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Shulin Wei,1,2,* Mingxing Li,1,2,* Qin Wang,1,2,* Yueshui Zhao,1,2 Fukuan Du,1,2 Yu Chen,1,2 Shuai Deng,1,2 Jing Shen,1,2 Ke Wu,1,2 Jiayue Yang,1,2 Yuhong Sun,1 Li Gu,1 Xiaobing Li,1 Wanping Li,1 Meijuan Chen,1 Xiao Ling,3 Lei Yu,3 Zhangang Xiao,1,2 Lishu Dong,3 Xu Wu1,2 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, 646100, People’s Republic of China; 3Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lishu Dong, Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China, Email 1275607519@qq.com Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@126.comAbstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.Keywords: mesenchymal stem cells, immunomodulation, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, cell therapy

Liang Lu, Yongfa Chen School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing City, Jiangsu, People’s Republic of ChinaCorrespondence: Yongfa Chen, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, People’s Republic of China, Tel +86 25 86185038, Fax +86 25 86185279, Email cyf@cpu.edu.cnObjective: This study aimed to clarify the association between suboptimal health status and health-related productivity loss among primary healthcare workers in China.Material and Methods: A field questionnaire survey was conducted with a multistage sampling among primary healthcare workers. The data on sub-health and health-related productivity loss were collected using the Sub-health Measurement Scale Version 1.0 and Work Productivity and Activity Impairment Questionnaire: General Health, respectively. Ordinary least squares regression was used to evaluate the association of the suboptimal health and health-related productivity loss. Subgroup analyses were performed by occupation (physician and nurse).Results: Front-line primary healthcare workers (N = 1709) from 31 provinces in China responded to the survey. Of all participants, 73.43% experienced suboptimal health. The status of being in physical suboptimal health (Coef. = 0.050, p < 0.001, 95% CI = [0.031,0.070]) and mental suboptimal health (Coef. = 0.040, p < 0.001, 95% CI = [0.020,0.059]) status exerted significant effect on the extent of health-related productivity loss among primary healthcare workers in China. Nurses in social adaptation suboptimal health status (Coef. = 0.030, p = 0.027, 95% CI = [0.003,0.057]) had significant effect on health-related productivity loss.Conclusion: The prevalence of suboptimal health is high among the respondents. Providing support for primary healthcare workers from bio-psycho-social aspects is an effective measure to promote their occupational health and improve their productivity.Keywords: occupational health, productivity, presenteeism, healthcare workers, cross-sectional survey

Fanfan Zhao,1 Min Zhou,2 An Mao,3 Yingjiao Zhang,4 Yao Chen2 1Center for Rehabilitation Medicine, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Radiology, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Outpatient, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Gastroenterology, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yao Chen, Department of Radiology, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of China, Email chenyao19970712@163.comBackground: Kimura disease (KD) is a rare chronic inflammatory disease that affects mainly young Asian men and is characterized by painless subcutaneous masses, lymphadenopathy, and elevated serum IgE levels. Despite its benign nature, KD poses a diagnostic and therapeutic challenge due to its rarity and clinical variability.Objective: This study aimed to provide a comprehensive analysis of the clinical and radiological features of KD in a retrospective case series, to assess treatment outcomes, and to discuss the implications for diagnosis and management.Methods: We retrospectively analyzed four histologically confirmed cases of KD admitted to Zhejiang Provincial People’s Hospital from January 2018 to October 2023. Clinical and radiological data were retrospectively analyzed, and imaging findings were analyzed by two neuroradiologists to determine lesion characteristics and contrast enhancement patterns.Results: Our findings showed that the patients were predominantly male, with a mean age of 43 years and an age range of 13– 71 years. All patients presented with painless subcutaneous masses and three of them had peripheral blood eosinophilia and elevated serum IgE levels. Radiographically, the lesions were predominantly ill-defined with heterogeneous enhancement, accompanied by subcutaneous fat atrophy. Complete surgical excision and oral corticosteroids were effective treatments, and no recurrence was noted during follow-up.Conclusion: KD should be considered in the differential diagnosis of painless subcutaneous masses in the head and neck region, especially in the presence of eosinophilia and elevated IgE levels. Our findings contribute to the understanding of KD’s clinical and radiological spectrum and highlight the need for long-term follow-up due to the risk of recurrence.Keywords: Kimura disease, computed tomography, CT, magnetic resonance imaging, MRI, eosinophilia

Yanchen Chen,1,2 Yuqin Tu,2,3 Guiling Yan,2,3 Xinyao Ji,2,3 Shu Chen,2,3 Changchun Niu,2 Pu Liao1,2 1Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, People’s Republic of China; 2Department of Clinical Laboratory, Chongqing General Hospital, Chongqing, People’s Republic of China; 3Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Pu Liao, Chongqing General Hospital, 118 Xingguang Avenue, Yubei District, Chongqing, People’s Republic of China, Tel +86 13628358003, Fax +23-63519127, Email liaopu@sina.comPurpose: There is growing evidence that the immune system plays an important role in the progression of Parkinson’s disease, the second most common neurodegenerative disorder. This study aims to address the comprehensive understanding of the immunopathogenesis of Parkinson’s disease and explore new inflammatory biomarkers.Patients and Methods: In this study, Immune-related differential expressed genes (DEIRGs) were obtained from GEO database and Immport database. The hub gene was screened in DEIRGs using LASSO regression and random forest algorithm, and the mRNA expression of the identified hub gene was validated using clinical blood samples.Results: We obtained a total of 157 DEIRGs that played an important role in the immune response. The results of immune cell infiltration analysis showed that the degree of memory B cells infiltration was higher in PD patients, while the degree of Monocytes, resting mast cells and M0 macrophages infiltration was lower (p< 0.05). A total of 8 hub genes were screened by machine learning methods, and RT-PCR results showed that the expression level of CBL gene in PD was significantly increased (p< 0.05).Conclusion: Our findings suggest that CBL is a new potential diagnostic biomarker for PD and that abnormal immune cell infiltration may influence PD development.Keywords: Parkinson’s disease, immune cell infiltration, bioinformatics, immport database, gene expression omnibus database

Yiyu Chen,1 Chuxuan Fang,1 Jun Luo,1 Xueling Pan,2 Zongyan Gao,3 Shuangyi Tang,1 Meng Li4– 6 1Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Newborn ICU, Guigang Maternal and Child Health Care Hospital, Guigang City, Guangxi, People’s Republic of China; 3Newborn ICU, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Key Laboratory of Clinical Laboratory Medicine, Guangxi Department of Education, Nanning, Guangxi, People’s Republic of China; 6Key Laboratory of Fungi and Mycosis Research and Prevention, Guangxi Health Commission, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Meng Li, Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +8613367809642, Email gxmulimeng@foxmail.comAbstract: The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasing in recent years. Chinese Infectious Disease Surveillance of Pediatrics (ISPED) showed that in 2022, its resistance rate to meropenem was 18.5%. However, there is limited data available on the treatment of CRKP infection in neonates. In this study, we present a case involving a premature infant infected with OXA-48-producing Klebsiella pneumoniae. The combined susceptibility test revealed a significant synergistic effect between ceftazidime–avibactam(CAZ-AVI), and aztreonam(ATM). The infection was successfully treated with a combination of CAZ-AVI, ATM, and fosfomycin. This case represents the first reported instance of sepsis in a premature infant caused by OXA-48-producing Klebsiella pneumoniae in China. The objective of our study is to evaluate the effectiveness and safety of combination therapy in treating CRKP infections in premature infants. We hope that the findings of this study will provide valuable insights for clinicians in their treatment approach.Keywords: OXA-48, Klebsiella pneumoniae, premature infant, ceftazidime–avibactam, aztreonam

Minli Hu,1,&ast; Hao Fang,2,&ast; Yibing Hu,1 Chong Lu,1 Yuan Chen,1 Zhifeng Zhong,3 Hongqi Shi,4 Qunying Wang1 1Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China; 2Department of Traumatology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China; 3Department of Anus & Intestine Surgery, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China; 4Department of Pathology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qunying Wang, Department of Gastroenterology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, People’s Republic of China, Email wqy616717@126.comBackground: Allied disorders of Hirschsprung’s disease (ADHD) exhibit symptoms akin to those of Hirschsprung’s disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa.Case Report: A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient’s symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient’s symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition.Conclusion: Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.Keywords: allied disorders of Hirschsprung’s disease, colonic ulcer, amyloid, intestinal obstruction, colonoscopy biopsy colonic

