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Jiying Wang,1,&ast; Weisheng Xu,1,&ast; Qingqing Wang,2,&ast; Peng Yang,3,&ast; Yanpeng Kan,1 Chao Huang,4 Fuqing Lin1 1Department of Pain Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Department of Anesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 3Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 4Chongming Branch, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuqing Lin; Chao Huang, Email fuqinglin@tongji.edu.cn; m13524572828@163.comBackground: The best tool for the management of pain associated with distal symmetric peripheral neuropathy (DSPN) is a matter of debate. Therefore, the study aimed to explore whether ultrasound-guided pulsed radiofrequency (PRF) therapy of the stellate ganglion (SG) in type 2 diabetes mellitus (T2DM) patients with painful DSPN could decrease pain severity and the need for analgesics.Methods: Fifty-six T2DM patients with refractory painful DSPN were enrolled in this study, who then received bilateral ultrasound-guided PRF therapy of SG. The patients completed visual analog scale (VAS), simplified McGill pain questionnaire (SF-MPQ), Toronto clinical score system (TCSS), sleep duration at night (SDN), pain disability index (PDI), Karnofsky performance status (KPS), and depression screening scale (PHQ-9). After procedures, the degree of perceived pain relief, numbness relief and chills relief of the patients, and side effects were assessed. All patients underwent evaluation after the last procedure at 1, 4, 12 and 24-week follow-up periods.Results: The postoperative VAS, SF-MPQ, TCSS, PDI and PHQ-9 scores were significantly lower, while the KPS values higher than the preoperative (P< 0.05). The postoperative SDN was longer than the preoperative (P< 0.05). The degree of perceived pain relief, chills relief, and numbness relief at 4, 12, and 24 weeks were lower than that at 1 week after the procedures (P< 0.05). The postoperative rates of administration of analgesic were lower than those of preoperative period (P< 0.05). The significant effective rates at 1, 4, 12, and 24 weeks after the procedure were 67.86%, 42.86%, 21.43%, and 17.86% and the total effective rates were 89.29%, 71.43%, 46.43%, and 32.14%. No serious complication was observed.Conclusion: Ultrasound-guided stellate ganglion PRF therapy can effectively relieve pain and improve the quality of life in T2DM patients with refractory painful DSPN.Keywords: painful diabetic neuropathy, type 2 diabetes mellitus, stellate ganglion, pulsed radiofrequency

Peng Yang,1 Jieying Duan,2,3 Mingxuan Li,2,3 Rui Tan,1 Yuan Li,1 Zeqing Zhang,4 Ying Wang1 1Department of Geriatric Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Cardiology, Henan Provincial Chest Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Cardiology, Chest Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Ying Wang; Zeqing Zhang, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13939019726 ; +86 18339967695, Email wangying56994@126.com; tjzzq1899@126.comPurpose: Current scoring systems used to predict major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI) lack some key components and their predictive ability needs improvement. This study aimed to develop a more effective scoring system for predicting 3-year MACE in patients with AMI.Patients and Methods: Our statistical analyses included data for 461 patients with AMI. Eighty percent of patients (n=369) were randomly assigned to the training set and the remaining patients (n=92) to the validation set. Independent risk factors for MACE were identified in univariate and multifactorial logistic regression analyses. A nomogram was used to create the scoring system, the predictive ability of which was assessed using calibration curve, decision curve analysis, receiver-operating characteristic curve, and survival analysis.Results: The nomogram model included the following seven variables: age, diabetes, prior myocardial infarction, Killip class, chronic kidney disease, lipoprotein(a), and percutaneous coronary intervention during hospitalization. The predicted and observed values for the nomogram model were in good agreement based on the calibration curves. Decision curve analysis showed that the clinical nomogram model had good predictive ability. The area under the curve (AUC) for the scoring system was 0.775 (95% confidence interval [CI] 0.728– 0.823) in the training set and 0.789 (95% CI 0.693– 0.886) in the validation set. Risk stratification based on the scoring system found that the risk of MACE was 4.51-fold higher (95% CI 3.24– 6.28) in the high-risk group than in the low-risk group. Notably, this scoring system demonstrated better predictive ability than the GRACE risk score (AUC 0.776 vs 0.731; P=0.007).Conclusion: The scoring system developed from the nomogram in this study showed favorable performance in prediction of MACE and risk stratification of patients with AMI.Keywords: acute myocardial infarction, long-term outcome, MACE, nomogram, risk prediction model

Jing Hu, Yang Song, Yuxing Zhang, Peng Yang, Siyu Chen, Zhaoyan Wu, Jun Zhang Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 13953109816, Fax +86 53188382923, Email zhangj@sdu.edu.cnPurpose: This study examines the effects and mechanisms of catalpol (CAT) on the proliferation and osteogenic differentiation of cultured human periodontal ligament stem cells (hPDLSCs) in vitro and assesses the impact of CAT on periodontal remodeling in vivo using an orthodontic tooth movement (OTM) model in rats.Methods: hPDLSCs were cultured in a laboratory setting, and their proliferation and osteogenic differentiation were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. Additionally, the expression of collagen type 1 (COL-1), ALP, and runt-related transcription factor-2 (RUNX-2) was evaluated through qRT-PCR and Western blot analysis. To verify the function of the estrogen receptor-α (ER-α)-mediated phosphatidylinositol-3-kinase-protein kinase B (PI3K/AKT) pathway in this mechanism, LY294002 (a PI3K signaling pathway inhibitor) and the ER-α specific inhibitor methyl-piperidine-pyrazole (MPP) were used. The osteogenic markers ER-α, AKT, and p-AKT (phosphoprotein kinase B) were identified through Western blot analysis. Eighteen male Sprague-Dawley rats were assigned to two groups randomly: a CAT group receiving CAT and a control group receiving an equivalent volume of saline. Micro-computed tomography (micro-CT) analysis was employed to evaluate tooth movement and changes in alveolar bone structure. Morphological changes in the periodontal tissues between the roots were investigated using hematoxylin and eosin (HE) staining and tartaric-resistant acid phosphatase (TRAP) staining. The expression of COL-1, RUNX-2, and nuclear factor-κB (NF-κB) ligand (RANKL) was assessed through immunohistochemical staining (IHC) to evaluate periodontal tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences among more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by the Tukey’s test. Values of p

