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Mingyuan Ren,1,2,* Yijia He,1,* Jianzhong Zhang,3 Jinfang Zhang,1,2 Guoqiang Zhang1,2 1Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Technical Innovation Center for Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China; 3Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinfang Zhang; Guoqiang Zhang, Email 58303110@hebmu.edu.cn; 57702800@hebmu.edu.cnAbstract: Tjalma’s syndrome is a benign combination of ascites, pleural effusion, and elevated CA-125 occurring in patients with systemic lupus erythematosus. Reports of Tjalma’s syndrome are scarce. An elevated CA-125 level often suggests the possibility of the presence of a malignant tumor. We report a case of generalised erythema and blisters with pruritus, massive unilateral pleural effusion and elevated CA-125. This patient was finally diagnosed with bullous systemic lupus erythematosus after exclusion of tumour and other maculopapular disorders. We hope that this particular case may provide a more comprehensive and novel diagnostic idea of systemic lupus erythematosus and pleural effusion, avoiding unnecessary anxiety, laboratory tests and surgical interventions.Keywords: systemic lupus erythematosus, bullous systemic lupus erythematosus, pleural effusion, Tjalma’s syndrome, CA-125

Chi Zhou,1,&ast; Xu Li,1,&ast; Wenli Shen,2 Qunfang Huang,1 Xiaoling Lin,1 Gaofeng Zhang,3 Yin Dong3,4 1Department of Health Management, School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Health Development, Hangzhou Xixi Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3The People’s Hospital of Yuhuan, Taizhou, Zhejiang, People’s Republic of China; 4Vanke School of Public Health, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yin Dong, The People’s Hospital of Yuhuan, No. 18 Changle Road, Yucheng Street, Yuhuan, Taizhou, 317600, People’s Republic of China, Tel +86-18957678008, Email 9597082@qq.comBackground: The responsiveness of community health centers can reflect the soft capacity of medical institutions and is related to the improvement of health outcome indicators. This study is aimed at assessing the level and distribution of community health centers’ responsiveness and its associated factors among outpatients under the health-oriented integrated healthcare system in China.Methods: A total of 634 outpatients were recruited from six community health centers in Zhejiang Province, China, in July 2022. SPSS software was used to conduct the analysis (version 23.0). Health system responsiveness was used as a measure of outpatient responsiveness to health care services through a self-administered questionnaire. Determinants of community health centers’ responsiveness were determined by using a multiple linear regression model at a p-value < 0.05.Results: The total score of community health centers responsiveness was 8.25± 1.01, and the Gini coefficient is 0.027. Within these domains, social support and dignity received the highest scores, while choice of providers and autonomy scored the lowest. Age group between 60– 74 years (β: 0.129; 95% CI: 0.042– 0.529), ≥ 75 years (β: 0.095; 95% CI: 0.006– 0.707), monthly income with 8000 RMB and above (β: 0.098; 95% CI: 0.035– 0.653), having a family doctor (β: 0.124; 95% CI: 0.096– 0.410), and satisficing with community health service (β: 0.298; 95% CI: 0.848– 1.428) were significant predictors of community health centers’ responsiveness.Conclusion: The Chinese community health centers show high responsiveness, indicating that the construction of a health-oriented integrated healthcare system has been effective. The family doctor contract service is important and should continually enhance both technical proficiency and health promotion capabilities. Encourage residents to actively participate in their treatment process is also essential.Keywords: responsiveness, community health center, outpatient

Gongjie Zhang,1 Xinlyu Huang,1 Hanlin Li,1 Huizi Gong,1 Yabin Zhou,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Yabin Zhou, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, No. 56 Nan Lishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10 59616884, Email chouyabin@163.com Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti Nan Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 18611369216, Email roseliufang@qq.comBackground: Hair loss is common in hypothyroidism patients. However, the link with alopecia areata (AA) and androgenetic alopecia (AGA) is unclear. Previous observational studies have presented completely opposite results. This study aims to causally link hypothyroidism with AA and AGA.Methods: A two-sample Mendelian Randomization (MR) study, utilizing data from FinnGen Consortium, investigated the causal link between hypothyroidism and AA and AGA. We employed Inverse Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode to assess the risk association.Results: The discovery samples included 13,429 hypothyroidism cases (94,436 controls), 767 alopecia areata cases (394,105 controls), and 220 androgenetic alopecia cases (219,249 controls). MR analysis showed a causal link between hypothyroidism and AA, with significant results from IVW (OR, 1.34; CI, 1.16– 1.56; P = 0.0001), MR-Egger (OR, 1.56; CI, 1.09– 2.23; P = 0.0240), and weighted median (OR, 1.34; CI, 1.06– 1.69; P = 0.0140). However, no clear causal relationship was found between genetically predicted hypothyroidism and AGA risk (p > 0.05).Conclusion: The results show hypothyroidism causally associated with AA onset, but not AGA. These findings address contentious issues in observational studies. Comprehensive thyroid function assessments are crucial for AA patients, emphasizing thorough clinical examinations’ importance.Keywords: hypothyroidism, alopecia areata, androgenetic alopecia, Mendelian randomization study, causality

Xiaoyan Huang,1,2 Xiangrong Zhao,1,2 Yaping Li,1,2 Yangmeng Feng,1,2 Guoan Zhang,3 Qiyu Wang,4 Cuixiang Xu1,2 1Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 3Department of Cardiovascular Surgery, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 4Department of Graduate School, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Cuixiang Xu, Email xucuixiang1129@163.comBackground: Dilated cardiomyopathy (DCM) is the second leading cause of heart failure, with intricate pathophysiological underpinnings. In order to shed fresh light on the mechanistic research of DCM, we combined bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data to examine significant cells and genes implicated in the disease.Methods: This analysis employed publicly accessible bulk RNA-seq and scRNA-seq DCM datasets. The scRNA-seq data underwent normalization, principal component, and t-distribution stochastic neighbor embedding analysis. Cell-to-cell communication networks and activity analysis were conducted using CellChat. Utilizing enrichment analysis, the marker genes’ role in the active cells was evaluated. After screening by limma software and weighted gene co-expression network analysis, the differentially expressed genes (DEGs) served as hub genes. Furthermore, these hub genes were subjected to immunological studies, transcription factor expression, and gene set enrichment. Lastly, the expression of the four hub genes and their connection to DCM were verified using the rat models.Results: Fibroblasts and monocytes were chosen as hub cells from among the eight identified cell clusters; their marker genes intersected with DEGs to yield six hub genes. In addition, the six hub genes and the essential module genes intersected to yield four essential genes (ASPN, SFRP4, LUM, and FRZB) that were connected to the Wnt signaling pathway and highly expressed in fibroblast. The four hub DEGs had an expression pattern in the DCM rat model experiment results that was in line with the findings of the bioinformatics study. Additionally, there was a strong correlation between decreased cardiac function and the up-regulation of ASPN, SFRP4, LUM, and FRZB.Conclusion: Ultimately, bulk RNA-seq and scRNA-seq data identified fibroblasts and monocytes as the main cell types implicated in DCM. The highly expressed genes ASPN, FRZB, LUM, and SFRP4 in fibroblasts may aid in the mechanistic investigation of DCM.Keywords: dilated cardiomyopathy, single cell RNA-seq, bulk RNA-seq, weighted gene co-expression network analysis, wnt signaling pathway, fibroblasts

Xinlyu Huang,1 Pengxiang Zhao,2 Gongjie Zhang,1 Xiangxi Su,1 Hanlin Li,1 Huizi Gong,1 Xuemei Ma,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2College of Chemistry and Life Science, Beijing University of Technology, Beijing, People’s Republic of ChinaCorrespondence: Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email roseliufang@qq.comPurpose: Alopecia significantly affects the appearance and psychology of patients, and pharmacological therapies and hair transplantation are the main treatments for alopecia, but both have limitations. This review aimed to summarize the non-pharmacological therapies that promote hair growth and regeneration.Patients and Methods: This is a non-systematic review. Multiple databases was searched with relevant data published between 1997 and 2024. Searching and screening followed the PRISMA guidelines.Results: Novel therapeutic modalities, such as gas molecules, platelet-rich plasma, laser, and microneedling, can change the microenvironment of hair follicles, activate hair follicle stem cells, and promote hair growth and regeneration.Conclusion: This paper reviews research on the application of non-pharmacological therapies in alopecia treatment and hair regeneration, with a view to providing an important basis for future research on alopecia treatment and the postoperative treatment of patients after hair transplantation.Keywords: alopecia, hair regrowth, non-pharmacologic, gas therapy, regenerative cellular therapy, laser therapy, microneedle therapy

Xiaojuan Wu, Guoyue Zhang, Xianzhi Du Department of Respiratory Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Xianzhi Du, Department of Respiratory Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86 023 62887761, Email dxzdjy868@sina.comBackground: Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious external particles, air pollution, and the inhalation of cigarette smoke. Airway mucus hypersecretion particularly mucin5AC (MUC5AC), is a crucial pathological feature of COPD and is associated with its initiation and progression. In this study, we aimed to investigate the effects of cigarette smoke extract (CSE) on MUC5AC expression, particularly the mechanisms by which reactive oxygen species (ROS) induce MUC5AC expression.Methods: The effects of CSE on the expression of MUC5AC and mucin5B (MUC5B) were investigated in vitro in Calu-3 cells. MUC5AC and MUC5B expression levels were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Total cellular levels of ROS and Ca2+ were determined using DCFH-DA and Fluo-4 AM. Subsequently, the expression levels of IP3R, IRE1α, p-IRE1α and XBP1s were measured by Western blotting. Gene silencing was achieved by using small-interfering RNAs.Results: Our findings revealed that exposure to CSE increased MUC5AC levels and upregulated ROS, IP3R/Ca2+ and unfolded protein response (UPR)-associated factors. In addition, knockdown of IP3R using siRNA decreased CSE-induced Ca2+ production, UPR-associated factors, and MUC5AC expression. Furthermore, 10 mM N-acetyl-l-cysteine (NAC) treatment suppressed the effects of CSE, including ROS generation, IP3R/ Ca2+, UPR activation, and MUC5AC overexpression.Conclusion: Our results suggest that ROS regulates CSE-induced UPR and MUC5AC overexpression through IP3R/ Ca2+ signaling. Additionally, we identified NAC as a promising therapeutic agent for mitigating CSE-induced MUC5AC overexpression.Keywords: chronic obstructive pulmonary disease, mucin5AC, cigarette smoke extract, reactive oxygen species, unfolded protein response, IP3R, Ca2+