Yan Chen,&ast; Xiaohuan Huang,&ast; Hongfei Chen, Junru Tong, Lingling Huang, Junyou Su, Li Deng Department of Obstetrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Deng; Junyou Su, Email dengli@gxmu.edu.cn; sujunyou@sr.gxmu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH.Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient’s temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH).Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.Keywords: hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, pregnancy, case report

Chenlu Wang,1,2 Lanxin Li,1,2 Gang Xiao,1– 3 Yuanyuan Chen,1,2 Yingshuo Wang,1,2 Zhimin Chen,1,2 Yunlian Zhou1,2 1Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Yunlian Zhou; Zhimin Chen, Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, No. 3333. Binsheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email zhouyunlian@zju.edu.cn; zmchen@zju.edu.cnPurpose: To explore the clinical characteristics, treatment, and long-term prognosis of mycoplasma pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in children.Patients and Methods: The medical records of 16 children who were diagnosed with MPP associated with PE between January 2016 and January 2023 at Children’s Hospital, Zhejiang University School of Medicine were retrospectively reviewed.Results: The average age patients were 8.24 ± 1.99 years. All cases were diagnosed with refractory mycoplasma pneumoniae pneumonia (RMPP) and presented complications in the form of necrotizing pneumonia (NP). The main symptoms observed were cough and fever (n = 16, 100%), chest pain (n = 8, 50%), dyspnea (n = 8, 50%), and hemoptysis (n = 4, 25%). In these cases, 12 patients had involvement of the pulmonary artery, 3 patients experienced issues with the pulmonary vein, and 1 patient had simultaneous involvement of both the pulmonary artery and pulmonary vein. Among the 12 pulmonary artery embolism cases, 6 involved the right pulmonary artery, 4 involved the left pulmonary artery, and 2 involved both the right and left pulmonary arteries. The mean D-dimer level was 8.50 ± 4.76 mg/L. All patients received anticoagulant therapy, and after treatment, there was a significant improvement in their symptoms and lung lesions.Conclusion: Children with RMPP, chest pain, hemoptysis, and elevated D-dimer levels should be closely monitored for the potential development of PE. The co-occurrence of MPP and PE often involves the presence of NP. In cases of confirmed PE, anticoagulation therapy may be a suitable consideration. PE and NP resulting from MPP generally had a favorable overall prognosis.Keywords: mycoplasma pneumoniae, pulmonary embolism, necrotizing pneumonia, children

Jie Chen,1,&ast; Yan Xiao,2,&ast; Chaofang Yan,1 Xiaoju Li,1 Yafang Zhang,1 Ying Chen,1 Yuan Huang,1 Rui Deng1 1School of Public Health, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Foreign Languages Department, Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Deng; Yuan Huang, Email dengruirita@126.com; huangyuan@kmmu.edu.cnPurpose: With population aging, individuals in underdeveloped areas may experience a higher prevalence of chronic non-communicable diseases (NCDs), a lower level of health-related quality of life (HRQoL), and distinct lifestyles. However, this triadic association remains inadequately studied, particularly regarding the role of health lifestyle. This study aims to examine the relationship between the number of NCDs and HRQoL, while considering the moderating effect of health lifestyle among middle-aged and older adults residing in resource-limited areas.Methods: This cross-sectional study was conducted in Yunnan Province from July to December 2022. Participants completed a self-report questionnaire related to socio-demographic information, NCDs conditions, health lifestyle status, and HRQoL, which was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) scale. Hierarchical regression and simple slope tests were used to examine the moderating effect of health lifestyle.Results: Out of the total 2704 participants, 57.91% presented at least one NCD. The mean scores for health lifestyle and health utility value were 11.109 and 0.944 respectively. The number of NCDs was negatively associated with health utility value, while positively correlated with the health lifestyle score (P< 0.001). The results of hierarchical regression indicated that health lifestyle exerted a negative moderating effect on the relationship between the number of NCDs and HRQoL (β=0.006, P< 0.001), which was also observed for specific health-related behaviors such as sleep duration (β=0.013, P< 0.001), physical examination attendance (β=0.006, P< 0.05) and physical activity (β=0.013, P< 0.001).Conclusion: These findings highlight the crucial role of a healthy lifestyle in attenuating the association between the number of NCDs and HRQoL. Recognizing the potential modulating influence of a healthy lifestyle in this relationship could be pivotal for developing effective interventions for this population, even within resource-constrained rural settings.Keywords: chronic non-communicable diseases, health-related quality of life, health lifestyle, health-related behavior, rural, moderating effect

Yaping Jiang,1,&ast; Yuying Cai,1,&ast; Xin Zhang,1 Li Chen,1 Xingtao Zhou,2 Yihui Chen1 1Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Eye Institute and Department of Ophthalmology, Institute for Medical and Engineering Innovation, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingtao Zhou, Eye Institute and Department of Ophthalmology, Institute for Medical and Engineering Innovation, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, No. 19 Baoqing Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email doctzhouxingtao@163.com Yihui Chen, Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai, 200090, People’s Republic of China, Email 1300089@tongji.edu.cnBackground: Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends.Methods: We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks.Results: From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies.Conclusion: This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.Keywords: laser, bibliometric, research trend, systematic review, CiteSpace

Xinran Yang,1,&ast; Chenglin Yu,2,&ast; Yixin Chen,1 Bin Nian,3 Min Chai,1 Dilimulat Maimaiti,4 Dahai Xu,1 Xiuxian Zang1 1Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 2Department of Emergency Medicine, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 3Department of Ultrasonography, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 4Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dahai Xu; Xiuxian Zang, Department of Emergency Medicine, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130000, People’s Republic of China, Tel +86-15043032548 ; +86-13596097922, Email xudahai0319@jlu.edu.cn; zangxx@jlu.edu.cnAbstract: Hemorrhagic fever with renal syndrome (HFRS), a naturally occurring epidemic disease, is primarily caused by hantaviruses. It frequently involves the lungs and is characterized by symptoms such as fever, hemorrhage, and renal failure. However, the occurrence of acute pancreatitis (AP) in HFRS patients can be neglected, and high intraocular pressure (IOP) is exceedingly uncommon. In this report, we discuss the case of a 30-year-old male who presented with fever, nausea, vomiting, and abdominal pain. Physical examination revealed extremity petechiae rashes and elevated IOP. Laboratory tests indicated coagulopathy and renal failure. A computed tomography scan confirmed AP. Further testing revealed a positive anti-hantavirus IgM antibody. The patient received supportive care, fluid hydration, hemofiltration, mannitol, brinzolamide, and brimonidine to reduce IOP. Three days post-admission, the patient developed shortness of breath and chest pain. Subsequent chest computed tomography revealed pulmonary edema and bilateral pleural effusion. Treatment included oxygen supply, respiratory support, and thoracentesis, with continued hemofiltration. The patient recovered, regaining normal pulmonary and renal functions and normalized IOP. This case underscores the importance of comprehensive evaluations and vigilant monitoring in HFRS patients, particularly measuring IOP in those with visual complaints, to save lives and reduce morbidity.Keywords: hemorrhagic fever with renal syndrome, acute pancreatitis, high intraocular pressure, pulmonary edema

Lirong Li,1,&ast; Yawen Zhang,1,&ast; Weizhong Wang,1 Yanmin Chen,1 Fang He,1 Yan Yu2 1Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Center for Rehabilitation Medicine, Department of Ophthalmology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yu; Fang He, Email yuyan0202@163.com; hetrue@163.comPurpose: Klebsiella variicola has emerged as a human pathogen in the past decade. Here, we present findings related to a K. variicola strain carrying the blaNDM-1 gene, which was isolated from a urinary tract infection in China. Global transmission dynamics and genomic epidemiology of blaNDM-carrying K. variicola were further investigated.Material and Methods: The complete genome sequence of the strain was determined using the Illumina NovaSeq 6000 and Nanopore MinION sequencer. Genomic features and resistance mechanisms were analyzed through diverse bioinformatics approaches. Additionally, genome sequences of K. variicola strains carrying blaNDM were retrieved from the NCBI database, and a comprehensive analysis of the global dissemination trends of these strains was conducted.Results: K. variicola strain 353 demonstrated resistance to multiple antimicrobials, including carbapenems. Within its genome, we identified fourteen antimicrobial resistance genes associated with β-lactam, aminoglycoside, fosfomycin, quinolone, trimethoprim, rifamycin, and sulfonamide resistance. The carbapenem-resistant gene blaNDM-1 was located on an IncU-type plasmid spanning 294,608 bp and flanked by ISCR1 and IS 26. Downstream of blaNDM-1, we identified an Intl1 element housing numerous antibiotic resistance genes. A comprehensive search of the NCBI database revealed 72 K. variicola strains carrying blaNDM from twelve different countries, predominantly from clinical sources, with the highest prevalence observed in the USA and China. A total of 28 distinct sequence types (STs) were identified, with ST115 being the most prevalent, followed by ST60.Conclusion: In summary, this study presents the genomic characterization of a K. variicola strain carrying blaNDM-1 on an IncU-type plasmid. The research highlights the global dissemination of blaNDM-carrying K. variicola, observed in both healthcare settings and natural environments. Our data have revealed a diverse array of antimicrobial resistance determinants in K. variicola, providing valuable insights that could aid in the development of strategies for the prevention, diagnosis, and treatment of K. variicola infections.Keywords: Klebsiella variicola, blaNDM-1, whole-genome sequencing, IncU type plasmid, urinary tract infection

