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Xiaorong Ye,1 Bingzhen Li,2 Fang Xu,3 Debiao Pan,4 Jing Wu1 1Department of Anorectal Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 3Department of Gastroenterology, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 4Department of Hepatobiliary Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of ChinaCorrespondence: Bingzhen Li, Department of Gastrointestinal Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China, Email 18957097838@163.comObjective: Delirium is a common complication of acute pancreatitis. Receptor-interacting protein kinase 3 (RIP3) is an activator of programmed cell necrosis. This study aimed to determine its ability to predict delirium after acute pancreatitis.Methods: In total, 297 patients with acute pancreatitis were prospectively enrolled in this study. Patients were divided into two subgroups (study and validation groups: 197 and 100 cases, respectively). Serum RIP3 levels were measured in all patients and in 100 healthy controls. Acute Physiology and Chronic Health Evaluation (APACHE) II, Ranson, and sequential organ failure assessment (SOFA) scores were used for the severity assessment. In-hospital delirium was observed as an outcome variable. Multifactorial analyses were performed to discern severity correlations and outcome associations.Results: Serum RIP3 levels were significantly higher in the patients than in the controls. Serum RIP3 levels had linear relationships under the restricted cubic spline and were independently correlated with APACHE II, Ranson, and SOFA scores. Serum RIP3 levels were linearly correlated with the likelihood of developing in-hospital delirium and exhibited a strong discrimination efficiency under the receiver operating characteristic curve. Serum RIP3 levels, coupled with APACHE II scores, Ranson scores, and SOFA scores, were the four independent predictors of in-hospital delirium. No interactions were revealed regarding its relevance to sex, age, or body mass index in subgroup analysis. These were integrated to form a model graphically represented by a nomogram that showed effective stability, clinical fit, and predictive ability for in-hospital delirium. The model was verified in the validation group.Conclusion: An incremental trend in serum RIP3 levels was notable after acute pancreatitis. Serum RIP3 levels are independently related to illness severity and occurrence of in-hospital delirium, indicating that serum RIP3 may be a potential biomarker of acute pancreatitis.Keywords: acute pancreatitis, delirium, receptor-interacting protein kinase 3, severity

Qingcheng Song,1,2,* Yiran Zhang,3,* Hongzhi Hu,4,* Xuemei Yang,5 Xin Xing,1,2 Jianhua Wu,6 Yanbin Zhu,1,2 Yingze Zhang1,2 1Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Orthopaedic Institution of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China; 4Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China; 6The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingze Zhang; Yanbin Zhu, Email yzling_liu@163.com; 38600312@hebmu.edu.cnIntroduction: Ferroptosis-driven tumor ablation strategies based on nanotechnology could be achieved by elevating intracellular iron levels or inhibiting glutathione peroxidase 4 (GPX4) activity. However, the intracellular antioxidative defense mechanisms endow tumor cells with ferroptosis resistance capacity. The purpose of this study was to develop a synergistic therapeutic platform to enhance the efficacy of ferroptosis-based tumor therapy.Methods: In this study, a multifunctional nano-catalytic therapeutic platform (mFeB@PDA-FA) based on chemodynamic therapy (CDT) and photothermal therapy (PTT) was developed to effectively trigger ferroptosis in tumor. In our work, iron-based mesoporous Fe3O4 nanoparticles (mFe3O4 NPs) were employed for the encapsulation of L-buthionine sulfoximine (BSO), followed by the modification of folic acid-functionalized polydopamine (PDA) coating on the periphery. Then, the antitumor effect of mFeB@PDA-FA NPs was evaluated using Human OS cells (MNNG/HOS) and a subcutaneous xenograft model of osteosarcoma.Results: mFe3O4 harboring multivalent elements (Fe2+/3+) could catalyze hydrogen peroxide (H2O2) into highly cytotoxic ˙OH, while the tumor microenvironment (TME)-responsive released BSO molecules inhibit the biosynthesis of GSH, thus achieving the deactivation of GPX4 and the enhancement of ferroptosis. Moreover, thanks to the remarkable photothermal conversion performance of mFe3O4 and PDA shell, PTT further synergistically enhanced the efficacy of CDT and facilitated ferroptosis. Both in vivo and in vitro experiments confirmed that this synergistic therapy could achieve excellent tumor inhibition effects.Conclusion: The nanotherapeutic platform mFeB@PDA-FA could effectively disrupted the redox homeostasis in tumor cells for boosting ferroptosis through the combination of CDT, PTT and GSH elimination, which provided a new perspective for the treatment of ferroptosis sensitive tumors. Keywords: ferroptosis, chemodynamic therapy, photothermal therapy, Fenton reaction, BSO

Qi Wu,1,* Kexin Liu,2,* Ruijuan Hou,1 Xingxing Wu,3 Xiaoyu Ruan,4 Mao Wang,5 Zhiting Sun,6 Lingchang Meng,6 Guoliang Dai,7 Changyin Li,7 Jing Wu,1,6 Genglin Mu6 1Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Gastroenterology, The 981th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Chengde, Hebei, 067000, People’s Republic of China; 3Department of Gastroenterology, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, 450053, People’s Republic of China; 4Internal Medicine Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 5Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 6Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 7Clinical Pharmacology Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wu, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Institute of Chinese Medicine of Nanjing University, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email wujing@njucm.edu.cnPurpose: Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods: The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results: Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion: These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.Keywords: inflammatory bowel disease, lipid pseudotargeted metabolomics, amino acids targeted metabolomics, Rhizoma Paridis saponins, cytokines

Zhoushu Zheng,1 Lulu Yan,2,3 Lu Ding,1 Yinghui Zhang,1 Meihong Wang,1 Yihui Yang,1 Junhua Wu,3 Changshui Chen,3 Ming Tang,1 Haibo Li2,3 1Department of Otolaryngology Head and Neck Surgery, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 2The Central Laboratory of Birth Defects Prevention and Control, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 3Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Haibo Li, The Central Laboratory of Birth Defects Prevention and Control, Women and Children’s Hospital of Ningbo University, No. 339, Liuting Road, Haishu District, Ningbo City, Zhejiang Province, People’s Republic of China, Email lihaibo-775@163.com Ming Tang, Department of Otolaryngology head and neck surgery, Ningbo Women and Children’s Hospital, No. 339, Liuting Road, Haishu District, Ningbo City, Zhejiang Province, People’s Republic of China, Email tmtm-50@163.comIntroduction: Syndromic hearing loss (SHL) is characterized by distinctive clinical phenotypes as well as genetic and phenotypic heterogeneity. More than 400 species of SHL have been described, the majority of which are autosomal dominant.Methods: 11 forms of SHL were obtained from 14 unrelated families with probands ranging in age from 5 to 78 months. The results of whole exome sequencing(WES), audiological characteristics, middle and inner ear radiological findings, and additional clinical phenotype characteristics were retrospectively analyzed.Results: Fourteen people with SHL were found. Two of them had Waardenburg syndrome, two had Branchio-Oto-Renal syndrome, two had CHARGE syndrome, and one had Treacher Collins syndrome, Kleefstra syndrome, Muenke syndrome, Osteopathia Striata with Cranial Sclerosis, Ayme-Gripp syndrome, Tatton-Brown-Rahman syndrome, Stickler syndrome, or Stapes Ankylosis with Broad Thumbs and Toes. In this investigation, ten variants were first reported.Discussion: The combination of a neonatal hearing screening and WES can diagnose syndrome-type hearing loss in infancy and childhood, according to our findings, expansion of the gene variant spectrum and phenotype for various age groups of SHL is essential and can provide valuable guidelines for clinical intervention decisions. It is imperative for medical practitioners to conduct diligent and prolonged patient monitoring due to the inherent variability in both the auditory impairment and the comprehensive clinical manifestation of SHL.Keywords: syndromic hearing loss, whole exome sequencing, neonatal hearing screening, phenotype-genotype correlations

Minghui Li,1,* Jiabi Wu,1,* Tao Yang,1 Yuhang Zhao,1 Ping Ren,1 Lingling Chang,2 Pilong Shi,1 Jing Yang,1 Yuhang Liu,2 Xiaolei Li,3 Peng Wang,2 Yonggang Cao1 1Department of Pharmaceutics, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Department of Physiology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Pathology, Jiangsu College of Nursing, Jiangsu, 223003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Wang, Department of Physiology, Harbin Medical University, Xinyang Road 39, Gaoxin District, Daqing, Heilongjiang, People’s Republic of China, Email wangpeng810122@126.com Yonggang Cao, Department of Pharmaceutics, Harbin Medical University, Xinyang Road 39, Gaoxin District, Daqing, Heilongjiang, People’s Republic of China, Email caoyonggang@hmudq.edu.cnBackground: Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed.Methods: In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR.Results: We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression.Conclusion: Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.Keywords: neutrophil membrane, ischemia-reperfusion, allicin, cardiac microvascular endothelial cells, ferroptosis