Jie Cheng,1,&ast; Ya Liu,2,&ast; Guangli Zhang,3 Liping Tan,1 Zhengxiu Luo3 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of China; 3Department of Respiratory Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengxiu Luo, Email luozhengxiu816@hospital.cqmu.edu.cnObjective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation.Methods: This retrospective observational cohort study was conducted at the Children’s Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation.Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31– 17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively).Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).Keywords: azithromycin effectiveness, A2063/2064G mutation, mycoplasma pneumoniae pneumonia, children

Jiachen Ge,1,&ast; Ming Tao,2,&ast; Gaolei Zhang,1 Jianping Cai,1 Deyu Li,1 Lianyuan Tao1 1Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyu Li; Lianyuan Tao, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Zhengzhou City, Henan Province, People’s Republic of China, Email lideyu19@hotmail.com; tly2007tly@hotmail.comPurpose: Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC.Materials and Methods: We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells.Results: We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis.Conclusion: CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.Keywords: hepatocellular carcinoma, lncRNA, T cell exhaustion, single-cell RNA-seq, machine learning, prognostic signature

Li`ao Wang,1 Zhiming Zheng,2 Jia Zheng,2 Guifeng Zhang,3 Zheng Wang4 1Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, 300203, People’s Republic of China; 2Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Neurology, Liaocheng People’s Hospital, Liaocheng, 252004, People’s Republic of China; 4Department of Neurosurgery, Liaocheng Traditional Chinese Medicine Hospital, Liaocheng, 252000, People’s Republic of ChinaCorrespondence: Guifeng Zhang, Department of Neurology, Liaocheng People’s Hospital, Liaocheng, 252004, People’s Republic of China, Tel +86 18063513155, Email GFZhangNo.1@gmail.com Zheng Wang, Department of Neurosurgery, Liaocheng Traditional Chinese Medicine Hospital, Liaocheng, 252000, People’s Republic of China, Tel +86 18063560328, Email zhengyimingdao@gmail.comPurpose: Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are urgently needed to predict LGG prognosis effectively.Methods: The data for LGG were obtained from the Bioinformatics database. A consensus clustering analysis was performed to identify molecular subtypes linked with invasion in LGG. Differential expression analysis was performed to identify differentially expressed genes (DEGs) between the identified clusters. Enrichment analyses were then conducted to explore the function for DEGs. Prognostic signatures were placed, and their predictive power was assessed. Furthermore, the invasion-related prognostic signature was validated using the CGGA dataset. Subsequently, clinical specimens were procured in order to validate the expression levels of the distinct genes examined in this research, and to further explore the impact of these genes on the glioma cell line LN229 and HS-683.Results: Two invasion-related molecular subtypes of LGG were identified, and we sifted 163 DEGs between them. The enrichment analyses indicated that DEGs are mainly related to pattern specification process. Subsequently, 10 signature genes (IGF2BP2, SRY, CHI3L1, IGF2BP3, MEOX2, ABCC3, HOXC4, OTP, METTL7B, and EMILIN3) were sifted out to construct a risk model. Besides, the survival (OS) in the high-risk group was lower. The performance of the risk model was verified. Furthermore, a highly reliable nomogram was generated. Cellular experiments revealed the ability to promote cell viability, value-addedness, migratory ability, invasive ability, and colony-forming ability of the glioma cell line LN229 and HS-683. The qRT-PCR analysis of clinical glioma samples showed that these 10 genes were expressed at higher levels in high-grade gliomas than in low-grade gliomas, suggesting that these genes are associated with poor prognosis of gliomas.Conclusion: Our study sifted out ten invasion-related biomarkers of LGG, providing a reference for treatments and prognostic prediction in LGG.Keywords: LGG, prognosis, invasion, overall survival, EMILIN3

Wenqing Wang,1,2,&ast; Chuchu Ye,2,3,&ast; Bing Zhao,1 Yingjie Zheng,4 Ge Zhang,5 Jinghua Su,1 Hong Huang,1 Lipeng Hao,1,2 Mingliang Chen6 1Department of Microbiology, Pudong New Area Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 2Fudan University Pudong Institute of Preventive Medicine, Shanghai, People’s Republic of China; 3Department of Infectious Disease Control and Prevention, Pudong New Area Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 4Department of Epidemiology/Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning/Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 5School of Public Health, Dali University, Yunnan, People’s Republic of China; 6Research and Translational Laboratory of Acute Injury and Secondary Infection, and Department of Laboratory Medicine, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingliang Chen; Lipeng Hao, Email cmlbright@126.com; hlpmail@126.comBackground: The occurrence and dissemination of hypermucoviscous and hypervirulent Klebsiella pneumoniae (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.Methods: In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.Results: The overall prevalence of hm K. pneumoniae isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv K. pneumoniae. The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried blaSHV gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of rmpA/rmpA2-iro-iuc-ybt-irp-clb. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the clb gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.Conclusion: Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.Keywords: hypermucoviscous, hypervirulent, Klebsiella pneumoniae, drug resistance determinants, virulence determinants, whole-genome sequencing

Qing Zhu,1,2,&ast; Yijia He,1,2,&ast; Sijia Chen,1,2 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Provincial Innovation Center of Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqiang Zhang, Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China, Email 57702800@hebmu.edu.cnAbstract: Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.Keywords: hypertrophic discoid lupus erythematosus, lupus erythematosus, vitiligo, association

Biao Hou,1– 3,&ast; Bo Li,4,&ast; Wanjun Deng,3,&ast; Bo Li,1,2 Bibo Ren,5 Chao Hu,3 Guowei Zhang,1,2 Fen Yang,6 Meimei Xiao,3 Songlin Xie,3 Denghui Xie1,2 1Department of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5College of Biomass Science and Engineering, Sichuan University, Chengdu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Denghui Xie; Songlin Xie, Email smuspine@163.com; xiesonglin0929@163.comPurpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme’s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes’ potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.Keywords: copper nanozyme, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance, diabetic wound healing

Lan Hong,1,&ast; Huihui Xu,2,&ast; Jiaqi Zheng,2 Xiujian Lin,2 Lijun Wang,2 Chengjia Zhao,3 Xiaolian Tu,4 Jingjing Zhang,5 Ke Zhao,1,6 Guohua Zhang6,7,&ast; 1Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Education, Renmin University of China, Beijing, 100872, People’s Republic of China; 4School of Renji, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 5School of Nursing, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7Institute Of Aging, Key Laboratory Of Alzheimer’s Disease Of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Zhang, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email zghcnu@wmu.edu.cn Ke Zhao, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China, Email cocozk1986@163.comBackground: Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.Methods: The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.Results: Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05– 1.12), more depression (OR: 1.17; 95% CI = 1.06– 1.29) and anxiety (OR: 1.16; 95% CI = 1.05– 1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12– 1.19), anxiety (OR: 1.10; 95% CI = 1.06– 1.14), and depression (OR: 1.10; 95% CI = 1.06– 1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.Conclusion: This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.Keywords: bedtime procrastination, latent profile analysis, latent transition analysis, problematic smartphone use, depression, anxiety, self-control

Zhengjie Chen,1,2,&ast; Jinjie Zeng,3,&ast; Xiang Pei,1,2 Jingjing Zhao,1,2 Fang Zhao,1,2 Guoxin Zhang,1,2 Kexin Liang,1,2 Jiarong Li,2 Xiaoyun Zhao1,2,4,5 1Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Respiratory & Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China; 3Department of Respiratory, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 4Department of Respiratory & Critical Care Medicine, Chest Hospital of Tianjin University, Tianjin, People’s Republic of China; 5DeepinBreath Union Laboratory, Tianjin Chest Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun Zhao, Department of Respiratory & Critical Care Medicine, Tianjin Chest Hospital, No. 261 Taierzhuang South Road, Jinnan District, Tianjin, People’s Republic of China, Email zxydoctor@163.comPurpose: Clinical studies have demonstrated the intricate association between the onset and progression of obstructive sleep apnea (OSA) and the activation of the inflammatory cascade reaction. This study delves into investigating the causal links between 91 circulating inflammatory proteins (CIPs) and OSA through the application of Mendelian randomization (MR) techniques.Methods: Utilizing genetic data on OSA sourced from the Finnish Biobank (FinnGen) Genome-wide Association Studies (GWAS) of the European population, alongside summary-level GWAS data of CIPs from 14,824 European participants, we conducted a bidirectional MR study.Results: This study suggests that several factors may be associated with the risk of OSA. IL-17C (odds ratio (OR) = 1.090, p = 0.0311), CCL25 (OR = 1.079, p = 0.0493), FGF-5 (OR = 1.090, p = 0.0003), CD5 (OR = 1.055, p = 0.0477), and TNFSF14 (OR = 1.092, p = 0.0008) may positively correlate with OSA risk. Conversely, IL-20RA (OR = 0.877, p = 0.0107), CCL19 (OR = 0.933, p = 0.0237), MIP-1 alpha (OR = 0.906, p = 0.0042), Flt3L (OR = 0.941, p = 0.0019), CST5 (OR = 0.957, p = 0.0320), OPG (OR = 0.850, p = 0.0001), and TRAIL (OR = 0.956, p = 0.0063) may reduce the risk of OSA. Additionally, elevated levels of IL-10RA (OR = 1.153, p = 0.0478) were observed as a consequence of OSA. Conversely, OSA may potentially lead to decreased levels of CCL28 (OR = 0.875, p = 0.0317), DNER (OR = 0.874, p = 0.0324), FGF-21 (OR = 0.846, p = 0.0344), and CSF-1 (OR = 0.842, p = 0.0396).Conclusion: Through this bidirectional MR study, we have identified 12 upstream regulatory proteins and 5 downstream effect proteins that are linked to OSA. These findings hold promise in providing potential therapeutic targets for the inflammatory mechanisms underlying OSA.Keywords: Mendelian randomization, bidirectional, obstructive sleep apnea, circulating inflammatory proteins