Shi-Hua Yan,1,2 Yong Chen,3 Zhi-Qian Huang,1 Wen-Xi Zhong,1 Xiao-Tian Wang,1 Yang-Can Tang,1 Xu-Yi Zhao,1 Yu-Shan Wu,1 Chun Zhou,4 Wei Zhu,5 Wei Xiao,1,6 Xuan Li,2 Dong-Shu Zhang1,2 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China; 6Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of ChinaCorrespondence: Dong-Shu Zhang, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email nyzds@sina.com Wei Xiao, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China, Email xw7688@smu.edu.cnPurpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen.Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.Keywords: autologous whole blood, acupoint injection, atopic dermatitis, anti-idiotypic immunomodulation, Tregs

Lu Liu,1,&ast; Zili Tang,1,&ast; Qian Zeng,1,&ast; Wenchuan Qi,1 Ziyang Zhou,1 Daohong Chen,1 Dingjun Cai,1– 3 Ying Chen,1 Shiqi Sun,1 Siyao Gong,1 Bin He,1 Shuguang Yu,1– 3 Ling Zhao1– 3 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu City, Sichuan Province, People’s Republic of China; 2Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu, Sichuan, People’s Republic of China; 3Key Laboratory of Acupuncture for Senile Disease (Chengdu University of Traditional Chinese Medicine), Ministry of Education, Chengdu City, Sichuan Province, China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao; Shuguang Yu, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu City, Sichuan Province, 611137, People’s Republic of China, Tel +86 28 6180 0000, Email zhaoling@cdutcm.edu.cn; ysg28588@126.comBackground: Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking.Methods: A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively.Results: EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module–trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB.Conclusion: Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.Keywords: chronic obstructive pulmonary disease, electroacupuncture, intensity, transcriptome profiling, weighted gene co-expression network analysis

Yilin Chen,1,2 Zi Ye,1,2 Haixu Chen,3 Zhaohui Li1,2 1School of Medicine, Nankai University, Tianjin, People’s Republic of China; 2Senior Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 3Institute of Geriatrics, National Clinical Research Center for Geriatrics Diseases, The Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Zhaohui Li, Senior Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email zhaohuili650@hotmail.comAbstract: Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including antioxidants and protein aggregation reversal agents, have attracted great attention in the treatment of cataracts in recent years. Due to the anatomical and physiological barriers of the eye, the effectiveness of traditional eye drops for delivering drugs topically to the lens is hindered. The advancements in nanomedicine present novel and promising strategies for addressing challenges in drug delivery to the lens, including the development of nanoparticle formulations that can improve drug penetration into the anterior segment and enable sustained release of medications. This review introduces various cutting-edge drug delivery systems for cataract treatment, highlighting their physicochemical properties and surface engineering for optimal design, thus providing impetus for further innovative research and potential clinical applications of anti-cataract drugs.Keywords: nanomedicine, cataract, ocular barrier, drug delivery system

Beiying Deng,1,2,&ast; Ying Chen,1,2,&ast; Pengzhan He,1,2,&ast; Yinghui Liu,3 Yangbo Li,1,2 Yuli Cai,4 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email dongweiguo@whu.edu.cnBackground: This study aims to elucidate the role of mitochondrial autophagy in metabolic dysfunction-associated steatohepatitis (MASH) by identifying and validating key mitophagy-related genes and diagnostic models with diagnostic potential.Methods: The gene expression profiles and clinical information of MASH patients and healthy controls were obtained from the Gene Expression Omnibus database (GEO). Limma and functional enrichment analysis were used to identify the mitophagy-related differentially expressed genes (mito-DEGs) in MASH patients. Machine learning models were used to select key mito-DEGs and evaluate their efficacy in the early diagnosis of MASH. The expression levels of the key mito-DEGs were validated using datasets and cell models. A nomogram was constructed to assess the risk of MASH progression based on the expression of the key mito-DEGs. The mitophagy-related molecular subtypes of MASH were evaluated.Results: Four mito-DEGs, namely MRAS, RAB7B, RETREG1, and TIGAR were identified. Among the machine learning models employed, the Support Vector Machine demonstrated the highest AUC value of 0.935, while the Light Gradient Boosting model exhibited the highest accuracy (0.9189), kappa (0.7204), and F1-score (0.9508) values. Based on these models, MRAS, RAB7B, and RETREG1 were selected for further analysis. The logistic regression model based on these genes could accurately predict MASH diagnosis. The nomogram model based on these DEGs exhibited excellent prediction performance. The expression levels of the three mito-DEGs were validated in the independent datasets and cell models, and the results were found to be consistent with the findings obtained through bioinformatics analysis. Furthermore, our findings revealed significant differences in gene expression patterns, immune characteristics, biological functions, and enrichment pathways between the mitophagy-related molecular subtypes of MASH. Subtype-specific small-molecule drugs were identified using the CMap database.Conclusion: Our research provides novel insights into the role of mitophagy in MASH and uncovers novel targets for predictive and personalized MASH treatments.Keywords: metabolic dysfunction-associated steatohepatitis, mitophagy, biomarkers, diagnostic model, machine learning

Jie Liu,1,&ast; Xiajie Huang,1,&ast; Hongjie Su,1 Jie Yu,1 Xinyu Nie,1 Kaibing Liu,1 Wencong Qin,1 Yongxin Zhao,1 Yongfeng Su,1 Xiaocong Kuang,2 Di Chen,3 William W Lu,4 Yan Chen,1 Qikai Hua1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Yulin Campus of Guangxi Medical University, Yulin, Guangxi, People’s Republic of China; 3Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 4Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Qikai Hua, Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email cy003@connect.hku.hk; hqk100@yeah.netPurpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration.Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA.Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001).Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.Keywords: distraction osteogenesis, tibial cortex transverse transport, diabetic foot, HIF-1α, angiogenesis

Qasim Mansoor,1,2 Neda Qurashi,1 Yunzi Chen1 1Department of Ophthalmology, James Cook University Hospital, Middlesbrough, UK; 2Teesside Newmedica Eye Health Clinic & Surgical Centre, Middlesbrough, UKCorrespondence: Qasim Mansoor, James Cook University Hospital, Marton Road, Middlesbrough, Cleveland, TS4 3BW, UK, Email qasim.mansoor@nhs.netSynopsis: High volume cataract lists are cost-effective, reduce waiting times, and facilitate surgical teaching. We propose a stepwise training model that incorporates human factor principles and a reflective pedagogical approach, which has not been documented previously.Background/Aims: Surgical training in ophthalmology is effective when a modular approach is utilised. High volume lists further enhance training by increasing exposure to a newer way of learning and working. We evaluated the efficiency and safety of trainee-assisted cataract surgery across a single NHS eye unit and an independent sector (IS) provider.Methods: We examined results from audits of surgical efficiency and safety in trainee-assisted high-volume lists, including a single-centre comparative evaluation of consultant-only and trainee lists. The quantitative and qualitative information gained from these projects helped us to implement a modular, structured training programme that utilises a reflective cycle of pedagogy, suitable for any grade of trainee.Results: Our projects included an audit following cataract surgery performed by a surgical trainee over a 5-month period, which showed excellent post-op refractive results and no cases of intra-operative and post-operative complications. A single-centre observational study demonstrated comparable surgical throughput and safety results for trainee and solo consultant high volume lists. Systemic and ocular complication rates were reported to be similar for low and medium risk cataract surgery among trainee supervised IS and NHS lists.Conclusion: Cataract surgery outcomes and patient feedback support the effectiveness of the surgical training model. Combining Gibbs’ reflective cycle of critical reflection with the International Council of Ophthalmology’s principles helped us to develop the QM Model of modular teaching for cataract surgery, which we believe is suitable for utilisation in all surgical centres in the NHS and IS settings, for both low volume and high-volume surgical lists regardless of trainee experience.Plain Language Summary: What Is Already Known on This TopicHigh volume lists are increasingly popular for cataract surgery; however, trainee exposure to high flow cataract surgery lists is limited.What This Study AddsA modular approach to training via high volume training lists is possible.Origination and implementation of a stepwise cataract surgery training model that incorporates human factors and a pedagogical learning approach within high volume lists in the independent sector and NHS setting.How This Study Might Affect Research, Practice, or PolicyPromote the widespread adoption of the QM model which integrates modular-based experiential learning approaches for surgical training in both NHS and independent sector settings, applicable to low and high volume surgical lists, irrespective of trainee experience.Keywords: Cataract, surgery, training, education, teaching, pedagogy