Yuexiang Qin,1,2 Shanhu Yao,3,4 Gaoyuan Wang,5 Ziyuan Xu,6,7 Gangcai Zhu,8 Ying Li,1,2 Pingting Yang,1,2 Jiangang Wang,1,2 Chunbo Zou,5 Changhan Chen7,9 1Department of Health Management Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 2Hunan Chronic Disease Health Management Medical Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 3Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 4Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 5Department of Nephrology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 8Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 9National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaCorrespondence: Changhan Chen, National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Tel +86-13875974606, Email changhanchen@csu.edu.cnObjective: Inflammation plays a crucial role in the development of metabolic syndrome (MetS). However, the roles of pepsinogens (PGs) and gastrin, known biomarkers linked to gastric inflammation, in MetS and the transition of MetS status are unclear. This research aimed to explore the relationship between MetS, the transition of MetS status, and levels of gastric biomarkers.Methods: This large-scale cross-sectional study included 19162 participants aged 18– 80 years between August 2021 and March 2024. Serum levels of the gastric biomarkers PGI, PGII, and gastrin-17 were analyzed using enzyme-linked immunosorbent assay. In addition, the relationship between transitions of MetS status based on 1032 MetS-negative participants from baseline to the second health exam after 2 years was considered. The association between MetS and the transitions of MetS status and gastric biomarkers was analyzed using logistic regression models.Results: The prevalence of MetS in the study population was 31.4%, with higher rates in males (35.2%) than females (24.6%). Gastrin-17 levels were markedly elevated in participants with MetS, a trend observed in both genders. In the logistic regression analysis, after adjusting for confounding factors, gastrin-17 levels were strongly and positively correlated with MetS in the entire cohort and in males but not in females. Male participants with MetS had lower levels of PGI and PGII than those without MetS, whereas the opposite trend was observed in females. Logistic regression analysis indicated that PGI and PGII were not independently associated with MetS. During the follow-up of 2 years, 199 (19.28%) of the 1032 MetS-negative participants transitioned to MetS-positive status. As compared to the stable MetS-negative subjects, transition from MetS-negative to MetS-positive was associated with higher levels of gastrin-17, especially in males, but not in females.Conclusion: Gastrin-17 is a promising biomarker for MetS, exhibiting potential utility in monitoring the transition of MetS status and revealing gender difference.Keywords: gastric biomarkers, gastrin-17, metabolic syndrome, transition, gender difference

Na Chen,1,2 Xuben Yu,3 Lu Li,1 Ping Yang,1 Rong Dong,1,4 Yizhen Huang,1,5 Xiao Ling,1,6 Qiaoqiao Shentu,1,7 Wenqiao Yu,8 Saiping Jiang1 1Department of Clinical Pharmaceutical, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Clinical Pharmacy, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 6Department of Pharmacy, The People’s Hospital of Yuhuan, Taizhou, People’s Republic of China; 7Department of Pharmacy, Dongyang Red Cross Hospital, Jinhua, People’s Republic of China; 8Department of Hepatobiliary and Pancreatic Surgery and Intensive Care Unit, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Saiping Jiang; Wenqiao Yu, Email j5145@zju.edu.cn; yuwenqiao1980@zju.edu.cnBackground: The population pharmacokinetics of nirmatrelvir/ritonavir (NIR/RIT) has not yet been described for critically ill adult patient.Purpose: This was a prospective observational population pharmacokinetic study of nirmatrelvir/ritonavir (NIR/RIT) in critically ill adult patients and identify optimal dosing regimens.Patients and Methods: The prescription of NIR/RIT is determined by the attending physician and ranges from 150mg/100mg to 300mg/100mg twice a day. Two to three serial blood samples were collected for each patient after the second doses. We developed and validated PK model for plasma NIR and plasma RIT. Monte Carlo dosing simulations were performed to assess target attainment.Results: We analyzed 89 plasma samples from 31 adult patients. The data were best described by a one-compartment model. Among the covariates tested on pharmacokinetic parameters, creatinine clearance (CrCL) and area under curve (AUC) of RIT had a significant effect on apparent clearance (CL/F) of NIR. Mean (SD) parameters estimates for the absorption rate constant (Ka), apparent distribution (V/F) and CL/F were 0.42 (0.10) h− 1. 36.5 (8.5) L, 3.6 (0.26) L/h, respectively. Dosing simulations showed that the target in vitro 90% effective concentration (EC90) was more likely to be achieved twice a day than once a day at the same daily dose of NIR. High CrCL, low AUC of RIT were associated with a reduced likelihood of NIR reaching the target EC90.Conclusion: Based on our dosing simulations, the initial dosage of NIR/RIT was 300mg/100mg twice a day in critically ill patients with CrCL> 45 mL/min; When CrCL in critically ill patients is between 15 and 45 mL/min, NIR/RIT is 150mg/100mg twice a day. The maintenance dose is adjusted according to CrCL and AUC of RIT, with the dosages varying between 75mg/100mg and 300mg/100mg.Keywords: nirmatrelvir, ritonavir, pharmacokinetics, critically ill, creatinine clearance

Ruien Chen,1,&ast; Huamei Zou,1,&ast; Xiuwen Ye,1,&ast; Bailing Xie,2 Aizhi Zhang,3 Lihua Mo,4 Yu Liu,4 Huanping Zhang,5 Gui Yang,1 Pingchang Yang2 1Department of Otolaryngology, Longgang Central Hospital affiliated to Guangzhou University of Chinese Traditional Medicine Shenzhen Clinical College, Shenzhen, 518116, People’s Republic of China; 2State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University and Institute of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, 518055, People’s Republic of China; 3Department of Critical Care Medicine, Second Hospital, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of General Medicine Practice, Third Affiliated Hospital, Shenzhen University, Shenzhen, 518005, People’s Republic of China; 5Department of Allergy Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pingchang Yang; Gui Yang, Email pcy2356@163.com; guiyang1981@hotmail.comIntroduction: The therapeutic efficacy for airway allergies needs to be improved. Th2 polarization is a primary pathological feature of airway allergies. We constructed chimeric antigen-LgDNA (Lactobacillus rhamnosus DNA) nanoparticles (CAP-NPs). The effects of CAP-NPs on reconciling airway Th2 polarization were tested.Methods: In this study, disulfide bond-linked antigen-major histocompatibility complex II (MHC II)-LgDNA nanoparticles (NPs) were constructed and designated CAP-NPs. An airway Th2 polarization mouse model was established to test the effects of CAP-NPs on suppressing the Th2 response.Results: The CAP-NP components of ovalbumin (OVA), major histocompatibility complex II (MHC II), and LgDNA were confirmed in a series of laboratory tests. The CAP-NPs remained stable at pH7.2 for at least 96 h. In in vitro experiments, CAP-NPs bound to the surface of OVA-specific CD4+ T cells, which resulted in apoptosis of the antigen-specific CD4+ T cells. Removal of any of the three components from the NPs abolished the induction of apoptosis of antigen specific CD4+ T cells. CAP-NPs increased the expression of lysine-specific demethylase 5A (KDM5A) in CD4+ T cells. Histone H3K9 and the gene promoter of caspase 8 were demethylated by KDM5A, which led to transcription and expression of the caspase 8 gene. Administration of CAP-NPs significantly alleviated experimental airway Th2 polarization through activating the caspase 8-apoptosis signaling pathway.Discussion: In this paper, we constructed CAP-NPs that could induce antigen-specific CD4+ T cell apoptosis. Administration of CAP-NPs efficiently alleviated experimental airway Th2 polarization.Keywords: airway allergy, T cell, therapy, vaccine, nanoparticle