Peng Ge,1– 3,&ast; Yalan Luo,3,&ast; Jinquan Zhang,1– 3,&ast; Jie Liu,1– 3 Caiming Xu,1,4 Haoya Guo,1– 3 Aixia Gong,3 Guixin Zhang,1– 3 Hailong Chen1– 3 1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 4Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Comprehensive Cancer Center, Duarte, CA, USA&ast;These authors contributed equally to this workCorrespondence: Guixin Zhang; Hailong Chen, Email zgx0109@126.com; chenhailong@dmu.edu.cnBackground: Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components and mechanisms underlying the action of Qingyi Granule (QYKL) remain elusive.Methods: This study consists of four parts. First, we used Mendelian randomization (MR) to investigate the causal relationship between AP, cytokine, and ARDS. Next, 321 patients were collected to evaluate the efficacy of QYKL combined with dexamethasone (DEX) in treating AP. In addition, we used UHPLC-QE-MS to determine the chemical constituents of QYKL extract and rat serum after the oral administration of QYKL. The weighted gene coexpression network analysis (WGCNA) method was used to find the main targets of AP-related ARDS using the GSE151572 dataset. At last, a AP model was established by retrograde injection of 5% sodium taurocholate.Results: MR showed that AP may have a causal relationship with ARDS by mediating cytokine storms. Retrospective study results showed early administration of QYKL was associated with a lower incidence of ARDS, mortality, admissions to the intensive care unit, and length of stay in AP patients compared to the Control group. Furthermore, we identified 23 QYKL prototype components absorbed into rat serum. WGCNA and differential expression analysis identified 1558 APALI-related genes. The prototype components exhibited strong binding activity with critical targets. QYKL has a significant protective effect on pancreatic and lung injury in AP rats, and the effect is more effective after combined treatment with DEX, which may be related to the regulation of the IL-6/STAT3 signaling pathway.Conclusion: By integrating MR, retrospective analysis, and systematic pharmacological methodologies, this study systematically elucidated the therapeutic efficacy of QYKL in treating AP-related ARDS, establishing a solid foundation for its medicinal use. Keywords: acute pancreatitis, qingyi granule, dexamethasone, acute lung injury, clinical efficacy, Mendelian randomization, rat

Rong Zhou,1,2,&ast; Chen Suo,1,3,&ast; Yong Jiang,4,&ast; Liyun Yuan,5 Tiejun Zhang,1,3 Xingdong Chen,3,6 Guoqing Zhang5,7 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, People’s Republic of China; 2Shanghai Southgene Technology Co., Ltd., Shanghai, 201203, People’s Republic of China; 3Taizhou Institute of Health Sciences, Fudan University, Taizhou, 225300, People’s Republic of China; 4China National Clinical Research Center for Neurological Diseases, Beijing, 100070, People’s Republic of China; 5Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Science, Shanghai, 200031, People’s Republic of China; 6State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 7Shanghai Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqing Zhang, Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Science, Shanghai, 200031, People’s Republic of China, Email gqzhang@sinh.ac.cn Xingdong Chen, Taizhou Institute of Health Sciences, Fudan University, Taizhou, 225300, People’s Republic of China, Email xingdongchen@fudan.edu.cnPurpose: The prevalence of obstructive sleep apnea (OSA) is high worldwide. This study aimed to quantify the relationship between the incidence of OSA and sleep patterns and genetic susceptibility.Methods: A total of 355,133 white British participants enrolled in the UK Biobank between 2006 and 2010 with follow-up data until September 2021 were recruited. We evaluated sleep patterns using a customized sleep scoring method based on the low-risk sleep phenotype, defined as follows: morning chronotype, 7– 8 hours of sleep per day, never/rarely experience insomnia, no snoring, no frequent daytime sleepiness, never/rarely nap, and easily getting up early. The polygenic risk score was calculated to assess genetic susceptibility to OSA. Cox proportional hazard models were used to evaluate the associations between OSA and sleep patterns and genetic susceptibility.Results: During a mean follow-up of 12.57 years, 4618 participants were diagnosed with OSA (age: 56.83 ± 7.69 years, women: 31.3%). Compared with those with a poor sleep pattern, participants with a normal (HR: 0.42, 95% CI: 0.38– 0.46), ideal (HR: 0.21, 95% CI: 0.19– 0.24), or optimal (HR: 0.15, 95% CI: 0.12– 0.18) sleep pattern were significantly more likely to have OSA. The genetic susceptibility of 173,239 participants was calculated, and the results showed that poor (HR: 3.67, 95% CI: 2.95– 4.57) and normal (HR: 1.89, 95% CI: 1.66– 2.16) sleep patterns with high genetic susceptibility can increase the risk for OSA.Conclusion: This large-scale prospective study provides evidence suggesting that sleep patterns across seven low-risk sleep phenotypes may protect against OSA in individuals with varying degrees of genetic susceptibility.Keywords: obstructive sleep apnea, sleep phenotype, sleep pattern, healthy sleep score, genetic susceptibility, polygenic risk score

Ru Ban,&ast; Chengju Huo,&ast; Jingru Wang, Guifeng Zhang, Xin Zhao Department of Neurology, Liaocheng People’s Hospital and Liaocheng Hospital Affiliated to Shandong First Medical University, Liaocheng, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifeng Zhang; Xin Zhao, Department of Neurology, Liaocheng People’s Hospital and Liaocheng Hospital Affiliated to Shandong First Medical University, No. 67 West Dongchang Road, Liaocheng, Shandong, 252000, People’s Republic of China, Email GFZhangNo.1@gmail.com; zhaoxinsdlc@163.comPurpose: Atherosclerosis (AS) is a chronic inflammatory vascular disease and the predominant cause of ischemic stroke (IS). AS is a potential pathogenetic factor in IS. However, the processes by which they interact remain unknown. The purpose of this paper was to investigate the shared gene signatures and putative molecular processes in AS and IS.Methods: Gene Expression Omnibus (GEO) data for AS and IS microarrays were retrieved. The co-expression modules associated with AS and IS were identified using the Weighted Gene Co-Expression Network Analysis (WGCNA). We constructed an interaction network of shared differentially expressed genes in AS and IS and conducted an enrichment analysis using ClueGO software. We validated the results in a separate cohort through differential gene analysis. Additionally, we retrieved AS and IS-related miRNAs from the Human microRNA Disease Database (HMDD) and predicted their target genes using miRWalk. We then built a network of miRNAs-mRNAs-KEGG pathways using the shared genes.Results: Through WGCNA, we identified five modules and six modules as significant in AS and IS, respectively. A ClueGO enrichment analysis of common genes showed that highly active CCR1 chemokine receptor binding is critical to AS and IS pathogenesis. The differential analysis expression results in another cohort closely matched these findings. The miRNA-mRNA network suggested that hsa-miR-330-5p, hsa-miR-143-3p, hsa-miR-16-5p, hsa-miR-152-3p might regulate the shared gene KRAS, which could be a key player in AS and IS.Conclusion: We integrated ischemic stroke and carotid atherosclerosis public database data and found that ATF3, CCL3, CCL4, JUNB, KRAS, and ZC3H12A may affect both, making them novel biomarkers or therapeutic target genes. Clinical samples and expression trends supported our analyses of pivotal genes.Keywords: ischemic stroke, atherosclerosis, risk factors, co-expression, biomarker

Zhihan Zhu,1,&ast; Qiankun Zhang,1,&ast; Jia Feng,1 Sonia Zebaze Dongmo,1 Qianqian Zhang,1 Songze Huang,1 Xiaowen Liu,1 Guilong Zhang,2 Lukui Chen1 1Department of Neurosurgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lukui Chen, Department of Neurosurgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, People’s Republic of China, Email neuro_clk@hotmail.com Guilong Zhang, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email longshe05@sina.comAbstract: Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.Keywords: neural stem cells, small extracellular vesicles, ischemic stroke, neuroprotection, neural regeneration