Wanqi Gong,1 Jiamei Tang,1 Yang Chen,2 Jing Ma3 1School of Journalism and Communication, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China; 2Health Science Center, Jinan University, Guangzhou, People’s Republic of China; 3The First Affiliated Hospital of Guangzhou Medical University, Department of Gynecology and Obstetrics, Guangzhou, People’s Republic of ChinaCorrespondence: Jiamei Tang, School of Journalism and Communication, Guangdong University of Foreign Studies, No. 1689 Bai Yun Avenue, Guangzhou, 510420, People’s Republic of China, Tel +86 20 39328095, Email tangjiamei@gdufs.edu.cnPurpose: Clinical nursing in obstetrics and gynecology is a technically demanding job. Doctors and nurses have different professional backgrounds and work priorities, and there are differences in communication modes, which can easily lead to poor communication between medical staff and their patients. Therefore this study aims to examine the different communication roles and emphases of obstetrician and gynecologists, nurses and midwives in different sections of SEGUE framework, and further navigate the effectiveness and differences of offline and online provider-patient communication.Participants and Methods: This study employs in-depth interviews to address the research questions. A total of 24 health care providers, including 8 doctors, 5 midwives and 11 nurses, were interviewed face-to-face or by telephone.Results: Doctors pay more attention to the “giving information” stage, while nurses pay more attention to “set the stage” and “elicit information” steps. Midwives and nurses spend more time with patients before and after labor. In addition to information giving, they also accommodate the “understand the patient’s perspective” and “end the encounter” steps. Nurses and midwives would attach greater importance to “understanding of patients’ perspective”. Online medical consultation is more convenient for patients, which can be used as a follow-up complement to offline medical consultation.Conclusion: The health care providers of different types in obstetrics and gynecology communicate collaboratively with patients, highlighting the equally important role of midwives and nurses when communicating with patients. Nurses focus on “set the stage” and “elicit information” stage. Midwife is another important information source and medical care provider, especially for pregnant women in stable conditions. Nutrition clinic of midwife could be recommended for hospitals in second- and third-tier cities, which could help to alleviate obstetricians’ workload. The provision of an online collaborative consultation could be beneficial supplement after face-to-face doctor-patient communication.Keywords: SEGUE framework, physician-patient communication, obstetrician and gynecologist, online health consultation, midwife

Zhenzhu Wu,1 Jie Li,1 Peipei Fang,1 Chenwei Pan,1 Yi Chen2 1Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People’s Republic of China; 2Department of Gastroenterology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Yi Chen; Zhenzhu Wu, Email alivefish1993@qq.com; 15003890524@163.comBackground: The prevalence of pyogenic liver abscess (PLA) is increasing worldwide. However, evaluation on its economic burden is still lack.Methods: A retrospective study that included all patients identified PLA from 2017 to 2020 was conducted. Clinical information and hospital costs were collected through the electronic medical records. We evaluated the economic burden using disability-adjusted life years (DALYs). Differences in socioeconomic burdens between Klebsiella pneumoniae-caused liver abscesses (KPLA) and non-Klebsiella pneumoniae-caused liver abscesses (non-KPLA) were compared.Results: We found 327 patients identified PLA in the study, including 146 with KPLA and 181 with non-KPLA. The demographic characteristics, median hospital stay, severity, and in-hospital mortality were similar between the two groups. The median total in-hospital cost was higher in the non-KPLA than in the KPLA group, although no statistical difference was found (&dollar;3607.2 vs &dollar;3424.6; P = 0.446). The median DALY loss was significantly higher in the KPLA than in the non-KPLA group [1.49 (0.97– 2.30) vs 1.27 (0.87– 1.89); P = 0.033)], and male patients presented a higher average DALY loss than female patients. KPLA had a substantially greater median indirect economic loss than the non-KPLA group [&dollar;1442.8 (915.9– 17,221.5) vs &dollar;1232.5 (764.6– 15,473.0); P = 0.028], and indirect economic loss exhibited a significant increase from 2017 to 2020 in patients with PLA. No differences were found in the socioeconomic burden between the two groups [&dollar;8019.6 (4200.3– 21,832.1) vs &dollar;7436.4 (4023.2– 19,063.9); P = 0.172].Conclusion: The economic burden of PLA is significant, particularly in patients with KP. Patients with KPLA experienced increased DALY loss and indirect economic loss than non-KPLA. PLA must be prioritized as the indirect economic burden rises annually.Keywords: pyogenic liver abscess, Klebsiella pneumoniae, socioeconomic burden, disability-adjusted life years

Jia-Ying Pan,1,&ast; Yuan Chen,1,&ast; Zhi-He Lin,1 Bo Lv,1 Lei Chen,2 Shao-Yan Feng1 1Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shao-Yan Feng, Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No. 52, Meihua East Road, Xiangzhou District, Zhuhai, 519000, People’s Republic of China, Tel +86-13626927889, Email fshaoy@mail.sysu.edu.cn Lei Chen, Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China, Tel +86-13902878497, Email clzzzz@126.com; chenlei63@mail.sysu.edu.cnObjective: Sensorineural Hearing Loss (SNHL) is a representative human sensory impairment, few studies have paid attention to the correlation between the Triglyceride-Glucose (TyG) index and SNHL to date. We conducted this analysis to elucidate the correlation between the TyG index and pure tone hearing thresholds among US adults.Methods: Our analysis included 1226 adults (age range: 20 to 69 years old) from the 2015– 2016 National Health and Nutrition Examination Survey (NHANES) data. TyG index was scored into three quartiles. Weighted univariate analysis, weighted multivariate linear regression analyses as well as smooth curve fittings evaluated the associations between TyG index and pure tone hearing thresholds.Results: In the multiple regression analysis, the second tertile of TyG index was negatively associated with high-frequency hearing thresholds shifts. Furthermore, the non-linear relationships between TyG index and speech-frequency and high-frequency hearing thresholds were identified by smooth curve fittings. After adjusting for potential confounders, the fitted smooth curves were approximately U-shaped, and the two-segment linear regression models were constructed to calculate their inflection points.Conclusion: Our findings suggested that the TyG index was nearly U-shaped association with speech-frequency and high-frequency hearing thresholds. These results may imply the importance of maintaining a balanced TyG index in health management.Keywords: Sensorineural Hearing Loss, triglyceride glucose index, cross-sectional study, National Health and Nutrition Examination Survey

Yue Chen,1,&ast; Aili Gao,1,&ast; Yanan Ke,1 Xin Zhou,1 Li Lin,2 Sha Lu,2 Yumei Liu1 1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Liu, Director of Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, People’s Republic of China, Tel/Fax +86- 20-83593472, Email liuyumei1109@163.comAbstract: Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid–Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.Keywords: protothecosis, Prototheca wickerhamii, terbinafine

Xiaoyue Feng,&ast; Jianli Shang,&ast; Zhengping Gu, Xingyi Luo, Yong Chen, Youting Liu Product Research & Development Center, Beijing Underproved Medical Technology Co., LTD, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youting Liu, Product Research & Development Center, Beijing Underproved Medical Technology Co., LTD, Beijing, 102699, People’s Republic of China, Tel +86 1 851 025 6963, Email YtLiu.adpt@outlook.comAbstract: Lactic acid is the most widely occurring natural organic acid in nature. It not only exhibits mild and safe properties but also possesses multiple physiological activities, such as antibacterial effects, immune regulation, and promotion of wound healing, making it one of the most popular chemical peeling agents. Chemical peels are commonly used in the field of aesthetic dermatology as a non-invasive therapeutic approach. This research aims to provide valuable references for clinical dermatologists by summarizing the characteristics of lactic acid, elucidating its mechanism of action in peeling, and investigating the clinical applications of this compound. Furthermore, it anticipates the potential for lactic acid to be the most suitable chemical peeling agent for Chinese skin.Keywords: lactic acid, physiological activities, clinical applications, Chinese skin

