risk of atherosclerosis of the lower limbs and diabetic nephropathy in patients with T2DM. The RAR ratio may be an important clinical marker of vascular complications in T2DM.Keywords: Type 2 diabetes mellitus, red blood cell distribution width, albumin, complications, inflammation

Liang Wu,1 Yunxia Zhu,1 Shengcai Zhu,1 Deng Zhang,1 Xiuping Wang,1 Zhen Xiao,2 Yanping Tan,3 Xiaoliang Ouyang,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of China; 4Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoliang Ouyang, Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email ouliangncu@163.com Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email chunminglincu@163.comBackground: Acne vulgaris (AV), a chronic inflammatory pilosebaceous disorder, affects 80– 90% of teenagers. This study aimed to discover lipid profiles and biomarkers of the rabbit ear acne model, and investigate the mechanism of isotretinoin in treating acne at the lipid level.Methods: Untargeted lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was performed to identify skin lipid metabolites in blank control (groups C), model group (group M) and isotretinoin group (group T). Multivariate statistical analysis was used to process the lipidomics data.Results: A total of 43 lipid classes comprising 6989 lipid species were identified from the mass spectrometry data. The orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated significant separation in skin lipidomic profiles between group M and group C. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 299 significantly different lipid metabolites were identified. These lipid metabolites consisted mainly of ceramides (Cer) (53.85%), phosphatidylethanolamines (PE) (9.03%), phosphatidylcholines (PC)(5.35%), and sphingomyelin (SM)(4.01%). Combining with AUC ≥ 0.9 as the elected criteria, Cer (d18;1_24:0), zymosterol (ZyE)(33:5), Cer (t43:1), ZyE (33:6), ZyE (24:7), and ZyE (35:6) have “high” accuracy. Isotretinoin treatment normalized 25 lipid metabolites in the acne model.Conclusion: Our findings provide new insights into the role of lipid metabolism in the pathogenesis of acne and the action mechanism of isotretinoin.Keywords: acne vulgaris, lipidomics, isotretinoin, skin, animal model

Xusheng Zhang,1,&ast; Jiacheng Niu,2,&ast; Jing Fan,1 Miaomiao Hu,1 Chao Xing,1 Qianqian Yuan,1 Shen Yang,1 Baohu Wang,1 Peishun Li,1 Qirong Man,1 Yanchen Ren,1 Linlin Wu,1 Kaixian Zhang1 1Department of Oncology, Tengzhou Central People’s Hospital Affiliated to Jining Medical College, Tengzhou, Shandong Province, People’s Republic of China; 2Medical Imaging Center, Tengzhou Central People’s Hospital Affiliated to Jining Medical College, Tengzhou, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaixian Zhang, Email kaixianzhangtz@163.comPurpose: To evaluate the efficacy and safety of combined microwave ablation (MWA) and vertebral augmentation (VA) in the treatment of spinal metastases with posterior wall defects.Patients and Methods: A retrospective review was conducted for 67 patients (42 men, 25 women) with painful spine metastases and posterior wall defects who underwent MWA combined with VA. Among these patients, 52 vertebrae had no epidural invasion and 33 had mild invasion but did not compress the spinal cord. Procedural effectiveness was determined by comparing visual analog scale (VAS) scores and Oswestry disability index (ODI) scores before the procedure and during the follow-up period.Results: The procedure was technically successful in all patients. The mean VAS score declined significantly from 6.85 ± 1.81 before the procedure to 3.27 ± 1.97 at 24 h, 1.96 ± 1.56 at 1 week, 1.84 ± 1.50 at 4 weeks, 1.73 ± 1.45 at 12 weeks, and 1.71 ± 1.52 at 24 weeks post-procedure (p < 0.01). The mean ODI score was lower post-procedure than before the procedure (p < 0.001). Transient nerve injury occurred in two patients (SIR classification D), and the incidence of asymptomatic bone cement (SIR classification A) was 43.5% (37/85).Conclusion: MWA combined with VA is an effective and safe treatment for painful spine metastases with posterior wall defects.Keywords: microwaves, vertebroplasty, spinal, metastases

Mengmeng Yuan,1 Lijun Wu,2 Wen Li,1 Shuwen Li1 1School of Nursing, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Shuwen Li, School of Nursing, Anhui Medical University, No. 15 Feicui Road, Economic and Technological Development District, Hefei, 230601, People’s Republic of China, Email lishuwen@ahmu.edu.cnPurpose: We intended to explore the chain mediation role of resilience and different sources of social support on the relationship between symptom interference and life satisfaction from the patient-reported perspective.Patients and Methods: Two hundred and twenty-six patients after esophagectomy were investigated using four validated scales to estimate the symptom interference, resilience, different sources of social support, and life satisfaction. The chain mediation analysis was conducted using SPSS PROCESS Macro Model 6.Results: Mediation analysis showed that symptom interference indirectly influenced life satisfaction through two significant mediating pathways: (i) resilience (B = − 0.138, 95% CI: − 0.194 to − 0.091); (ii) the chain mediators involving in resilience and family support (B = − 0.049, 95% CI: − 0.073 to − 0.026). Surprisingly, the mediating pathway of family support was not significant.Conclusion: Interventions for resilience and family support could mitigate the adverse effects of symptom interference in patients after esophagectomy, improving life satisfaction. Of these, resilience may be more critical in terms of the utilization of social resources than family support.Keywords: life satisfaction, oesophageal cancer, social support, resilience, symptom interference

Hailing Yu,1,&ast; Yongquan Huang,2,&ast; Zhisheng Nong,3,&ast; Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

Yuqing Li,1,&ast; Lei Wu,1,2,&ast; Rui Zhao,1,2,&ast; Yi Gao,1 Geng Bai,1 Ziqiang Guo,1 Xiaolin Chen,1 Yuanlu Chen,2 Tong Liu,1 Guangping Li1 1Tianjin Key Laboratory of Logic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 2TEDA International Cardiovascular Hospital, Electrophysiological Department, Tianjin, 300457, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangping Li, Email tic_tjcardiol@126.comBackground: An electrocardiogram (ECG) was used to determine the type of acute myocardial infarction (MI) and locate the culprit vessel. Inferior wall myocardial infarction (IWMI) patients with the right coronary artery (RCA) as the culprit vessel may have a worse clinical prognosis than the left circumflex artery (LCx). We aimed to develop a new, simple, accurate scoring system to localize the RCA.Methods: From January 2018 to January 2020, patients were admitted to the Department of Cardiology of TEDA International Cardiovascular Hospital and the Second Hospital of Tianjin Medical University due to IWMI and coronary angiography confirmed that the infarct-related vessel was a single RCA or LCx. ECG of patients before percutaneous coronary intervention (PCI) was collected to quantitatively analyze the characteristics of ST-segment deviation in non-inferior wall leads (N-IWL) and establish the RCA score in N-IWL.Results: 149 patients were enrolled, including 83 in the RCA group and 66 in the LCx group. Finally, ST-segment depression (ST↓) lead I, aVR, V1, and V6, and ST↓≥ 1mm in lead V4 were found to be associated with the location of the RCA. The sensitivity, specificity, and area under the curve (AUC) of the N-IWL RCA scoring system were 77.1%, 72.7%, and 0.83, respectively. The diagnostic ability of the scoring system was better than that of other algorithms and scoring systems.Conclusion: ECG helps identify the RCA in patients with IWMI before PCI. The N-IWL RCA score may help identify the culprit vessel as the RCA in patients with IWMI.Keywords: electrocardiogram, inferior wall myocardial infarction, percutaneous coronary intervention, right coronary artery

Cai-Dong Liu,1,2,&ast; Qiang Peng,3,&ast; Shi-Yao Wang,3,&ast; Yang Deng,2 Zhong-Yuan Li,3 Zhao-Han Xu,3 Liang Wu,3 Ying-Dong Zhang,2,3 Rui Duan3 1Department of Laboratory Medicine, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 210006, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210006, People’s Republic of China; 3Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying-Dong Zhang; Rui Duan, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, Jiangsu, People’s Republic of China, Email zhangyingdong@njmu.edu.cn; duanruicpu@163.comPurpose: Acute ischemic stroke (AIS) has seriously threatened people’s health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS.Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4.Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients.Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.Keywords: ischemic stroke, miRNA, circRNA, ferroptosis, biomarker

Fengfeng Li,1 Yang Jia,1 Jun Fang,2 Linqiang Gong,3 Yazhou Zhang,4 Shanshan Wei,5 Linlin Wu,6 Pei Jiang5 1Neurosurgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 2Anesthesiology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 3Gastroenterology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 4Foot and Ankle Surgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 5Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China; 6Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of ChinaCorrespondence: Linlin Wu, Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China, Tel +86 632-5513457, Email linlinliff@163.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China, Tel +86 537-2106208, Email jiangpeicsu@sina.comBackground: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c.Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand–receptor interaction and retrograde endocannabinoid signaling.Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid β-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.Keywords: MOTS-c, TBI, transcriptomics, metabolomics, neuroprotective

Lina Du,1 Dezhi Yang,2 Lan Wu,1 Li Mei,1 Sarula Wu,1 Yasula Ba,1 Yongchang Bao,1 Rigugaqiqige Su,1 Lin Song1 1College of Mongolian Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Innovative Mongolian Medical Engineering Research Center, Inner Mongolia International Mongolian Hospital, Hohhot, Inner Mongolia, People’s Republic of ChinaCorrespondence: Lin Song, Inner Mongolia Medical University, Tel +15849163188, Email songlinwpsword@163.comObjective: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia.Methods: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot.Results: The weights of the insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses.Conclusion: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse. Keywords: Mongolian medicine sugemule-4 decoction, insomnia, metabolomics, gut microbiota, network pharmacology, molecular mechanism