Chao Meng,1 Ping Yang,2 Yanan Wang,3 Siyan Liu,3 Xueyan Wu,3 Shaolian Wang3 1Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Integrated Chinese and Western Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Shaolian Wang, Email 15318816221@sina.cnBackground: To investigate the prevalence of thyroid nodules among medical staff and health check-up population in a Level-A hospital (Primary-level hospital) in Jinan City and analyze its influencing factors.Methods: A total of 5812 cases from the two groups were screened. t-test and χ2 tests were used to analyze the differences in the prevalence of thyroid nodules. Multivariate Logistic regression analysis was used to explore the influencing factors.Results: The average age of medical staff was (36.20± 9.11) years old, and the total prevalence was 48.5%. The average age of the healthcare population was (57.89± 12.51) years old, and the total prevalence rate was 63.9%, with statistical significance between the two groups (P

Jing Liu, Ping Yang, Meng Hu Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Henan, 471000, People’s Republic of ChinaCorrespondence: Meng Hu, Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Henan, 471000, People’s Republic of China, Email 3259294525@qq.comAbstract: In this report, the patient was a 57-year-old woman who had been diagnosed with aplastic anemia for 3 years. This patient underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-four months after allo-HSCT, the patient experienced cognitive dysfunction, memory loss, and involuntary movements. Various central nervous system (CNS) complications may occur after allo-HSCT, which can lead to severe clinical problems. Diagnosis is often difficult because of the absence of distinctive clinical symptoms. In addition, different neurological disorders may show similar symptoms. Although antibodies in the CSF or serum have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report the case of a patient who developed encephalitis associated with antibodies against glial fibrillary acidic protein (GFAP) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against GFAP in post-transplantation encephalitis. Of course, all processes met the ethical and patient consents were obtained.Keywords: glial fibrillary acidic protein, autoimmune encephalitis, allo-HSCT

Zhe Xiong,1,2 Ying Fang,1,2 Shuangshuang Lu,1 Qiuyue Sun,1,3 Yuhui Sun,1,3 Pengcheng Yang,4,&ast; Jin Huang1,&ast; 1Department of Gastroenterology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Graduate School of Dalian Medical University, Dalian, Liaoning Province, China; 3Graduate School of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 4Department of Gastroenterology, Hengshanqiao People’s Hospital, Changzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengcheng Yang; Jin Huang, Email 496808936@qq.com; hj042153@hotmail.comBackground: Ulcerative colitis (UC) is a nonspecific inflammatory disease confined to the intestinal mucosa and submucosa, and its prevalence significantly increases each year. Disulfidptosis is a recently discovered new form of cell death that has been suggested to be involved in multiple diseases. The aim of this study was to explore the relevance of disulfidptosis in UC.Methods: First, the UC datasets were downloaded from the Gene Expression Omnibus (GEO) database, and UC samples were typed based on upregulated disulfidptosis-related genes (DRGs). Then, weighted gene co-expression network analysis (WGCNA) was performed on the datasets and molecular subtypes of UC, respectively, to obtain candidate signature genes. After validation of the validation set and qRT-PCR, we constructed a nomogram model by signature genes to predict the risk of UC. Finally, single-cell sequencing analysis was used to study the heterogeneity of UC and to demonstrate the expression of DRGs and signature genes at the single-cell level.Results: A total of 7 DRGs were significantly upregulated in the expression profiles of UC, and 180 UC samples were divided into two subtypes based on these DRGs. Five candidate signature genes were obtained by intersecting two key gene modules selected by WGCNA. After evaluation, four signature genes with diagnostic relevance (COL4A1, PRRX1, NNMT, and PECAM1) were eventually identified. The nomogram model showed excellent prediction ability. Finally, in the single-cell analysis, there were eight cell types (including B cells, T cells, monocyte, smooth muscle cells, epithelial cells, neutrophil, endothelial cells and NK cells) were identified. The signature genes were significantly expressed mainly in endothelial cells and smooth muscle cells.Conclusion: In this study, subtypes related to disulfidptosis were identified, and single-cell analysis was performed to understand the pathogenesis of UC from a new perspective. Four signature genes were screened and a prediction model with high accuracy was established. This provides novel insights for early diagnosis and therapeutic targets in UC.Keywords: ulcerative colitis, disulfidptosis, molecular clusters, WGCNA, nomogram

Jianmin Gong,1,2,&ast; Bo Shi,1,3,&ast; Ping Yang,1 Adeel Khan,4 Tao Xiong,2 Zhiyang Li1 1Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2College of Life Science, Yangtze University, Jingzhou, 434025, People’s Republic of China; 3Department of Clinical Laboratory, Nanjing Jiangning Hospital of Chinese Medicine (CM), Nanjing, 211100, People’s Republic of China; 4Department of Biotechnology, University of Science and Technology Bannu, Bannu, 28100, Islamic Republic of Pakistan&ast;These authors contributed equally to this workCorrespondence: Tao Xiong, College of Life Science, Yangtze University, Jingzhou, 434025, People’s Republic of China, Tel +8613872387410, Email xiongtao@yangtzeu.edu.cn Zhiyang Li, Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China, Tel +8618951703765, Email lizhiyang@nju.edu.cnBackground: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways.Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database.Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings.Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications.Keywords: hypertrophic cardiomyopathy, bioinformatic, immune cells infiltration, biomarker

Yixue Huang,&ast; Wenhao Wang,&ast; Linlin Zhang,&ast; Yun Teng, Zihao Zhan, Huilin Yang, Peng Yang Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Yang; Huilin Yang, Department of Orthopaedics, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Tel +86 512 67972157, Email ypspine@163.com; szyhlspine@163.comBackground: To determine the factors in posterior ligamentous complex indicating lumbar instability in patients diagnosed with degenerative spondylolisthesis on conventional magnetic resonance imaging (MRI).Methods: We retrospectively analyzed patients who underwent PLIF surgery for degenerative spondylolisthesis at our institution between 2018 and 2020 and who had complete eligible preoperative imaging data for review and study, including lumbar MRI and anteroposterior and flexion-extension radiographs.Results: Fifty-three patients were confirmed to have lumbar instability (Unstable Group, 44%), while sixty-seven patients (Stable Group, 56%) did not have instability on radiographs. The patients in the stable group had more advanced status of the degeneration of intervertebral disc than in the unstable group (p< 0.05). The degeneration of supraspinous ligament (SSL) was more severe in the unstable group (p< 0.05). Compared with the patients with rotatory instability, advanced degeneration of interspinous ligament (ISL) and SSL was observed in patients with translatory instability (p< 0.05). However, there was no significant difference with regard to the height of the spinous process and the interspinous distance in patients with or without instability.Conclusion: This MRI analysis showed that abnormal segmental motion is closely associated with the pathological characteristics of supraspinal ligament. Advanced degeneration of SSL in patients with degenerative spondylolisthesis should raise the suspicion for lumbar instability and additional evaluations. The status of ISL and ligamentum flavum (LF) may not be helpful for the diagnosis of lumbar instability. Functional radiographs combined with MRI may provide valuable information when diagnosing lumbar instability in patients with mechanical back pain.Keywords: interspinous distance, lumbar instability, MRI, posterior ligament complex, spinal process

Longfei Fan,1 Zhongqiang Qin,1 Di Wu,1 Yunchuan Yang,2 Yigang Zhang,2 Bo Xie,1 Jingyu Qian,1 Jianzhu Wei,1 Zhaoying Wang,1 Peipei Yang,1 Zhen Qian,1 Mu Yuan,1 Ziyi Zhu,1 Yulin Tan,1 Yi Tan2 1Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of ChinaCorrespondence: Yi Tan, Email doctortanyi2007@126.comPurpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC).Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators.Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators.Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.Keywords: hepatocellular carcinoma, leucyl-tRNA synthetase 1, bioinformatics analysis, biomarker, the cancer genome atlas