Yanping Wu,1 Yueqin Zheng,1 Sumei Sha,1 Yu Wang,2 Junyan Wang,3 Wei Zhang,4 Yixuan Lu,1 Yan Cheng,1 Jie Wu,5 Bin Qin,1 Yuan Gao6 1Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Gastroenterology, Xi’an Central Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 3Department of Gastroenterology, the Second Affiliated Hospital of Xi ‘an Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 4Department of General Internal Medicine, Staff Hospital of Changqing Oilfield, Xi’an, Shaanxi Province, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 6Department of Gastroenterology, Ankang Central Hospital, Ankang, Shaanxi Province, People’s Republic of ChinaCorrespondence: Bin Qin, Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi Province, 710004, People’s Republic of China, Email qinbin@xjtu.edu.cn Yuan Gao, Department of Gastroenterology, Ankang Central Hospital, Ankang City, Shaanxi Province, 725000, People’s Republic of China, Email gaoyuan015@163.comPurpose: Ischemic colitis appears to be a rare but serious complication of COVID-19. About 33.3% hospitalized COVID-19 patients who underwent endoscopy showed features resembling ischemic colitis. The aim of this prospective study was to describe the symptoms, treatment, and outcomes of these patients, particularly their colonoscopy and histologic findings.Patients and methods: We conducted a prospective study on ischemic bowel disease associated with COVID-19 across four centers from December 2022 to January 2023. All cases were identified through a comprehensive search of electronic medical records for procedure-related data. The initial diagnosis of ischemic bowel disease was confirmed using colonoscopy and biopsy findings. After the patients were discharged, a 12-month follow-up was conducted through regular phone interviews to assess their clinical outcomes.Results: Overall, the study included 3 male patients and 9 female patients (age range, 33– 76 years). Abdominal pain and hematochezia always occurred within 2 weeks after COVID-19 infection (average 5.5 days). Gastrointestinal manifestations did not parallel the severity of COVID-19 infection. The descending colon was the most susceptible segment, which was involved in 10 patients (83.33%). Colonoscopy revealed diffuse redness, edema, bleeding, erosion, and ulceration of the intestinal mucosa, similar to the findings of ischemic colitis, and biopsy revealed crypt atrophy, reduction, and interstitial bleeding. All patients were self-limited without converting to chronic changes in the next 12 months.Conclusion: SARS-CoV-2 infection may induce transient acute colon ischemia within 2 weeks, accompanied by severe clinical symptoms such as acute abdominal pain and hematochezia, which are self-limiting and do not lead to chronic symptoms.Keywords: SARS-CoV-2, lower gastrointestinal bleeding, ischemic colitis, colonoscopy

Tongzuo Liu,1,2,* Jingyi Zhang,1,2,* Zhiqiang Zhao,1 Yingfei Bi,1 Ying Zheng,1 Shuai Wang,1 Xiaohua Dai,3 Jun Li,4 Qian Lin,5 Daimei Ni,6 Chenglong Wang,7 Jianguang Wu,8 Yitao Xue,9 Mingjun Zhu,10 Xianliang Wang,1,* Jingyuan Mao1,* 1Cardiovascular Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 2Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Cardiovascular Department, The First Affiliated Hospital of Anhui University of Chinese Medicine, Anhui, People’s Republic of China; 4Cardiovascular Department, Guang’anmen Hospital of China Academy of Chinese Medicine Science, Beijing, People’s Republic of China; 5Cardiovascular Department, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Cardiovascular Department, Taihe Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Chinese Medicine, Anhui, People’s Republic of China; 7Cardiovascular Department, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 8Cardiovascular Department, Affiliated Hospital of Jiangxi University of Chinese Medicine, Jiangxi, People’s Republic of China; 9Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong, People’s Republic of China; 10Cardiovascular Department, The First Affiliated Hospital of He’nan University of Traditional Chinese Medicine, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingyuan Mao; Xianliang Wang, Cardiovascular Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China, Tel +86-13820498886 ; +86-13920007825, Email jymao@126.com; xlwang1981@126.comBackground: Stable angina pectoris (SAP), as a common type of coronary heart disease (CHD), is characterized by transient retrosternal squeezing pain or suffocation induced by exercise, mood swings, or other stress. Most patients with stable angina pectoris do not benefit from interventional therapy and medication, so optimizing treatment plans has important clinical significance. Jiuxin pill is a Chinese patent medicine developed by Huatuo Chinese Medicine Co. Ltd. (Bozhou, China) to relieve the symptoms of stable angina pectoris (SAP). However, there is a lack of evidence support from high-quality clinical studies.Methods: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 170 patients with SAP were recruited from 11 centers in China. The patients were randomized to either the treatment group (Jiuxin pill, 2 pills, bid) or the control group (Jiuxin pill simulant, 2 pills, bid) without changing the original conventional western medicine. The trial was set up with a run-in period of 7 days, a treatment period of 28 ± 2 days, and a follow-up period of 28 ± 2 days. Total exercise time (TED) in the treadmill test and Seattle Angina Questionnaire (SAQ) scores were set as the main efficacy outcomes, and the 1-minute heart rate recovery (HRR1), metabolic equivalents (METs), maximum ST segment depression, Borg perceived exertion after exercise, the average number of angina attacks per week, usage of nitroglycerin, drug withdrawal and reduction rate, information scoring of four diagnostic methods in traditional Chinese medicine and incidence of major adverse cardiovascular events were set as the secondary efficacy outcomes. Adverse events were monitored throughout the trial.Discussion: In China, the use of Chinese patent medicine in the treatment of stable angina pectoris is more common. This trial evaluated the efficacy and safety of the Jiuxin pill in the treatment of patients with SAP, and the trial results provide high-quality research evidence for its clinical application.Trial Registration: This trial has been registered in the China Clinical Trial Registry on 11 June 2022 (Registration No.: ChiCTR2200060780, https://www.chictr.org.cn/showproj.html?proj=172352).Keywords: traditional Chinese medicine, Jiuxin pill, stable angina pectoris, protocol, randomized controlled trial

Zhongbao Zuo,1,&ast; Jing Wu,1,&ast; Miaochan Wang,1 Rui Wu,2 Xiaojing Zhang,2 Lanlan Hu,1 Huaizhong Cui,1 Ting Feng,3 Aifang Xu,1 Shourong Liu2 1Department of Clinical Laboratory, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China; 2Department of Hepatology, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China; 3Ultrasound Department, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aifang Xu; Shourong Liu, Email 13616500869@163.com; lsr85463990@126.comIntroduction: This study aimed to explore serum HBV pre-genomic RNA (pgRNA) levels and its associated factors among HBV-infected patients in the real world.Methods: This retrospective cohort study was conducted from May 10, 2023, to January 15, 2024. Univariate logistic analysis for positive serum HBV pgRNA was performed first, and variables with statistical significance were included in a multivariate logistic model. A decreasing trend of serum HBV pgRNA and HBV DNA levels was also detected first by univariate logistic regression and then by multivariate logistic regression.Results: 482 patients were included in our analysis at baseline, and 191 patients were followed up. Multivariate logistic regression revealed that positive HBV DNA (AOR: 2.63, 95% CI: 1.46– 4.75, P=0.001), ≥ 1000 hBsAg (AOR: 2.29, 95% CI: 1.08– 4.89, P=0.03), positive HBeAg (AOR: 28.26, 95% CI: 15.2– 52.55, P< 0.001), and ALP (AOR: 1.01, 95% CI: 1.001– 1.02, P=0.03) were positively correlated with positive HBV pgRNA at baseline. Two independent multivariate logistic regression models were constructed for the decreasing trend of serum HBV pgRNA and HBV DNA for the 191 follow-up patients. Results showed that the decreasing trend of HBV pgRNA was positively correlated with positive baseline HBV DNA (AOR: 4.60, 95% CI: 1.84– 11.51, P=0.001), baseline HBsAg ≥ 1000 IU/mL (AOR: 8.74, 95% CI: 1.09– 70.10, P=0.04), and HDL (AOR: 5.01, 95% CI: 1.28– 19.66, P=0.02). The decreasing trend of HBV DNA was positively correlated with positive baseline HBV pgRNA (AOR: 3.80, 95% CI: 2.00– 8.83, P< 0.001) and AST (AOR: 1.06, 95% CI: 1.03– 1.08, P< 0.001).Conclusion: Our study revealed that HBV DNA, HBsAg, HBeAg, and ALP were significantly correlated with positive HBV pgRNA at baseline. The baseline HBV DNA, HBsAg, and HDL were significantly correlated with decreasing levels of HBV pgRNA. A decreasing trend of HBV DNA significantly correlated with patients’ baseline HBV pgRNA and AST.Keywords: chronic hepatitis B, HBsAg, HBV pgRNA, HBV DNA

Huilan Zheng,1 Jingping Wu,2 Jinhong Feng,2 Hongbin Cheng3 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of China; 2Department of Medical Cosmetology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of China; 3Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of ChinaCorrespondence: Hongbin Cheng, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, No. 39, Shierqiao Road, Jinniu District, Chengdu, Sichuan Province, 610075, People’s Republic of China, Email chenghongbin@cdutcm.edu.cnBackground: Skin aging is the most obvious feature of human aging, and delaying aging has become a hot and difficult research topic in aesthetic medicine. The accumulation of dysfunctional senescent cells is one of the important mechanisms of skin aging, based on which a series of anti-aging strategies have been generated. In this paper, from the perspective of cellular senescence, we utilize bibliometrics and research review to explore the research hotspots and trends in this field, with a view to providing references for skin health and aesthetic medicine.Methods: We obtained literature related to this field from the Web of Science Core Collection database from 1994 to 2024. Bibliometrix packages in R, CiteSpace, VOSviewer, Origin, and Scimago Graphica were utilized for data mining and visualization.Results: A total of 2,796 documents were included in the analysis. The overall trend of publications showed a continuous and rapid increase from 2016– 2023, but the total citations improved poorly over time. In this field, Journal of Cosmetic Dermatology, Journal of Investigative Dermatology, Experimental Gerontology are core journals. Kim J, Lee JH, Lee S, Rattan SIS, Chung JH and Kim JH are the core authors in this field. Seoul National University is the first in terms of publications. Korea is the country with the most publications, but USA has the most total citations. Top 10 keywords include: gene-expression, skin, cellular senescence, cell, oxidative stress, antioxidants, in vitro, fibroblasts, mechanism, cancer. Current research trends are focused on neurodegeneration, skin rejuvenation, molecular docking, fibrosis, wound healing, SASP, skin barrier, and antioxidants. The core literature and references reflect topics such as the major molecular pathways in the aging process, and the relationship with tumors.Conclusion: This field of research has been rapidly rising in recent years. Relevant research hotspots focus on oxidative stress, fibroblasts, and senescence-associated secretory phenotype. Anti-aging strategies targeting cellular senescence hold great promise, including removal of senescent cells or attenuation of SASP factors, corresponding to senolytics and senomorphics therapies, respectively.Keywords: cellular senescence, skin aging, aesthetic medicine, senolytic, anti-aging