Liuping Cui,1,2 Ran Liu,1 Fubo Zhou,1 Yumei Liu,1 Bing Tian,1 Ying Chen,2,&ast; Yingqi Xing1,3,4,&ast; 1Department of Vascular Ultrasound, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Beijing Diagnostic Center of Vascular Ultrasound, Beijing, People’s Republic of China; 4Center of Vascular Ultrasound, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingqi Xing, Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Beijing, Xicheng District, 100053, People’s Republic of China, Tel +86-18610047846, Email xingyq2009@sina.comPurpose: Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification.Patients and Methods: We recruited 360 patients with ≥ 50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer–Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test.Results: We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666– 0.768) and a Hosmer–Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138– 0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029– 0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617– 0.723) increased the C-statistics (p=0.028).Conclusion: Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥ 50% carotid stenosis.Plain Language Summary: We studied whether using contrast-enhanced ultrasound (CEUS) to detect intraplaque neovascularization could help better determine the risk of ischemic stroke. We compared the combined use of color Doppler ultrasound (CDUS) and CEUS with CDUS alone in patients with more than 50% carotid narrowing. Our findings showed that combining clinical details, CDUS, and CEUS was more effective (0.719 vs 0.672). This means that CEUS provides extra insight when gauging ischemic stroke risk compared with CDUS alone. This could help in accurately identifying patients at high risk of stroke. However, more extensive studies are needed to fully understand the role of these tests in the evaluation of stroke risk. Keywords: atherosclerosis, contrast-enhanced ultrasound, vulnerable plaque, carotid ultrasound

Zhongwei Wen, Yiqiang Chen, Tangjuan Liu, Jiahui Han, Yuting Jiang, Ke Zhang Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Yiqiang Chen, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email chenyiq0708@163.comIntroduction: Respiratory infections are a major global health concern, with Klebsiella pneumoniae standing out due to its evolving antibiotic resistance. This study compares the resistance profiles of hypervirulent Klebsiella pneumoniae (hvKP) and classical Klebsiella pneumoniae (cKP), aiming to shed light on their clinical implications.Methods: We analyzed 86 cases, comprising 42 hvKP and 44 cKP strains, using comprehensive antimicrobial susceptibility testing and clinical data evaluation to assess antibiotic tolerance and resistance mechanisms.Results: Our findings reveal distinct resistance patterns between hvKP and cKP, highlighting the role of chromosomal mutations and plasmid-mediated gene transfer in conferring antibiotic resistance. Notably, hvKP strains exhibited unique resistance trends, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, differing from those of cKP.Discussion: This research underscores the importance of continuous surveillance and the development of targeted therapies against antibiotic-resistant Klebsiella pneumoniae. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat respiratory infections caused by these increasingly resistant pathogens.Keywords: Klebsiella pneumoniae, antibiotic resistance, hypervirulent Klebsiella pneumoniae, hvKP, classical Klebsiella pneumoniae, cKP, public health

Guodong Yang,1– 3 Shuang Zhou,4 Yue Feng,5 Jiaran Lang,1– 3 Yaxin Chen,1– 3 Huipeng Ren1– 3 1Mental Health Center, Hebei Medical University and Hebei Technical Innovation Center for Mental Health Assessment and Intervention, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 4The Sixth People’s Hospital of Hebei Province, Baoding, Hebei, 071000, People’s Republic of China; 5Maternity & Child Care Center of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Huipeng Ren, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renhuipeng@126.comPurpose: In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies.Methods: This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal–Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders.Results: Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P< 0.05).Conclusion: The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.Keywords: hyperuricemia, uric acid, age, psychiatric disorders, bipolar disorder

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

Xiaoguang Xiao,1 Jianhai Sun,2 Dongsheng Zhang,3 Linjun Li,4 Haibo Zhou,5 Yongjun Li,6 Quan Li,7 Zhongshi He,8 Yang Fu,9 Qiwen Duan,10 Guping Zheng,11 Ze Tang,12 Qian Chu,1,&ast; Yuan Chen1,&ast; 1Department of Oncology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Oncology, Hubei Zhongshan Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 4Department of Oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Oncology, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 6Department of Oncology, Yichang Second People’s Hospital, Yichang, Hubei, People’s Republic of China; 7Department of Oncology, Xiangyang Central Hospital, Xiangyang, Hubei, People’s Republic of China; 8Department of Oncology, Xiangyang No 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, People’s Republic of China; 9Department of Oncology, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, Hubei, People’s Republic of China; 10Department of Oncology, Taihe Hospital, Shiyan, Hubei, People’s Republic of China; 11Department of Oncology, Xiaogan Central Hospital, Xiaogan, Hubei, People’s Republic of China; 12Department of Oncology, Huangshi Central Hospital, Huangshi, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Chu; Yuan Chen, Email qianchu@tjh.tjmu.edu.cn; chenyuantj2023@126.comBackground: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain.Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST).Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5– 11.5] hours vs.16.0 [95% CI:11.5– 22.5] hours; p< 0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0– 3.5) than in the oxycontin group.(3.0; 2.5– 4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5– 3.0) vs 4.5;3.0– 6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32).Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p< 0.001), without significantly increasing adverse events (p=0.32).Keywords: cancer pain, opioid titration, oxycontin tablets, hydromorphone, patient-controlled subcutaneous analgesia

Qingzhu Zhang,1,2 Yinhui Yao,3 Yufeng Chen,1 Dong Ren,1 Pengcheng Wang1 1Orthopedic Trauma Service Center, Third Hospital of Hebei Medical University, Major Laboratory of Orthopedic Biomechanics in Hebei Province, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Orthopedics, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, People’s Republic of China; 3Department of Pharmacy, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, People’s Republic of ChinaCorrespondence: Pengcheng Wang, Orthopedic Trauma Service Center, Third Hospital of Hebei Medical University, Major Laboratory of Orthopedic Biomechanics in Hebei Province, Shijiazhuang, Hebei Province, People’s Republic of China, Email zhengzainingmeng@163.comAim: A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens.Methods: Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis.Results: The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA.Conclusion: Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging.Keywords: decision support, knee osteoarthritis, nomogram, predictors, risk factors

Tongtong Zhang,1,&ast; Xincheng Liao,2,&ast; Yuzhi Chen,3,&ast; Xinru Shu,3 Deshan Liu,4 Yusheng Yao3,5 1Department of Anesthesiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 4Department of Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 5Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deshan Liu; Yusheng Yao, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, 134, Dongjie Street, Fuzhou, 350001, People’s Republic of China, Email liudeshan198491@163.com; fjslyys@126.comPurpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons.Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation.Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.Keywords: dexmedetomidine, hyperpolarization-activated cyclic nucleotide-gated channel, intravenous regional anesthesia, lidocaine

Yujian Shao,1,2 Yonglu Chen,2 Mingyue Zhu,3 Yuanyuan Liu,2 Chen Fang,3 Minjun Wang,2 Peng Sun,3 Weiling Fu,2 Jing Huang,3 Shimei Sheng,2 Yanshan Huang2 1Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3First Research Institute, Zhejiang Heze Pharmaceutical Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yanshan Huang, Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China, Email yanshanhuang@doerbio.comIntroduction: Diabetes and obesity are momentous risk factors threatening people’s lives and health. Currently available incretin analogue glucagon-like peptide 1 (GLP-1) possesses huge hypoglycemic effect with the unsatisfactory effect of weight loss. Co-agonists targeting GLP-1R plus glucagon receptor (GCGR) or gastric inhibitory polypeptide receptor (GIPR) show synergistic benefits in glycaemic control and weight loss. Here, we describe a novel dual GIP and GLP-1 receptor agonist, DR10627, and performed a preclinical assessment of it.Methods: The agonistic ability of DR10627 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary (CHO) cells transfected with GLP-1R or GIPR in vitro. The plasma pharmacokinetics of DR10627 were analysed in cynomolgus monkeys. The OGTTs were performed in Sprague‑Dawley (SD) rats. The glucose lowering effects were evaluated by repeated administration of DR10627 in diabetic (db/db) mice for 4 weeks. The effects of anti-obesity and improving metabolism of DR10627 were evaluated by repeated administration of DR10627 in diet-induced obesity (DIO) mice for 57 days.Results: DR10627 had the capacity to activate both GLP-1R and GIPR in vitro. The terminal half-life of DR10627 was found to be approximately 4.19– 5.8 h in cynomolgus monkeys. DR10627 had a great improvement in oral glucose tolerance in SD rats. Moreover, DR10627 had a potent glucose-lowering effect in db/db mice, and the hypoglycemic effect of 18 nmol/kg DR10627 was better than that of 50 nmol/kg liraglutide. In addition, 10 and 30 nmol/kg DR10627 possessed the ability of potentiating the weight-loss, lipid-lowing efficacy and improving metabolism to a greater extent than 80 nmol/kg liraglutide.Conclusion: Preclinical assessment demonstrated that administration of DR10627 resulted in glucose lowering in SD rats and db/db mice, and substantial body weight reduction and metabolism improvement in DIO mice. DR10627 is a promising agent deserving further investigation for the treatment of type 2 diabetes and obesity.Keywords: glucagon-like peptide-1, gastric inhibitory polypeptide receptor, obesity, type 2 diabetes, inflammation