Yujun He,1,2,&ast; Furui Miao,2,&ast; Cai He,1 Yushan Fan,2 Fangzhi Zhang,2 Pu Yang,3 Miaodong Wang,3 Jiujie He2 1Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 2Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 3Graduate School of Guangxi University of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cai He, Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, No. 356 Nanmian Street, Xixiangtang District, Nanning City, 530011, People’s Republic of China, Email 578485231@qq.com Yushan Fan, Faculty of acupuncture, moxibustion and tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning City, 530001, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS) is the most prevalent upper limb compressive neuropathy. A considerable number of clinical trials and meta-analyses have provided evidence supporting the effectiveness of acupuncture in treating CTS. Nevertheless, the ideal choice of acupoints remains ambiguous.Objective: A data mining analysis was conducted with the objective of determining the most effective acupoint combinations and selection for CTS.Methods: A search was conducted across seven Chinese and English electronic bibliographic databases spanning from their inception to March 2023. Selected were clinical trials that evaluated the efficacy of acupuncture therapy for CTS, with or without randomised controlled methods. Data extraction mainly included acupoint prescriptions. Information such as first author, study design and study setting were also extracted. The principal outcomes comprised the clinical manifestations linked to CTS. Statistical descriptions were generated using Excel 2019. The analysis of association rules was conducted using SPSS Modeler 18.0. Using SPSS Statistics 26.0, exploratory factor analysis and cluster analysis were conducted.Results: 142 trials (including 86 RCTs and 56 non RCTs) were identified, and 193 groups of effective prescriptions involving 68 acupoints were extracted. The most frequently used acupoints were Da-ling (PC7), Nei-guan (PC6), He-gu (LI4), Wai-guan (TE5), and Yang-xi (LI5). The most frequently used meridians were the pericardial meridian and the large intestine meridian. The majority of special acupoints used were Five-shu points and Yuan-source points, with acupoints on the upper limbs being the most frequently used. The core acupoint groups were analyzed and 11 groups of association rules, 8 factors, and 5 effective cluster groups were obtained.Conclusion: The evidence-based acupoint selection and combinations of acupuncture therapy for carpal tunnel syndrome were provided by the findings of this study.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

Qingqing Luo,1,&ast; Yibo Quan,1,&ast; Wei Liu,1 Zixin Wu,1 Wenjing Qiu,1 Wenlong Liang,1 Ping Yang,1 Qing Huang,1 Guanwei Li,1 Jianchang Wei,1 Qiang Wang,1 Fei Shen,2 Wanglin Li,1 Feng He,3 Jie Cao1 1Department of Gastrointestinal Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 2Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 3Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Cao, Department of Gastrointestinal Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China, Email eycaojie@scut.edu.cn Feng He, Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China, Email eyhefeng@scut.edu.cnPurpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases.Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the “CMS classifier” and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected.Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting “seed” of tumor cells of different CMS groups had a preference for metastasis to “soil” of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases.Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.Keywords: colorectal cancer, primary tumors, metastases, consensus molecular subtypes, tumor microenvironment

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

Hao Yang,1– 3,&ast; Guanglin Lei,2,&ast; Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Yuchen Li,1,&ast; Yinfeng Gu,1,&ast; Pengyue Yang,1 Yan Wang,1 Xibao Yu,1 Yangqiu Li,1 Zhenyi Jin,1,2 Ling Xu1,3 1Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Pathology, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Xu; Zhenyi Jin, Email lingxu114@163.com; jinzhenyijnu@163.comAbstract: Immunotherapy utilizing T cells that attack tumors is a promising strategy for treatment, but immune suppressive T cell subsets, such as regulatory T cell (Treg), and immune checkpoint molecules, including programmed death-1 (PD-1), can suppress the intensity of a T cell immune reaction and thereby impair tumor clearance. Cluster of differentiation 69 (CD69), known as an early leukocyte activation marker, can be used as a measure or early marker of T cell activation. In recent years, the functions of CD69 in the regulation of Treg/Th17 (T helper cell 17) differentiation and in the tissue retention of T cells have attracted considerable interest. These functions are related to the role of CD69 in immune suppression in tumor environments (TME). In this review, we first summarized current perspectives in the biological function of CD69 and demonstrated that CD69 acts as a regulator of T cell activation, differentiation, retention, and exhaustion. Then, we discussed recent advances in understanding of CD69 deficiency and anti-CD69 antibody administration and shed light on the value of targeting on CD69 for cancer immunotherapy and prognosis prediction.Keywords: CD69, T cell, immunotherapy

Siyun Cheng,1,2,&ast; Zhijie Tu,2,&ast; Shuai Zheng,3 Adeel Khan,4 Ping Yang,1 Han Shen,1 Bing Gu2,3 1Department of Clinical Laboratory, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Medical Technology School of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Biotechnology, University of Science and Technology, Bannu, KP, Pakistan&ast;These authors contributed equally to this workCorrespondence: Han Shen, Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China, Tel +8602583304616, Fax +02568183912, Email shenhan@njglyy.com Bing Gu, Department of Clinical Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China, Tel +8602083827812, Fax +02083875881, Email gubing@gdph.org.cnIntroduction: Ultrasensitive bacterial detection methods are crucial to ensuring accurate diagnosis and effective clinical monitoring, given the significant threat bacterial infections pose to human health. The aim of this study is to develop a biosensor with capabilities for broad-spectrum bacterial detection, rapid processing, and cost-effectiveness.Methods: A magnetically-assisted SERS biosensor was designed, employing wheat germ agglutinin (WGA) for broad-spectrum recognition and antibodies for specific capture. Gold nanostars (AuNSs) were sequentially modified with the Raman reporter molecules and WGA, creating a versatile SERS tag with high affinity for a diverse range of bacteria. Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) antibody-modified Fe3O4 magnetic gold nanoparticles (MGNPs) served as the capture probes. Target bacteria were captured by MGNPs and combined with SERS tags, forming a “sandwich” composite structure for bacterial detection.Results: AuNSs, with a core size of 65 nm, exhibited excellent storage stability (RSD=5.6%) and demonstrated superior SERS enhancement compared to colloidal gold nanoparticles. Efficient binding of S. aureus and P. aeruginosa to MGNPs resulted in capture efficiencies of 89.13% and 85.31%, respectively. Under optimized conditions, the developed assay achieved a limit of detection (LOD) of 7 CFU/mL for S. aureus and 5 CFU/mL for P. aeruginosa. The bacterial concentration (10– 106 CFU/mL) showed a strong linear correlation with the SERS intensity at 1331 cm− 1. Additionally, high recoveries (84.8% - 118.0%) and low RSD (6.21% - 11.42%) were observed in spiked human urine samples.Conclusion: This study introduces a simple and innovative magnetically-assisted SERS biosensor for the sensitive and quantitative detection of S. aureus or P. aeruginosa, utilizing WGA and antibodies. The developed biosensor enhances the capabilities of the “sandwich” type SERS biosensor, offering a novel and effective platform for accurate and timely clinical diagnosis of bacterial infections. Keywords: SERS, WGA, pathogenic bacteria, bacterial detection, dual-recognition