Xiaojun Zhang,1,&ast; Ying Zhao,2,&ast; Zhaogang Teng,3 Tangyao Sun,3 Jun Tao,3 Jiang Wu,4 Yu Wang,3 Fan Qiu,4 Feng Wang4 1Department of Radiology, Children’s Hospital of Nanjing Medical University, Nanjing, 210018, People’s Republic of China; 2Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China; 3Key Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, 210023, People’s Republic of China; 4Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fan Qiu; Feng Wang, Email qiufan0928@163.com; fengwangcn@hotmail.comIntroduction: Photothermal therapy (PTT) is a promising therapeutic procedure with minimal side effects, which can not only kill tumor directly but also cause immunogenic cell death (ICD). However, most solid tumors, including neuroblastoma, are abundant in fibroblasts, which limit the penetration and delivery of nanoparticles. Losartan is an antihypertensive drug approved by the FDA, and it has been proved to have the effect of breaking down excessive ECM network.Methods: In this study, we investigated the application and potential mechanism of the combination of mesoporous platinum nanoparticles (MPNs) and losartan in the PTT of neuroblastoma by establishing neuroblastoma models in vitro and in vivo.Results: Compared to the MPNs group without 808 nm laser irradiation, Neuro-2a cells pretreated with PTT and losartan showed lower survival rates, increased surface calreticulin, and higher release of HMGB1 and ATP. The group also exhibited the highest anti-tumor efficacy in vivo, with a tumor suppression ratio of approximately 80%. Meanwhile, we found that CD3+ T cells, CD4+ T cells and CD8+ T cells from the peripheral blood of experimental group mice were significantly higher than control groups, and CD8+PD-1+ cells were significantly lower than those in MPNs + Los group and Los + laser group. And the expression of PD-1 and α-SMA in Neuro-2a tumors tissue was reduced. Furthermore, losartan could reduce damage of liver function caused by MPNs and laser treatment.Conclusion: This study demonstrated that losartan-induced fibroblasts ablation increased the penetration of MPNs into tumors. Enhanced penetration allowed PTT to kill more tumor cells and synergistically activate immune cells, leading to ICD, indicating the great promise of the strategy for treating neuroblastoma in vivo. Keywords: photothermal therapy, immunogenic cell death, neuroblastoma, losartan, extracellular matrix

Decai Zeng, Linyan Li, Shuai Chang, Xiaofeng Zhang, Yanfen Zhong, Yongzhi Cai, Tongtong Huang, Ji Wu Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Ji Wu, Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email gxnnwuji@163.comBackground: Despite the efficacy of catheter ablation (CA) as a treatment for non-valvular atrial fibrillation (NVAF), many patients still experience atrial fibrillation (AF) recurrence after CA. This study aimed to evaluate the predictive value of speckle tracking echocardiographic (STE) parameters for AF recurrence post-ablation.Methods: A total of 380 NVAF patients treated with CA at the First Affiliated Hospital of Guangxi Medical University from January 2020 to March 2023 were prospectively recruited. The mean age was 59.4 ± 10.8 years, and 72.1% were male, including 150 patients (39.5%) with persistent AF and 230 patients (60.5%) with paroxysmal AF. STE was used to evaluate baseline left atrial (LA) function before CA within 48h. Over a median follow-up of 9 (interquartile range, 4– 17) months, AF recurrence occurred in 132 patients (34.7%).Results: The recurrence group showed lower left ventricular ejection fraction, LA reservoir strain (LASr), and conduit strain (LAScd), but higher LA stiffness than non- recurrence group (all P < 0.05). Multivariable Cox regression identified LA stiffness and LASr as independent risk factors. Time-dependent ROC analysis showed that LA stiffness (AUC 0.768, 95% CI 0.705– 0.831) and LASr (AUC 0.755, 95% CI 0.691– 0.820) were better at predicting 1-year AF recurrence than other risk factors. For 2-year AF recurrence post-catheter ablation, LA stiffness (AUC 0.866, 95% CI 0.804– 0.928) and LASr (AUC 0.860, 95% CI 0.800– 0.920) also demonstrated superior predictive performance. Kaplan-Meier curves showed a significant difference in AF recurrence rate for patients with LA stiffness > 0.55 and LASr ≤ 24.3% (Log rank P < 0.01).Conclusion: Evaluation of LA function using STE assists in stratifying the risk of AF recurrence in NVAF patients and guiding follow-up management. LASr and LA stiffness are independent predictors of AF recurrence following CA in NVAF patients, and potentially outperforming other morphological parameters.Keywords: non-valvular atrial fibrillation, catheter ablation, speckle tracking echocardiography, atrial fibrillation recurrence

Shuai Chang,1 Xiaofeng Zhang,1 Chenliang Ge,2 Yanfen Zhong,1 Decai Zeng,1 Yongzhi Cai,1 Tongtong Huang,1 Ji Wu1 1Department of Ultrasonic Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Ji Wu, Department of Ultrasonic Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86 15773435752, Email gxnnwuji@163.comPurpose: Left atrial low-voltage areas (LA-LVAs) identified by 3D-electroanatomical mapping are crucial for determining treatment strategies and prognosis in patients with atrial fibrillation (AF). However, convenient and accurate prediction of LA-LVAs remains challenging. This study aimed to assess the viability of utilizing automatically obtained echocardiographic parameters to predict the presence of LA-LVAs in patients with non-valvular atrial fibrillation (NVAF).Patients and Methods: This retrospective study included 190 NVAF patients who underwent initial catheter ablation. Before ablation, echocardiographic data were obtained, left atrial volume and strain were automatically calculated using advanced software (Dynamic-HeartModel and AutoStrain). Electroanatomic mapping (EAM) was also performed. Results were compared between patients with LA-LVAs ≥ 5% (LVAs group) and < 5% (non-LVAs group).Results: LA-LVAs were observed in 81 patients (42.6%), with a significantly higher incidence in those with persistent AF than paroxysmal AF (55.6% vs 19.3%, P

Juan Zhang, Juan Wu, Hongbin Zhang, Jie Li, Hezhou Li Department of Ultrasound, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Hezhou Li, The Third Affiliated Hospital of Zhengzhou University, No. 7 Kangfuqian Street, Erqi District, Zhengzhou City, Henan Province, Email 15517560603@163.comPurpose: To investigate whether fetal prenatal ultrasound, fetal growth rate, and pregnancy outcome statistically differ between women infected with novel coronavirus (COVID-19) in mid-pregnancy and an uninfected control group.Patients and Methods: A retrospective analysis of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and z-scores for each among 46 pregnant women diagnosed with COVID-19 in mid-pregnancy between December 01, 2022 and June 31, 2023 was conducted. A control group included 92 pregnant women negative for COVID-19 during the same period and was also analyzed. To examine fetal growth, rate of increase in BPD, HC, AC, FL, and estimated fetal weight (EFW) between second and third trimester scans were analyzed. In addition, pregnancy outcome, maternal comorbidities, and neonatal prognosis were assessed.Results: The occurrence of gestational diabetes differed significantly between groups, but the fetal growth rate and EFW did not. Similarly, pregnancy outcomes and neonatal prognoses did not differ significantly between groups.Conclusion: Gestational diabetes was a complication that differed between patients with and without COVID-19 in this study. COVID-19 in pregnant women did not affect fetal development. Therefore, these preliminary data suggest that increased fetal monitoring is not necessary for women infected with COVID-19 during the second trimester, and these women should be reassured of the low risk of adverse fetal outcomes.Keywords: novel coronavirus, pregnant women, prenatal fetal growth, pregnancy outcome, ultrasound imaging

Jiahua Wu, Xihua Lin, Xueyao Yin, Zhiye Xu, Nan Wu, Ziyi Zhang, Jiaqiang Zhou,&ast; Hong Li&ast; Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Li; Jiaqiang Zhou, Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, People’s Republic of China, Email srrshnfm@zju.edu.cn; zjq8866@zju.edu.cnPurpose: Metabolic syndrome (MetS) is an increasingly prevalent issue in China’s public health landscape. Few studies have investigated the metabolic syndrome (MetS) in overweight people. We proposed to analyze and contrast the occurrence of MetS in normal-weight and overweight individuals and identify potential indicators for forecasting MetS in adults in Zhejiang Province.Methods: This cohort study included 359 adults aged 40– 65 years and followed up for five years in Zhejiang Province. The study assessed the predictive capabilities of five indicators linked to obesity and lipid levels, namely body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-glucose index (TyGi), and their combined indices (TyG-BMI, TyG-WHtR). The evaluation was done employing the area under the Receiver Operating Characteristic (ROC) Curve (AUC). DeLong test was applied to compare area under different ROC curves.We evaluated the relationships between five variables and MetS using multivariate logistic regression.Results: In normal-weight individuals, the five-year cumulative incidence of MetS was 21.85%, but in overweight people, it was 60.33%. After adjusting for confounding factors, BMI, WHtR, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in normal-weight individuals, while BMI, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in overweight individuals. In normal-weight individuals, the WHtR (AUC=0.738 and optimal threshold value =0.469) and TyG-WHtR (AUC=0.731 and optimal threshold value =4.121) had the larger AUC, which was significantly greater than that of the different three indicators. The TyG-BMI (AUC=0.769 and optimal threshold value = 211.099) was the best predictor of MetS in overweight individuals.Conclusion: The five-year cumulative incidence of MetS in overweight people was approximately triple that of normal-weight people in Zhejiang Province. In the overweight population, the TyG-BMI performed better than the other indices in predicting MetS. WHtR and TyG-WHtR outperformed BMI, TyGi, and TyG-BMI in anticipating MetS in a normal-weight population.Keywords: metabolic syndrome, normal weight, overweight, WHtR, BMI, TyG