Guiyun Zhang,1 Yufeng Lu,2 Lin Qi,1 Chunli Yao1 1Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Thoracic Surgery, Sino-Japanese Friendship Hospital of Jilin University, Changchun, 130012, People’s Republic of ChinaCorrespondence: Chunli Yao, Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Tel +86-431-81136244, Email ycl@jlu.edu.cnIntroduction: Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper extremity.Case Presentation: Seven-year-old monozygotic twins presented to our department with a palpable, painless, and solid mass in the subcutaneous tissue of the right upper limb. A 1.5-cm diameter nodule was seen on the anterolateral aspect of the right upper extremity of the twins. The node was irregular in shape, and upon palpation, the patients reported no noticeable tenderness. Following the administration of local anesthesia, the twins underwent surgical procedure to excise the solid mass. Finally, they were diagnosed with pilomatricoma based on the clinical and histopathological features. Complete surgical resection followed by primary closure was performed. During a follow-up period of three years, there has been no recurrence observed in the twins.Conclusion: We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper arm. Our findings underscore the requirement of considering genetic factors in the diagnosis and treatment of the rare conditions.Keywords: pilomatricoma, pilomatrixoma, calcifying epithelioma of malherbe, case report

Junwei Zhan,1 Chengfei Peng,2 Yuxin Liu,1 Zhanhua Bi,1 Guoxiu Lu,1 Shanhu Hao,1 Yanan Tong,1 Guoxu Zhang1 1Department of Nuclear Medicine, General Hospital of Northern Theater Command, Shenyang, 110016, People’s Republic of China; 2Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Guoxu Zhang; Yanan Tong, Department of Nuclear Medicine, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenyang, 110016, People’s Republic of China, Email zhangguoxu_502@163.com; tongyn1119@foxmail.comObjective: Atrial fibrillation (AF) is a common arrhythmia. This study explored serum miR-29b-3p expression in AF patients and its value in predicting AF recurrence after radiofrequency catheter ablation (RFCA).Methods: Totally 100 AF patients who underwent RFCA were enrolled, with 100 individuals without AF as controls. Serum miR-29b-3p expression in participants was determined using RT-qPCR. The correlation between miR-29b-3p and atrial fibrosis markers (FGF-21/FGF-23) was assessed by Pearson analysis. The diagnostic efficacy of serum miR-29b-3p and FGF-21/FGF-23 in predicting AF recurrence after RFCA was analyzed by the receiver operating characteristic (ROC) curves. The Kaplan-Meier method was adopted to evaluate the effect of miR-29b-3p expression on the incidence of AF recurrence after RFCA. The independent risk factors for AF recurrence after RFCA were analyzed by logistic regression analysis.Results: Serum miR-29b-3p was poorly expressed in AF patients. After RFCA, AF patients showed elevated serum miR-29b-3p expression. Serum miR-29b-3p expression in AF patients negatively correlated with serum FGF-21 and FGF-23 concentrations. The cut-off values of serum miR-29b-3p, FGF-21, and FGF-23 in identifying AF recurrence were 0.860 (sensitivity: 100.00%, specificity: 39.71%), 222.2 pg/mL (sensitivity: 96.88%, specificity: 32.35%) and 216.3 ng/mL (sensitivity: 53.13%, specificity: 70.59%), respectively. Patients with low miR-29b-3p expression had a significantly higher incidence of AF recurrence than patients with high miR-29b-3p expression. Serum miR-29b-3p expression was one of the independent risk factors for AF recurrence after RFCA.Conclusion: Low miR-29b-3p expression in AF patients has certain predictive values and is one of the independent risk factors for AF recurrence after RFCA.Keywords: miR-29b-3p, atrial fibrillation, radiofrequency catheter ablation, recurrence, fibrosis marker, logistic regression analysis

Chang Su,1– 3 Zeyu Wang,4 Zhen Qin,1– 3 Yan Lv,1– 3 Yachen Hou,1– 3 Ge Zhang,1– 3 Mengdie Cheng,1– 3 Xinyue Cui,1– 3 Zhiyu Liu,1– 3 Pengchong Du,1– 3 Tianding Liu,1– 3 Peiyu Yuan,1– 3 Junnan Tang,1– 3 Jinying Zhang1– 3 1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Junnan Tang; Jinying Zhang, Department of Cardiology, First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166 ; +86 13503830283, Email fcctangjn@zzu.edu.cn; jyzhang@zzu.edu.cnBackground: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis.Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98– 25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702– 7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962– 6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771– 7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268– 7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months.Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.Keywords: TyG index, advanced chronic heart failure, renal dysfunction, prognosis factor

Haonan Guan,&ast; Guoyou Zhang,&ast; Qiqi Li, Jie Lian, Zhaoyang Dong, Lian Zhu, Kaiyan Xiao Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaiyan Xiao, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People’s Republic of China, Tel +86 021 23271699, Fax +86 021 63136856, Email xky7026@163.comAbstract: Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.Keywords: soft-tissue tumors, lipoprotein, atorvastatin, foam cells, lipid-lowering therapy

Xulei Sui,1 Peipei Feng,1 Xiaoyuan Sun,1 Peng Liang,1 Ying Liu,2 Guowei Zhang3 1Department of Radiology, Yantaishan Hospital, Yantai City, 264001, People’s Republic of China; 2Department of Pathology, Yantaishan Hospital (East Courtyard), Yantai City, 264003, People’s Republic of China; 3Department of Radiology, Yantaishan Hospital (East Courtyard), Yantai City, 264003, People’s Republic of ChinaCorrespondence: Guowei Zhang, Department of Radiology, Yantaishan Hospital (East Courtyard), No. 10087 Keji Avenue, Laishan District, Yantai City, 264003, People’s Republic of China, Tel +86-0535-6602048, Email zhangguoweiyt@163.comPurpose: This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features.Patients Methods: Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups.Results: Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (< 45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients.Conclusion: PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was < 2 cm in diameter. PIMPC mainly occurs in middle-aged women 45– 59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index > 30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.Keywords: pure invasive micropapillary breast carcinoma, digital mammography, ultrasonography, breast cancer, pathologic features

Ying Chen,1,2,&ast; Wen-Xia Li,1,2,&ast; Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

Yulong Xiao,1 Genhao Zhang2 1Department of Medical Laboratory, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Genhao Zhang, Email smilegenhao@163.comBackground: Pediatric sepsis has a very high morbidity and mortality rate. The purpose of this study was to evaluate diagnostic biomarkers and immune cell infiltration in pediatric sepsis.Methods: Three datasets (GSE13904, GSE26378, and GSE26440) were downloaded from the gene expression omnibus (GEO) database. After identifying overlapping genes in differentially expressed genes (DEGs) and modular sepsis genes selected via a weighted gene co-expression network (WGCNA) in the GSE26378 dataset, pivotal genes were further identified by using LASSO regression and random forest analysis to construct a diagnostic model. Receiver operating characteristic curve (ROC) analysis was used to validate the efficacy of the diagnostic model for pediatric sepsis. Furthermore, we used qRT-PCR to detect the expression levels of pivotal genes and validate the diagnostic model’s ability to diagnose pediatric sepsis in 65 actual clinical samples.Results: Among 294 overlapping genes of DEGs and modular sepsis genes, five pivotal genes (STOM, MS4A4A, CD177, MMP8, and MCEMP1) were screened to construct a diagnostic model of pediatric sepsis. The expression of the five pivotal genes was higher in the sepsis group than in the normal group. The diagnostic model showed good diagnostic ability with AUCs of 1, 0.986, and 0.968. More importantly, the diagnostic model showed good diagnostic ability with AUCs of 0.937 in the 65 clinical samples and showed better efficacy compared to conventional inflammatory indicators such as procalcitonin (PCT), white blood cell (WBC) count, C-reactive protein (CRP), and neutrophil percentage (NEU%).Conclusion: We developed and tested a five-gene diagnostic model that can reliably identify pediatric sepsis and also suggest prospective candidate genes for peripheral blood diagnostic testing in pediatric sepsis patients.Keywords: pediatric sepsis, diagnostic model, ROC curves, WGCNA

Zhenhu Zhang,1,&ast; Bin Shang,1,&ast; Xinyu Mao,1 Yamin Shi,2 Guodong Zhang,1 Dong Wang1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 2School of Foreign Languages, Shandong University of Finance and Economics, Jinan, 250014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang, Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jing Wu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +8615168863605, Email sdphwd@163.comBackground: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types.Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of β-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration.Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. β-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma.Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.Keywords: ESCC, epithelial cells, risk signature, β-sitosterol, TME

Guangming Zhang,1 Jing Yang,1 Hanghang Xing,1 Hongning Yin,2 Guoqing Gu1 1Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of China; 2Department of Heart ultrasound, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of ChinaCorrespondence: Guangming Zhang, Department of Cardiology, The Second Hospital of Hebei Medical University, 215, Heping West Road, Shijiazhuang, Hebei, 050004, People’s Republic of China, Tel +86 311-66002999, Email ZhangGuangming4@163.comObjective: This study aims to investigate the correlation between vascular endothelium-dependent diastolic function (FMD) and the degree of coronary artery disease (CAD), plaque vulnerability, and its predictive value for cardiovascular events.Methods: Initially, patients (n=100) who were admitted from January 2020 to January 2021 and intended to undergo percutaneous coronary intervention (PCI) were selected. Further, FMD in all patients was determined before the procedure and divided into a high-FMD group (≥ 4.2%) and a low-FMD group (< 4.2%). Further, the data of two groups, including general information, coronary artery lesions, and plaque fibrous cap, were compared. Finally, the relationship between FMD and the degree of coronary artery lesions and plaque vulnerability was analyzed.Results: No significant differences were observed concerning general information, number of coronary arteries-associated branches, lesion type, involvement of the left main stem (LM), the proportion of chronic occluded lesions (CTO), and lipid pool angle between the low-FMD group and the high-FMD group (P > 0.05). Nevertheless, the degree of stenosis of the lesions in the low-FMD group was significantly higher than in the high-FMD group (P < 0.05). In addition, the thickness of the fibrous cap was considerably lower than that in the high-FMD group (P < 0.05). Moreover, the incidence rate of TCFA was significantly higher than the high-FMD group (P < 0.05). The correlation analysis showed that FMD was significantly negatively correlated with the degree of coronary artery lesion stenosis and TCFA (P < 0.05) and positively correlated with the fibrous cap thickness (P < 0.05).Conclusion: Overall, a negative correlation between FMD and the degree of coronary stenosis, plaque vulnerability, and a high predictive value for post-PCI cardiovascular events suggested that FMD could be a critical diagnostic marker for CAD.Keywords: coronary heart disease, endothelium-dependent diastolic function, lesion extent, plaque vulnerability, predictive value