Wei He,&ast; Quan Zhou,&ast; Jiaheng Lv,&ast; Yujie Shen, Hao Liu, Huilin Yang, Peng Yang, Tao Liu Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Yang; Tao Liu, Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 899 Pinhai Road, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67781420, Fax +86-512-67781165, Email ypspine@163.com; liutao821108@163.comBackground: Few studies have focused on percutaneous kyphoplasty (PKP) in the treatment of thoracic osteoporotic vertebral compression fractures (OVCFs) with intervertebral cleft (IVC). Hence, the objective of this retrospective study was to compare the clinical and radiographic outcomes of PKP in elderly patients with thoracic OVCFs, with or without IVC.Methods: A total of 106 patients were enrolled in this study and divided into two groups: the IVC group and the NIVC group (without IVC). Radiographic measures included anterior vertebral height (AVH), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Clinical function measures included Oswestry disability index (ODI) and visual analog scale (VAS) scores.Results: There were no significant differences in the preoperative basic data between the groups classified as IVC and NIVC. However, both groups showed significant improvements in AVH and TK throughout the follow-up periods compared to the preoperative measurements (P< 0.05). The recovery of AVH in the IVC group was found to be inferior to that in the NIVC group at 3 years after operation (P< 0.05). There were no significant differences in LL, PI, PT and SS in both groups compared with the preoperative results and no statistically significant differences between the two groups at the same follow-up time (P> 0.05). The VAS and ODI scores during all follow-up periods were significantly lower than those before operation (P< 0.05). At 3 years after operation, the VAS and ODI scores of the IVC group were higher than those of the NIVC group (P< 0.05).Conclusion: PKP is an adoptable measure to treat thoracic OVCFs with or without IVC. Our study revealed that the NIVC group was superior to the IVC group in terms of improved vertebral height and pain recovery at long-term follow-up (3 years).Keywords: percutaneous kyphoplasty, thoracic, osteoporotic vertebral compression fracture, intervertebral cleft, sagittal balance

Na Chen,1,2 Xiaojuan Wang,1,2 Yinyan Li,1,2 Ping Yang,1,2 Mingzhu Huang,1,2 Xiaoyang Lu1,2 1Department of Pharmaceutical, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaoyang Lu; Mingzhu Huang, Email luxiaoyang@zju.edu.cn; hmzj2002@zju.edu.cnAbstract: Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40– 400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.Keywords: isavuconazonium sulfate, isavuconazole, population pharmacokinetics, covariates

Puxin Yang,&ast; Xiao Liang,&ast; Xingzhu Xu, Qingtao Liu, Zhiyuan Guo, Hongru Yuan, Hui Wang, Wenyuan Ding Department of Spine Surgery, HeBei Medical University Third Hospital, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenyuan Ding; Hui Wang, Department of Spine Surgery, HeBei Medical University Third Hospital, Shijiazhuang, The People’s Republic of China, Tel +86 311 88602317, Fax +86 311 87023626, Email dingwymanuscript@163.com; wanghuiwenxian@163.comIntroduction: To explore the incidence and predictive factors of new onset postoperative sacroiliac joint pain (PSJP) after posterior lumbar fusion surgery for degenerative lumbar disease.Methods: Three hundred and sixty-seven patient medical records from January 2020 to December 2021 were retrieved. The patients were divided into two groups: PSJP group and N-PSJP (non-postoperative sacroiliac joint pain group). To investigate potential risk factors for PSJP, HU value (Hounsfield unit value) was assessed on CT scans. ImageJ software was used to assess the fat and muscle of the lumbar multifidus muscle (LMM) in the axial MRI image, the red area was marked as fat and the rest were muscles to calculate the ratio of fatty infiltration. Patient characteristics, surgical variables and radiographic parameters were analyzed statistically.Results: Twenty of 367 patients were diagnosed with PJSP at postoperative follow-up. Patients with PSJP presented with significantly higher HU value. For surgical variables, PSJP patients received more operations including distal fusion level at sacrum than the N-PSJP group. For radiographic parameters, most of the patients in the PSJP group had more severe fatty atrophic muscle in the LMM compared to the N-PSJP group. There was no statistically significant difference between the two groups in preoperative and postoperative lumbar lordosis (LL), angle of lumbar lordosis of fixed lumbar vertebrae (FV-LL), pelvic incidence (PI), sacrum slope (SS). The bivariate logistic regression model revealed preoperative fat infiltration rate of the LMM, and higher HU value were independently associated with PSJP.Conclusion: PSJP for degenerative lumbar disease was 5.4%, the predictive factors included preoperative severe infiltration of LMM, distal fusion level at sacrum and higher HU value.Keywords: sacroiliac joint pain, lumbar instrumented fusion surgery, bone mineral density, paraspinal muscles

Pu Yang,1 Tian Wang,1 Yu-Jun He,2 Sheng-Yong Su3,4 1The First School of Clinical Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Faculty of Acupuncture-Moxibustion and Tuina, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 3Department of Acupuncture-Moxibustion, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Sheng-Yong Su, Email ssy21008@126.comBackground: Chronic pain (CP) as a long-lasting stressor can often cause mood disorders, such as depression or anxiety. The comorbidity of CP and mood disorders poses challenges for treatment and increases healthcare costs. Acupuncture has emerged as a widely utilized approach to alleviate both CP and mood disorders. However, there is a lack of well-established bibliometric analyses in this area of research. Therefore, this study aimed to identify the current hotspots and research trends regarding the use of acupuncture for treating CP-related depression or anxiety.Methods: We searched the Web of Science Core Collection spanning from 2003 to 2023 to identify relevant literature about the use of acupuncture for treating CP-related depression or anxiety. Bibliometric and visualization analyses were performed using CiteSpace 5.7.R5 and Vosviewer 1.6.19 software.Results: A total of 254 articles published between 2003 and 2023 were included, revealing an upward trajectory with some fluctuations in publication numbers over the past two decades. China and the Beijing University of Chinese Medicine were the most productive country and institution in this field. Fang JQ and Vickers AJ ascended as the most prolific and influential authors, respectively. Trials was the journal with the highest number of publications, while Pain and BMJ-British Medical Journal exhibited the highest citation and centrality, respectively. “Acupuncture”, “depression”, and “chronic pain” were the top three keywords. The hotspots in this domain encompass types of chronic pain that predispose to negative mood, including fibromyalgia, irritable bowel syndrome (IBS), and neuropathic pain. Randomized controlled trials (RCTs), mechanisms, and evidence-based evaluations are the main research directions.Conclusion: This study uses bibliometric techniques to analyze the research hotspots and forefronts of acupuncture as a therapeutic approach for CP-related depression or anxiety. Our objective is to provide researchers with valuable references and identify research focal points for future investigations.Keywords: acupuncture, chronic pain, depression, anxiety, citespace, VOSviewer, bibliometric analysis