Yunuo Zhang,1 Jingna Wu,1 Weiming Chen,2 Xinhong Liang3 1Department of Medical Oncology, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Data Center, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Radiology Department, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Xinhong Liang, Radiology Department, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email xinhong1988liang@163.comObjective: Immune inflammatory response are involved in the development and progression of cancer. However, there are still inconsistent research results on the value of peripheral blood inflammatory indicators for evaluating the efficacy of neoadjuvant therapy (NAT) in breast cancer. The purpose of this study was to investigate the relationship between pretreatment systemic immune inflammatory response index (SII), systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and NAT efficacy in breast cancer.Methods: A retrospective analysis was performed on 326 patients with breast cancer who underwent NAT at Meizhou People’s Hospital from November 2017 to October 2023. Clinicopathological data was collected, including gender, age, body mass index (BMI), hypertension, diabetes mellitus, family history of cancer, TNM stage, and the molecular subtypes of breast cancer. The optimal cutoff values of SII, SIRI, NLR, PLR, and LMR were calculated using receiver operating characteristic (ROC) curve, and the relationship between inflammatory indexes and other clinicopathological features and the efficacy of NAT was analyzed.Results: In this study, 162 (49.7%) breast cancer patients did not respond to NAT and 164 (50.3%) patients responded to NAT. The levels of SII (p=0.002), SIRI (p< 0.001), and NLR (p=0.006) in patients who responded to NAT were significantly higher than those in patients who did not. When the efficacy of NAT was considered as the endpoint of SII, SIRI, and NLR, the critical value of the SII, SIRI, and NLR was 572.53 (under the ROC curve (AUC)=0.598), 0.745 (AUC=0.630), and 2.325 (AUC=0.588), respectively. Logistic regression analysis showed that a high SIRI level (≥ 0.745/< 0.745, OR: 2.447, 95% CI: 1.375– 4.357, p=0.002) was an independent factor associated with the efficacy of NAT in breast cancer patients.Conclusion: High SIRI levels (≥ 0.745) may be an independent factor associated with the efficacy of NAT in patients with breast cancer.Keywords: breast cancer, neoadjuvant therapy, systemic immune inflammatory response index, efficacy

Dong Liu,1,&ast; Jianmin Wu,2,&ast; Han Wang,3 Hui Dong,3 Lei Chen,4 Ningyang Jia1 1Department of Radiology, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200438, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 4The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ningyang Jia; Lei Chen, Email ningyangjia@163.com; chenlei@smmu.edu.cnObjective: To investigate the role of eosinophil counts (EC) in microvascular invasion (MVI) for enhancing the radiomics based diagnostic model. Additionally, its correlation with early recurrence and tumor immune microenvironment was explored.Methods: Propensity score matching was employed to evaluate on 462 cases whether EC was an independent risk factor for MVI. Subgroup analyses examined EC’s effect on MVI across varying hypersplenism degrees. Univariate-multivariate logistic regression identified MVI’s independent factors to develop a diagnostic model. Univariate-multivariate COX regression determined early recurrence factors. Co-detection by indexing (CODEX) constructed the immune score (IS), and Spearman correlation analyzed its association with peripheral immunity.Results: EC was an independent risk factor for MVI (p=0.038, OR=1.304 (95% CI: 1.014– 1.677)), and its effect on MVI disappeared with the severity of hypersplenism. The diagnostic model with EC was significantly improved (AUC=0.787 (95% CI: 0.737– 0.836) vs AUC=0.748(95% CI: 0.694– 0.802, p=0.005)). MVI was an independent risk factor for early recurrence (p< 0.001, HR = 2.254 (95% CI: 1.557– 3.263)). IS was negatively correlated with lymphocyte counts (R=− 0.311, p=0.022), and positively correlated with EC (R=0.301, p=0.027) and RS (R = 0.315, p = 0.018).Conclusion: EC was an independent risk factor for MVI and was related to the tumor immune microenvironment. EC should be included in the diagnosis of MVI to improve diagnostic efficiency.Keywords: hepatocellular carcinoma, eosinophils, radiomics

Dong Wu,1,&ast; Bingyu Long,1,&ast; Bangxiao Huang,1,&ast; Xiaomei Zhong,1 Xiaoer Chen,1 Xiaoping Shen,1 Qiu Huang,1 Wenchao Zhang,1 Jiayuan Wu,2 Min Chen,1 Dongming Li,1 Bin Wu,1 Dong Lv,3 Dan Huang,1 Xuanna Zhao1 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanna Zhao; Dan Huang, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Road, Zhanjiang, Guangdong, 524013, People’s Republic of China, Email 792665234@qq.com; 287538250@qq.comBackground: Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain.Methods: The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI).Results: Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06– 2.29 and OR:2.15, 95% CI 1.51– 2.05) or depression (OR:1.62, 95% CI 1.17– 2.27 and OR: 2.01, 95% CI 1.46– 2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83– 16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77– 24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41– 95.27; RERI: 6.31, 95% CI 1.60– 11.01; AP: 0.8, 95% CI 0.66– 0.94) and depression (SI: 31.31, 95% CI 1.59– 617.04; RERI: 10.44, 95% CI 2.66– 18.23; AP: 0.89, 95% CI 0.8– 0.97).Conclusion: Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.Keywords: anxiety, China, COPD, depression, education, living environment

Xiangan Gong,1,2 Qian Zhao,1,2 Huimin Zhang,1,2 Rui Liu,1,2 Jie Wu,1,2 Nanxin Zhang,3 Yuanxian Zou,1,2 Wen Zhao,1,2 Ran Huo,1,2,4 Rongtao Cui1– 4 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.Keywords: mesenchymal stem cells-derived exosomes, metabolic reprogramming, scar, wound healing, fibroblast

Jing Zhong,1 Hua Zhang,1 Jie Wu,2 Bosen Zhang,2,3 Liubing Lan1,2 1Department of Obstetrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Liubing Lan, Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email lanliubing@126.comObjective: Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM.Methods: A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed.Results: The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥ 30 years old, body mass index (BMI) in early pregnancy≥ 24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥ 30 years old (≥ 30 vs < 30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183– 3.878, p=0.012), BMI≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, OR: 1.887, 95% CI: 1.041– 3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022– 3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046– 7.863, p=0.041) were associated with GDM.Conclusion: Age of pregnant woman ≥ 30 years old, BMI≥ 24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.Keywords: gestational diabetes mellitus, advanced age, overweight, history of adverse pregnancy, history of oral contraceptive use

Bingyang Xu,1 Biao Yu,2 Zining Xu,1 Shuhong Ye,1 Yuxin Qing,1 Hong Sun,3 Bin Zhao,4 Na Wu,5 Jiawen Wu1 1Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Dermatology, Taihe Hospital, Hubei University of Medicine, Shi’yan, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Dermatology, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 5Department of Nursing, Xi’an Jiaotong University Medical School, Xi’an, People’s Republic of ChinaCorrespondence: Jiawen Wu, Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email jiawen702@126.comPurpose: Psoriasis is not yet completely curable, and its etiology and pathogenesis are unclear. Necroptosis, also known as programmed necrosis, is a regulated mode of necrotic cell death. The interaction between inflammatory diseases and necrotic apoptosis has recently attracted significant attention. We explored the molecular mechanisms of necrotic apoptosis-related genes in psoriasis using bioinformatics methods to identify potential biomarkers for psoriasis.Patients and Methods: In this study, we screened psoriasis differentially expressed genes from the datasets GSE13355 and GSE14905 and took intersections with necrotic apoptosis-related genes for the next analysis. We used multiple machine learning algorithms to screen key genes and perform enrichment analysis. In addition, we performed an immune infiltration analysis. Transcription factors were predicted by the R package “RcisTarget”. We also observed the cellular clustering of key genes in different cell types at the single-cell sequencing level. We used real-time fluorescence-based quantitative-polymerase chain reaction, Western blot, and immunohistochemistry to analyze gene expression in clinical samples. We constructed an imiquimod-induced psoriasis-like dermatitis model in mice for further validation.Results: Seven key genes were screened as follows: AIM2, CARD6, HPSE, MYD88, PYCARD, RAI14, and TNFSF10. Enrichment analysis showed that the key genes were mainly involved in inflammatory pathways. Immune infiltration analysis showed significantly higher levels of CD8 T cells, CD4 initial T cells, and CD4 memory-activated T cells in the disease group’s samples than in the normal patients’ samples. The key gene expression in single cells analyzed showed that PYCARD was significantly expressed in keratinocytes. PYCARD was selected for gene expression analysis; the results showed that its expression was significantly elevated in the skin lesion tissues of patients with psoriasis. We also verified that PYCARD might play a vital role in the development of psoriasis skin lesions using animal experiments.Conclusion: PYCARD plays a vital role in psoriasis development and is a potential biomarker for psoriasis.Keywords: necrotic apoptosis-related gene, bioinformatics, inflammatory disease, immune disease

Shandong Jiang,1,2 Libin Hu,1,2 Hang Zhou,1,2 Jianan Wu,1,2 Jiayin Zhou,1,2 Xian Yu,1,2 Gao Chen1,2 1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 2Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, 310016, People’s Republic of ChinaCorrespondence: Gao Chen, Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, 310009, People’s Republic of China, Email d-chengao@zju.edu.cnAbstract: Intracerebral hemorrhage (ICH) is a primary, non-traumatic cerebral event associated with substantial mortality and disability. Despite advancements in understanding its etiology and refining diagnostic techniques, a validated treatment to significantly improve ICH prognosis remains elusive. Exosomes, a subtype of extracellular vesicles, encapsulate bioactive components, predominantly microRNAs (miRNAs), facilitating and regulating intercellular communication. Currently, exosomes have garnered considerable interests in clinical transformation for their nanostructure, minimal immunogenicity, low toxicity, inherent stability, and the ability to traverse the blood-brain barrier. A wealth of studies has demonstrated that exosomes can improve the prognosis of ICH through anti-apoptosis, neurogenesis, angiogenesis, anti-inflammation, immunomodulation, and autophagy, primarily via the transportation or overexpression of selected miRNAs. More importantly, exosomes can be easily customized with specific miRNAs or bioactive compounds to establish delivery systems, broadening their potential applications. This review focuses on the therapeutic potential of exosomes in ICH, reviewing the mechanisms of molecular biology mediated by certain miRNAs, discussing the benefits, challenges, and future prospects in ICH treatment. We hope comprehensive understanding of exosomes based on miRNAs will provide new insights into the treatment of ICH and guide the translation of exosome’s research from laboratory to clinical practice. Keywords: intracerebral hemorrhage, exosomes, extracellular vesicles, microRNAs, stem cells