Xu Zhou,1,2,&ast; Aolin Tang,2,3,&ast; Chengjie Xiong,2,&ast; Guoquan Zhang,2 Liangliang Huang,1,2 Feng Xu1,2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, 430070, People’s Republic of China; 3Department of Orthopaedics, Minda Hospital of Hubei Minzu University, Enshi, 445000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangliang Huang; Feng Xu, Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, 430070, People’s Republic of China, Email hll666789@163.com; fengxu1969@163.comBackground: Treating peripheral nerve injuries (PNI) with defects remains challenging in clinical practice. The commercial conduits have shown suboptimal nerve regeneration and functional recovery due to their basic tubular design without electroactive and oriented topographical cues.Purpose: To develop a new scaffold with oriented microstructure and electroactive Graphene oxide (GO) and investigate its’ therapeutic effect on nerve regeneration in vitro and in vivo.Methods: This study employed a straightforward approach to co-spin PCL and GO, yielding an oriented hybrid nanofibrous scaffold known as the O-GO/PCL scaffold. The physical and chemical properties of nanofibrous scaffold were tested by scanning electron microscopy (SEM), transmission electron microscope (TEM), tensile test and so on. Primary Schwann cells (SCs) and dorsal root ganglia (DRG) were used to investigate the impact of the newly developed scaffolds on the biological behavior of neural cells in vitro. Transcriptome sequencing (mRNA-seq) was employed to probe the underlying mechanisms of the synergistic effect of electroactive GO and longitudinal topographic guidance on nerve regeneration. Furthermore, the developed O-GO/PCL scaffold was utilized to bridge a 10-mm sciatic nerve defect in rat, aiming to investigate its therapeutic potential for peripheral nerve regeneration in vivo.Results and discussion: The SEM and TEM revealed that the newly developed O-GO/PCL scaffold showed longitudinally oriented microstructure and GO particles were homogenously and uniformly distributed inside the nanofibers. Primary SCs were utilized to assess the biocompatibility of the GO-based scaffold, revealing that negligible cytotoxicity when GO concentration does not exceed 0.5%. In vitro analysis of nerve regeneration demonstrated that axons in the O-GO/PCL group exhibited an average length of 1054.88 ± 161.32 μm, significant longer than those in the other groups (P < 0.05). Moreover, mRNA sequencing results suggested that the O-GO/PCL scaffold could enhance nerve regeneration by upregulating genes associated with neural regeneration, encompassing ion transport, axon guidance and cell–cell interactions. Most importantly, we employed the O-GO/PCL scaffold to repair a 10-mm sciatic nerve defect in rat, resulting in augmented nerve regeneration, myelination, and functional recovery.Conclusion: The O-GO/PCL scaffold with oriented microstructure and electroactive GO represents a promising heral nerve reconstruction. Keywords: nanofibers, topographical guidance, electroactive, graphene oxide, nerve regeneration

Lina Guo,1 Jaclene A Zauszniewski,2 Gege Zhang,1 Xiaoyu Lei,1 Mengyu Zhang,1 Miao Wei,1 Keke Ma,1 Caixia Yang,1 Yanjin Liu,3 Yuanli Guo1 1Department of Neurology, National Advanced Stroke Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 3Department of Nursing, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Yuanli Guo, Email gylzd@163.comObjective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness.Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (± 1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories.Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2= 6.805, P= 0.009), education (x2= 44.865, P= 0.000), monthly income (x2= 13.063, P= 0.001), NIHSS scores (x2= 44.730, P= 0.000), mRS scores (x2= 51.788, P= 0.000), Hcy (x2= 9.345, P= 0.002), GSES (x2= 56.933, P= 0.000), FAD-GF (x2= 41.305, P= 0.000) and SSRS (x2=52.373, P= 0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness.Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.Keywords: initial ischemic stroke, resourcefulness, longitudinal study, social ecology theory, predictive factors, nursing care

Jing Zhao,1 Yan Li,1 Miao Guo,1 Guijuan Zhang,2 Ping Chen1 1Department of Gynaecology and Obstetrics, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Department of Gynaecology and Obstetrics, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Ping Chen, Department of Gynaecology and Obstetrics, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China, Tel +8613783589566, Fax +86037166262974, Email pingping6768@126.comBackground: COVID-19 is a highly contagious respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which became a global public health crisis. In the past 3 years, the COVID-19 pandemic has resulted in a dramatic increase in the occurrence of psychological symptoms such as depression, anxiety, and stress in global populations. Therefore, it is important to help pregnant women cope with major public emergencies and improve their physical and mental health.Objective: To investigate the status and influencing factors of anxiety, insomnia, and psychological stress disorder in pregnant women with COVID-19 to provide a theoretical basis for psychological intervention in pregnant women in the case of public health emergency events.Patients and methods: A cross-sectional survey was conducted with 435 pregnant women from multiple tertiary hospitals in Zhengzhou from November 6 to December 6, 2022. The questionnaire contents included the general information of pregnant women, insomnia scale, generalized anxiety scale, and the revised version of the Accident Impact Scale.Results: There are 251 pregnant women with anxiety (57.7%, 95% CI: (53.0%-62.4%).There are 166 pregnant women with insomnia.(38.2%, 95% CI: 33.6%-42.7%), There are 314 pregnant women with stress disorder.(72.2%, 95% CI: 68.0%– 76.4%). During the epidemic prevention and control period, whether pregnant women had a history of adverse pregnancy had a statistically significant difference in anxiety, insomnia and stress disorders.Conclusion and Recommendation: During the COVID-19 pandemic, pregnant women appeared to generally have anxiety, insomnia, and stress disorders. Poor pregnancy history is a protective factor for pregnant women with anxiety, insomnia, and post-traumatic stress disorder. In the case of similar public health emergencies, attention bias modification (ABM) may be a potential intervention measure to provide potentially new ideas for alleviating the psychological disorders of pregnant women during this special period.Keywords: novel coronavirus infection, pregnancy, anxiety, insomnia, psychological stress disorder

Chao Huang,1,&ast; Jixiang Pei,1,&ast; Daisong Li,1 Tao Liu,2 Zhaoqing Li,1 Guoliang Zhang,1 Ruolan Chen,1 Xiaojian Xu,1 Bing Li,3,4 Zhexun Lian,1 Xian-Ming Chu1,5 1Department of Cardiology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266100, People’s Republic of China; 2The Affiliated Qingdao Central Hospital of Qingdao University, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong, 266042, People’s Republic of China; 3Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266000, People’s Republic of China; 4Department of Dermatology, The Affiliated Haici Hospital of Qingdao University, Qingdao, 266033, People’s Republic of China; 5The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhexun Lian; Xian-Ming Chu, Tel +86-532-82913257, Email lianzx566@163.com; chuxianming@qdu.edu.cnPurpose: Doxorubicin-induced cardiotoxicity (DIC) is a severe side reaction in cancer chemotherapy that greatly impacts the well-being of cancer patients. Currently, there is still an insufficiency of effective and reliable biomarkers in the field of clinical practice for the early detection of DIC. This study aimed to determine and validate the potential diagnostic and predictive values of critical signatures in DIC.Methods: We obtained high-throughput sequencing data from the GEO database and performed data analysis and visualization using R software, GO, KEGG and Cytoscape. Machine learning methods and weighted gene coexpression network (WGCNA) were used to identify key genes for diagnostic model construction. Receiver operating characteristic (ROC) analysis and a nomogram were used to assess their diagnostic values. A multiregulatory network was built to reveal the possible regulatory relationships of critical signatures. Cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) analysis was used to investigate differential immune cell infiltration. Additionally, a cell and animal model were constructed to investigate the relationship between the identified genes and DIC.Results: Among the 3713 differentially expressed genes, three key genes (CSGALNACT1, ZNF296 and FANCB) were identified. A nomogram and ROC curves based on three key genes showed excellent diagnostic predictive performance. The regulatory network analysis showed that the TFs CREB1, EP300, FLI1, FOXA1, MAX, and MAZ modulated three key genes. An analysis of immune cell infiltration indicated that many immune cells (activated NK cells, M0 macrophages, activated dendritic cells and neutrophils) might be related to the progression of DIC. Furthermore, there may be various degrees of correlation between the three critical signatures and immune cells. RT‒qPCR demonstrated that the mRNA expression of CSGALNACT1 and ZNF296 was significantly upregulated, while FANCB was significantly downregulated in DOX-treated cardiomyocytes in vitro and in vivo.Conclusion: Our study suggested that the differential expression of CSGALNACT1, ZNF296 and FANCB is associated with cardiotoxicity and is also involved in immune cell infiltration in DIC. They might be potential biomarkers for the early occurrence of DIC.Keywords: doxorubicin, cardiotoxicity, biomarker, machine learning, immune infiltration