Menggege Liu,1,2 Qing Zhang,1,3 Juan Liu,1 Huiling Bai,1 Ping Yang,1 Xinhua Ye,1,3 Xiaoqing Yuan1,3 1Department of Endocrinology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Second Clinical College, Dalian Medical University, Dalian, People’s Republic of China; 3Changzhou Medical Center, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Xiaoqing Yuan; Xinhua Ye, Email adiposeyy@126.com; Endocrine1314@163.comObjective: To analyze the relationship between leg skeletal muscle mass index (LSMI) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) and the ability of LSMI to predict NAFLD.Methods: Two hundred patients with T2DM and NAFLD treated at Changzhou Second People’s Hospital Affiliated with Nanjing Medical University and the National Metabolic Management Center from June 2022 to June 2023 were divided into four LSMI quartiles. The clinical information from the four patient groups was compared, and the relationship between type 2 diabetes and LSMI and NAFLD was examined. We used receiver operating characteristic curves to determine how well the LSMI predicts NAFLD in T2DM.Results: The lowest quartile (Q1) had a higher prevalence of NAFLD than group Q4 (P < 0.05). LSMI was negatively associated with body mass index, LS, CAP, and other markers (P < 0.05). Receiver operating characteristic curve analysis LSMI predicted NAFLD with an ideal critical value of 0.64 and an area under the curve of 70.9%. The combined predictive value of the LSMI and the appendicular skeletal muscle mass index was more significant.Conclusion: Reduced LSMI is associated with NAFLD.Keywords: non-alcoholic fatty liver disease, type 2 diabetes mellitus, LSMI, ASMI

Wei Su,1,2 Dong Liu,2 Pingliang Yang,3 Ling Ye1 1Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Pain Management, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610011, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of ChinaCorrespondence: Ling Ye, Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423593, Email zerodq_hx@163.comPurpose: The aim of this study was to analysis of the opioid use of opioid native zoster-related pain (ZRP) patients to evaluate the impact of opioid use on pain control and quality of life improvement based on the clinical database.Patients and Methods: We conducted a retrospective cohort study to identify opioid native patients who were hospitalized in the pain department between May 1, 2020, and May 1, 2021. The primary outcomes were persistent opioid use after discharge, visual analogue scale (VAS) at the admission, VAS remission rate during hospitalization, VAS score and quality of life at follow-up. Then, we assessed patient-level risk factors for persistent opioid use after the discharge.Results: A total of 350 patients met the inclusion criteria. Of those patients, 255 (72.9%) were administered with opioid during hospitalization, and 95 (27.1%) patients were not. Opioid prescription during hospitalization was independently associated with increased odds of persistent use after the discharge (adjusted odds ratio, 20.74; 95% CI, 4.504– 95.474; P < 0.01). In the two groups, the VAS score at admission and the VAS score at follow-up were different. In the group with opioids during hospitalization, the persistent opioid use after discharge was more common (38% vs 2.1%) compared to patients without opioids, and VAS remission rate during hospitalization was less, restrictions on daily life, work or housework, and social activities were more common, and mood, diet and sleep were worse, respectively.Conclusion: Opioids prescription during hospitalization might increase the risk of chronic opioid use in opioid native ZRP patients, and it has limited benefits in pain control and quality of life improvement. Even though PHN was painful and intractable, the use of opioids should also be more cautious, and strict follow-up, management in this population.Keywords: opioids, persistent opioid use after discharge, real-life, zoster-related pain, postherpetic neuralgia

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

Kaixin Xiong,1,&ast; Peng Yang,2,&ast; Yujia Cui,1 Jia Li,1 Yan Li,1 Boyu Tang1,3 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Center for Oral Diseases & Department of Conservation Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Li, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Email feifeiliyan@163.com Boyu Tang, Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Center for Oral Diseases & Department of Conservation Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Email boyutang@126.comAbstract: Periodontitis is a common chronic bacteria-initiated inflammatory disease that is closely associated with various systemic diseases, including chronic obstructive pulmonary disease (COPD). Periodontitis and COPD share similar risk factors, pathology and microorganisms. Epidemiological and clinical research have shown positive correlation between the two diseases. Individuals with severe periodontitis had a higher risk of developing COPD. Moreover, the relative risk of COPD in severe periodontitis was much higher compared to people without periodontal disease and patients with mild to moderate periodontitis. COPD patients with periodontitis had a higher frequency of COPD exacerbation and periodontal treatment demonstrated some control of COPD. However, the nature of periodontitis affecting COPD still needs further exploration. Periodontitis caused microbial and immune imbalances of the lung through several aspects: (I) under periodontitis status, periodontal pathogens directly caused the lung inflammatory reaction after inhalation and colonization on the lung, (II) periodontitis status promoted the oral colonization of pneumonia-associated pathogens, (III) periodontitis status affected the respiratory epithelium structure and (IV) periodontitis status caused imbalances in neutrophils, macrophages and inflammatory cytokines. In this review, we conclude the association between periodontitis and COPD through several aspects and further discuss the potential mechanism by which periodontitis affects COPD.Plain Language Summary: Epidemiological and clinical research have shown positive correlation between periodontitis and COPD. Individuals with severe periodontitis had a higher risk of developing COPD. COPD patients with periodontitis had a higher frequency of COPD exacerbation. Meanwhile, periodontal treatment demonstrated some control of COPD. In this review, we concluded the association between periodontitis and further summarized that periodontitis caused microbial and immune imbalances of the lung through several aspects: (I) under periodontitis status, periodontal pathogens directly caused the lung inflammatory reaction after inhalation and colonization on the lung, (II) periodontitis status promoted the oral colonization of pneumonia-associated pathogens, (III) periodontitis status affected the respiratory epithelium structure and (IV) periodontitis status caused imbalances in neutrophils, macrophages and inflammatory cytokines.Keywords: COPD, microorganism, immune, inflammation

Rui Ma,1,&ast; Yanwen Su,2,3,&ast; Ruomu Cao,1 Kunzheng Wang,1 Pei Yang1 1Department of Bone and Joint Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, 710004, People’s Republic of China; 2State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 3National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kunzheng Wang; Pei Yang, Email wkzh1955@163.com; yangpei@xjtu.edu.cnBackground: Tissue engineering scaffolds are porous and can be loaded with growth factors to promote osteogenesis and bone repair, which can solve the problem of clinical bone defects. The direct loading of growth factors on scaffolds is hindered by the disadvantages of low loading capacities, and uncontrollable burst release. Zeolitic imidazolate framework-8 (ZIF-8) has osteoinductive activity and drug-loading potential and can be loaded with growth factors to achieve sustained release. In this study, we aimed to establish a sustained release system of composite scaffolds loaded with growth factors to achieve the goal of slow controlled release and effective bone repair.Methods: ZIF‑8 nanoparticles loaded with bone morphogenetic protein-2 (BMP-2) were incorporated into poly-(lactide-co-glycolide)/mesoporous bioactive glass (PLGA/MBG) porous scaffolds by a 3D-printing method. The surface morphology, chemical properties and BMP-2 release of the prepared scaffold were investigated. The osteoblast adhesion, proliferation, spreading, and osteogenic differentiation in vitro and the bone repair ability in vivo of the PLGA/MBG/ZIF-8/BMP-2 (PMZB) scaffold were evaluated, and compared with those of PLGA/MBG (PM) and PLGA/MBG/ZIF-8 (PMZ) scaffolds.Results: The results showed that the PMZB scaffold exhibited a slow and continuous BMP-2 release pattern, enhanced osteoblast adhesion, proliferation, spreading and osteogenic differentiation in vitro, and promoted new bone formation and bone repair in vivo.Conclusion: The PLGA/MBG/ZIF-8/BMP-2 porous scaffold could continuously and slowly release BMP-2, enhance osteogenic activity, and promote new bone formation and bone repair at bone defects. The PMZB scaffold can be used as a bone graft material to repair bone defect at non-weight-bearing sites.Keywords: bone repair, controlled release, zeolitic imidazolate frameworks-8, mesoporous bioactive glass, scaffold