Kehua Jiang,1 Qing Wang,1 Xiao-Long Chen,1 Xiaodong Wang,1 Xiaoya Gu,1 Shuangshuang Feng,1 Jian Wu,2 Haojie Shang,2 Xiaozhuo Ba,2 Yanlong Zhang,1 Kun Tang2 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Yanlong Zhang, Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China, Email ylzhang3030@163.com Kun Tang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Email tangsk1990@163.comAbstract: Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.Keywords: indoleamine 2, 3-dioxygenase 1, IDO1, IDO1 inhibitors, nanodrugs, nanodelivery, cancer immunotherapy, combination therapy

Zhangnan Sun,1,&ast; Ji Shi,2,&ast; Chaolei Liu,1 Jingjing Zhang,1 Yue Liu,1 Yini Wu,3 Xin Han,3 Hong Dai,3 Jimin Wu,3 Lijun Bo,1 Faxing Wang3 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faxing Wang, Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, No. 15, Dazhong Street, Lishui, Zhejiang Province, 323000, People’s Republic of China, Email wfx2023@wmu.edu.cn Lijun Bo, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email 27901566@hebmu.edu.cnObjective: This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Patients and Methods: This double-blind trial enrolled 80 elderly ERCP patients randomized to receive dexmedetomidine (Group D) or placebo (Group S). Group D received dexmedetomidine at 0.4 μg·kg− 1·h− 1 starting 15 minutes before surgery until completion, along with propofol at 1.5 mg/kg for anesthesia. Group S received saline and propofol in a similar manner. Anesthesia was maintained with dexmedetomidine at 0.4 μg·kg− 1·h− 1 and propofol at 1– 2 mg/kg during surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and on postoperative days 1, 3, and 5. Primary outcome was perioperative neurocognitive disorder (PND) incidence on day 5; secondary outcomes included changes in perioperative IL-6, cortisol, S100-β, hemodynamics, anesthesia parameters, postoperative pain, agitation scores, and adverse events.Results: All 80 patients completed the trial. On postoperative day 5, the cumulative probability of PND incidence was significantly lower in Group D than in Group S (12.5% vs 35%, P=0.018). Group D also had lower levels of IL-6 (F=199.472, P< 0.001), S100-β (F=2681.964, P< 0.001), and cortisol (F=137.637, P< 0.001). Propofol doses were lower in Group D (706.1 ± 202.4 vs 1003.3 ± 203.7, P< 0.001), and bradycardia rates were higher (45% vs 15%, P=0.003), though atropine use did not significantly differ between groups. Group D showed greater stability in mean arterial pressure. Postoperative complications and adverse reactions were similar across groups.Conclusion: Perioperative low-dose dexmedetomidine infusion with propofol in elderly ERCP patients ensures safe and effective monitored anesthesia care (MAC), reducing PND incidence by mitigating peripheral inflammation and stress responses. Long-term follow-up is needed to fully evaluate PND incidence.Keywords: ERCP, PND, dexmedetomidine, elderly patients

Lei Gao,1,2,&ast; Yidi Xu,1,2,&ast; Xixue Zhang,1,2 Zhaoshun Jiang,1,2 Jiajun Wu,1,2 Yanjun Dong,1,2 Ming Li,3 Liang Jin,3 Jianjian Qiu,4 Lijue You,5 Chunhui Qin,6 Weidong Gu1,2 1Department of Anaesthesiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Radiology, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 4Department of Radiation Oncology, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Computer Center, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 6Department of Pain Management, Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Gu, Email hdmz0800@163.comBackground: Performing spinal anaesthesia in elderly patients with ligament calcification or hyperostosis is challenging for novice practitioners. This pilot study aimed to compare the effectiveness of mixed reality-assisted spinal puncture (MRasp) with that of landmark-guided spinal puncture (LGsp) by novice practitioners in elderly patients.Methods: In this pilot study, 36 patients (aged ≥ 65 years) scheduled for elective surgery under spinal anaesthesia by anaesthesiology residents were included. Patients were randomly assigned to the MRasp group (n = 18) or the LGsp group (n = 18). The outcomes included the number of needle insertion attempts, redirection attempts, passes, the rate of successful first-attempt needle insertion, the rate of successful first needle pass, the spinal puncture time, the total procedure time, and the incidence of perioperative complications.Results: The median number of needle insertion attempts was significantly fewer in the MRasp group than in the LGsp group (1.0 vs 2.0, P = 0.023). The proportion of patients with successful first-attempt needle insertion was 72.2% in the MRasp group and 44.4% in the LGsp group (P = 0.176). The incidence of perioperative complications did not significantly differ between the two groups.Conclusion: This pilot study found that novice practitioners made significantly fewer needle insertion attempts in the MRasp group compared to the LGsp group when performing spinal anaesthesia on elderly patients. A future randomized controlled trial (RCT) is warranted to validate its effectiveness.Trial Registration: This trial was registered at https://www.chictr.org.cn/showproj.html?proj=178960 (ChiCTR-IPR-2300068520). Public title: Mixed reality-assisted versus landmark-guided spinal puncture in elderly patients: a randomized controlled pilot study. Principal investigator: Lei Gao. The registration date was February 22, 2023. The date of the first participant enrolment was February 27, 2023.Plain Language Summary: We developed virtual spine-presenting technology and patented optimal trajectory design technology to assist in spinal puncture and reported that the median number of needle insertion attempts was significantly fewer in the mixed reality-assisted spinal puncture group than in the landmark-guided spinal puncture group.Keywords: augmented reality, computer simulation, mixed reality, spinal puncture

Jiankang Wu,1– 4 Yan Chen1– 4 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China; 3Clinical Medical Research Center for Pulmonary and Critical Care Medicine, Changsha, Hunan, People’s Republic of China; 4Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yan Chen, Email chenyan99727@csu.edu.cnAbstract: Extracellular vesicles (EVs) are nanoscale lipid bilayer vesicles released during cell activation, cellular damage, or apoptosis. They carry nucleic acids, proteins, and lipids facilitating intercellular communication and activate signaling pathways in target cells. In non-small cell lung cancer (NSCLC), EVs may contribute to tumor growth and metastasis by modulating immune responses, facilitating epithelial-mesenchymal transition, and promoting angiogenesis, while potentially contributing to resistance to chemotherapy drugs. EVs in liquid biopsies serve as non-invasive biomarkers for early cancer detection and diagnosis. Due to their small size, inherent molecular transport properties, and excellent biocompatibility, EVs also act as natural drug delivery vehicles in NSCLC therapy. Keywords: extracellular vesicles, non-small cell lung cancer, immunity, metastasis, drug, biomarkers

Jing Han,1,2,&ast; Qingxun Meng,1,2,&ast; Taicheng Liu,1,2 Mengru Lv,1,2 Wenxuan Su,1,2 Beibei Liu,1,2 Jiannan Wu1,2 1Department of Oral Implantology, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, 300041, People’s Republic of China; 2Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Han; Jiannan Wu, Department of Oral Implantology, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, 300041, People’s Republic of China, Email hanj0203@163.com; bdxiaosier@163.comBackground: Wound healing has always been a focal point in clinical work. Bacterial infections and immune microenvironment disorders can both hinder normal wound healing. Current wound dressings only serve a covering function. Developing wound dressings with antibacterial and immunomodulatory functions is crucial for aiding wound healing. To address this issue, we have developed a hydrogel with antibacterial and immunomodulatory functions for managing infected wounds.Methods: The present study describes a photo-crosslinked antibacterial hydrogel composed of curcumin, silver nanoparticles-loaded reduced graphene oxide, and silk fibroin methacryloyl for the treatment of infected wounds. The study assessed its antibacterial properties and its capacity to induce macrophage M2 polarization through in vitro and in vivo experiments.Results: The hydrogel demonstrates robust antibacterial properties and enhances macrophage M2 polarization in both in vitro and in vivo settings. Moreover, it accelerates the healing of infected wounds in vivo by stimulating collagen deposition and angiogenesis.Conclusion: Overall, this hydrogel shows great potential in managing wound infections. Keywords: infected wound healing, silk fibroin methacryloyl, curcumin, silver nanoparticles-reduced graphene oxide, immunomodulation, antibacterial

Yan Wang,1,2,&ast; Fengmei Li,1,2,&ast; Shanshan Wei,1,2,&ast; Wenqun Li,1,2 Junyong Wu,1,2 Shengnan Li,1,2 Xiongbin Hu,1,2 Tiantian Tang,1,2 Xinyi Liu1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institution of Clinical Pharmacy, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-731-8529-2095, Email liuxinyi128@csu.edu.cnPurpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury.Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury.Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size.Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.Keywords: mitochondrial targeting, triphenylphosphonium cations, puerarin, ischemic myocardium-targeting peptide, liposomes

Zhuoran Li,1,&ast; Yirui Zhai,1,&ast; Fan Wu,2,&ast; Dayong Cao,2,&ast; Feng Ye,3,&ast; Yan Song,4 Shulian Wang,1 Yueping Liu,1 Yongwen Song,1 Yuan Tang,1 Hao Jing,1 Hui Fang,1 Shunan Qi,1 Ningning Lu,1 Ye-Xiong Li,1 Jianxiong Wu,2 Bo Chen1 1State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 3Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 4Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Chen, State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87788280, Email chenboo@outlook.com Jianxiong Wu, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87781700, Email Dr_wujx@163.comPurpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30– 65 Gy for planning target volume and 40– 65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level > 1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588– 20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027– 0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.Keywords: liver cancer, immunotherapy, systemic therapy, radiation therapy