Zhao Guo,1,&ast; Haoyun Song,1,&ast; Yingxia Tian,2,&ast; Jie Xu,3 Guokun Zhang,1 Yanan Guo,1 Rong Shen,1 Degui Wang1 1Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, People’s Republic of China; 2Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, People’s Republic of China; 3Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Degui Wang; Rong Shen, Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, People’s Republic of China, Tel +86 13893609120 ; +86 13909483373, Fax +86 931 8915023, Email wangdegui@lzu.edu.cn; shenr@lzu.edu.cnBackground: The evident side effects and decreased drug sensitivity significantly restrict the use of chemotherapy. However, nanoparticles based on biomaterials are anticipated to address this challenge.Methods: Through bioinformatics analysis and colon cancer samples, we initially investigated the expression level of RNF8 in colon cancer. Next, we constructed nanocarrier for delivering siRNF8 based on DNA tetrahedron (si-Tet), and Doxorubicin (DOX) was further intercalated into the DNA structure (si-DOX-Tet) for combination therapy. Further, the effects and mechanism of RNF8 inhibition on the sensitivity of colon cancer cells to DOX chemotherapy have also been studied.Results: RNF8 expression was increased in colon cancer. Agarose gel electrophoresis, transmission electron microscopy, and size distribution and potential analysis confirmed the successful preparation of the two nanoparticles, with particle sizes of 10.29 and 37.29 nm, respectively. Fluorescence imaging reveals that the carriers can be internalized into colon cancer cells and escape from lysosomes after 12 hours of treatment, effectively delivering siRNF8 and DOX. Importantly, Western blot analysis verified treatment with 50nM si-Tet silenced RNF8 expression by approximately 50% in colon cancer cells, and combined treatment significantly inhibited cell proliferation. Furthermore, the CCK-8 assay demonstrated that si-Tet treatment enhanced the sensitivity of colon cancer cells to the three chemotherapeutic drugs. Significant more DNA damage was detected after treatment with both si-Tet or si-DOX-Tet. Further flow cytometry analysis revealed that si-DOX-Tet treatment led to significantly more apoptosis, approximately 1.6-fold higher than treatment with DOX alone. Mechanistically, inhibiting RNF8 led to decreased ABCG2 expression and DOX efflux, but increased DNA damage, thereby enhancing the chemotherapeutic effect of DOX.Conclusion: We have successfully constructed si-DOX-Tet. By inhibiting the expression of RNF8, it enhances the chemotherapy sensitivity of DOX. Therefore, this tetrahedral FNA nanocarrier offers a new approach for the combined treatment of colon cancer. Keywords: DNA framework nucleic acid, RNF8, chemosensitivity, RNAi, colorectal cancer

Dingyue Wang, Gaosen Zhang, Yana Yu, Zhen Zhang Department of Ultrasound, the First Affiliated Hospital China Medical University, Shenyang City, Liaoning Province, 110001, People’s Republic of ChinaCorrespondence: Zhen Zhang, Email zhangzhen@cmu.edu.cnAbstract: Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass, muscular strength, and muscle function. In older adults, type 2 diabetes mellitus (T2DM) constitutes a significant health burden. Skeletal muscle damage and deterioration have emerged as novel chronic complications in patients with diabetes, often linked to their increased longevity. Diabetic sarcopenia has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Nevertheless, effectively managing metabolic disorders in patients with T2DM through appropriate therapeutic interventions could potentially mitigate the risk of sarcopenia. Utilizing imaging technologies holds substantial clinical significance in the early detection of skeletal muscle mass alterations associated with sarcopenia. Such detection is pivotal for arresting disease progression and preserving patients’ quality of life. These imaging modalities offer reproducible and consistent patterns over time, as they all provide varying degrees of quantitative data. This review primarily delves into the application of dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging, and ultrasound for both qualitative and quantitative assessments of muscle mass in patients with T2DM. It also juxtaposes the merits and limitations of these four techniques. By understanding the nuances of each method, clinicians can discern how best to apply them in diverse clinical scenarios.Keywords: diagnostic imaging, older adults, sarcopenia, skeletal muscle mass, type 2 diabetes mellitus

Miao Wan,1,&ast; Xiangrong Xu,2,&ast; Xiaojiao Zhao,1 Xia You,1 Guiying Zhang,3 Hai Long,3 Ping He,1 Jian Long,1 Jianjian Zhu1 1Department of Dermatovenerology of the First People’s Hospital of Changde City, Changde Hospital Affiliated to Xiangya School of Medicine of Central South University, Changde, 415000, People’s Republic of China; 2Department of Plastic Surgery of the First People’s Hospital of Changde City, Changde Hospital Affiliated to Xiangya School of Medicine of Central South University, Changde, 415000, People’s Republic of China; 3Department of Dermatovenerology of the Second Xiangya Hospital of Central South University, Changsha, 410000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianjian Zhu, No. 388, Renmin East Road, Changde, Hunan Province, People’s Republic of China, Tel +15873658886, Email lidocute@163.comAbstract: Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.Keywords: debridement, infection, multidisciplinary consultation, necrotizing fasciitis, pemphigus

Songli Ruan,1,&ast; Xin Wang,2,&ast; Chengjia Zhao,3,&ast; Qian Li,2 Wing Ming Li,2 Guohua Zhang,4,5 Jianshe Pan,4 Xue Yang2 1Mental Health Education and Guidance Center of College Students, Henan University of Urban Construction, Pingdingshan, People’s Republic of China; 2JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Psychiatry, The Affiliated Kangning Hospital, Wenzhou, People’s Republic of China; 5Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Yang, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China, Email sherryxueyang@cuhk.edu.hkBackground: Enhancing abstinence motivation of drugs is an effective strategy for the rehabilitation of people who used drugs and prevention of drug use relapse. However, little is known about its risk and protective factors. This study aimed to examine the potential intrapersonal (ie, impulsivity, depression, anxiety, sleep quality) and interpersonal factors (ie, perceived social support) of abstinence motivation among people who completed the community rehabilitation treatment.Methods: A total of 222 participants (mean age = 43; male = 89.2%) were recruited from eleven communities located in Wenzhou, China. Data were collected using a self-reported questionnaire in counselling room settings between April and June 2021.Results: The proportions of participants with depression, anxiety, and poor sleep quality were 38.8%, 19.5%, and 21.2%, respectively. Age and family history of physical disease were significant background factors of abstinence motivation. Impulsivity, depressive symptoms, anxiety symptoms, and poor quality of sleep were negatively associated with abstinence motivation. Perceived social support from family and important others was positively associated with abstinence motivation. Structural equation modeling fitted the data well in which impulsivity and perceived social support were both associated with abstinence motivation indirectly through mental health problems.Conclusion: The identified psychosocial factors should be addressed in community rehabilitation treatment and follow-up service to enhance abstinence motivation and the long-term effectiveness of the treatment.Keywords: abstinence motivation to drugs, mental health problems, personality, social support, community-based rehabilitation treatment, Chinese people who used drugs

Yumeng Cao,1,&ast; Huaqin Pan,2,&ast; Yanwei Yang,3 Jingrun Zhou,1 Guqin Zhang1 1Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Transplantation Intensive Care Unit, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People’s Republic of China; 3Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guqin Zhang, Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China, Email zgqxiaoxiao@126.comPurpose: Ferroptosis plays essential roles in the development of COPD. We aim to identify the potential ferroptosis-related genes of COPD through bioinformatics analysis.Methods: The RNA expression profile dataset GSE148004 was obtained from the GEO database. The ferroptosis-related genes were obtained from the FerrDb database. The potential differentially expressed ferroptosis-related genes of COPD were screened by R software. Then, protein–protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed ferroptosis-related genes. Finally, hub gene-microRNA(miRNA), hug gene-transcription factor interaction networks were constructed by miRTarBase v8.0 and JASPAR respectively, and hub gene drugs were predicted by the Enrichr database.Results: A total of 41 differentially expressed ferroptosis-related genes (22 up-regulated genes and 19 down-regulated genes) were identified between 7 COPD patients and 9 healthy controls. The PPI results demonstrated that these ferroptosis-related genes interacted with each other. The GO and KEGG enrichment analyses of differentially expressed ferroptosis-related genes indicated several enriched terms related to ferroptosis, central carbon metabolism in cancer, and the HIF-1 signaling pathway. The crucial miRNAs and drugs associated with the top genes were identified.Conclusion: We identified 41 potential ferroptosis-related genes in COPD through bioinformatics analysis. HIF1A, PPARG, and KRAS may affect the development of COPD by regulating ferroptosis. These results may expand our understanding of COPD and might be useful in the treatment of COPD.Keywords: ferroptosis, COPD, bioinformatics analysis, gene expression omnibus dataset

Wenbo Wu,1,&ast; Xiaoli Yu,2,&ast; Jiaxiang Sun,3 Yuanyuan Han,3 Yuanye Ma,1 Guoqing Zhang,1 Qingming Ma,4 Qiang Li,3 Hongfei Xiang1 1Department of Orthopedics, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao, 266100, People’s Republic of China; 3College of Physics, Center for Marine Observation and Communications, Qingdao University, Qingdao, 266021, People’s Republic of China; 4Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, 266021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfei Xiang; Qingming Ma, Tel +86-532-61807860, Email xianghf@qdu.edu.cn; qma@qdu.edu.cnBackground: As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.Methods: In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.Results: DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p< 0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p< 0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.Conclusion: In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.Keywords: osteosarcoma chemotherapy, zeolite imidazolate framework, PH-responsive, nanocarriers, tumor targeting