Yujun He,1 Furui Miao,1 Yushan Fan,1 Jiujie He,1 Fangzhi Zhang,1 Zibin Wang,1 Yu Wu,1 Yiping Zhao,1 Pu Yang2 1Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of ChinaCorrespondence: Furui Miao; Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning City, People’s Republic of China, Email snowymiao@163.com; doctorfanyushan@163.comBackground: Piriformis syndrome (PS) is a neuromuscular condition characterized by discomfort in the gluteal region. The efficacy of acupuncture as a treatment modality for PS has been substantiated through a multitude of clinical trials. However, certain queries persist, such as the optimal approach for identifying the most efficacious acupoints. The objective of this study is to perform an initial data mining analysis aimed at identifying the optimal acupoint selection and combinations for the treatment of PS.Methods: We will search 7 electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and Chongqing VIP Database) from inception to June 2023. We will select clinical trials that evaluate the efficacy of acupuncture therapy in the management of PS. Exclusions will be made for reviews, protocols, animal trials, case reports, systematic reviews, and meta-analyses. The primary outcome measure will be clinical outcomes associated with PS. Descriptive statistics will be performed in Excel 2019. Association rule analysis will be performed in SPSS Modeler 18.0. Exploratory factor analysis and cluster analysis will be performed in SPSS Statistics 26.0.Results: This study will investigate the most effective acupoint selection and combinations for patients with PS.Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with PS, helping clinicians and patients make a more informed decision together.Keywords: piriformis syndrome, acupuncture, data mining

Yujun He,1 Furui Miao,1 Yushan Fan,1 Fangzhi Zhang,1 Pu Yang,2 Xinyi Zhao,3 Miaodong Wang,2 Cai He,1 Jiujie He1 1Faculty of Acupuncture, Moxibustion and Tui Na of Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of China; 2Graduate School of Guangxi University of Traditional Chinese Medicine, Nanning, 530200, People’s Republic of China; 3Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of ChinaCorrespondence: Furui Miao; Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning, Guangxi, 530001, People’s Republic of China, Email snowymiao@163.com; doctorfanyushan@163.comBackground: Piriformis syndrome (PS) is a common disease that is difficult to clinically treat, which seriously affects people’s health and living quality. Multiple clinical studies have demonstrated that acupuncture therapy is an effective treatment for PS, but the optimal method of various acupuncture methods has remained unknown. The aim of this study protocol is to compare the efficacy and the safety of different acupuncture methods for PS.Methods: We will search seven electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chongqing VIP Database) from inception to June 2023. Randomized controlled trials (RCTs) will be selected for assessing the effectiveness of acupuncture therapy on PS. Primary outcome measure for this study is pain intensity, and the secondary outcomes are clinical symptoms and signs, physical activity, effective rate, and adverse events. Study selection, data extraction, and risk of bias assessment will be independently completed by at least two reviewers. Then, standard pairwise meta-analysis and network meta-analysis will be conducted using Revman 5.3, Stata V.15.1 and OpenBUGS V.3.2.3. The heterogeneity will be explored by subgroup, meta-regression, and sensitivity analysis, if applicable. Finally, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) pro system will be used to evaluate the quality of evidence.Results: Our systematic review and network meta-analysis will identify the best acupuncture treatment method for PS patients.Conclusion: The results of our review will help decision-makers make educated choices regarding evidence-based acupuncture management options for PS.Prospero Registration Number: No. CRD42022335028.Keywords: piriformis syndrome, systematic review, network meta-analysis, protocol

Pu Yang,1,&ast; Hai-Yan Chen,2,&ast; Xi Zhang,2 Tian Wang,1 Ling Li,2 Hong Su,1 Jing Li,1 Yan-Jun Guo,1 Sheng-Yong Su2,3 1Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 3Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng-Yong Su, Email ssy21008@126.comPurpose: Cervical spondylotic radiculopathy (CSR) is a common neurologic condition that causes chronic neck pain and motor functions, with neuropathic pain (NP) being the primary symptom. Although it has been established that electroacupuncture (EA) can yield an analgesic effect in clinics and synaptic plasticity plays a critical role in the development and maintenance of NP, the underlying mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms underlying EA’s effect on synaptic plasticity in CSR rat models.Materials and Methods: The CSR rat model was established by spinal cord compression (SCC). Electroacupuncture stimulation was applied to LI4 (Hegu) and LR3 (Taichong) acupoints for 20 min once a day for 7 days. Pressure pain threshold (PPT) and mechanical pain threshold (MPT) were utilized to detect the pain response of rats. A gait score was used to evaluate the motor function of rats. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM) were performed to investigate the effects of EA.Results: Our results showed that EA alleviated SCC-induced spontaneous pain and gait disturbance. ELISA showed that EA could decrease the concentration of pain mediators in the cervical nerve root. WB, IHC, and IF results showed that EA could downregulate the expression of synaptic proteins in spinal cord tissues and promote synaptic plasticity. TEM revealed that the EA could reverse the synaptic ultrastructural changes induced by CSR.Conclusion: Our findings reveal that EA can inhibit SCC-induced NP by modulating the synaptic plasticity in the spinal cord and provide the foothold for the clinical treatment of CSR with EA.Keywords: electroacupuncture, synaptic plasticity, cervical spondylotic radiculopathy, spinal dorsal horn

Yujun He,1 Furui Miao,1 Yushan Fan,1 Fangzhi Zhang,1 Pu Yang,2 Xinyi Zhao,3 Miaodong Wang,2 Cai He,1 Jiujie He1 1Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 3Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, People’s Republic of ChinaCorrespondence: Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS), as the most common compression neuropathy in the upper limb, can lead to upper limb dysfunction in patients. The effectiveness of acupuncture in treating CTS has been validated based on numerous clinical trials and meta-analyses, but questions remain, such as how to select the best acupoints. Our purpose is to conduct the first data mining analysis to identify the most effective acupoint selection and combinations for treating CTS.Methods: We will search 7 electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and Chongqing VIP Database) from inception to March 2023. Clinical trials assessing the effectiveness of acupuncture therapy on the management of CTS will be selected. Reviews, protocols, animal trials, case reports, systematic reviews, and meta-analyses will be excluded. The primary outcome measure will be clinical result associated with CTS. Descriptive statistics will be performed in Excel 2019. Association rule analysis will be performed in SPSS Modeler 18.0. Exploratory factor analysis and cluster analysis will be performed in SPSS Statistics 26.0.Results: This study will investigate the most effective acupoint selection and combinations for patients with CTS.Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with CTS, helping clinicians and patients make a more informed decision together.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