Na Zhang,1,&ast; Xinru Chen,1,&ast; Tianhui Ye,1 Hongping Ge,1 Xiaoli Zhai,2 Jun Wu,1 Min Zhang,1 Meiyan Wang1 1Department of Dermatology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 2Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Zhang, Department of Dermatology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No. 365 Renmin East Road, Jinhua, 321000, People’s Republic of China, Tel +86 18757806099, Email sallyzhang1986@163.comAbstract: Verrucae vulgaris are highly contagious keratotic lesions occurring on the skin caused by human papillomavirus. Generally, verrucae vulgaris are harmless to the body, but when they occur in specific areas such as the face or soles of the feet, they can profoundly impact an individual’s quality of life and necessitate therapeutic intervention. Although several pharmacological and physical topical treatments are available, the results are often unsatisfactory in terms of efficacy and cosmetic outcome. Verrucae which typically occur widely on the face are usually Verrucae Planae. When Verrucae vulgaris does occur, it usually presents as single or occasional multiple lesions, rather than covering almost the entire face. In immunocompromised situations, verruca vulgaris can exhibit rare proliferative behavior. In this report, we present a 17-year-old male adolescent who was successfully treated for generalized facial verrucae vulgaris by using a combination of curettage and photodynamic therapy (PDT). The patient’s prolonged use of topical corticosteroids and tacrolimus ointment on the face for eczema over several years is believed to have led to a localized immunosuppressive state of the facial skin, which is considered a significant factor in the outbreak of verrucae vulgaris. Additionally, the patient has a history of acne and frequently scratched face. The appearance of the Koebner phenomenon following scratching is considered another potential reason. This treatment achieved complete resolution and improved the patient’s pre-existing acne problem, resulting in a satisfactory cosmetic outcome without any notable adverse effects or recurrence during the follow-up period. This highlighted that pre-treatment with curettage before PDT enhanced the efficiency of verrucae vulgaris treatment and reduced the cost.Keywords: photodynamic therapy, curettage, verruca vulgaris, adolescent, cosmetic

Zijun Liu,1,&ast; Tianhao Bao,2 Zhilan Yang,2,&ast; Ye Ruan,2 Changqing Gao,2 Jie Wu2 1The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Wu, Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan, 650224, People’s Republic of China, Email wujie@kmmu.edu.cn Tianhao Bao, Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan, 650224, People’s Republic of China, Email Doctor@kmmu.edu.cnObjective: Based on Conservation of resources theory, process model of emotion regulation and attachment theory, the present study examined how psychological capital affects anxiety through the mediation of emotion regulation strategies and explored the moderating role of parent-child relationship.Methods: Using a longitudinal study method, 962 college students were surveyed twice at one-year intervals.Results: (1) College students’ emotion regulation strategies (including cognitive reappraisal and expressive suppression) partially mediated psychological capital and anxiety mood; (2) parent-child relationship moderated the pathways of psychological capital and expressive suppression on anxiety, respectively.Conclusion: College students with higher levels of parent-child relationship had stronger predictive effects of psychological capital and weaker predictive effects of expressive suppression on anxiety mood. The research findings clarify the combined effects of emotion regulation and parent-child relationships on anxiety among college students, providing valuable reference for the design and implementation of interventions to promote individual psychological well-being.Keywords: psychological capital, emotion regulation strategies, anxiety, parent-child relationship

Xu Yang,1,&ast; Jianwei Wu,1,&ast; Longlong Fan,2 Binghua Chen,3 Shiqiang Zhang,4 Wenzhong Zheng1 1Department of Urology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China; 3Department of Urology, Pingtan Branch of Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 4Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhong Zheng, Department of Urology, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian Province, 200001, People’s Republic of China, Email wenzhong_zheng@yeah.net Shiqiang Zhang, Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 628, Zhenyuan Road, Guangming Dist, Shenzhen, 518107, People’s Republic of China, Email zhangshq55@mail.sysu.edu.cnBackground: The involvement of cytotoxic CD4+ T cells (CD4+ CTLs) and their potential role in dictating the response to immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC) remains an unexplored area of research.Methods: Utilizing single-cell RNA sequencing, we analyzed the immunophenotype and expression patterns of CD4+ T lymphocyte subtypes in mRCC patients, followed by preliminary validation via multi-immunofluorescent staining. In addition, we obtained a comprehensive immunotherapy dataset encompassing single-cell RNA sequencing datasets and bulk RNA-seq cohorts from the European Genome-Phenome Archive and ArrayExpress database. Utilizing the CIBERSORTx deconvolution algorithms, we derived a signature score for CD4+ CTLs from the bulk-RNA-seq datasets of the CheckMate 009/025 clinical trials.Results: Single-cell analysis of CD4+ T lymphocytes in mRCC reveals several cancer-specific states, including diverse phenotypes of regulatory T cells. Remarkably, we observe that CD4+ CTLs cells constitute a substantial proportion of all CD4+ T lymphocyte sub-clusters in mRCC patients, highlighting their potential significance in the disease. Furthermore, within mRCC patients, we identify two distinct cytotoxic states of CD4+ T cells: CD4+GZMK+ T cells, which exhibit a weaker cytotoxic potential, and CD4+GZMB+ T cells, which demonstrate robust cytotoxic activity. Both regulatory T cells and CD4+ CTLs originate from proliferating CD4+ T cells within mRCC tissues. Intriguingly, our trajectory analysis indicates that the weakly cytotoxic CD4+GZMK+ T cells differentiate from their more cytotoxic CD4+GZMB+ counterparts. In comparing patients with lower CD4+ CTLs levels to those with higher CD4+ CTLs abundance in the CheckMate 009 and 25 immunotherapy cohorts, the latter group exhibited significantly improved OS and PFS probability.Conclusion: Our study underscores the pivotal role that intratumoral CD4+ CTLs may play in bolstering anti-tumor immunity, suggesting their potential as a promising biomarker for predicting response to ICIs in patients with mRCC.Keywords: single-cell analysis, granzyme K and granzyme B, cytotoxic CD4+ T cells, immune checkpoint inhibitors, renal cell carcinoma

Xiaorong Qin, Hongyan Li, Jianqiu Wu, Weiyan Tang, Wenjuan Li, Kejin Li Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People’s Republic of ChinaCorrespondence: Hongyan Li, Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42, Baiziting, Xuanwu District, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel/Fax +86-025-83284611, Email drlihongyan12@163.comPurpose: Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5‐AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms.Patients and Methods: A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8+ T cells cytotoxicity was evaluated by LDH cytotoxicity kit.Results: In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8+ T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8+ T cells increased. These effects were mitigated by miR-503-5p inhibitors.Conclusion: PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.Keywords: PGM5-AS1, miR-503-5p, DLBCL, immune escape

Yue Lu,1– 3,&ast; Simin Pan,4,&ast; Wenzhen Li,5 Yao Qi,6,7 Li Li,1– 3 Yu-Hong Yan,1– 3 Jianan Wei,1– 3 Dan-Ni Yao,1– 3 Jingjing Wu,1– 3 Hao Deng,1– 3 Shuyan Ye,1– 3 Haiming Chen,1– 3 Qubo Chen,1– 3 Hengjun Gao,6,7 Ling Han,1– 3 Chuanjian Lu1– 3 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5The Clinical College of Acupuncture Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6Shanghai Molecular Medicine Engineering Technology Research Center, Shanghai, People’s Republic of China; 7Shanghai National Engineering Research Center of Biochip, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Han; Chuanjian Lu, Email linghan99@gzucm.edu.cn; lcj@gzucm.edu.cnBackground: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.Keywords: PSORI-CM01, Psoriasis vulgaris, MicroRNA expression profile, network pharmacology, autophagy

Yuping Zhu,1 Xunfu Lai,1 Mengting Wang,2 Xin Tang,1 Tianyi Wan,3 Bin Li,1 Xiaoming Liu,1 Jialin Wu,1 Lei He,1 Yulin He1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Radiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Yulin He, Department of Radiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 0791 8869 3802, Email ndyfy02171@ncu.edu.cnObjective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks.Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters.Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p< 0.01 and cluster-level p< 0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=− 4.93, p=0.017), Hamilton Anxiety Scale (r=− 0.46, p=0.027), and Hamilton Depression Scale (r=− 0.563, p< 0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p< 0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters.Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.Keywords: toothache, independent component analysis, resting-state networks, Granger causality

Xiaoling Zhou,1,2 Jing Wu,3 Ying Liu,3 Yuzhong Yan,2 Geyao Zhou,1 Ming Li1,4 1School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, People’s Republic of China; 2Research Department, Shanghai University of Medicine&Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 3School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Party Committee office, Tongji University Affiliated Shanghai East Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ming Li; Geyao Zhou, Email liming1070202306@163.com; zhougeyao@163.comBackground: The health status of the occupational population is critical to the development of countries and regions as it is the main force of social and economic development. However, there is a dearth of comprehensive and systematic indicators to evaluate the health of occupational groups. This study aimed to construct a multi-dimensional evaluation index system for the general population.Methods: This study combined a literature review and initially established a multidimensional health system framework for the occupational population based on health ecology theory and then used two rounds of Delphi expert consultation to construct the final multidimensional health index system for the occupational population. Fifteen experts from related fields were selected for two rounds of Delphi expert consultation.Results: The recovery rates of the two rounds of expert questionnaires were 100.00% and 93.33% respectively, the expert authority coefficient were 0.90, and the Kendall’s coordination coefficients of the first and second level indexes were 0.32 and 0.42 (P ≥ 0. 001). The final index system includes four primary indicators (individual characteristics, health knowledge, health behavior, and health skills), 13 second-level indicators, and 41 third-level indicators; the weight coefficients of the four primary health dimensions are relatively close, and the “health knowledge” is slightly higher.Conclusion: The multi-dimensional health index system of the occupational population established in this study is comprehensive and reasonable from the perspective of health ecology, which can provide a solid foundation for the further development of a comprehensive health status prediction model for the occupational population.Keywords: health ecology, delphi method, multidimensional health, index system

