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Articular cartilage damage and degeneration are among hallmark manifestations of joint injuries and arthritis, classically osteoarthritis. Cartilage compositional MRI (Cart-C MRI), a quantitative technique, which aims to detect early-stage cartilage matrix changes that precede macroscopic alterations, began development in the 1990s. However, despite the significant advancements over the past three decades, Cart-C MRI remains predominantly a research tool, hindered by various technical and clinical hurdles. This paper will review the technical evolution of Cart-C MRI, delve into its clinical applications, and conclude by identifying the existing gaps and challenges that need to be addressed to enable even broader clinical application of Cart-C MRI.

BACKGROUND: Given the complexity of arthroscopic rotator cuff repair (ARCR) and increasing prevalence, there is a need for comprehensive, large-scale studies that investigate potential correlations between surgeon-specific factors and postoperative outcomes after ARCR. This study examines how surgeon-specific factors including case volume, career length, fellowship training, practice setting, and regional practice impact two-year reoperation rates, conversion to total shoulder arthroplasty (anatomic or reverse), and 90-day post-ARCR hospitalization. METHODS: The PearlDiver Mariner database was used to collect surgeon-specific variables and query patients who underwent ARCR from 2015 to 2018. Patient outcomes were tracked for two years, including reoperations, hospitalizations, and International Classification of Diseases, Tenth Revision codes for revision rotator cuff repair (RCR) laterality. Hospitalizations were defined as any emergency department (ED) visit or hospital readmission within 90 days after primary ARCR. Surgeon-specific factors including surgeon case volume, career length, fellowship training, practice setting, and regional practice were analyzed in relation to postoperative outcomes using both univariate and multivariate logistic regression. RESULTS: 94,150 patients underwent ARCR by 1489 surgeons. On multivariate analysis, high-volume surgeons demonstrated a higher risk for two-year total reoperation (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01-1.12, P = .03) and revision RCR (OR = 1.06, 95% CI: 1.01-1.12, P = .02) compared to low-volume surgeons. Early-career surgeons showed higher rates of 90-day ED visits (mid-career surgeons: OR = 0.78, 95% CI: 0.73-0.83, P

BACKGROUND: The impact of early glenohumeral osteoarthritis (GHOA) on clinical outcomes after rotator cuff repair (RCR) remains unclear. The magnetic resonance imaging (MRI)-based Shoulder Osteoarthritis Severity (SOAS) score is a comprehensive approach to quantifying glenohumeral degeneration. PURPOSE: To investigate the association between SOAS scores and changes in American Shoulder and Elbow Surgeons (ASES) scores in patients who underwent RCR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Two reviewers independently analyzed the preoperative MRI scans of 116 shoulders and assigned SOAS scores. Spearman correlation was used to calculate the association of mean SOAS scores with patient demographic characteristics and change in ASES scores over the 2-year follow-up period (ΔASES). Multivariate regression analysis was performed between the independent variables of patient age, sex, body mass index, and significant SOAS score components as determined by univariate analysis, with the dependent variable being ΔASES. Significance was defined as P < .05 for univariate analysis and P < .0125 after application of the Bonferroni correction for multivariate analysis. RESULTS: The mean ASES scores were 55.8 ± 18.6 preoperatively and 92.1 ± 12.1 at 2 years postoperatively. The mean preoperative SOAS score was 15.2 ± 7.1. On univariate analysis, the total SOAS score was positively correlated with patient age (r S = 0.41; P < .001), whereas ΔASES was negatively correlated with patient age (r S = -0.27; P = .0032). Increasing SOAS subscores for supraspinatus/infraspinatus tear size (r S = -0.28; P = .024), tendon retraction (r S = -0.23; P = .015), muscle atrophy (r S = -0.20; P = .034), paralabral ganglia (r S = -0.23; P = .015), and cartilage degeneration (r S = -0.21; P = .024) were negatively correlated with ΔASES. A negative correlation was found between increasing total SOAS score and ΔASES (r S = -0.22; P = .016). On multivariate analysis, increasing supraspinatus/infraspinatus tear size was significantly and negatively correlated with ΔASES (β = -3.3; P = .010). CONCLUSION: Increasing the total SOAS score was predictive of less improvement in ASES scores at 2 years postoperatively. On univariate analysis, SOAS subscores with the strongest negative correlations with ΔASES scores included tear size, muscle atrophy, tendon retraction, paralabral ganglia, and cartilage wear. On multivariate analysis, only tear size was significantly associated with a lower change in the ASES score.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondiis invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk populations exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

OBJECTIVE: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears. METHODS: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis. RESULTS: A total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2 increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01-1.81) increased odds among individuals with full-thickness tear. CONCLUSIONS: Higher BMI was associated with significantly higher odds of muscle atrophy in patiens with rotator cuff tears. More study is needed to unders1tand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients. LEVEL OF EVIDENCE: III.