Fang Rong,1,2,&ast; Ziyi Liu,3,4,&ast; Pengbin Yang,3,4 Feng Wu,5 Yu Sun,5 Xuewei Sun,5 Jun Zhou5 1Department of General Practice, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Graduate School Department of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 4Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhou, Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225009, People’s Republic of China, Email zj662121@163.comObjective: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged and spread worldwide. It can usually cause a serious threat complicating treatment options in clinical settings. However, treatment options are limited. The present study investigates the prevalence and genetic characteristics of blaNDM-1 and blaKPC-2 co-harboring clinical isolates of Klebsiella pneumoniae.Methods: In this study, Multiplex polymerase chain reaction (PCR) was performed to detect the carbapenem-resistant genes, and the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of antibacterial drugs. The transferability of carbapenem-resistant phenotypes was examined using filter mating assays. Overall, we used Illumina sequencing to evaluate the epidemiological and molecular characteristics of blaNDM-1 and blaKPC-2 (genes encoding carbapenemase) co-occurrence in CRKP strains.Results: All strains exhibited resistance to carbapenems and other antibiotics. However, they were still susceptible to polymyxin E. Among them, 18 isolates were positive for blaKPC-2, blaNDM-1, and multiple virulence determinants, such as genes encoding the virulence factor aerobactin, yersiniabactin, and the regulator of the mucoid phenotype (rmpA and rmpA2). Whole genome sequencing revealed that the 18 CRKP strains belonged to ST11 and capsular serotype KL64, and could be grouped into two evolutionary branches. Furthermore, these strains displayed hypervirulence potential since all of them carried pLVPK-like plasmid.Conclusion: These findings suggested that ST11-KL64 CRKP strains are major threats in terms of nosocomial infections in this hospital. Hence, new strategies should be urgently developed to monitor, diagnose, and treat this high-risk CRKP clone.Keywords: Klebsiella pneumoniae, carbapenem resistance, illumina sequencing, blaKPC-2, blaNDM-1

Peixiang Yang, Xiangxia Rong, Tao Wang, Xiuqun Gong, Chuanqing Yu, Bu Xu, Xiaoli Xing Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, People’s Republic of ChinaCorrespondence: Xiangxia Rong, Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital), Huainan, Anhui, People’s Republic of China, Email rongxiangxia1584@163.comObjective: To explore the effects of cluster nursing on self-care ability, length of hospital stay, complications and neurological function of patients with mechanical thrombectomy of large vessel occlusion in acute cerebral infarction.Methods: A total of 83 patients with acute cerebral infarction who underwent thrombolectomy in a tertiary hospital in Anhui Province from June 2019 to March 2021 were randomly divided into observation group and control group. The observation group was treated with cluster nursing intervention mode, and the control group was treated with routine nursing mode. Barthel index scores and National Institute of Health Stroke Scale (NIHSS) scores were compared between the two groups at admission and at 1 week, 1 month and 3 months of nursing intervention. The length of stay and incidence of complications were compared between the two groups.Results: There was no significant difference in baseline data, Barthel index and NIHSS score between the two groups at admission (P> 0.05). The Barthel index at 1 week, 1 month and 3 months after operation in the observation group was significantly higher than that in the control group (P< 0.05), while the NIHSS score, incidence of complications and length of hospital stay were significantly lower than those of the control group (P< 0.05).Conclusion: Cluster nursing can improve the neurological function, improve the self-care ability, reduce the incidence of complications, shorten the hospitalization period, improve the prognosis and promote the recovery of patients with acute cerebral infarction thrombolysis.Keywords: acute cerebral infarction, cluster nursing, mechanical thrombectomy, complication, the quality of life

Xing Rong,1,2 Yuying Kou,1,2 Yuan Zhang,1,2 Panpan Yang,1,2 Rong Tang,1,2 Hongrui Liu,1,2 Minqi Li1,2 1Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, People’s Republic of China; 2Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Minqi Li; Hongrui Liu, Center of Osteoporosis and Bone Mineral Research, Shandong University, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, People’s Republic of China, Tel +86-531-88382095 ; +86-531-88382493, Fax +86-531-8838 2923, Email liminqi@sdu.edu.cn; yf1blhr@126.comPurpose: Long-term glucocorticoid- usage can lead to glucocorticoid-induced osteoporosis (GIOP). The study focused on the preventative effects of a novel active vitamin D3 analog, eldecalcitol (ED-71), against GIOP and explored the underlying molecular mechanisms.Methods: Intraperitoneal injection of methylprednisolone (MPED) or dexamethasone (DEX) induced the GIOP model within C57BL/6 mice in vivo. Simultaneously, ED-71 was orally supplemented. Bone histological alterations, microstructure parameters, novel bone formation rates, and osteogenic factor changes were evaluated by hematoxylin-eosin (HE) staining, micro-computed tomography, calcein/tetracycline labeling, and immunohistochemical (IHC) staining. The osteogenic differentiation level and mineralization in pre-osteoblast MC3T3-E1 cells were evaluated in vitro using alkaline phosphatase (ALP) staining, alizarin red (AR) staining, quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescence staining.Results: ED-71 partially prevented bone mass reduction and microstructure parameter alterations among GIOP-induced mice. Moreover, ED-71 also promoted new bone formation and osteoblast activity while inhibiting osteoclasts. In vitro, ED-71 promoted osteogenic differentiation and mineralization in DEX-treated MC3T3-E1 cells and boosted the levels of osteogenic-related factors. Additionally, GSK3-β and β-catenin expression levels were elevated after ED-71 was added to cells and were accompanied by reduced Notch expression. The Wnt signaling inhibitor XAV939 and Notch overexpression reversed the ED-71 promotional effects toward osteogenic differentiation and mineralization.Conclusion: ED-71 prevented GIOP by enhancing osteogenic differentiation through Notch and Wnt/GSK-3β/β-catenin signaling. The results provide a novel translational direction for the clinical application of ED-71 against GIOP.Keywords: glucocorticoid-induced osteoporosis, eldecalcitol, osteoblasts, Notch signaling, Wnt/GSK-3β/β-catenin signaling

Ping Yang,1,2 Chao Liu,3 Zhenchao Wu,2 Jiajia Zheng,4 Juan Yi,1 Nan Wu,2 Zhangli Wu,1,2 Ming Lu,2,3 Liyan Cui,4,&ast; Ning Shen1– 3,&ast; 1Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Infectious Diseases, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Laboratory Medicine, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyan Cui; Ning Shen, Email cliyan@163.com; shenningputh@163.comPurpose: This study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection.Materials and Methods: A retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥ 1 carbapenem, ≥ 1 extended-spectrum cephalosporin, and ≥ 1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA-, or rmpA2-positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed.Results: Fifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P< 0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as blaKPC-2, blaTEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections.Conclusion: DTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.Keywords: Klebsiella pneumoniae, difficult-to-treat resistance, mortality, risk factor