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

Xing Wang,1,2,&ast; Xiaojing Yang,1,3,&ast; Yiming Zhang,1 Afei Guo,1 Suju Luo,1 Meng Xiao,1 Lu Xue,1 Guohui Zhang,2 Huiping Wang1 1Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Dermatovenereology, Baotou Central Hospital, Baotou City, Inner Mongolia, People’s Republic of China; 3Department of Dermatovenereology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiping Wang; Guohui Zhang, Email huiping1208@163.com; 1259314465@qq.comIntroduction: Skin cutaneous melanoma is becoming more dangerous since it has a poor prognosis and is resistant to treatment. Previous research has shown that lncRNAs and fatty acid metabolism are essential for numerous biological activities. There are no studies on the relationship between fatty acid metabolism-Related lncRNAs and skin cutaneous melanoma.Methods and Results: In order to better understand the prognosis and survival of SKCM patients, we investigated the significance of lncRNAs related to fatty acid metabolism. In this work, we looked at the fatty acid metabolism genes and lncRNAs expression patterns. On the basis of lncRNAs associated with fatty acid metabolism, a nomogram and a prognosis prediction model were created. Based on the profile of lncRNAs associated with fatty acid metabolism, functional and pharmacological sensitivity investigations were also carried out. We also looked at the connection between immunotherapy and the immune response. The findings demonstrated that a risk score model based on 11 essential lncRNAs for fatty acid metabolism may discriminate between the clinical condition of SKCM and more accurately predict prognosis and survival. We conducted quantitative reverse transcription polymerase-chain reaction (RT-PCR) to verify the model.Conclusion: These important lncRNAs further showed a strong association with the tumor immune system, and these important lncRNAs also showed a connection between SKCM and chemotherapeutic treatment sensitivity. Our research strives to provide fresh viewpoints and innovative approaches to the treatment and administration of SKCM.Keywords: skin cutaneous melanoma, lncRNA, fatty acid metabolism, bioinformatics, tumor immune

Tengfei Chen,1,&ast; Sihan Li,1,&ast; Dongyin Lian,1 Qin Hu,2 Hongping Hou,1 Delian Niu,1 Han Li,1 Ling Song,1 Yunhang Gao,1 Ying Chen,1 Xiaoru Hu,3 Jianrong Li,1 Zuguang Ye,1 Bo Peng,1 Guangping Zhang1 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2College of Life Sciences and Bio-Engineering, Beijing University of Technology, Beijing, People’s Republic of China; 3National Institute for Food and Drug Control, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Peng; Guangping Zhang, Tel +8610 64056575, Email bpeng@icmm.ac.cn; gpzhang@icmm.ac.cnPurpose: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification.Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis.Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-κB signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-κB pathway including IL-17A, IL-17RA, NF-κB p65, C-X-C motif ligand 2, MMP1 and MMP13.Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-κB pathway. Keywords: rheumatoid arthritis, Jin Gu Lian capsules, network pharmacology, experimental validation, immune-mediated inflammation

Yang Yang,1 Genhao Zhang2 1Department of Nuclear Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Blood Transfusion, Zhengzhou University First Affiliated Hospital, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Genhao Zhang, Email smilegenhao@163.comBackground: There is currently no biomarker that can reliably identify sepsis, despite recent scientific advancements. We systematically evaluated the value of lysosomal genes for the diagnosis of pediatric sepsis.Methods: Three datasets (GSE13904, GSE26378, and GSE26440) were obtained from the gene expression omnibus (GEO) database. LASSO regression analysis and random forest analysis were employed for screening pivotal genes to construct a diagnostic model between the differentially expressed genes (DEGs) and lysosomal genes. The efficacy of the diagnostic model for pediatric sepsis identification in the three datasets was validated through receiver operating characteristic curve (ROC) analysis. Furthermore, a total of 30 normal samples and 35 pediatric sepsis samples were gathered to detect the expression levels of crucial genes and assess the diagnostic model’s efficacy in diagnosing pediatric sepsis in real clinical samples through real-time quantitative PCR (qRT-PCR).Results: Among the 83 differentially expressed genes (DEGs) related to lysosomes, four key genes (STOM, VNN1, SORT1, and RETN) were identified to develop a diagnostic model for pediatric sepsis. The expression levels of these four key genes were consistently higher in the sepsis group compared to the normal group across all three cohorts. The diagnostic model exhibited excellent diagnostic performance, as evidenced by area under the curve (AUC) values of 1, 0.971, and 0.989. Notably, the diagnostic model also demonstrated strong diagnostic ability with an AUC of 0.917 when applied to the 65 clinical samples, surpassing the efficacy of conventional inflammatory indicators such as procalcitonin (PCT), white blood cell (WBC) count, C-reactive protein (CRP), and neutrophil percentage (NEU%).Conclusion: A four-gene diagnostic model of lysosomal function was devised and validated, aiming to accurately detect pediatric sepsis cases and propose potential target genes for lysosomal intervention in affected children.Keywords: pediatric sepsis, diagnostic marker, ROC curves, lysosomal, GSEA

Mingxiang Cai,1,&ast; Huizhen Peng,1,&ast; Minyi Liu,1,&ast; Maohua Huang,2,3 Wen Zheng,1 Guilan Zhang,1 Wenjia Lai,1 Chufang Liao,1 Lizhao Cai,1 Dongmei Zhang,2,3 Xiangning Liu1 1The First Affiliated Hospital of Jinan University, School of Stomatology, Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, 510630, People’s Republic of China; 2College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangning Liu, The First Affiliated Hospital of Jinan University, School of Stomatology, Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, 510630, People’s Republic of China, Email liuxiangning@jnu.edu.cn Dongmei Zhang, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China, Email dmzhang701@jnu.edu.cnPurpose: Blood vessels distribute cells, oxygen, and nutrients throughout the body to support tissue growth and balance. Pericytes and endothelial cells form the inner wall of blood vessels, crucial for organ development and tissue homeostasis by producing paracrine signaling molecules. In the skeletal system, pericyte-derived vascular factors along with angiogenic factors released by bone cells regulate angiogenesis and bone formation. Although the involvement of angiogenic factors and skeletal blood vessels in bone homeostasis is relatively clear, the role of pericytes and the underlying mechanisms remain unknown. Here, our objective was to elucidate the significance of pericytes in regulating osteoclast differentiation.Methods: We used tissue staining to detect the coverage of pericytes and osteoclasts in femoral tissues of osteoporotic mice and mice of different ages, analyzing their correlation. We developed mice with conditionally deleted pericytes, observing changes in bone mass and osteoclast activity using micro-computer tomography and tissue staining to detect the regulatory effect of pericytes on osteoclasts. Pericytes-derived exosomes (PC-EVs) were collected and co-cultured with monocytes that induce osteoclast differentiation to detect the effect of the former on the exosomes. Finally, the specific mechanism of PC-EVs regulating osteoclast differentiation was verified using RNA sequencing and Western blotting.Results: Our study indicates a significant correlation between pericytes and age-related bone resorption. Conditional deletion of pericytes activated bone resorption and led to osteopenia in vivo. We discovered that PC-EVs inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, which is mediated by tumor necrosis factor receptor-associated factor 3 (Traf3), negatively regulating osteoclast development and bone resorption. Silencing Traf3 in PC-EVs canceled their inhibitory effect on osteoclast differentiation.Conclusion: Our study provides a novel perspective into the regulatory role of pericytes on bone resorption and may provide potential strategies for developing novel anti-bone resorption therapies. Keywords: pericytes, exosomes, bone resorption, Traf3

Qi Yang,1– 4 Yalan Luo,1– 3 Peng Ge,1– 3 Bowen Lan,1– 3 Jin Liu,1– 3 Haiyun Wen,1– 3 Yinan Cao,1– 3 Zhenxuan Sun,1– 3 Guixin Zhang,1– 3 Huiming Yuan,5 Lihua Zhang,5 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 5CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, 116023, People’s Republic of ChinaCorrespondence: Hailong Chen, Email chenhailong@dmu.edu.cnBackground: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear.Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO.Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats.Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO. Plain Language Summary: Exosomes extracted from plasma/BALF of EMO-treated SAP rats show a substantial therapeutic impact on SAP-Associated ALI, with BALF-derived exosomes having a higher therapeutic effect than plasma-derived exosomes.EMO dramatically altered the miRNA expression patterns of plasma and BALF-derived exosomes in SAP rats.The lung protective effect of EMO in SAP rats is somewhat reliant on Novel-rno-miR-29a-3p expression.Keywords: severe acute pancreatitis, acute lung injury, emodin, exosome, microRNA

Daopeng Fan,1,&ast; Shuqi Wang,1,&ast; Ran Huang,1,&ast; Xiaoning Liu,1 Hua He,1 Gaiping Zhang1– 3 1College of Veterinary Medicine, International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, 450046, People’s Republic of China; 2Longhu Laboratory, Zhengzhou, 450046, People’s Republic of China; 3School of Advanced Agriculture Sciences, Peking University, Beijing, 100871, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua He, College of Veterinary Medicine, International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, 450046, People’s Republic of China, Email hhe@henau.edu.cnBackground: Nanomedicine presents a promising alternative for cancer treatment owing to its outstanding features. However, the therapeutic outcome is still severely compromised by low tumor targeting, loading efficiency, and non-specific drug release.Methods: Light-assisted “nano-neutrophils (NMPC-NPs)”, featuring high drug loading, self-amplified tumor targeting, and light-triggered specific drug release, were developed. NMPC-NPs were composed of neutrophil membrane-camouflaged PLGA nanoparticles (NPs) loaded with a hypoxia-responsive, quinone-modified PTX dimeric prodrug (hQ-PTX2) and photosensitizer (Ce6).Results: hQ-PTX2 significantly enhanced the drug loading of NPs by preventing intermolecular π–π interactions, and neutrophil membrane coating imparted the biological characteristics of neutrophils to NMPC-NPs, thus improving the stability and inflammation-targeting ability of NMPC-NPs. Under light irradiation, extensive NMPC-NPs were recruited to tumor sites based on photodynamic therapy (PDT)-amplified intratumoral inflammatory signals for targeted drug delivery to inflammatory tumors. Besides, PDT could effectively eliminate tumor cells via reactive oxygen species (ROS) generation, while the PDT-aggravated hypoxic environment accelerated hQ-PTX2 degradation to realize the specific release of PTX, thus synergistically combining chemotherapy and PDT to suppress tumor growth and metastasis with minimal adverse effects.Conclusion: This nanoplatform provides a prospective and effective avenue toward enhanced tumor-targeted delivery and synergistic cancer therapy.Keywords: neutrophil, self-amplified tumor targeting, high drug loading, hypoxia-responsive, chemo-photodynamic therapy