Na Li,1 Liufu Cui,1 Gary Tse,2,3 Panagiotis Korantzopoulos,4 Konstantinos P Letsas,5 George Bazoukis,6,7 Shuohua Chen,8 Nan Zhang,2 Xuemei Yang,9 Peipei Liu,10 Lili Wu,11 Gan-Xin Yan,12,13 Gregory Yoke Hong Lip,14,15 Shouling Wu,8 Tong Liu2 1Department of Rheumatology and Immunology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 4First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; 5Arrhythmia Unit, Laboratory of Cardiac Pacing and Electrophysiology, Onassis Cardiac Surgery Center, Athens, Greece; 6Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus; 7European University Cyprus, Medical School, Nicosia, Cyprus; 8Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 9School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 10School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 11Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 12Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA, USA; 13Department of Cardiology, Fuwai Huazhong Hospital, Zhengzhou, Henan Province, People’s Republic of China; 14Liverpool Centre for Cardiovascular Sciences, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; 15Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China, Email liutong@tmu.edu.cn; liutongdoc@126.com Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China, Email drwusl@163.comObjective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP.Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB.Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP.Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. Keywords: hyperuricemia, inflammation, cardiac conduction block, combined exposure, risk factors, mediation

Li-Chao Ma,1,2 Shi-Ning Lou,3 Xiao-Li Zhu,3 Ruo-Lan Zhang,1 Lin Wu,1 Jiang-Yuan Xu,1 Xiao-Juan Ding,1 Juan Liu,4 Yan Wang1 1School of Nursing, Hebei University, Baoding, Hebei, 071000, People’s Republic of China; 2Operating Room, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Traditional Chinese Medicine, Work’s Hospital of China Lucky Group Corporation, Baoding, Hebei, 07100, People’s Republic of China; 4Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, People’s Republic of ChinaCorrespondence: Juan Liu, Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, No. 212 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13582292161, Email juanliulj07@126.com Yan Wang, School of Nursing, Hebei University, No. 342 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13833258628, Email ywang_dr06@163.comObjective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population.Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi’s method of descriptive data analysis.Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) “Insufficient CR resources for patients”: Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) “Patient CR initiative”: Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise.Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.Keywords: coronary heart disease, cardiac rehabilitation, community sanitation service, self-care, patient needs

Jinrui Ji,1,2,&ast; Xiaoyun Wei,1,2,&ast; Dongyun Wan,1,2,&ast; Lei Wu,1,2,&ast; Guangyao Chen,1,3,&ast; Hengliang Liu1,2,&ast; 1Clinical Medical Department, Faculty of Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 2Department of Cardiology, People’s Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 3Zhengzhou Institute of Gastroenterology, People’s Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengliang Liu, Henan University of Traditional Chinese Medicine, No. 33, Huanghe Road, Jinshui District, Zhengzhou, Henan Province, 450000, People’s Republic of China, Tel/Fax +86 0371-67077158, Email hnzzjjr@163.comPurpose: This study investigated the influence of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) levels on the degree of atherosclerosis and major adverse cardiovascular and cerebrovascular events (MACCE) in older adults with non-alcoholic fatty liver disease.Methods: The degree of atherosclerosis severity was assessed by the standard Gensini score quartile method. According to the degree of atherosclerosis, patients were divided into mild (0– 24 points; n=84), moderate (25– 53 points; n=86), and severe groups (≥ 54 points; n=84) and then categorized as MACCE (n=30) or non-MACCE (n=224) according to 6-month follow-up data. The patients’ age, sex, smoking history, medical history, and early morning fasting venous blood, for measuring biochemical indexes, were collected. Clinical data were compared between groups and the relationship between Gensini scores and PCSK9 was evaluated.Results: Compared with the mild group, the moderate and severe groups had higher high-sensitivity C-reactive protein(hs-CRP), PCSK9, triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)[Lp(a)] levels and lower high-density lipoprotein cholesterol(HDL-C) levels (all P< 0.05). Moreover, PCSK9 positively correlated with Gensini scores (r=0.657, P< 0.01). The MACCE and non-MACCE groups had significantly different ages, statin use, Gensini scores, PCSK9, and LDL-C (all P< 0.05). Multi-factorial Cox risk regression analysis showed the Gensini score (HR=1.018, 95% CI: 1.006~1.029) and PCSK9 (HR=1.147, 95% CI: 1.038~1.287) were independent risk factors for MACCE.Conclusion: The Gensini score and PCSK9 levels can be used as predictive indicators for the degree of illness and occurrence of MACCE in older NAFLD patients.Keywords: older adults, non-alcoholic fatty liver disease, proprotein convertase subtilisin/kexin 9, atherosclerosis, major adverse cardiovascular and cerebrovascular events

Wei Zheng, Jianhua Liu, Haixia Bai, Xin Xu, Lina Wu, Xiaosong Qin Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Liaoning Clinical Research Center for Laboratory Medicine, Shengyang, People’s Republic of ChinaCorrespondence: Xiaosong Qin, Email qinxs@sj-hospital.orgBackground: Gordonia terrae is an opportunistic pathogen that rarely causes clinical infections. Here, we first report a case of spontaneous bacterial peritonitis in patients with hepatitis C cirrhosis caused by Gordonia terrea.Case Presentation: A 71-year-old male patient was diagnosed with spontaneous bacteria peritonitis secondary to hepatitis C cirrhosis. The result of bacterial culture in ascites was positive, and the pathogenic bacteria was preliminarily identified as the Gordonia genus by matrix-assisted laser desorption ionization–time of flight mass spectrometry. After 16S rRNA sequencing analysis, it was determined to be the Gordonia terrea. Symptoms relieved after treatment with ceftazidime.Conclusion: This case indicates that the clinical infections caused by Gordonia terrea should be brought to the forefront. Accurate and rapid bacterial identification results are highly beneficial to the diagnosis and therapeutic regime.Keywords: spontaneous bacterial peritonitis, rare pathogen, Gordonia terrae, identification

Jing Zhang,1,&ast; Le Wu,1,&ast; Chenchen Wang,2,&ast; Xin Xie,1 Yuying Han1– 3 1Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Critical Care Medicine, the 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu, People’s Republic of China; 3Science and Education Department, Xi’an No. 5 Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuying Han; Xin Xie, Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, 229 Taibai North Road, Xi’an, Shaanxi, 710069, People’s Republic of China, Email hanyuying@nwu.edu.cn; xiexin@nwu.edu.cnAbstract: In the past few decades, chemotherapy has been one of the most effective cancer treatment options. Drug resistance is currently one of the greatest obstacles to effective cancer treatment. Even though drug resistance mechanisms have been extensively investigated, they have not been fully elucidated. Recent genome-wide investigations have revealed the existence of a substantial quantity of long non-coding RNAs (lncRNAs) transcribed from the human genome, which actively participate in numerous biological processes, such as transcription, splicing, epigenetics, the cell cycle, cell differentiation, development, pluripotency, immune microenvironment. The abnormal expression of lncRNA is considered a contributing factor to the drug resistance. Furthermore, drug resistance may be influenced by genetic and epigenetic variations, as well as individual differences in patient treatment response, attributable to polymorphisms in metabolic enzyme genes. This review focuses on the mechanism of lncRNAs resistance to target drugs in the study of tumors with high mortality, aiming to establish a theoretical foundation for targeted therapy.Keywords: lncRNA, drug resistance, chemotherapy, tumor, immune escape

Liang Wu,1,2 Martijn H van Heugten,3 Thierry PP van den Bosch,4 Hans Duimel,5 Carmen López-Iglesias,5 Dennis A Hesselink,2 Carla C Baan,2 Karin Boer2 1Department of Nephrology, the First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 2Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Internal Medicine, Division of Nephrology and Transplantation, Rotterdam, the Netherlands; 3University Medical Center Rotterdam, Department of Internal Medicine, Division of Nephrology and Transplantation, Rotterdam, the Netherlands; 4Department of Pathology, University Medical Center Rotterdam, Rotterdam, the Netherlands; 5The Microscopy CORE Laboratory at the Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the NetherlandsCorrespondence: Liang Wu, Erasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center Rotterdam Erasmus MC, Room No. Na-514, Doctor Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands, Tel +31 0622145029, Email l.wu.1@erasmusmc.nlPurpose: Kidney transplantation is the optimal treatment for patients with end-stage kidney disease. Donor-specific urinary extracellular vesicles (uEVs) hold potential as biomarkers for assessing allograft status. We aimed to develop a method for identifying donor-specific uEVs based on human leukocyte antigen (HLA) mismatching with the kidney transplant recipients (KTRs).Patients and Methods: Urine and plasma were obtained from HLA-A2+ donors and HLA-A2- KTRs pre-transplant. CD9 (tetraspanin, EV marker) and HLA-A2 double-positive (CD9+ HLA-A2+) EVs were quantified using isolation-free imaging flow cytometry (IFCM). Healthy individuals’ urine was used to investigate CD9+ HLA-class-I+ uEV quantification using IFCM, time-resolved fluoroimmunoassay (TR-FIA), and immunogold staining cryo-electron microscopy (cryo-EM). Culture-derived CD9+ HLA-class-I+ EVs were spiked into the urine to investigate urine matrix effects on uEV HLA detection. Deceased donor kidneys and peritumoral kidney tissue were used for HLA class I detection with histochemistry.Results: The concentrations of CD9+ HLA-A2+ EVs in both donor and recipient urine approached the negative (detergent-treated) control levels for IFCM and were significantly lower than those observed in donor plasma. In parallel, universal HLA class I+ uEVs were similarly undetectable in the urine and uEV isolates compared with plasma, as verified by IFCM, TR-FIA, and cryogenic electron microscopy. Culture supernatant containing HLA class I+ vesicles from B, T, and human proximal tubule cells were spiked into the urine, and these EVs remained stable at 37°C for 8 hours. Immunohistochemistry revealed that HLA class I was predominantly expressed on the basolateral side of renal tubules, with limited expression on their urine/apical side.Conclusion: The detection of donor-specific uEVs is hindered by the limited release of HLA class I+ EVs from the kidney into the urine, primarily due to the polarized HLA class I expression on renal tubules. Identifying donor-specific uEVs requires further advancements in recognizing transplant-specific uEVs and urine-associated markers.Keywords: kidney transplantation, donor-specific biomarker, HLA, extracellular vesicles, human urine, renal tubule