Leonardo Kapural,1 Jim Melton,2 Billy Kim,3 Priyesh Mehta,4 Abindra Sigdel,5 Alexander Bautista,6 Erika A Petersen,7 Konstantin V Slavin,8,9 John Eidt,10 Jiang Wu,11 Said Elshihabi,12 Jason Matthew Schwalb,13 H Edward Garrett Jr,14 Elias Veizi,15 Giancarlo Barolat,16 Ravi R Rajani,17 Peter C Rhee,18 Maged Guirguis,19 Nagy Mekhail20 1Carolinas Pain Institute and Center for Clinical Research, Winston-Salem, NC, USA; 2Department of Vascular Surgery, Cardiovascular Health Clinic, Oklahoma City, OK, USA; 3Department of Vascular Surgery, The Surgical Clinic, Nashville, TN, USA; 4Department of Pain Medicine, Meta Medical Research Institute, Dayton, OH, USA; 5Department of Surgery, University of Louisville, Louisville, KY, USA; 6Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA; 7Department of Neurosurgery, University of Arkansas, Little Rock, AR, USA; 8Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA; 9Department of Neurology, Jesse Brown VA Medical Center, Chicago, IL, USA; 10Department of Vascular Surgery, Baylor Scott and White Heart and Vascular Hospital Dallas, Dallas, TX, USA; 11Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle, WA, USA; 12Department of Neurosurgery, Legacy Brain & Spine Surgical Center, Atlanta, GA, USA; 13Department of Neurosurgery, Henry Ford Medical Group, Detroit, MI, USA; 14Department of Vascular Surgery, University of Tennessee-Memphis, Memphis, TN, USA; 15Department of Pain Medicine, VA Northeast OH Healthcare System, Cleveland, OH, USA; 16Department of Neurosurgery, Barolat Neuroscience, Presbyterian/St Luke’s Medical Center, Denver, CO, USA; 17Department of Vascular Surgery, Emory University and Grady Memorial Hospital, Atlanta, GA, USA; 18Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; 19Department of Interventional Pain Management, Ochsner Health System, New Orleans, LA, USA; 20Department of Pain Management, Cleveland Clinic, Cleveland, OH, USACorrespondence: Leonardo Kapural, Carolinas Pain Institute and Center for Clinical Research, 145 Kimel Park Dr &num;330, Winston-Salem, NC, 27103, USA, Email lkapuralmd@gmail.comPurpose: This multicenter, randomized, double-blinded, active sham-controlled pivotal study was designed to assess the efficacy and safety of high-frequency nerve block treatment for chronic post-amputation and phantom limb pain.Patients and Methods: QUEST enrolled 180 unilateral lower-limb amputees with severe post-amputation pain, 170 of whom were implanted with the Altius device, were randomized 1:1 to active-sham or treatment groups and reached the primary endpoint. Responders were those subjects who received ≥ 50% pain relief 30 min after treatment in ≥ 50% of their self-initiated treatment sessions within the 3-month randomized period. Differences between the active treatment and sham control groups as well as numerous secondary outcomes were determined.Results: At 30-min, (primary outcome), 24.7% of the treatment group were responders compared to 7.1% of the control group (p=0.002). At 120-minutes following treatment, responder rates were 46.8% in the Treatment group and 22.2% in the Control group (p=0.001). Improvement in Brief Pain Inventory interference score of 2.3 ± 0.29 was significantly greater in treatment group than the 1.3 ± 0.26-point change in the Control group (p = 0.01). Opioid usage, although not significantly different, trended towards a greater reduction in the treatment group than in the control group. The incidence of adverse events did not differ significantly between the treatment and control groups.Conclusion: The primary outcomes of the study were met, and the majority of Treatment patients experienced a substantial improvement in PAP (regardless of meeting the study definition of a responder). The significant in PAP was associated with significantly improved QOL metrics, and a trend towards reduced opioid utilization compared to Control. These data indicate that Altius treatment represents a significant therapeutic advancement for lower-limb amputees suffering from chronic PAP.Keywords: post-amputation pain, phantom limb pain, neuromodulation, peripheral nerve stimulation, high-frequency nerve block

Jingliang Wu,1,&ast; Qiao Lu,1,2,&ast; Jialin Zhao,3,&ast; Wendi Wu,3 Zhihua Wang,1 Guohua Yu,4 Guixiang Tian,2 Zhiqin Gao,2 Qing Wang5 1School of Medicine, Weifang University of Science and Technology, Weifang, 262700, People’s Republic of China; 2School of Life Science and Technology, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 4Department of Oncology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 5Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China, Tel +86 158 6362 6389, Email wfwq8899@163.comPurpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro “condition medium of fibroblasts + MCF-7” cell model and in vivo “ 4T1/NIH-3T3” co-implantation mice model were established to evaluate the anti-tumor effect of drugs.Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.Keywords: drug delivery, cancer-associated fibroblasts, glucocorticoids, combination therapy

Ziyu Zhu,1,2,&ast; Jiabao Wu,1,2,&ast; Wenjun Chen,1– 3 Fei Luo,1,2 Xia Zhao1,2 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Jiangsu Key Laboratory of Children’s Health and Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Liyang Branch of Jiangsu Provincial Hospital of Chinese Medicine, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Zhao, Jiangsu Key Laboratory of Children’s Health and Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Tel +13915994006, Email zhaoxiahy@njucm.edu.cnPurpose: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by recurrent coughing, a prevalent cause of chronic cough in children and adults. As a unique form of asthma, researchers have recently become increasingly interested in developing effective diagnostic and treatment methods. Currently, there has been no bibliometric analysis in CVA. Therefore, this study aims to enrich this knowledge network by examining the current development status, research focal points, and emerging trends in this field.Methods: Articles and reviews on CVA published between 1993 and 2022 were collected from the Web of Science Core Collection (WoSCC) database. Relevant data from the reports were extracted, and collaborative network analysis was performed using CiteSpace and VOSviewer software.Results: 772 articles were included in this study, indicating a significant increase since 2019. The countries with the highest output are China, Japan. The Journal of Asthma and Pulmonary Pharmacology Therapeutics emerged as the most prolific journals in this field. Keyword analysis revealed 22 clusters, highlighting airway inflammation, airway hyperresponsiveness, and eosinophil as the main focus and frontier of research on CVA.Conclusion: From the visual analysis results, the research of CVA is still in the development stage, and there is no unified definition of pathogenesis, diagnostic criteria and treatment strategies. Therefore, researchers and teams should actively carry out cross-institutional and cross-regional cooperation, expand cooperation areas, and carry out high-quality clinical research in the future.Keywords: Citespace, VOSviewer, keywords, hotspots

Jufei Wu,1,&ast; Jishi Wu,2,&ast; Yan Zhou,3 Xiaohua Lu,4 Wane Zhao,4 Fengmei Xu1 1Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of General Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhou, Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email 992054881@qq.com Xiaohua Lu, Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email yhlu@163.comPurpose: To develop a prediction model for hypoglycemia in type 2 diabetes mellitus (T2DM) patients treated with an insulin pump during enteral nutrition.Methods: This retrospective study included T2DM patients treated with an insulin pump during enteral nutrition at the First Affiliated Hospital of Jinan University, Guangzhou Red Cross Hospital, Foshan First People’s Hospital, and Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2016 and December 2023. The patients were randomized 3:1 to the training and validation sets. The risk factors for hypoglycemia were analyzed. A prediction model was developed.Results: This study included 122 patients, and 57 patients had at least one hypoglycemic event during their hospitalization (46.72%). The multivariable logistic regression analysis showed that the time to reach the glycemic targets (odds ratio (OR)=1.408, 95% confidence interval (CI)=1.084– 1.825, P=0.006), average glycemia (OR=0.387, 95% CI=0.233– 0.643, P=0.010), coronary heart disease (OR=0.089, 95% CI=0.016– 0.497, P< 0.001), and the administration of hormone therapy (OR=6.807, 95% CI=1.128– 41.081, P=0.037) were independently associated with hypoglycemia. A nomogram was built. The receiver operating characteristics analysis showed that the area under the curve of the model was 0.872 (95% CI=0.0.803– 0.940) for the training set and 0.839 (95% CI=0.688– 0.991) in the validation set.Conclusion: A nomogram was successfully built to predict hypoglycemia in T2DM patients treated with an insulin pump during enteral nutrition, based on the time to reach the glycemic targets, average glycemia, coronary heart disease, and the administration of hormone therapy.Keywords: T2DM, hypoglycemia, enteral nutrition, insulin pump therapy, nomograms

Lini Chen,&ast; Weiyong Qin,&ast; Jiangdong Wu, Guilin Zhao, Xiaoqing Jiang, Minghui Li, Zijin Huang,&ast; Xueke Du&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijin Huang; Xueke Du, Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 of Daxue East Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86-13768114848 ; Tel +86-17307711159, Email batistuta921@163.com; duxueke@gxmu.edu.cnPurpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients.Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15– 0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0– 2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3– 1.0 mg·kg− 1·h− 1 and propofol was injected IV at a dose of 1– 12 mg·kg− 1·h− 1 in Group R, propofol was injected IV at a dose of 3– 12 mg·kg− 1·h− 1 in Group P. All patients have the same remaining anesthesia durgs.Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05).Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.Keywords: remimazolam, propofol, general anesthesia, kidney transplant

Jianing Tang,1,2,&ast; Yuexin Luo,1,2,&ast; Qirui Wang,1,2 Juntao Wu,1,2 Yulong Wei1 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2First Clinic School, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulong Wei, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, People’s Republic of China, Email yulongwei_HUST@163.comAbstract: As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.Keywords: stimulus response, delivery system, intervertebral disc degeneration, biomaterial

Si Liu, Dan Yang, Wen Li, Qiuping Chen, Danni Lu, Liang Xiong, Junjie Wu, Hui Ao, Lihua Huang State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaCorrespondence: Lihua Huang; Hui Ao, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email huanglihua@cdutcm.edu.cn; aohui2005@126.comPurpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer’s disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas).Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.Keywords: polygala tenuifolia, PI3K/AKT/NF-κB, gut microbiota, inflammation, intestinal injury

Qiaomin Xu,1 Xintong Zou,2 Jimin Wu,1 Gongchen Duan,1 Haiyan Lan,1 Liangrong Wang2 1Department of Anesthesiology, Lishui People’s Hospital, Lishui, 323000, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Liangrong Wang, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Road, Lucheng District, Wenzhou City, Zhejiang Province, 325000, People’s Republic of China, Tel +86 13587884540, Email arerong1984@126.comBackground: Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough.Patients and methods: Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 μg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period.Results: The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05).Conclusion: Pretreatment with low-dose alfentanil (2 μg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction.Clinical Trial Registration Number: Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).Keywords: alfentanil, sufentanil, cough, anesthesia induction