Jianxia Ma,&ast; Ke Wang,&ast; Jun Wang, Qinlian Zeng, Kangwei Liu, Songbai Zheng, Yuanwen Chen, Jianfeng Yao Department of Gastroenterology, Hua Dong Hospital of Fu Dan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Yao, Department of Gastroenterology, HuaDong Hospital of Fu Dan University, No. 221. Road West Yanan, Shanghai, 200040, People’s Republic of China, Tel +8602162483180, Email yjf1966@126.comObjective: The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD.Methods: Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn’s disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis.Results: There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly.Conclusion: There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, gut microbiota, 16S rRNA gene sequencing

Yifu Chen,1– 3 Yu Xia,1,3,4 Menghao Ren,1,3,4 Wei Zheng,2 Xiao Wang,2 Feng Gao2 1Center for Mind and Brain Sciences, Hunan Normal University, Changsha, 410081, People’s Republic of China; 2Hunan Railway Professional Technology College, Zhuzhou, 412001, People’s Republic of China; 3China Research Center for Mental Health Education of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of China; 4Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of ChinaCorrespondence: Feng Gao, Hunan Railway Professional Technology College, Zhuzhou, 412001, People’s Republic of China, Email 542322378@qq.comPurpose: We aim to explore the relationship between overparenting and social avoidance among emerging adults, and the mediating effects of peer attachment and gender differences.Participants and Methods: A total of 1161 Chinese college students completed the questionnaire. The structural equation model was established to validate the main effect model and the mediation model.Results: The results found that both paternal and maternal overparenting positively predicted social avoidance among emerging adults. Both attachment avoidance and attachment anxiety played a significant mediating role in the relationship between paternal overparenting and social avoidance. Attachment anxiety played a significant mediating role in the relationship between maternal overparenting and social avoidance, while, the mediating effect of attachment avoidance was not significant. In addition, gender differences were found in the mediating effects of peer attachment. The mediating effect of attachment anxiety in males’ families had an opposite-gender matching effect, while in females’ families, the mediating effect of attachment avoidance had an opposite-gender matching effect.Conclusion: This study contributes to the understanding of the effects of overparenting on emerging adults, enriching empirical research in related fields.Keywords: overparenting, social avoidance, peer attachment, gender differences, emerging adults

Yingfan Chen,1,2,&ast; Zhenhui Wu,3,&ast; Shaodan Li,2 Qi Chen,2 Liang Wang,2 Xiaorong Qi,1 Chujiao Tian,1 Minghui Yang2 1Medical School of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Traditional Chinese Medicine, the Six Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 3College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghui Yang, Department of Traditional Chinese Medicine, the Six Medical Center, Chinese People’s Liberation Army General Hospital, 6 Fucheng Road, Beijing, 100048, People’s Republic of China, Tel +86-10-66939651, Email ymh9651@sina.comMethods: Related studies on PD and ferroptosis were searched in Web of Science Core Collection (WOSCC) from inception to 2023. VOSviewer, CiteSpace, RStudio, and Scimago Graphica were employed as bibliometric analysis tools to generate network maps about the collaborations between authors, countries, and institutions and to visualize the co-occurrence and trends of co-cited references and keywords.Results: A total of 160 original articles and reviews related to PD and ferroptosis were retrieved, produced by from 958 authors from 162 institutions. Devos David was the most prolific author, with 9 articles. China and the University of Melbourne had leading positions in publication volume with 84 and 12 publications, respectively. Current hot topics focus on excavating potential new targets for treating PD based on ferroptosis by gaining insight into specific molecular mechanisms, including iron metabolism disorders, lipid peroxidation, and imbalanced antioxidant regulation. Clinical studies aimed at treating PD by targeting ferroptosis remain in their preliminary stages.Conclusion: A continued increase was shown in the literature within the related field over the past decade. The current study suggested active collaborations among authors, countries, and institutions. Research into the pathogenesis and treatment of PD based on ferroptosis has remained a prominent topic in the field in recent years, indicating that ferroptosis-targeted therapy is a potential approach to halting the progression of PD.Keywords: Parkinson’s disease, ferroptosis, bibliometric analysis, iron accumulation, alpha-synuclein, mitochondrial dysfunction, oxidative stress, lipid peroxidation

Tao Jiang,1,2 Weijian Chen,3 Chao Lu,1,2 Jiyong Yang,3 Ziquan Zeng,1,2 Wenqiang Li,4 Hongsheng Liu,5 Nana Huang,5 Yuhui Chen,6 Wengang Liu1,2 1Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 2Department of Orthopedics, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 3The Fifth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 4Engineering Technology Research Center for Sports Assistive Devices of Guangdong, School of Sport and Health, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 5Guangdong Huayan Biomedical Science and Technology Center, Guangzhou, 511441, People’s Republic of China; 6Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of ChinaCorrespondence: Wengang Liu, Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Hengfu Road 60, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email liuwengang74@163.com Yuhui Chen, Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China, Email ah1990726@163.comBackground: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy.Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo.Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe’s remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day.Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.Keywords: Cu-HMCe nanozyme, antioxidation, antibacterial, vascularization, wound healing

Jieping Yan,1,2 Xue Zhang,3 Lili Yu,4 Meihua Ye,4 Yun Chen5 1Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, 310014, People’s Republic of China; 3Department of Pharmacy, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China; 4Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 5Cancer Center, Department of Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of ChinaCorrespondence: Jieping Yan, Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou, 310014, People’s Republic of China, Tel +86 571 85893117, Email yanjieping@hmc.edu.cn Yun Chen, Department of Oncology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou, 310014, People’s Republic of China, Tel +86 571 85893609, Email chenyun@hmc.edu.cnAbstract: Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm for which a standardized treatment approach has yet to be established. The prevailing therapeutic strategy typically involves resection followed by adjuvant chemotherapy or radiation. This case report details the long-term follow-up of a 59-year-old Chinese male diagnosed with gallbladder FDCS and liver metastases. The patient received a combination therapy of sintilimab and anlotinib, resulting in a substantial partial response (PR) lasting for a noteworthy duration of 30 months. Notably, this is the first documented instance of gallbladder FDCS with liver metastases being treated with PD-1 antibody and antiangiogenic agents as first-line therapy. These findings suggest that this treatment regimen may offer a potential therapeutic option for patients with gallbladder FDCS and liver metastases, with a duration of PR lasting up to 30 months.Keywords: gallbladder follicular dendritic cell sarcoma, long-term follow-up, PD-1 antibody, antiangiogenic agents, first-line therapy, partial response

Shuling Wang,1,2,&ast; Yuqin Chen,1– 3,&ast; Weidong Li,2,4,&ast; Chunfang Hao,1,2 Li Zhang,1,2 Weipeng Zhao,1,2 Yehui Shi,1,2 Zhongsheng Tong1,2 1Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 2Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, People’s Republic of China; 3Department of Respiratory Center, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, People’s Republic of China; 4Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yehui Shi; Zhongsheng Tong, Email shiyehui@tjmuch.com; tongzhongsheng_on@163.comBackground: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer.Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP).Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p< 0.001), liver metastasis (p< 0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels.Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.Keywords: serum HER2, advanced breast cancer, clinicopathological characteristics, therapeutic efficacy, prognosis