Yexiao Wang,1,&ast; Zibin He,2,&ast; Bingqin Luo,2 Hioteng Wong,1 Liangcai Wu,3 Hui Zhou1 1Department of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Dermatology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangcai Wu; Hui Zhou, Tel +86 13380019222 ; +86 13660389658, Email wulc@mail.sysu.edu.cn; zhouhui5@mail.sysu.edu.cnBackground: Mesenchymal stem cell-derived exosomes (MSC-Exo) have therapeutic potential. However, the impact of MSC-Exo on the survival and melanogenesis of human primary melanocytes following H2O2-induced damage has not been clarified. We therefore investigated the effects of MSC-Exo on the H2O2-affected survival of human primary melanocytes and their proliferation, apoptosis, senescence, and melanogenesis in vitro.Methods: MSC-Exo were prepared from human MSCs by sequential centrifugations and characterized by Transmission Electron Microscopy, Western blot and Nanoparticle Tracking Analysis. Human primary melanocytes were isolated and treated with different concentrations of MSC-Exo, followed by exposing to H2O2. Furthermore, the impact of pretreatment with MSC-Exo on the proliferation, apoptosis, senescence and melanogenesis of melanocytes were tested by CCK-8, flow cytometry, Western blot, L-Dopa staining, tyrosinase activity and RT-qPCR.Results: Pretreatment with lower doses of MSC-Exo protected human primary melanocytes from the H2O2-triggered apoptosis, while pretreatment with higher doses of MSC-Exo enhanced the H2O2-induced melanocyte apoptosis. Compared with the untreated control, pretreatment with a lower dose (1 μg/mL) of MSC-Exo enhanced the proliferation of melanocytes, abrogated the H2O2-increased p53, p21, IL-1β, IL-6 and IL-8 expression and partially rescued the H2O2-decreased L-dopa staining reaction, tyrosinase activity, MITF and TRP1 expression in melanocytes.Conclusion: Our findings indicate that treatment with a low dose of MSC-Exo promotes the proliferation and melanogenesis of human primary melanocytes by ameliorating the H2O2-induced apoptosis and senescence of melanocytes. MSC-Exo may be a promising therapeutic strategy of vitiligo.Keywords: mesenchymal stem cell-derived exosomes, melanocytes, apoptosis, proliferation, senescence

Jiao Chen, Danmei Luo, Chengxia Sun, Xiaolan Sun, Changmao Dai, Xiaohong Hu, Liangqing Wu, Haiyan Lei, Fang Ding, Wei Chen, Xueping Li Geriatric Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xueping Li, Chengdu University of Traditional Chinese Medicine, No. 37, Shier Bridge Road, Chengdu, Sichuan, People’s Republic of China, Tel +86-18380251086, Email 3173907@qq.comPurpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults.Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a “non-re-positive” group and a “re-positive” group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model’s goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively.Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was > 8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was > 80%, the positive estimated value was closer to the actual number of cases.Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.Keywords: malnutrition, COVID-19, re-positive, clinical prediction model

Kaixiong Liu,1– 3,&ast; Luling Wu,4,5,&ast; Gongping Chen,1– 3,&ast; Dunhuan Zeng,1– 3 Qiwei Zhong,6 Li Luo,1,2 Bin Song,7 Xiuhong Ying,1,2 Fayu Ni,8 Lifang Yu,8 Liyu Xu,9 Xin Lin,9 Xiaoyan Chen,10 Xin Zou,11 Jianhong Xiao,7 Yuekai Hu5,12,13 1Department of Respiratory and Critical Care medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People’s Republic of China; 4Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Minnan Hospital, the First Affiliated Hospital of Fujian Medical University, Quau zhou, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Mindong Hospital Affiliated to Fujian Medical University, Ningde, People’s Republic of China; 8Department of Respiratory, Fuqing General Hospital Affiliated to Fujian Medical University, Fuzhou, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, Fuzhou First Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 10Department of Emergency Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, LongYan First Hospital Affiliated to Fujian Medical University, Longyan, People’s Republic of China; 12Department of Infectious Diseases, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 13Department of Infectious Diseases, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuekai Hu; Jianhong Xiao, Email huyuekai@fudan.edu.cn; xjh1030@sina.comObjective: This study aimed to describe and compare the epidemiological, demographic, clinical, laboratory and radiological characteristics as well as the complications, treatments, and outcomes of these patients.Methods: We retrospectively investigated clinical data of patients with C. psittaci infection (psittacosis) in eight Grade IIIA hospitals of Fujian. Metagenomic next-generation sequencing (mNGS) was used identify C. psittaci in clinical samples of all included patients.Results: A total of 74 patients (39 severe/35 non-severe) was diagnosed with psittacosis, 25 (33.8%) of whom had history of poultry exposure. Common symptoms included high fever (98% [37/74]), fatigue (52.7% [39/74]), and dyspnea (51.4% [38/74]). Common manifestations in imaging included consolidation (89.2%), pleural effusion (77.0%), and air bronchogram (66.2%). Common complications included acute respiratory distress syndrome (55.4% [41/74]), type I respiratory failure (52.7% [39/74]), acute liver injury (41.9% [31/74]), and secondary infection (27.0% [20/74]). The in-hospital mortality rate was 8.11% (6/74).Conclusion: C. psittaci infection is represents an underestimated cause of CAP. For SCAP patients with poultry and bird contact history, specimens were encouraged to be sended for mNGS test in time. C. psittaci infection can lead to severe, multiple system involvement, and several complications. mNGS facilitate timely diagnosis of C. psittaci infection.Keywords: Chlamydia psittaci, metagenomic next-generation sequencing, community-acquired pneumonia, bronchoalveolar lavage fluid

Sheng Tian,1,2 Heqing Zheng,1,2 Wei Wu,1,2,&ast; Lanxiang Wu1,2,&ast; 1Department of Neurology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Institute of Neuroscience, Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu; Lanxiang Wu, Email 13807038803@163.com; 1127370500@qq.comPurpose: Previous studies have shown that pyroptosis plays a vital role in the progress of neuropathic pain (NP), but the molecular mechanisms have not been fully elucidated. The aim of this study was to identify crucial pyroptosis-related genes (PRGs) in NP.Methods: We identified pyroptosis-related differentially expressed genes (PRDEGs) in NP by machine learning analysis of the GSE24982 and GSE60670 datasets. Furthermore, these PRDEGs were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and Friends analysis, respectively. Meanwhile, receiver operator characteristic (ROC) analysis was performed to assess the diagnostic value of PRDEGs in NP. Finally, we performed immune infiltration analysis of key PRDEGs using CIBERSORTR R package.Results: We found that 5 PRDEGs by least absolute shrinkage and selection operator (LASSO) regression and random forest and verified by RT-qPCR. GO, KEGG and GSEA revealed that these PRDEGs were mainly enriched in regulation of neuron death, IL-4 signaling, IL-23 pathway, and NF-κB pathway. ROC analysis revealed that most of the PRDEGs performed well in diagnosing NP. We also revealed transcription factors, miRNA regulatory networks and drug interaction networks of PRDEGs. For immune infiltration analysis, PRDEGs were mainly correlated with dendritic cells, monocytes and follicular T helper cells, suggested that it might be involved in the regulation of neuroimmune-related signaling.Conclusion: A total of five PRDEGs were can be employed as NP biomarkers, particularly Tlr4, Il1b and Casp8, and provide additional evidence for a vital role of pyroptosis in NP.Keywords: pyroptosis, machine learning, neuropathic pain, neuroinflammation, bioinformatic analysis

Jianbo Zhong,1,&ast; Kamran Ali,1,2,&ast; Ping Yang,1,&ast; XingYun Zhao,1 LiMing Wu1 1Department of Dermatology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Oncology, the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: LiMing Wu, Department of Dermatology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, No. 261, Huansha Road, Hangzhou, People’s Republic of China, Tel/Fax +86 13750837205, Email limingwu1973@163.comAbstract: We present the case of a 58-year-old male patient who presented with pruritic skin plaques and papules on the scalp, face, back, and back of the hands for over a year. The symptoms worsened upon exposure to sunlight and improved on cloudy days. Despite previous attempts at treatment with glucocorticoid ointment and antihistamine drugs, the patient experienced progressive aggravation of symptoms. Physical examination revealed hypertrophic and infiltrating nodules, with significant scratches and local exudation. Skin biopsy confirmed the diagnosis of sun-induced dermatosis. The patient was initiated on tofacitinib, an oral Janus Kinase inhibitor, along with a halometasone ointment, oral ebastine tablets, and strict sun protection. Over the course of four revisits spanning four months, the patient experienced a significant improvement in symptoms, with the rash almost disappearing and pruritus subsiding. The treatment was well tolerated and no adverse effects were observed. Follow-up for six months post-treatment showed no recurrence of symptoms. This case highlights the efficacy of tofacitinib in managing sun-induced pruritic plaques and suggests it as a potential therapeutic option in similar cases.Keywords: tofacitinib, sun-induced dermatosis, chronic actinic dermatitis, pruritic plaques