Tao Wang,1,2,&ast; Qianwen Yang,3,&ast; Yan Gao,2 Rongping Zhang,2 Chaoxin Zhou,2 Weifang Kong,1 Guojin Zhang,1 Xinyue Chen,4 Hong Pu,1 Lan Shang1 1Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4CT Collaboration, Siemens-Healthineers, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Pu; Lan Shang, Department of Radiology, The First Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, Sichuan Province, 60072, People’s Republic of China, Tel +86 13882267217, Fax +86 87294280, Email ph196797@163.com; shanglan8282@163.comPurpose: This study aimed to investigate clinical features and computed tomography (CT) manifestations of rifampicin primary drug-resistant pulmonary tuberculosis in Liangshan Yi Autonomous Prefecture.Patients and Methods: A total of 100 inpatients with confirmed primary rifampicin-resistant pulmonary tuberculosis were recruited from January 2020 to December 2022 at an infectious disease hospital located in the Liangshan Yi Autonomous Prefecture. Additionally, 100 inpatients with confirmed drug-susceptible pulmonary tuberculosis during the same period were matched to the rifampicin-resistant group based on gender, age, and ethnicity. The clinical characteristics of the two groups were recorded separately. Furthermore, the CT manifestations in these patients were independently analyzed by three radiologists.Results: The results showed that comorbid diabetes mellitus was more prevalent in the drug-resistant tuberculosis (DR-TB) group than in the drug-susceptible tuberculosis (DS-TB) group (9% vs 0%, p=0.0032). In terms of imaging presentation, DR-TB patients exhibited a higher frequency of calcifications (55% vs 35.00%, p=0.0068), greater median number of cavities (5 vs 2, p=0.0027), and larger maximum cavity diameter (52.08± 25.55 mm vs 42.72± 17.48 mm, p=0.0097). Additionally, bilateral involvement was more common in DR-TB patients at the site of the lesion (89% vs 76%, p=0.0246), with a higher prevalence in the right middle (82% vs 68%, p=0.0332), right lower (82% vs 68%, p=0.0332), left upper (91% vs 77%, p=0.0113), and left lower lobes (92% vs 66%, p< 0.0001). Conversely, the involvement of only one lobe was less frequent in patients with DR-TB than in those with DS-TB (4% vs 13%, p=0.0398), whereas the involvement of all five lobes was more common (68% vs 51%, p=0.0209).Conclusion: Patients with DR-TB exhibit a higher prevalence of severe imaging manifestations, highlighting the importance of CT in the early detection and diagnosis of DR-TB.Keywords: drug-resistant tuberculosis, drug-susceptible tuberculosis, tuberculosis, comorbid diabetes mellitus

Linxi Zeng,1 Sen Feng,1 Lulu Yao,1 Jiaqing Zhao,1 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, People’s Republic of China; 2Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guoqiang Zhang, The First Hospital of Hebei Medical University, 89 Donggang Road, Yuhua District, Shijiazhuang City, Hebei Province, People’s Republic of China, Email zlx090702@163.comAbstract: Herpes zoster is typically a blister rash involving a single skin group, caused by the reactivation of primary varicella zoster virus infection. Disseminated herpes zoster refers to the presence of more than 20 small blisters outside the primary or adjacent skin, which is rare and usually occurs in individuals with weakened immune function. This case described a patient diagnosed with disseminated herpes zoster, with a decrease in CD4 count (379 cells/mm3) and certain skin lesions. He was subsequently screened positive for HIV. Also, we summarized other studies on the CD4 value of HIV patients with herpes zoster. Overall, for herpes zoster patients with decreased CD4 levels and certain skin manifestations, such as diffuse, ulcerative, or pustular lesions, clinicians should be aware of HIV infection.Keywords: disseminated herpes zoster, CD4, HIV infection

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

Ding P, Jin Q, Chen X, et al. Int J Nanomedicine. 2019;14:7533-7548. At the author’s request, we, the Editor and Publisher of the journal International Journal of Nanomedicine have retracted the following article. During a recent review of the article, the authors identified an error in the use of the transmission electron microscopy (TEM) images for Figure 2A, which could potentially confuse readers. After discussing this issue with the editorial team and providing the original data, the authors agreed that the potential confusion could not be adequately addressed through simple correction. Although the results of TEM were independent of the in vivo and in vitro experiments and did not affect the effectiveness of the nanovaccines in the study, they could have compromised the accuracy and reliability of the findings. The authors apologize for the errors in the article and appreciate the readership’s understanding in this matter. However, the authors remain confident in the results and conclusions of this study and with the original material well preserved, hope to submit a revised version of the article for republication following reevaluation. The journal has acknowledged this. In the meantime, in the interest of upholding research integrity and ensuring the trustworthiness of the scientific record, the authors believe that it is necessary to retract the article. We, the Editor and Publisher, understand and agreed with 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”.

Zhang G, Zhong L, Luo H, Wang S. Onco Targets Ther. 2019;12:7993–8002. At the author’s request, we, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 and 5 with images from other unrelated articles. Specifically, Images from Figure 4I have been duplicated with images from Figure 4C and Figure 5E from Wei W, Zhao X, Zhu J, et al. lncRNA‑u50535 promotes the progression of lung cancer by activating CCL20/ERK signaling. Oncology Reports. 2019;42:1946-1956. https://doi.org/10.3892/or.2019.7302 and Wang H, Lou C, Ma N. Forskolin exerts anticancer roles in non-Hodgkin’s lymphomas via regulating Axin/β-catenin signaling pathway. Cancer Manag Res. 2019;11:1685-1696. https://doi.org/10.2147/CMAR.S180754, respectively. Images from Figure 5 have been duplicated with images for Figure 6 from Chen W, Wu G, Zhu Y, et al. HOXA10 deteriorates gastric cancer through activating JAK1/STAT3 signaling pathway. Cancer Manag Res. 2019;11:6625-6635. https://doi.org/10.2147/CMAR.S201342. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with 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”.

Jialu Sun,1 Yijun Shi,1 Yaowei Ding,1 Siqi Wang,1 Lingye Qian,2 Xin Luan,1 Guoge Li,1 Yuxin Chen,1 Xiaotong Li,1 Hong Lv,1,3,4 Guanghui Zheng,1,3,4,&ast; Guojun Zhang1,3,4,&ast; 1Laboratory, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Laboratory, Beijing An Zhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 3NMPA Key Laboratory for Quality Control of in vitro Diagnostics, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Engineering Research Center of Immunological Reagents Clinical Research, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanghui Zheng; Guojun Zhang, Beijing Tiantan Hospital, NO. 119 Nansihuan West Road, Fengtai District, Beijing, People’s Republic of China, Tel +86 18600148997 ; +86 13811792425, Email zgh999@yeah.net; guojun.zhang@ccmu.edu.cnBackground: To investigate the factors associated with follow-up CSF cultures (FUCCs) in post-neurosurgical patients with gram-negative bacterial meningitis/encephalitis and the effect of FUCCs on treatment management and patient outcomes.Methods: This single-centered retrospective cohort study enrolled post-neurosurgical patients with gram-negative bacterial meningitis/encephalitis at a tertiary-care university hospital between 2012 and 2022. The risk factors for 28-day mortality were evaluated using multivariate Cox analysis. FUCC-related risk factors were also analyzed.Results: Among the 844 enrolled patients, 504 (59.7%) underwent FUCC, and FUCC was found to be associated with lower rates of both all-cause (hazard ratio (HR) 0.391; 95% confidence interval (CI), 0.235– 0.651; p< 0.001) and attributable mortality (HR 0.463; 95% CI, 0.239– 0.897; p=0.023) in Post-neurosurgical patients diagnosed with Gram-negative bacterial meningitis/encephalitis. Moreover, the results of the study underscored that patients with persistent gram-negative bacterial meningitis/encephalitis had a lower all-cause/attributable short-term survival rate according to 28-day mortality Kaplan–Meier analysis (P=0.001/0.006).Conclusion: Performing FUCC has been demonstrated to lower mortality rates in Post-neurosurgical patients suffering from Gram-negative bacterial meningitis/encephalitis. The higher mortality rate observed in patients with persistent gram-negative bacterial meningitis/encephalitis suggests that performing FUCC is a crucial component of proper patient care and management, and is therefore recommended for use by clinicians as a standard practice. This finding underscores the significance of consistent implementation of FUCC in the management and prognosis of patients with Post-neurosurgical infections.Keywords: gram-negative bacterial meningitis/encephalitis, follow-up cerebrospinal fluid cultures, all-cause 28-day mortality, persistent meningitis/encephalitis, risk factors