Mengyue Zhang,1 Xiaoxian Zhang,1 Yingrui Yang,2 Yu Weng,3 Xiaojun Chen,1 Yanyan Chen,3 Yinghui Shi3 1School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Nursing, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Nursing, The Eye Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Yanyan Chen; Yinghui Shi, The Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, 270 West Xueyuan Road, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +86 138 5885 5689 ; +86 138 6844 0966, Email cyy@eye.ac.cn; syh@eye.ac.cnBackground: Diabetes distress (DD) is a negative emotion related to diabetes management and a predictor of depression; it affects diabetic retinopathy (DR) patients’ quality of life and disease outcomes. The prevalence of DD was higher in patients undergoing surgery for DR. However, few studies have been conducted on DD in DR surgery patients. The present study aims to investigate the status of DD in DR surgery patients and identify factors associated with DD.Methods: Using a convenience sampling method, 210 DR surgery patients who were admitted to 2 tertiary-level hospitals in Wenzhou City (Zhejiang Province) and Zhengzhou City (Henan Province) from February to June 2023 were selected as research subjects. A questionnaire collecting demographic and disease-related information, the Diabetes Distress Scale, the Summary of Diabetes Self-Management Activities, the Family Care Index Scale, and the Social Support Rating Scale were used to collect data. Statistical analyses included descriptive statistics, t tests, ANOVAs, Pearson’s correlation analyses and stepwise multiple linear regression. This study is reported according to the STROBE guidelines.Results: In total, 156 out of 210 (74.29%) DR surgery patients experienced DD, with an average score of 2.13± 0.63. The results of the stepwise multiple regression analysis showed that residential location, employment status, self-management level, family support, and social support were significantly associated with DD. These variables accounted for 30.6% of the total variation in DD.Conclusions: DR surgery patients exhibit moderate levels of distress. Health care professionals should pay attention to DD in DR surgery patients and develop targeted interventions to improve the self-management ability of these patients, increase their family support and social support to reduce their DD levels.Keywords: diabetic retinopathy, diabetes distress, self-management, family support, social support

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

Haotian Shang, Yanan Chen, Qiulu Wang, Yongliang Yang, Jingyu Zhang Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of ChinaCorrespondence: Jingyu Zhang, Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, No. 41, Hailian East Road, Haizhou District, Lianyungang City, Jiangsu Province, People’s Republic of China, Email zhangjingyu@njmu.edu.cnPurpose: This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab.Patients and Methods: We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People’s Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted.Results: Lower LDH (OR=6.237, 95% CI: 1.625– 23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099– 0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone.Conclusion: LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.Keywords: esophageal squamous cell carcinoma, camrelizumab, immunotherapy, peripheral blood, prognostic index

Yinxi He,1 Yanxia Chen2 1Department of Orthopaedic Trauma, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Yanxia Chen, Department of Endocrinology, the Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email chenyx@hebmu.edu.cnAbstract: As a continuous process comprising bone resorption and formation, bone remodeling, plays an essential role in maintaining the balance of bone metabolism. One type of metabolic osteopathy is osteoporosis, which is defined by low bone mass and deteriorating bone microstructure. Osteoporosis patients are more likely to experience frequent osteoporotic fractures, which makes osteoporosis prevention and treatment crucial. A growing body of research has revealed that exosomes, which are homogenous vesicles released by most cell types, play a major role in mediating a number of pathophysiological processes, including osteoporosis. Exosomes may act as a mediator in cell-to-cell communication and offer a fresh perspective on information sharing. This review discusses the characteristics of exosomes and outlines the exosomes’ underlying mechanism that contributes to the onset of osteoporosis. Recent years have seen a rise in interest in the role of exosomes in osteoporosis, which has given rise to innovative therapeutic approaches for the disease prevention and management.Keywords: exosomes, extracellular vesicles, osteoporosis, osteoblast function, osteoclast function

Xiaoli Zhu,1 Yijun Chen,1 Mingan Zhu,2 Jinxi Hu3 1Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 2Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mingan Zhu, Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Shiyan, Hubei Province, 442000, People’s Republic of China, Tel +86 13872767288, Email 839239972@qq.com Jinxi Hu, Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No. 150 Ximen Road of Linhai, Taizhou, Zhejiang Province, 317000, People’s Republic of China, Tel +86 18257689350, Email hujinxi6886@163.comBackground: Prior research has established an association between small dense low-density lipoprotein cholesterol (sdLDL-C) and dyslipidemia, serving as a significant marker for predicting cardiovascular diseases. Nevertheless, the connection between sdLDL-C and metabolic syndrome (MetS) remains unclear.Methods: This study retrospectively analyzed 23,187 individuals who underwent health checkups at Taizhou Hospital’s health management center. Here, we investigated the relationship between sdLDL-C and MetS, along with its components, utilizing Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, logistic regression, and mediation analysis.Results: The MetS group exhibited significantly higher level of sdLDL-C compared to the non-MetS group (P< 0.001). We observed a strong correlation between sdLDL-C and several key factors: TG (r = 0.711), TC (r = 0.672), LDL-C (r = 0.781), GGT (r = 0.420), and HDL-C (r = − 0.417). After adjusting for age and gender, the odds ratio (OR) (95% confidence interval [CI]) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of sdLDL-C concentration were 2.264 (95% CI: 1.851, 2.770), 4.053 (95% CI: 3.350, 4.903), and 9.034 (95% CI: 7.531, 10.837). The optimal cut-off value for diagnosing MetS using sdLDL-C was determined to be 0.98 mmol/L, with an area under the ROC curve (AUC) of 0.716 (95% CI: 0.705, 0.726). Additionally, mediation analysis revealed that sdLDL-C mediated a 12.8% correlation between GGT and TG concentration.Conclusion: The sdLDL-C is correlated with MetS and it can successfully mediate the relationship between GGT and TG. Our data suggests that sdLDL-c and GGT are suitable parameters for preventing and monitoring MetS.Keywords: metabolic syndrome, small dense low-density lipoprotein cholesterol, mediation analysis, GGT

Liang Tan,1,&ast; Feilong Wang,1,&ast; Yi Huang,2 Chuhua Fu,3 Haijun Zhang,4 Jianfei Feng,5 Yincai Xu,6 Xinzhen Ye,7 Rongrui Tang,8 Yinglian Chen,9 Liansheng Mou,10 Ronghao Li,11 Jingyu Chen,1 Jishu Xian1 1Department of Neurosurgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, The Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Department of Neurosurgery, Xiangyang No.1 People’s Hospital, University of Medicine, Xiangyang, Hubei, People’s Republic of China; 4Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 5Department of Encephalopathy, Beibei Traditional Chinese Medical Hospital, Chongqing, People’s Republic of China; 6Department of Neurosurgery, Zheng Coal General Hospital, Zhengzhou, Henan Province, People’s Republic of China; 7Department of Neurosurgery, Songshan General Hospital, Chongqing, People’s Republic of China; 8Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 9Zhuhai Brainlightning Research Institute, Zhuhai City, Guangdong, People’s Republic of China; 10Department of Neurosurgery, Liangping District People’s Hospital, Chongqing, People’s Republic of China; 11Department of Basic Medicine, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyu Chen; Jishu Xian, Email Cjy1_2001@Hotmail.com; 1370321419@qq.comPurpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs.Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes.Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p> 0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1– 12) vs 4(1– 8), p< 0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p< 0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death.Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients.Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.Keywords: SARS-CoV-2, intensive care unit, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury

Yunpeng Feng,1 Shifeng Qiao,1 Jie Chen,1 Xin Wen,2 Yanlei Chen,3 Xiaoyu Song,1 Jiaxin Xu,1 Xiucheng Qiao,1 Jing Yang,2 Shenshen Zhang,1 Yang Feng,1 Yu Gao4 1The Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 3The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of ChinaCorrespondence: Yu Gao, School of Basic Medical Sciences, Jinzhou Medical University, No. 40, Section 3 Songpo Road, Jinzhou, Liaoning, 121000, People’s Republic of China, Tel +86 15904161717, Email jzykdxgy@163.comPurpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.Keywords: M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis

Jiandong Yang,1 Yaoqin Lu,2 Yanggui Chen,2 Yida Wang,1 Kai Wang3 1School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 2Department of Tuberculosis Control and Prevention, Urumqi Center for Disease Control and Prevention, Urumqi, 830026, People’s Republic of China; 3State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of ChinaCorrespondence: Kai Wang, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China, Email wangkaimath@sina.comObjective: This study aims to analyze the drug resistance spectrum, genetic diversity, and transmission dynamics to provide a basis for the prevention and control of drug-resistant (DR) tuberculosis (TB) epidemics.Methods: This retrospective study is based on routine national drug resistance surveillance. The demographic, epidemiological, and clinical information on DR-TB patients from 2016 to 2021 was collected and used for phenotypic drug susceptibility testing and whole-genome sequencing.Results: It was indicated that L2.2.1 was the dominant lineage in Urumqi. The drug resistance spectrum in Urumqi was narrow, which means more drug combinations can be used for clinical treatment. Furthermore, mutations identification of drug-resistance gene katG, rpoB, embA/B, rrs, rpsL, eis, gyrA/B, folC and tryA are important for clinical drug use. However, mutations in cross-resistance genes rrs have limited guidance for clinical selection of KM, CPM and AK. Moreover, there is an increased risk of cluster transmission of DR-TB, and the difference in clustering rate among L2, L3, and L4 was not statistically significant (χ2 = 2.6410, p = 0.2670).Conclusion: In the Urumqi, DR-TB has a complex prevalence state, a narrow drug resistance spectrum, and a high clustering rate and burden of drug resistance. To reduce the burden of DR-TB, related research should be strengthened, and the development of prevention, control, and treatment strategies should be accelerated.Keywords: Mycobacterium tuberculosis, resistance, whole genome sequencing, transmission dynamics, Urumqi

Ying Chen,1 Tzu-Hsuan Liu,2 Yiwei Xia,3 Zhihao Ma4 1Sports Institute, Huaqiao University, Quanzhou, People’s Republic of China; 2School of Political Science and Public Administration, Huaqiao University, Quanzhou, People’s Republic of China; 3School of Law, Southwestern University of Finance and Economics, Chengdu, People’s Republic of China; 4Computational Communication Collaboratory, School of Journalism and Communication, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Zhihao Ma, Computational Communication Collaboratory, School of Journalism and Communication, Nanjing University, Room 362, Zijin Building, Nanjing University (Xianlin Campus), 163 Xianlin Road, Qixia District, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel +86 17561538460, Email redclass@163.comBackground: This study assesses the psychometric properties of the Chinese version of the Zimbardo Time Perspective Inventory (C-ZTPI-20) in an adolescent population.Methods: The investigation encompasses a sample of 2634 middle school students from China and aims to evaluate the instrument’s reliability, structural validity, measurement invariance, criterion validity, and network structure attributes.Results: First, descriptive analysis revealed satisfactory reliabilities for four out of five C-ZTPI-20 dimensions, with Present Fatalistic (PF) exhibiting relatively low reliability. Moreover, Confirmatory Factor Analysis (CFA) supported the 5-dimensional structure across all samples and sexes, albeit with a modest Tucker-Lewis Index (TLI) for girls. Furthermore, measurement invariance analysis underscores unbiased assessment across sexes. Sex differences emerge in the Present Hedonistic (PH) dimension, where boys showed higher scores. Furthermore, criteria validity analysis revealed that Past Positive (PP) and Future (F) were positively associated with extraversion, agreeableness, conscientiousness, openness, grit, and mental health, while they were negatively associated with neuroticism. Past Negative (PN) and PF showed inverse trends, while PH perspective demonstrated complex, varied correlations with these psychological traits, underscoring the multifaceted nature of time perspectives. Finally, network analysis revealed positive inter-correlations within dimensions and significant edge differences between sexes, particularly in inter-dimension connections. Despite differing rankings, the most central and marginal items remained consistent between boys and girls in network models.Conclusion: These findings contribute to understanding the C-ZTPI-20’s effectiveness in assessing adolescent time perspectives and inform interventions promoting psychological well-being and coping strategies.Keywords: time perspective, Zimbardo Time Perspective Inventory, psychometric properties, measurement invariance, network analysis

Xin Huang, Yueying Chen, Fanglu Zhong, Bin Gui, Yugang Hu, Yuxin Guo, Qing Deng, Qing Zhou Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Qing Zhou; Qing Deng, Department of Ultrasound, Renmin Hospital of Wuhan University, 238&num; Jiefang Road, Wuhan, 430060, People’s Republic of China, Email qingzhou@whu.edu.cn; wudadq@163.comBackground: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types.Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs’ impact.Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells.Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.Keywords: Ce6, nanobubbles, ultrasound, sonodynamic therapy, immunotherapy

Daoda Qi,1,&ast; Yang Chen,1,&ast; Chengyi Peng,1 Yuan Wang,2 Zihao Liang,2 Jingjing Guo,1 Yan Gu1 1Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gu; Jingjing Guo, Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Tel +86 25 83626297, Email guyan703@foxmail.com; guojingjing0017@126.comBackground and Objective: Timely recognition of risk factors for early progression in older adult patients with COVID-19 is of great significance to the following clinical management. This study aims to analyze the risk factors and create a nomogram for early progression in older adult patients with COVID-19 in the Omicron era.Methods: A total of 272 older adults infected with COVID-19 admitted from December 2022 to February 2023 were retrospectively recruited. Risk factor selection was determined using the logistic and the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then created to predict early progression, followed by the internal validation and assessment of its performance through plotting the receiver operating characteristic (ROC), calibration, and decision curves.Results: A total of 83 (30.5%) older adult patients presented an early progression on chest CT after 3– 5 days of admission under standard initiate therapy. Six independent predictive factors were incorporated into the nomogram to predict the early progression, including CRP > 10 mg/L, IL-6 > 6.6 pg/mL, LDH > 245 U/L, CD4+ T-lymphocyte count < 400/μL, the Activities of Daily Living (ADL) score ≤ 40 points, and the Mini Nutritional Assessment Scale-Short Form (MNA-SF) score ≤ 7 points. The area under the curve (AUC) of the nomogram in discriminating older adult patients who had risk factors in the training and validation cohort was 0.857 (95% CI 0.798, 0.916) and 0.774 (95% CI 0.667, 0.881), respectively. The calibration and decision curves demonstrated a high agreement in the predicted and observed risks, and the acceptable net benefit in predicting the early progression, respectively.Conclusion: We created a nomogram incorporating highly available laboratory data and the Comprehensive Geriatric Assessment (CGA) findings that effectively predict early-stage progression in older adult patients with COVID-19 in the Omicron era.Keywords: early progression, CGA, nomogram, COVID-19, omicron era

Ye Liu,1,&ast; Lifan Zhang,1– 4,&ast; Yan Chen,1,&ast; Guiren Ruan,1– 3 Yuchen Liu,1 Shi Chen,1 Lantian Xie,1 Fengying Wu,1 Xiaochun Shi,1– 3 Xiaoqing Liu1– 4 1Division of Infectious Diseases, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Beijing, 100005, People’s Republic of China, Email shixch7722@163.com; liuxq@pumch.cnBackground: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB.Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis.Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61– 93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584– 644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430– 1570], and the incidence density was 240 per 100,000 person-years[95% CI:144– 375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273– 49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122– 7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 − 33.070), anemia (aHR=2.565, 95% CI:1.015– 6.479) and T-SPOT.TB level≥ 300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365– 12.892) were independent risk factors for ATB development in LTBI patients.Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥ 300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.Keywords: latent tuberculosis infection, active tuberculosis, incidence, risk factors

Wenzhen Tang,1 Yuanxi Xie,1 Qingfeng Yan,2 Yanjuan Teng,1 Li Yu,1 Liuying Wei,3 Jinmei Li,4 Yuhui Chen,1 Xiaolin Huang,1 Shaoli Yang,1 Kui Jia1 1The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2The Sanming Second Hospital, Sanming, Fujian Province, 366099, People’s Republic of China; 3Nanning Fourth People’s Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Wanxiu District Chengnan Community Health Service Center, Wuzhou, Guangxi Zhuang Autonomous Region, 543000, People’s Republic of ChinaCorrespondence: Kui Jia, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email 1960728884@qq.comAim: To investigate the current status of experience and support of nurses as second victims and explore its related factors in nurses.Design: A sequential, explanatory, mixed-method study was applied.Methods: A total of 406 nurses from seven tertiary hospitals in China were chosen as participants between September to October 2023. The Chinese version of the Second Victim Experience and Support Questionnaire (SVEST), Somatic Complaints of Sub-health Status Questionnaire (SCSSQ) and Generalized Anxiety Disorder (GAD-7) were applied to collect quantitative data. Eight nurses were selected for a qualitative study through in-depth interviews. Through interpretive phenomenological analysis, the interview data were analysed to explore the experience and support of nurses as second victims.Results: Practice distress (15.74 ± 4.97) and psychological distress (15.48 ± 3.74) were the highest dimensions, indicating Chinese nurses experienced second victim-related practice and psychological distress. Nurses with different gender, age, education, marital status, income, working hours, professional titles, and unit types have different levels of second victim-related experience and support (p