Wenjie Huang,1,2 Ting Luo,1,2 Mengqiu Lan,3 Wenting Zhou,1,2 Ming Zhang,1,2 Lihong Wu,3 Zhenni Lu,3 Li Fan1,2 1Department of Reproductive Medicine, Guangzhou Women and Children’s Medical Center Liuzhou Hospital, Liuzhou, Guangxi, 545616, People’s Republic of China; 2Department of Reproductive Medicine, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, 545001, People’s Republic of China; 3Clinical Laboratory Science, Liuzhou Municipal Liutie Central Hospital, Liuzhou, Guangxi, 545007, People’s Republic of ChinaCorrespondence: Wenjie Huang, Email a17377552242@163.comPurpose: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, characterized by intense lung infiltrations of immune cells (macrophages and monocytes). While existing studies have highlighted the crucial role of the competitive endogenous RNA (ceRNA) regulatory network in COPD development, the complexity and characteristics of the ceRNA network in monocytes remain unexplored.Methods: We downloaded messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) microarray data from GSE146560, GSE102915, and GSE71220 in the Gene Expression Omnibus (GEO) database. This data was used to identify differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs). Predicted miRNAs that bind to DElncRNAs were intersected with DEmiRNAs, forming a set of intersecting miRNAs. This set was then used to predict potential binding mRNAs, intersected with DEmRNAs, and underwent functional enrichment analysis using R software and the STRING database. The resulting triple regulatory network and hub genes were constructed using Cytoscape. Comparative Toxicomics Database (CTD) was utilized for disease correlation predictions, and ROC curve analysis assessed diagnostic accuracy.Results: Our study identified 5 lncRNAs, 4 miRNAs, and 149 mRNAs as differentially expressed. A lncRNA-miRNA-mRNA regulatory network was constructed, and hub genes were selected through hub analysis. Enrichment analysis highlighted terms related to cell movement and gene expression regulation. We established a LINC00482-has-miR-6088-PRRC2B ceRNA network with diagnostic relevance for COPD. ROC analysis demonstrated the diagnostic value of these genes. Moreover, a positive correlation between LINC00482 and PRRC2B expression was observed in COPD PBMCs. The CTD database indicated their involvement in inflammatory responses.Conclusion: In summary, our study not only identified pivotal hub genes in peripheral blood mononuclear cells (PBMCs) of COPD but also constructed a ceRNA regulatory network. This contributes to understanding the pathophysiological processes of COPD through bioinformatics analysis, expanding our knowledge of COPD, and providing a foundation for potential diagnostic and therapeutic targets for COPD.Keywords: COPD, PBMCs, ceRNA, bioinformatics analysis, PRRC2B, LINC00482

Jingchao Jia,1,2,&ast; Jing Yang,3,&ast; Leimin Qian,2 Biao Zhou,2 Xiaodong Tang,2 Shuanghai Liu,2 Li Wu,4 Jifeng Chen,5 Yuting Kuang1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People’s Republic of China; 3Jiangnan University Medical Center, Wuxi, People’s Republic of China; 4Department of Pharmaceutics, People’s Hospital of Shanggao, Yichun, People’s Republic of China; 5The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuting Kuang, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Email yuting_kuang@163.com Jifeng Chen, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China, Email chenjifeng-1987@163.comIntroduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range.Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2’-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy.Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth.Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.Keywords: NIR-controlled siRNA release, nanopolyplex, UCNPs, anti-tumor therapy

Xiuping Wang,1 Xiaoliang Ouyang,2 Deng Zhang,1 Yunxia Zhu,1 Liang Wu,1 Zhen Xiao,3 Simin Yu,1 Wei Li,2 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Plastic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 791 86278821, Email chunminglincu@163.comPurpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK.Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients.Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as “disease-causing” (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as “deleterious” (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.Keywords: porokeratosis, mutation, MVD, FDPS, genetics

Limin Wu,1 Jing Xu2 1Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Lucheng District, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Endocrinology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Lucheng District, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jing Xu, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 15068256508, Email 47914057@qq.comPurpose: Cardiometabolic index (CMI) has been suggested as innovative measures for assessing the cardiometabolic status. However, there is a lack of relevant studies on exploring the relationship between CMI and insulin resistance (IR). Consequently, this study aims to examine the relationship between CMI and IR in subjects with type 2 diabetes mellitus (T2DM).Patients and Methods: A cross-sectional study was performed on 2493 patients with T2DM (including 1505 males and 988 females). IR was measured through the homeostatic model assessment of insulin resistance (HOMA-IR), which was defined as HOMI-IR≥ 2.69. The relationship between CMI and IR was evaluated with Spearman’s correlation, ROC analysis, multiple logistic regression, generalized smooth curve fitting and subgroup analysis.Results: CMI was correlated with HOMA-IR in patients with T2DM (Spearman correlation coefficient = 0.391 in females and 0.346 in males, P< 0.001). Through the multiple logistic regression analysis, CMI was significantly correlated with IR (OR=1.30, 95% CI=1.15– 1.47 in males and OR=1.62, 95% CI=1.32– 1.99 in females). In addition, a non-linear correlation between CMI and IR risk was identified. The AUC of CMI (AUC = 0.702 for males and 0.733 for females, all p < 0.01) was the largest compared with traditional indexes of adiposity and blood lipids. According to the subgroup analysis, the two had a more significantly positive correlation in females, the elderly and subjects with HbA1c < 7%.Conclusion: In patients with T2DM, elevated CMI is significantly correlated with IR, as a useful index of IR.Keywords: high density lipoprotein cholesterol, cardiometabolic index, waist-to-height ratio, insulin resistance, type 2 diabetes mellitus

Huanhuan Zhu, Chen Chen, Luhan Geng, Qing Li, Chengning Zhang, Lin Wu, Bo Zhang, Suyan Duan,&ast; Changying Xing,&ast; Yanggang Yuan&ast; Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan, Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel/Fax +86-25-6813-6462, Email ygyuan@njmu.edu.cnBackground: Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN.Methods: Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student’s t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman’s rank correlation.Results: Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index.Conclusion: Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC levels were significantly correlated with renal functions and renal pathology activity.Keywords: lupus nephritis, mitochondrial pyruvate carrier, proliferative, membranous, tubulointerstitial lesions

Zhicheng Gao,1,2,&ast; Jiaqi Bao,1,2,&ast; Liuyang Wu,2 Kaiyu Shen,1 Qiqi Yan,2 Lifang Ye,2 Lihong Wang2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 85894275, Email wanglhnew@126.comPurpose: Lymphocyte to C-reactive protein ratio (LCR) is a recognized systemic inflammatory marker and novel prognostic indicator for several cancers. This study investigated the relationship between preoperative LCR and new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Patients and Methods: Patients with AMI (n=662) with no history of atrial fibrillation (AF) were enrolled and classified into NOAF and non-NOAF groups based on the occurrence of postoperative NOAF during hospitalization. Logistic regression models were used to analyze NOAF risk factors and to assess the association between preoperative LCR and NOAF incidence. We constructed a new nomogram from the selected NOAF risk factors, and tested its predictive performance, degree of calibration, and clinical utility using receiver operating characteristic and calibration curves, decision curve analysis, and clinical impact curves.Results: Overall, 84 (12.7%) patients developed NOAF during hospitalization. The LCR was significantly lower in the NOAF group. Preoperative LCR accurately predicted NOAF after AMI and was correlated with increased NOAF risk. Age, body mass index, diabetes, serum albumin levels, uric acid levels, left atrium (LA) diameter, left ventricular ejection fraction, left circumflex artery stenosis > 50%, and Killip class II status were independent predictors of NOAF after AMI. In addition, a new nomogram combined with LCR was constructed to stratify the risk of NOAF in patients with AMI. The performance of the new nomogram was satisfactory, as shown by the receiver operating characteristic curve, calibration curve, decision curve analysis and clinical impact curve.Conclusion: Preoperative LCR was an independent predictor of NOAF in patients with AMI after PCI. The novel nomogram combined with LCR could rapidly and individually identify and treat patients at a high risk of NOAF.Keywords: C-reactive protein, acute myocardial infarction, atrial fibrillation, nomogram, left ventricular ejection fraction

Wei W, Mo X, Yan L, et al. Cancer Manag Res. 2020;12:15–30. We, the Editor and Publisher of the journal Cancer Management and Research have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