Jian Sun,1,&ast; Zhaochun Tian,2,&ast; Jing Wu,3 Jiafei Li,3 Qixia Wang,3 Shuhong Huang,2,3 Meng Wang4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Science and Technology Innovation Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of General Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng Wang, Department of general surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369, Jingshi Road, Jinan, Shandong, 250014, People’s Republic of China, Email wangmtcm@163.com Shuhong Huang, School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 6699, Qingdao Road, Jinan, Shandong, 250117, People’s Republic of China, Email shuhonghuang@sdfmu.edu.cnAbstract: Pristimerin, a natural triterpenoid isolated from the plants of southern snake vine and Maidenwood in the family Weseraceae, is anti-inflammatory, insecticidal, antibacterial, and antiviral substance and has been used for its cardioprotective and antitumor effects and in osteoporosis treatment. These qualities explain Pristimerin’s therapeutic effects on different types of tumors and other diseases. More and more studies have shown that pristimerin acts in a wide range of biological activities and has shown great potential in various fields of modern and Chinese medicine. While Pristimerin’s wide range of pharmacological effects have been widely studied by others, our comprehensive review suggests that its mechanism of action may be through affecting fundamental cellular events, including blocking the cell cycle, inducing apoptosis and autophagy, and inhibiting cell migration and invasion, or through activating or inhibiting certain key molecules in several cell signaling pathways, including nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/protein kinase B/mammalian-targeted macromycin (PI3K/Akt/mTOR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1/2 (ERK1/2), Jun amino-terminal kinase (JNK1/2/3), reactive oxygen species (ROS), wingless/integrin1 (Wnt)/β-catenin, and other signaling pathways. This paper reviews the research progress of Pristimerin’s pharmacological mechanism of action in recent years to provide a theoretical basis for the molecular targeting therapy and further development and utilization of Pristimerin. It also provides insights into improved treatments and therapies for clinical patients and the need to explore pristimerin as a potential facet of treatment.Keywords: pristimerin, signaling pathway, pharmacological effects, review

Yu-Hang Cai,1,&ast; Cheng-Yu Wang,1,&ast; Yu-Bo Fang,1 Hong-Yu Ma,1 Yu-Qing Gao,1 Zhen Wang,2 Junzheng Wu,3 Han Lin,1 Hua-Cheng Liu1 1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, Cincinnati Children’s Hospital, Cincinnati, OH, 45229, USA&ast;These authors contributed equally to this workCorrespondence: Hua-Cheng Liu; Han Lin, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, 325000, People’s Republic of China, Tel +86-13957770577, Fax +86-577-88002925, Email huachengliu@163.com; nanlinhannansh@qq.comPurpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries.Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg− 1), Group D (intranasal dexmedetomidine 2 mcg kg− 1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS).Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010).Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation.Trial Registration: NCT 04720963, January 22, 2021, ClinicalTrials.Gov.Keywords: dexmedetomidine, paediatrics, preoperative anxiety, premedication, remimazolam

Ying Zhu,&ast; Yiyi Zhang,&ast; Miao Yang, Nie Tang, Limei Liu, Jichuan Wu, Yan Yang Department of Endocrinology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yang, Department of Endocrinology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email yangyan_2012@126.comPurpose: Diabetic nephropathy (DN), a major complication of diabetes mellitus, significantly impacts global health. Identifying individuals at risk of developing DN is crucial for early intervention and improving patient outcomes. This study aims to develop and validate a machine learning-based predictive model using integrated biomarkers.Methods: A cross-sectional analysis was conducted on a baseline dataset involving 2184 participants without DN, categorized based on their development of DN over a follow-up period of 36 months: DN (n=1270) and Non-DN (n=914). Various demographic and clinical parameters were analyzed. The findings were validated using an independent dataset comprising 468 participants, with 273 developing DN and 195 remaining as Non-DN over the follow-up period. Machine learning algorithms, alongside traditional descriptive statistics and logistic regression were used for statistical analyses.Results: Elevated levels of serum creatinine, urea, and reduced eGFR, alongside an increased prevalence of retinopathy and peripheral neuropathy, were prominently observed in those who developed DN. Validation on the independent dataset further confirmed the model’s robustness and consistency. The SVM model demonstrated superior performance in the training set (AUC=0.79, F1-score=0.74) and testing set (AUC=0.83, F1-score=0.82), outperforming other models. Significant predictors of DN included serum creatinine, eGFR, presence of diabetic retinopathy, and peripheral neuropathy.Conclusion: Integrating machine learning algorithms with clinical and biomarker data at baseline offers a promising avenue for identifying individuals at risk of developing diabetic nephropathy in type 2 diabetes patients over a 36-month period.Keywords: diabetic nephropathy, prediction, machine learning, biomarkers, risk stratification, type 2 diabetes

Ruiwei Guo,1,2 Jin Wu,1,2 Yanmin Zheng,1,2 Xiaona Lin,1,2 Zelin Zhuang,1,2 Jingjing Yin,1,2 Zhirong Lin,1 Lei Xie,1,2 Shuhua Ma1,2 1Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Laboratory of Medical Molecular Imaging, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaCorrespondence: Shuhua Ma; Lei Xie, Email shuhua6633@163.com; 13lxie1@stu.edu.cnBackground: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood.Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison.Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT.Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.Keywords: inflammatory bowel disease, graph theory, visuospatial working memory, cognitive impairment, mental rotation task

Li Ren, Zhaoling Li, Ji Wu, Lian Duan, Jialiang Gao Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Li Ren, Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Address: No. 5, Beixiange, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86 18600697916, Email renlirl7961@hotmail.comObjective: This study aimed to assess the knowledge, attitudes and practices (KAP) among elderly coronary heart disease (CHD) patients toward self-perceived health abilities.Methods: This web-based study was carried out between April 2023 and September 2023 at Guang’anmen Hospital, China Academy of Chinese Medical Sciences. A self-developed questionnaire was utilized to collect demographic information from elderly CHD patients, and evaluate their KAP towards self-perceived health abilities.Results: A total of 568 valid questionnaires were collected. Among the participants, the average age was 65.97± 5.50 years, and 298 (52.46%) were female, and the mean scores for knowledge, attitudes, and practices were 6.34± 2.29 (possible range: 0– 9), 35.24± 4.99 (possible range: 9– 45), and 27.79± 10.09 (possible range: 9– 45), respectively. The structural equation model demonstrated that elderly CHD patients’ knowledge directly affects attitudes and practices, with path coefficient of 0.93 (P< 0.001) and 0.39 (P=0.033), respectively. Moreover, attitudes play an intermediary role between knowledge and practice with path coefficient of 0.75 (P< 0.001). Furthermore, residence directly affects knowledge with path coefficient of 0.67 (P< 0.001), cardiac function directly affects knowledge with path coefficient of − 0.97 (P< 0.001) and history of interventional therapy directly affects practice with path coefficient of 4.23 (P< 0.001).Conclusion: Elderly CHD patients demonstrated sufficient knowledge, positive attitudes, and proactive practices towards self-perceived health abilities. However, educational programs and behavior modification are recommended, particularly for elderly with lower age and education, living in rural areas, lacking interventional therapy, obese, or taking multiple CHD medications.Keywords: knowledge, attitudes, practices, cross-dimensional study, coronary heart disease, self-perceived health abilities

Jie Wu,1 Yingzhuo Ma,1 Jun Wang,1 Mingzhao Xiao2 1Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Mingzhao Xiao, Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email xmz.2004@163.com Jun Wang, Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email smile@stu.cqmu.edu.cnPurpose: ChatGPT has a wide range of applications in the medical field. Therefore, this review aims to define the key issues and provide a comprehensive view of the literature based on the application of ChatGPT in medicine.Methods: This scope follows Arksey and O’Malley’s five-stage framework. A comprehensive literature search of publications (30 November 2022 to 16 August 2023) was conducted. Six databases were searched and relevant references were systematically catalogued. Attention was focused on the general characteristics of the articles, their fields of application, and the advantages and disadvantages of using ChatGPT. Descriptive statistics and narrative synthesis methods were used for data analysis.Results: Of the 3426 studies, 247 met the criteria for inclusion in this review. The majority of articles (31.17%) were from the United States. Editorials (43.32%) ranked first, followed by experimental studys (11.74%). The potential applications of ChatGPT in medicine are varied, with the largest number of studies (45.75%) exploring clinical practice, including assisting with clinical decision support and providing disease information and medical advice. This was followed by medical education (27.13%) and scientific research (16.19%). Particularly noteworthy in the discipline statistics were radiology, surgery and dentistry at the top of the list. However, ChatGPT in medicine also faces issues of data privacy, inaccuracy and plagiarism.Conclusion: The application of ChatGPT in medicine focuses on different disciplines and general application scenarios. ChatGPT has a paradoxical nature: it offers significant advantages, but at the same time raises great concerns about its application in healthcare settings. Therefore, it is imperative to develop theoretical frameworks that not only address its widespread use in healthcare but also facilitate a comprehensive assessment. In addition, these frameworks should contribute to the development of strict and effective guidelines and regulatory measures.Keywords: ChatGPT, large language model, medicine, nursing, scoping review, bibliometric analysis

Jiayan Li,1,&ast; Jie Ding,1,&ast; Haoyang Wu,1 Chenyan Lu,1 Jian Wu,2 Qianqian Luo1 1Department of Hypoxic Biomedicine, Institute of Special Environmental Medicine and Coinnovation Center of Neuroregeneration, Nantong University, Nantong, 226019, People’s Republic of China; 2Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wu, Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, People’s Republic of China, Tel +86-21-54601295, Email jianwu12@fudan.edu.cn Qianqian Luo, Department of Hypoxic Biomedicine, Institute of Special Environmental Medicine and Coinnovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, People’s Republic of China, Tel +86-513-85503378, Email qianqianluo@ntu.edu.cnBackground: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite.Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin–eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue.Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated.Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice.Keywords: frostbite, Tat-CIRP, inflammation, angiogenesis