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

Man Li,1,2,&ast; Xintao Li,3,&ast; Hongwei Gao,4 Peng Li,1 Li Zhang,1 Xiaoling Zhang,1 Peipei Liu,5 Xuemei Yang,2 Lili Wu,6 Jiangwei Zeng,2 Shouling Wu,7 Lixia Sun1 1Department of Emergency, The Affiliated Hospital of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Graduate School, North China University of Science and Technology, Tangshan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Soochow University, Jiangsu, People’s Republic of China; 4Department of Emergency, Caofeidian District hospital of Tangshan City, Tangshan, People’s Republic of China; 5School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 6Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 7Department of Cardiology, Kailuan Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixia Sun, Department of Emergency, The Affiliated Hospital of North China University of Science and Technology, Tangshan, 063000, People’s Republic of China, Email 13323151999@189.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, 063000, People’s Republic of China, Email drwusl@163.comPurpose: Inflammation plays a critical role in the development of cardiac conduction block (CCB), which is associated with an increased risk of morbidity and mortality. The monocyte-lymphocyte ratio (MLR) acts as a novel inflammatory marker; however, its association with CCB has not yet been studied. This study aimed to investigate the association between MLR and CCB risk.Patients and Methods: In total, 82,472 CCB-free participants were identified from the Kailuan study. MLR was calculated using the monocyte count/lymphocyte count. The participants were stratified based on quartiles of MLR levels. Incident CCB and its subtypes were ascertained from electrocardiograms at biennial follow-up visits. The Cox proportional hazards model and restricted cubic spline analysis were used to investigate the association between MLR with CCB and its subtypes.Results: During a median follow-up of 10.4 years, 3222 incident CCB cases were observed. A U-shaped association was observed between MLR and CCB risk (Pnonlinearity < 0.05). After multivariate adjustment, individuals in the highest MLR quartile had a hazard ratio (HR) of 1.212 (95% CI: 1.097-1.340; Q4 vs Q2), while those in the lowest MLR quartile had an HR of 1.106 (95% CI: 1.000-1.224; Q1 vs Q2). Sensitivity and subgroup analyses yielded consistent results. The U-shaped association persisted for atrioventricular block (AVB) in subtype analyses.Conclusion: MLR was significantly associated with an increased risk of new-onset CCB. Assessing MLR may have clinical relevance for predicting CCB risk, providing valuable insights for preventive strategies and patient management.Pre-Registered Clinical Trial Number: The pre-registered clinical trial number is ChiCTR-TNC-11001489. Keywords: cardiac arrhythmia, cardiac conduction block, inflammation, monocyte-lymphocyte ratio, risk factors

Jiajin Di,1 Qingxian Zhu,2 Lei Wu,2 Jiali Tan,2 Yi Gao,1 Jun Liu2 1Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2The Affiliated Maternity and Child Health Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of ChinaCorrespondence: Jun Liu, The Affiliated Maternity and Child Health Hospital of Jiangnan University, No. 48, Samuel Lane, Liangxi District, Wuxi, Jiangsu, People’s Republic of China, Tel +86 180 6836 0717, Email 6212807010@stu.jiangnan.edu.cnPurpose: The maintenance of stable blood glucose levels in gestational diabetes patients depends on their ability to make scientific decisions. Decision-making ability is influenced by factors such as preferences, knowledge acquisition, and risk perceptions. At present, problems such as irrational dietary structure, difficulties in decision-making, and poor adherence still exist in clinical practice. The key to guiding gestational diabetes patients in developing their scientific decision-making abilities lies in identifying the weak key points that affect their decision-making abilities. There is a lack of validated tools to assess these patients’ perceptions of dietary intake. In this study, we aimed to develop and validate the Dietary Intake Perceived Motivation Questionnaire for Patients with Gestational Diabetes Mellitus with the purpose of accurately identifying the obstacles encountered by gestational diabetes mellitus patients in the development of their scientific decision-making abilities.Patients and Methods: In this study, 304 individuals with gestational diabetes were recruited from a public hospital in Wuxi, China. The questionnaire was developed in 3 stages, consisting of questionnaire development, a pilot study, and a formal test, and the validity and reliability of the questionnaire were tested and confirmed. The content validity index and exploratory factor analysis were completed by expert correspondence to indicate the validity of the content and structure. In addition, Cronbach’s α was used to evaluate the internal consistency of each item of the questionnaire, and Spearman-Brown analysis was used to analyze the split-half reliability. In addition to the questionnaire, the study participants were asked to complete a general information questionnaire that included items on various demographic factors such as age, week of gestation, and mode of conception.Results: The questionnaire was validated through principal component analysis, resulting in a 31-item questionnaire named the Dietary Intake Perceived Motivation Questionnaire for Patients with Gestational Diabetes Mellitus. This questionnaire explained 86.267% of the variance and demonstrated good internal consistency (Cronbach’s α= 0.929).Conclusion: Our study determined that the questionnaire serves as a valuable tool in evaluating the motivation behind dietary intake in gestational diabetes patients.Keywords: questionnaire, gestational diabetes, pregnancy, validation

Lu Tong, Long Wu, Nianguo Dong Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Nianguo Dong, Email dongnianguo@hotmail.comAbstract: Ventricular septal rupture (VSR) after acute myocardial infarction (AMI) is a rare but often fatal complication. Surgery is considered the preferred treatment, although the optimal timing is discussed. The immediate preoperative hemodynamic status significantly impacts postoperative outcomes, making mechanical circulatory support (MCS) devices crucial for perioperative hemodynamic stability. We present the case of a 61-year-old woman with no remarkable cardiological history admitted to our hospital with a diagnosis of AMI and VSR. Due to hemodynamic instability and cardiogenic shock, we utilized an intra-aortic balloon pump (IABP) and an extracorporeal left ventricular assist device (extra-VAD) as a bridge to surgery. After 17 days of IABP support, the patient experienced hemodynamic instability, elevated lactate levels, pulmonary edema, and eventually bedside endotracheal infiltration inventor-assisted breathing. Subsequently, the IABP was removed, and the patient underwent 6 days of extra-VAD therapy, resulting in hemodynamic stability, a decline in lactate levels, and a reduction in pulmonary edema on X-ray. Surgical coronary artery bypass grafting and VSR repair were successfully performed without periprocedural complications, and the patient was subsequently discharged. Extra-VAD is useful for serious cardiogenic shock in patients with VSR after AMI and may be considered a reasonable approach as a bridge to surgery.Keywords: ventricular septal rupture, acute myocardial infarction, extracorporeal left ventricular assist device

Linlan Yang,1,&ast; Kaijiong Zhang,2,&ast; Dongming Zheng,1 Yuxin Bai,1 Daifan Yue,1 Lichun Wu,2 Han Ling,2 Sujiao Ni,2 Haimin Zou,2 Bo Ye,2 Chang Liu,2 Yao Deng,2 Qiancheng Liu,3 Yan Li,1 Dongsheng Wang1,2 1College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Clinical Laboratory of Mianyang People’s Hospital, Mianyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Wang, Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email wangdongshengnc@163.com Yan Li, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email Liliana@cdutcm.edu.cnAbstract: In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion, intravasation, extravasation, and so on. It means that this property of platelets can be used in anti-tumor therapy. However, traditional platelet-based antitumor drugs often cause autologous platelet damage due to lack of targeting, resulting in serious side effects. Therefore, the researchers designed a variety of anti-tumor drug delivery systems based on platelets by targeting platelets or platelet membrane coating. The drug delivery systems have special response modes, which is crucial in the design of nanoparticles. These modes enhance the targeting and improve the anti-tumor effect. Here, we present a review of recent discoveries in the field of the crosstalk between platelets and tumors and the progress of platelet-based anti-tumor nanoparticles.Keywords: platelet, tumor, targeted platelet, platelet membranes, stimuli-responsive drug delivery system, nanoparticle

Lianpeng Wu,1– 3 Yong Pan,1,2 Ke Xu1– 3 1Department of Clinical Laboratory Medicine, The Ding Li Clinical College of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Wenzhou, 325000, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Ke Xu, Wenzhou Central Hospital, Key Laboratory of Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, The Ding Li Clinical College of Wenzhou Medical University, No. 252 Baili East Road, Lucheng District, Wenzhou, 325000, People’s Republic of China, Tel +86-13566290303, Email wzxuke72@163.comPurpose: To analyze the clinical characteristics of AIDS with dTSM, especially in patients with poor prognosis.Patients and Methods: One hundred and seventy AIDS patients were enrolled in this single-center retrospective study. The epidemiological characteristics, clinical manifestations, laboratory tests, imaging examination, and treatment outcome were collected. Logistic regression analysis was used to estimate the risk of mortality in AIDS patients with dTSM. The predictive value was evaluated using the receiver operating characteristic (ROC) curve.Results: From 2015 to 2022, the incidence of AIDS with dTSM in the Wenzhou region increased yearly, mainly in young adults. The mortality rate was 16.47%. The most common clinical manifestations were lymph-node enlargement (92.35%) and fever (78.24%). Multivariate logistic regression analysis showed that procalcitonin (PCT), blood urea nitrogen (BUN), shock, and antiretroviral therapy (ART) were the risk factors for poor outcomes. The model comprised four risk factors and showed an excellent prediction performance, with an AUC of 0.987 in the training cohort (95% CI: 0.946– 0.999) and 0.976 in the validation cohort (95% CI: 0.887– 0.999).Conclusion: This study suggested that PCT, BUN, shock, and ART were associated with the prognosis and outcome of AIDS with dTSM and had a specific predictive value.Keywords: acquired immunodeficiency syndrome, Talaromycosis marneffei, clinical characteristics, risk factor, prediction model, poor prognosis

Shuyun Zhang,1,&ast; Lijuan Wu,1,&ast; Xue Li,1 Li Yang,1 Sujuan Shen,1 Hong Shen,1 Dan Zhao,2 Lin Qi2,3 1Center of Reproductive Medicine, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 2Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 3State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Qi, Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China, Tel +86-13962187070, Email drhuan@126.comPurpose: Karyotype analysis of villus chromosomes in spontaneous abortion by high-throughput ligation-dependent probe amplification (HLPA) was performed to explore relationship between spontaneous abortion and chromosomal abnormalities in spontaneous abortion tissues.Patients and Methods: The karyotypes of chromosomes of villus tissues from 516 patients with spontaneous abortion who were admitted to our hospital between 2014 and 2019 were analyzed. The data were grouped by the age (ie, ≤ 29, 30– 35, and ≥ 36 years old) in which embryonic chromosomal abnormality rate, and abnormal distribution of chromosome number in abortion tissue of 294 patients.Results: The examination of 516 samples of spontaneous abortion tissues showed that the chromosomes of 294 samples were abnormal, and the abnormality rate was 60.97%. Among 294 samples with chromosomal abnormalities, 136 (89.47%) samples had numerical chromosomal abnormalities, 15 (9.87%) samples had structural chromosomal abnormalities, and 1 (0.07%) sample had uniparental disomy. A total of 308 couples voluntarily underwent peripheral blood chromosome analysis. The results showed that 56 couples had abnormality in one or both spouses, and rate of embryonic chromosomal abnormality in these 26 cases with chromosomal abnormalities was 100%.Conclusion: Numerical and structural chromosomal abnormalities are among the important causes of embryonic arrest, while the increase in age could also be a high-risk factor for embryonic chromosomal abnormality. Therefore, examination of the karyotypes of embryo chorionic villus may help understand the reasons of embryonic arrest, which could provide important guidance for more genetic counseling for patients with early spontaneous abortion, as well as improving the preconception preparation.Keywords: spontaneous abortion, villus tissue, HLPA test, chromosomal abnormality

Xue-Qing Yu,1,2,&ast; Jia-Qi Di,2,&ast; Wei Zhang,3 Geng-Shu Wei,4 Zhan-Ping Ma,5 Lei Wu,6 Xue-Feng Yu,7 Hui-Zhi Zhu,8 Miao Zhou,9 Cui-Ling Feng,10 Ji-Hong Feng,11 Ping Fan,12 Jian-Sheng Li,1,2 Jian-Ya Yang1 1Department of Respiratory Disease, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, 450000, People’s Republic of China; 2Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Respiratory Disease, Shanghai Shuguang Hospital, Shanghai University of Chinese Medicine, Shanghai, 200000, People’s Republic of China; 4Department of Respiratory Disease, the Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, People’s Republic of China; 5Department of Respiratory Disease, Shaanxi Province Hospital of Traditional Chinese Medicine, Xi’an, Shaanxi Province, 710000, People’s Republic of China; 6Department of Respiratory Disease, Hebei Province Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, 050000, People’s Republic of China; 7Department of Respiratory Disease, the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, 110000, People’s Republic of China; 8Department of Respiratory Disease, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, 230000, People’s Republic of China; 9Department of Respiratory Disease, the Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, 450000, People’s Republic of China; 10Department of Traditional Chinese Medicine, People’s Hospital Affiliated to Peking University, Beijing, 100000, People’s Republic of China; 11Department of Respiratory Disease, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, People’s Republic of China; 12Department of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Sheng Li, Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China, Tel +86-371-65676568, Email li_js8@163.comPurpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD.Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3– 4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT).Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: − 0.35; 95% CI: − 0.61, − 0.10; P = 0.006) and AE-related hospitalizations (− 0.18; 95% CI: − 0.36, − 0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P

Francisco Javier Bonilla-Escobar,1– 3,&ast; Daniel Sánchez-Cano,1,&ast; Andres F Lasave,4 Jaime Soria,5 Valentina Franco-Cárdenas,6 Victor E Reviglio,7 Paulo EC Dantas,8 Claudia Palacio Pastrana,9 Juan Carlos Corbera,10 Rita Yee Chan,11 Alberto Luis Diaz,12 Milton Garcia Hernandez,13 Mauricio Maia,14 Cristian Carpentier,15 Lihteh Wu,16 Martin Sanchez,17 Marcelo Murillo Sasamoto,18 Gonzalo Murillo Azcárraga,18 Jose A Roca,19 Martin A Serrano,20 Arturo A Alezzandrini,21 Juan Gonzalo Sanchez Montoya,22 Gregorio Gabela,23 Gerardo Garcia-Aguirre,24 J Fernando Arevalo25,&ast; 1Fundación Somos Ciencia al Servicio de la Comunidad, Fundación SCISCO/Science to Serve the Community Foundation, SCISCO Foundation, Cali, Colombia; 2Ophthalmology Department, Institute for Clinical Research Education, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 3Vision y Salud Ocular, VISOC, Ophthalmology Department, Universidad del Valle, Cali, Colombia; 4The Retina and Vitreous Department, Private Eyes Clinic, Mar del Plata, Argentina; 5Ophthalmology Department, Clínica Real Visión, Uniofken, CIVE y Funcrisa, Guayaquil, Ecuador; 6Ophthalmology Department, Sanatorio Oftalmológico Mérida, Mexico City, Mexico; 7Ophthalmology Department, Instituto de la Visión Cerro, Sanatorio Allende Cerro & Universidad Católica de Córdoba, Health Science Faculty, Cordoba, Argentina; 8Ophthalmology Department, Sorocaba Eye Bank Hospital, Sorocaba, Brazil; 9Department of Microsurgery of the Anterior Segment, Fundación Hospital Nuestra Señora de la Luz IAP, Mexico City, Mexico; 10Ophthalmology Department, Oftalmica Clinica de la Vision, Lima, Peru; 11Ophthalmology Department, Clinica Nacional de Oftalmologia, Panama City, Panama; 12Ophthalmology Department, Complejo Medico FOSCAL Internacional, Floridablanca, Santander, Colombia; 13Ophthalmology Department, Private Practice, El Salvador, El Salvador; 14Ophthalmology Department, Federal University of Sao Paulo, Sao Paulo, Brazil; 15Ophthalmology Department, Fundación Oftalmológica Los Andes, Santiago, Chile; 16Retina Department, Asociados de Macula Vitreo y Retina de Costa Rica, San Jose, Costa Rica; 17Ophthalmology Department, Hospital de Minas, Montevideo, Uruguay; 18Ophthalmology Department, Instituto Privado de Oftalmología, La Paz, Bolivia; 19Ophthalmology Department, Universidad Peruana Cayetano Heredia, Lima, Peru; 20Retina Department, Centro Médico Docente La Trinidad, Caracas, Venezuela; 21Ophthalmology Department, OFTALMOS, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina; 22Ophthalmology Department, Instituto Nacional de Investigacion en Oftalmologia –INIO and Clinica Oftalmologica de Antioquia, Medellin, Colombia; 23Ophthalmology Department, Hospital Metropolitano, Quito, Ecuador; 24Retina Department, School of Medicine, Tecnológico de Monterrey Asociación Para Evitar la Ceguera en México, Mexico City, Mexico; 25Ophthalmology Department, Johns Hopkins University, Wilmer Eye Institute, Baltimore, MD, USA&ast;These authors contributed equally to this workCorrespondence: J Fernando Arevalo, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Maumenee 713, Baltimore, MD, 21287, USA, Email arevalojf@jhmi.eduPurpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries’ ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO).Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations.Results: There was a marked decline in ophthalmology patient visits (80– 95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a “new normal”. Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited.Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic.Keywords: COVID-19, pandemics, international agencies, ophthalmology, retina, medical societies

Yanfei Lu,1,2,&ast; Wenying Xia,1,2,&ast; Shuxian Miao,1,2 Min Wang,1,2 Lei Wu,1,2 Ting Xu,1,2 Fang Wang,1,2 Jian Xu,1,2 Yuan Mu,1,2 Bingfeng Zhang,1,2 Shiyang Pan1,2 1Department of Laboratory Medicine, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People’s Republic of China; 2National Key Clinical Department of Laboratory Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyang Pan, Department of Laboratory Medicine, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Guangzhou Street No. 300, Nanjing, 210029, People’s Republic of China, Tel +8625-6830-6287, Fax +8625-8372-4440, Email sypan@njmu.edu.cnObjective: This study aimed to investigate the clinical characteristics and risk factors of death in severe coronavirus disease 2019 (COVID-19) during the epidemic of Omicron variants, assess the clinical value of plasma cell-free DNA (cfDNA), and construct a prediction nomogram for patient mortality.Methods: The study included 282 patients with severe COVID-19 from December 2022 to January 2023. Patients were divided into survival and death groups based on 60-day prognosis. We compared the clinical characteristics, traditional laboratory indicators, and cfDNA concentrations at admission of the two groups. Univariate and multivariate logistic analyses were performed to identify independent risk factors for death in patients with severe COVID-19. A prediction nomogram for patient mortality was constructed using R software, and an internal validation was performed.Results: The median age of the patients included was 80.0 (71.0, 86.0) years, and 67.7% (191/282) were male. The mortality rate was 55.7% (157/282). Age, tracheal intubation, shock, cfDNA, and urea nitrogen (BUN) were the independent risk factors for death in patients with severe COVID-19, and the area under the curve (AUC) for cfDNA in predicting patient mortality was 0.805 (95% confidence interval [CI]: 0.713– 0.898, sensitivity 81.4%, specificity 75.6%, and cut-off value 97.67 ng/mL). These factors were used to construct a prediction nomogram for patient mortality (AUC = 0.856, 95% CI: 0.814– 0.899, sensitivity 78.3%, and specificity 78.4%), C-index was 0.856 (95% CI: 0.832– 0.918), mean absolute error of the calibration curve was 0.007 between actual and predicted probabilities, and Hosmer-Lemeshow test showed no statistical difference (χ 2=6.085, P=0.638).Conclusion: There was a high mortality rate among patients with severe COVID-19. cfDNA levels ≥ 97.67 ng/mg can significantly increase mortality. When predicting mortality in patients with severe COVID-19, a nomogram based on age, tracheal intubation, shock, cfDNA, and BUN showed high accuracy and consistency.Keywords: severe COVID-19, Omicron, clinical characteristics, mortality, CfDNA, predicting nomogram

Ping Yang,1,&ast; JianBo Zhong,1,&ast; XingYun Zhao,1 Kamran Ali,1,2 Liming Wu,1 ZhangYu Bu1 1Department of Dermatology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Oncology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Wu, Department of Dermatology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, People’s Republic of China, Tel/Fax +86 13750837205, Email limingwu1973@163.comBackground: Hypertrophic scars, commonly occurring after trauma or surgery in critical areas like the head and joints, pose significant challenges to both physical and mental health due to their impact on skin function and aesthetics. While the complex pathogenesis involves fibroblast activation and collagen deposition, effective treatments are lacking, underscoring the importance of exploring pathogenesis and targeted therapies. Hesperidin, a bioactive compound in citrus fruits with diverse health benefits, including anti-fibrotic and anti-angiogenic effects, is the focus of this study with the aim of investigating its impact on hypertrophic scar formation, given its potential to promote blood flow and improve skin microcirculation.Objective: This study aimed to observe the inhibitory effect of topical hesperidin on hypertrophic scars in rabbits.Methods: A total of 8 healthy adult New Zealand white rabbits were used to establish a rabbit hypertrophic scarring animal model. Five wounds were created on each rabbit’s two ears, with three wounds on the left ear (groups A, B, and C) and two wounds on the right ear (groups D and E). After six days of wound drying postoperatively, the wounds were locally treated with medication as followed: group A, 0.1% hesperidin; group B, 1% hesperidin; group C, 1% triamcinolone acetonide; group D, Vaseline; and group E, blank control without any medication. After 28 days, the scar tissue samples were collected for histological examination.Results: The results showed that the scar texture of groups B and C was softer and lighter in color, and the number of fibroblasts, capillaries, and inflammatory cells in the tissue was significantly less than those in the other three groups. The hypertrophic scar indices of groups B and C were significantly smaller than those of groups A, D, and E, and the difference was statistically significant (P < 0.05). There were no significant difference between groups B and C.Conclusion: Topical application of hesperidin demonstrated promising potential for reducing hypertrophic scar formation in rabbits.Plain Language Summary: Hypertrophic scars are a common problem that can occur after trauma or surgery, causing functional and aesthetic issues in areas such as the head, face, neck, and joints. The formation of these scars involves complex processes including fibroblast activation and collagen deposition. Effective treatments for hypertrophic scars are currently lacking, and understanding their pathogenesis and developing targeted therapies are important.Hesperidin (HDN), a compound found in plants like bitter orange and citrus peel, has various biological activities and has been found to have anti-fibrotic and anti-angiogenic effects in some studies. Traditional Chinese medicine believes that scars are caused by Qi stagnation and blood stasis, and that hesperidin has been shown to improve skin microcirculation, aligning with the principles of blood activation and stasis removal.This study aimed to observe the effects of hesperidin on hypertrophic scar formation using animal models. Eight rabbits were divided into different groups and treated with different formulations of hesperidin or other control substances. Scar tissue samples were collected and examined after 28 days.The results showed that hesperidin-treated scars had a softer texture and lighter color than the control scars. Histological analysis revealed reduced scar thickness, more organized collagen fibers; and fewer fibroblasts, capillaries, and inflammatory cells in the hesperidin-treated groups. The 1% hesperidin group showed comparable effects to the corticosteroid triamcinolone acetonide group.These findings suggest that hesperidin has anti-inflammatory, anti-fibroblast proliferation, and anti-angiogenic properties and effectively inhibits hypertrophic scar formation in rabbits. Further research is needed to determine its efficacy and safety in human, and to establish appropriate dosages for therapeutic use. Overall, hesperidin holds promise as a potential treatment for preventing and treating skin scars.Keywords: hesperidin, hypertrophic scar, rabbit ear

Zhongyuan Xin,1,2,&ast; Mengya Zhang,2,&ast; Hengqing Cui,3,&ast; Xiuwen Ding,2,&ast; Tinglin Zhang,2 Lili Wu,2 Haipo Cui,1 Qian Xue,2 Cuimin Chen,2 Jie Gao2 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, ‎People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Gao; Cuimin Chen, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel +86 21 31162092, Fax +86 21 31161111, Email gaojiehighclea@smmu.edu.cn; 535428425@qq.comAbstract: Cancer is the second leading cause of death worldwide. Its incidence has been increasing in recent years, and it is becoming a major threat to human health. Conventional cancer treatment strategies, including surgery, chemotherapy, and radiotherapy, have faced problems such as drug resistance, toxic side effects and unsatisfactory therapeutic efficacy. Therefore, better development and utilization of biomaterials can improve the specificity and efficacy of tumor therapy. Algae, as a novel living material, possesses good biocompatibility. Although some reviews have elucidated several algae-based biomaterials for cancer treatment, the majority of the literature has focused on a limited number of algae. As a result, there is currently a lack of comprehensive reviews on the subject of anticancer algae. This review aims to address this gap by conducting a thorough examination of algal species that show potential for anticancer activity. Furthermore, our review will also elucidate the engineering strategies of algae and discuss the challenges and prospects associated with their implementation.Keywords: algae, neoplasms, engineering strategies, biomaterials, anticancer mechanism

Lianpeng Wu,1– 3 Dandan Xia,1– 3 Ke Xu1– 3 1Department of Clinical Laboratory Medicine, The Ding Li Clinical College of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Wenzhou, 325000, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Ke Xu, Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Wenzhou, 325000, People’s Republic of China, Tel +86 135 6629 0303, Email wzxuke72@163.comPurpose: Although highly active antiretroviral therapy (HA-ART) can effectively suppress the disease process in patients with acquired immunodeficiency syndrome (AIDS), opportunistic infections, mainly bloodstream infections (BSI), are still the main cause of death in people living with HIV. There is no effective diagnostic strategy for HIV-infected people with BSI. This study aimed to develop an AI diagnostic model with high sensitivity to improve the early detection of HIV-infected people with BSI.Patients and Methods: This study retrospectively analyzed the 40 clinical factors of 498 HIV-infected people (171 with BSI positive and 327 with BSI negative) who admitted to Wenzhou Central Hospital from September 2014 to July 2021. This study used the hospital information management system to collect the clinical characteristics, laboratory and imaging examination results, and clinical diagnosis of the two groups. The diagnostic results of all patients were in line with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of AIDS (2021 Edition), and the BSI diagnosis was in line with the diagnostic criteria of sepsis and bacteremia in Practical Internal Medicine (13th Edition). On this basis, various risk prediction models were established by combining 8 artificial intelligence (AI) algorithms in the training set and validating the diagnosis performance in the testing set. The model with the best diagnostic performance was selected as the final diagnostic model.Results: The clinical characteristics of HIV-infected people with BSI are atypical, and the pathogens in this area are mainly fungi. Ten risk factors were selected: low level of hemoglobin, CD4+T cell and platelets, high level of lactate dehydrogenase and blood urea nitrogen, splenomegaly, without ART treatment, strip shadow, nodular shadow, and shock. The combination of the ten risk factors, age, gender and the “svmRadial” model can identify the HIV-infected people with BSI from the HIV-infected people without BSI with an area under the curve of 0.916 and a sensitivity and specificity of 0.824 and 0.855, respectively.Conclusion: The model showed excellent performance in diagnosing HIV-infected people with BSI. Internal and external validation showed that the diagnosis model had high clinical application value.Keywords: acquired immunodeficiency syndrome, bloodstream infections, clinical risk factors, diagnosis, artificial intelligence model

Qiu Du,1,2,&ast; Yingda Lin,3,4,&ast; Changping Ding,5,&ast; Ling Wu,3 Yuan Xu,3 Qingling Feng6 1Department of Neurosurgery, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 2Department of Central Laboratory, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 3Department of Pharmacy, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 4Department of Pharmacy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 5Department of Medical Laboratory, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 6Department of Emergency Intensive Care Unit, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingling Feng, Department of Emergency Intensive Care Unit, the Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, 225012, People’s Republic of China, Email 15216401512@163.com Yuan Xu, Department of Pharmacy, the Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, 225012, People’s Republic of China, Email feebyxuyuan@163.comPurpose: Matrine (Mat), the main active ingredient of traditional Chinese herbal plant Sophora flavescens Ait, has significant antitumor effects, but its pharmacological mechanism on colon cancer (CC) remains unclear. This study aimed to investigate the therapeutic effect of Mat on CC as well as the potential mechanism.Methods: The vasculogenic mimicry (VM) of CC cells was observed by three-dimensional (3D) Matrigel cell culture. Cell proliferation, apoptosis, migration, invasion, and actin filament integrity were detected by CCK8, flow cytometry, wound healing, Transwell and Phalloidin staining assays. qRT-PCR and Western blotting were applied to detect the expression of EMT factors. RNA-sequencing was conducted to screen differentially expressed genes (DEGs), and the GO and KEGG pathway enrichment analyses were performed. Then, the expression of the key MAPK pathway genes and the target gene Claudin-9 (Cldn9) were analyzed. RNA interference was used to silence Cldn9 expression, and the effects of Cldn9 silencing and simultaneous treatment with Mat on VM formation, proliferation, apoptosis, invasion, and migration were investigated. Finally, the expression of EMT factors and MAPK pathway key genes was detected.Results: CT26 cells formed the most typical VM structure. Mat disrupted the VM of CT26 cells, significantly suppressed their proliferation, migration, invasion, actin filament integrity, induced apoptosis, and inhibited EMT process. RNA-sequencing revealed 163 upregulated genes and 333 downregulated genes in Mat-treated CT26 cells, and the DEGs were significantly enriched in cell adhesion molecules and MAPK signaling pathways. Further confirmed that Mat significantly inhibited the phosphorylation levels of JNK and ERK, and the target gene Cldn9 was significantly upregulated in human CC tissues. Silencing Cldn9 markedly inhibited the VM, proliferative activity, invasiveness, and actin filament integrity of CT26 cells, blocked the EMT process, and downregulated the phosphorylation of JNK and ERK, whereas Mat intervention further strengthened the above trends.Conclusion: This study indicated that Mat may synergistically inhibit the EMT process and MAPK signaling pathway through downregulation Cldn9, thereby exerting pharmacological effects on inhibiting VM formation, proliferation, and invasion of CC cells.Keywords: matrine, colon cancer, Cldn9, EMT, MAPK signal pathway

Wanshan Zhu, Lexia Wu, Jiaming Wu, Sihong Lin, Cantu Fang, Huatang Zhang Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Huatang Zhang, Email paul201503@163.comAbstract: Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is on the rise annually. It is characterized by low differentiation, high malignancy, and rapid growth. Consequently, treatment options are limited, and the patient’s prognosis is poor. The emergence of immunotherapy has partially improved the survival and prognosis of SCLC patients. However, a unique response known as “pseudoprogression” during immunotherapy has raised concerns. The occurrence of tumor enlargement despite a positive response to immune checkpoint inhibitor therapy undoubtedly affects the assessment of clinical drug efficacy and the selection of subsequent treatment strategies. In this article, we analyze a clinical case of pseudoprogression in a patient with SCLC who received immune therapy (Durvalumab). Currently, there is insufficient evidence-based medicine to guide the diagnosis, differentiation and subsequent treatment strategies for pseudoprogression in SCLC following immunotherapy. Through this case report and literature review, we aim to provide diagnostic and therapeutic insights for the clinical use of immunotherapy in advanced SCLC. Additionally, we hope that fellow readers of this article can engage in further collaborative discussions through more clinical research.Keywords: small cell lung cancer, immunotherapy, pseudoprogression

Gang Qin,1 Bo Wang,2 Geng Zhang,2 Lili Wu,1 Peng Zhu,1 Qian Zhang2 1Department of Gastroenterology, Suining First People’s Hospital, Suining, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Qian Zhang, Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email zhangqian105@swmu.edu.cnPurpose: To screen out potential prognostic biomarkers for HBV-related acute-on-chronic liver failure (HBV-ACLF).Patients and Methods: Peripheral blood samples of HBV-ACLF patients (n=56) and normal controls (n=15) from the Affiliated Hospital of Southwest Medical University from January 2021 to April 2022 were collected, 5 normal patients and 10 patients with ACLF were randomly selected for Data independent acquisition (DIA) mass spectrometry analysis, and the potential core proteins were screened out via bioinformatics. All samples were validated by Enzyme linked immunosorbent assays (ELISA) technology, and the survival curve was constructed based on the patient’s 90-day survival time.Results: A total of 247 differentially expressed proteins (DEPs) were screened, of which 148 were upregulated and 99 were down-regulated. The DEPs were mainly enriched in high-density lipoprotein particle remodeling, coagulation, and hemostasis and participated in signaling pathways such as cholesterol metabolism, coagulation cascades, and PPAR signaling pathway. Finally, bikunin was selected for further study and validated via the ELISA, compared with the normal group, bikunin was poorly expressed in the HBV-ACLF group, the difference was statistically significant (P < 0.0001), the area under the curve (AUC) for Receiver operating characteristic (ROC) analysis was 0.917. Furthermore, compared with the non-survival group, bikunin was highly expressed in the HBV-ACLF survival group, the difference was statistically significant (P=0.0015), and the survival curve showed a positive correlation with patient survival (P=0.0063).Conclusion: The level of plasma bikunin in HBV-ACLF is down-regulated, which is positively correlated with the survival of the patients with HBV-ACLF, and is expected to become a new prognostic biomarker.Keywords: HBV-ACLF, AMBP, bikunin, DIA

Zhixin Liu,1,2,&ast; Huanyu Zhang,1 Nan Wang,1,&ast; Yajie Feng,1,&ast; Junping Liu,1 Lin Wu,1 Zhaoyue Liu,1 Xinru Liu,1 Libo Liang,1 Jie Liu,3 Qunhong Wu,1 Chaojie Liu4 1Department of Social Medicine, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Health Policy and Management, School of Public Health, Peking University, Beijing, People’s Republic of China; 3Intensive Care Unit, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Public Health, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia&ast;These authors contributed equally to this workCorrespondence: Libo Liang; Jie Liu, Email llbhit@163.com; liujie21814@126.comBackground: This study aimed to test the mediating role of anxiety and insomnia in the association between fear of infection and fatigue.Methods: A cross-sectional questionnaire survey was conducted on the nurses deployed to Heihe. A serial multiple mediation model was established to determine the role of anxiety and insomnia in the association between fear of infection and fatigue.Findings: Over half (53.0%) of the study participants reported experiencing fear of infection despite stringent personal protection measures. The scores of anxiety (11.87± 5.19), insomnia (16.33± 5.95), and fatigue (45.94± 12.93) were moderately correlated, with a Pearson correlation coefficient ranging from 0.501 to 0.579. Anxiety, either alone or in combination with insomnia, mediated the association between fear of infection and fatigue.Conclusion: The findings suggest that anxiety and insomnia play a mediating role in the relationship between fear of infection and fatigue. These results emphasize the importance of implementing targeted mental health interventions and work arrangements to address the well-being of healthcare professionals.Keywords: fear of infection, anxiety, insomnia, fatigue, COVID-19

Deng Zhang,1 Simin Yu,1 Xiaoliang Ou Yang,1 Xiuping Wang,1 Yunxia Zhu,1 Zhen Xiao,2 Yanping Tan,3 Liang Wu,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email chunminglincu@163.comBackground: Acne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. The study aimed to explore the plasma lipidome signatures and identify specific lipid biomarkers in moderate-to-severe acne patients.Patients and Methods: Untargeted plasma lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was employed on 30 moderate-to-severe acne patients aged between 16– 25 years and 30 healthy controls. Multivariate data analyses were used to identify the distinguishing lipid metabolites.Results: All 1449 species of 37 lipid subclasses were identified from the MS data. There were apparent differences in plasma lipid profiles between acne groups and control groups. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 26 significantly different lipid metabolites were identified. These metabolites consisted mainly of glycerophospholipids (GPs), sphingolipids (SPs), and glycerolipids (GLs). Combining with AUC≥ 0.800 as the elected criteria, we obtained five differential lipids with good diagnostic performance for acne severity, including 2 sphingomyelins (SM), 1 phosphatidylglycerol (PG), 1 trihexosylceramide (Hex3Cer), and 1 Phosphatidylcholine (PC). Among them, PG (44:0) had the highest AUC values.Conclusion: Our study revealed the plasma lipidome signature of patients with moderate-to-severe acne. The results will provide a novel light into the perturbed lipid metabolism leading to the development of acne.Keywords: moderate-to-severe acne, lipidomics, sphingolipids, glycerophospholipids

Chengfei Zhang,1,2,&ast; Qiue Zhang,3,&ast; Lingling Qin,4,&ast; Zhiyi Yan,5 Lili Wu,4,5 Tonghua Liu5 1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Technology Department, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tonghua Liu, Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email thliu@vip.163.comBackground: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear.Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively.Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group.Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.Graphical Abstract: Keywords: dioscin, autoimmune thyroiditis, transcriptome, TLR4/NF-κB

Lizhu Liu,1,&ast; Xiaolin Pang,2,&ast; Ke Zhao,3,&ast; Yaxue Chen,4 Yanli Li,1 Ruimin You,1 Tingting Xu,5 Mengmei Liu,6 Lin Wu,7 Zhenhui Li,1 Hongjiang Pu8 1Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, 650118, People’s Republic of China; 2Department of Radiotherapy, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China; 3Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Department of Nursing, Dazhou Vocational and Technical College, Dazhou, Sichuan, 635000, People’s Republic of China; 5Department of Oncology, The People’s Hospital of Chuxiong Yi Autonomous Prefecture, Chuxiong, 675000, People’s Republic of China; 6School of Public Health, Kunming Medical University, Kunming, 650000, People’s Republic of China; 7Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, People’s Republic of China; 8Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, 635000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenhui Li, Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, 650118, People’s Republic of China, Tel/Fax +86 87168179549, Email lizhenhui621@qq.com Hongjiang Pu, Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, 635000, People’s Republic of China, Tel/Fax +86 87168179549, Email puhongjiang@qq.comBackground: It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy.Purpose: The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II–III colorectal cancer (CRC).Methods: The retrospective cohort analysis was performed on patients with stage II–III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II–III CRC.Results: A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age (P=0.001), postoperative carcinoembryonic antigen (CEA)(P=0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80– 2.0; log-rank P=0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52– 3.70; log-rank P=0.66).Conclusion: Patients over the age of 75 with stage II–III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II–III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy.Keywords: colorectal cancer, adjuvant chemotherapy, recurrence-free survival, prognosis