BACKGROUND: Anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA) reliably alleviate pain and restore shoulder function for a variety of indications. However, these procedures are not well-studied in patients with neurocognitive impairment. Therefore, the purpose of this study was to investigate whether patients with dementia or mild cognitive impairment (MCI) have increased odds of surgical or medical complications following arthroplasty. METHODS: The PearlDiver database was queried from 2010 through October 2021 to identify a cohort of patients who underwent either ATSA or RTSA and had a minimum 2-year follow-up. Current Procedural Terminology and International Classification of Diseases codes were used to stratify this cohort into three groups: (1) patients with dementia, (2) patients with MCI, and (3) patients with neither condition. Surgical and medical complication rates were compared among these three groups. RESULTS: The overall prevalence of neurocognitive impairment among patients undergoing total shoulder arthroplasty was 3.0% in a cohort of 92,022 patients. Patients with dementia had increased odds of sustaining a periprosthetic humerus fracture (odds ratio [OR] = 1.46, P

Chaoping Ma,1,&ast; Weisong Jiang,2,&ast; Juan Li,1,&ast; Wenwu Sun,2,&ast; Jiyuan Zhang,1 Peixian Xu,1 Yiran Guo,1 Ning Ning,2 Jiaoyan Li,2 Bing Zhao,2 Enqiang Mao,2 Chengjin Gao1 1Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China; 2Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao; Enqiang Mao, Email gaochengjin@xinhuamed.com.cn; maoeq@yeah.netIntroduction: In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels.Methods: Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients.Results: A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile.Discussion: In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.Keywords: sepsis, stress hyperglycemia ratio, mortality, Hyperglycemia

Jing Ye,1,2,&ast; Ping Li,1,2,&ast; Pengcheng Liu,1,2 Wenjing Pei,1,2 Ruowen Wang,1,2 Hui Liu,1,2 Changxiu Ma,1,2 Dahai Zhao1,2 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 2Institute of Respiratory Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dahai Zhao, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Email zhaodahai@ahmu.edu.cnBackground: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis.Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways.Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long−term depression, retrograde endocannabinoid signaling, and so on.Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression.Keywords: metabolomics, AECOPD, anxiety, depression, exacerbation

Yong Zhu,1,&ast; Yongzhe Zhang,2,&ast; Xiuli Yu,3 Huaqiang Zhao,1 Chuan Ma1 1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of China; 2Department of Prosthodontics, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 3Department of Stomatology, Chengyang People’s Hospital, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Ma, Department of Oral and Maxillofacial Surgery, 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 & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Fax +86 53188382923, Email machuan@sdu.edu.cnObjective: Tumor cells, inflammatory cells, and chemical factors collaboratively orchestrate a sophisticated signaling network, culminating in the formation of the inflammatory tumor microenvironment (TME). The present study sought to explore the nature of the inflammatory response in HNSCC and to decipher its influence on immunotherapeutic.Materials and Methods: A thorough analysis was performed utilizing the TCGA cohort along with two GEO cohorts. Unsupervised clustering of 200 inflammatory response-related genes (IRGs) was applied using the k-means algorithm to explore the heterogeneity of HNSCC. Additionally, a prognostic signature based on IRGs genes was constructed using Lasso regression. Meanwhiles, the expression of IRGs were identified in tumors and paracancerous tissues at the single-cell level. The crosstalk between IRGs was explored using CellChat and the patterns of incoming and outgoing signals were identified. Finally, qPCR was used to verify the expression of hub genes.Results: There were significant differences in immune-cell function and immune-cell infiltration among three inflammatory response clusters. Additionally, we also constructed a prognostic model which could predicted the responses of common chemotherapeutic drugs and immunotherapy. Furthermore, qPCR and sc-RNA seq corroborated that the expression profiles of the prognostic genes were largely in alignment with the findings from the bioinformatics analysis. Ultimately, the molecular docking demonstrated favorable binding affinities between the pivotal gene-SCC7 and four chemotherapeutic drugs.Conclusion: This research has uniquely shed light on the intricate connection between the inflammatory response profiles and the immune infiltration patterns in HNSCC.Keywords: HNSCC, TME, inflammatory response, immunotherapy, sc-RNA seq

Mina Wang,1,2,&ast; Yashuo Ren,1,&ast; Hongli Xiao,1 Anming Liu,1,2 Chunying Ma,2 Zhuohao Li,2 Zixi Wang,2 Qiuyu Xia,2 Pu Dou,1 Bin Li,2 Peng Chen2 1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Chen; Bin Li, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23 Meishuguanhou Street, Beijing, Dongcheng District, 100010, People’s Republic of China, Email chenpenger@126.com; libin@bjzhongyi.comIntroduction: Parkinson’s disease (PD)-related chronic pain is a prevalent non-motor symptom, this study aimed to detect the effect and safety of fire needling therapy (FNT) for PD-related chronic pain relief.Methods: Patients with PD-related chronic pain were randomly allocated to FNT group and control group with a treatment phase of 8 weeks and a follow-up phase of 4 weeks. Primary outcome was the King’s Parkinson’s Pain Scale (KPPS), Secondary outcomes included Visual Analogue Scale (VAS), Unified Parkinson’s Disease Rating Scale-III (UPDRS-III), and the Parkinson’s Disease Questionnaire-39 (PDQ-39). Study was registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2400084951).Results: 60 participants were randomized, with 30 in the FNT group and 30 in the control group. KPPS was significantly influenced by the interaction of treatment and time, with a significant reduction in pain observed in the FNT group compared to the control group at Week 4 (difference [95% CI]: − 20.693[− 27.619,-13.767], P< 0.001), Week 8 (difference [95% CI]: 44.680[− 52.359,-37.000], P< 0.001), and Week 12 (difference [95% CI]: − 44.982[− 52.771,-37.193], P< 0.001). For VAS, UPDRS-III, and PDQ-39, there were significant differences between groups at Week 4, Week 8, and Week 12.Conclusion: FNT could be an effective and safe method for managing PD-related chronic pain. However, large-sample studies conducted in multiple centers are necessary to further verify the findings in the future.Keywords: parkinson’s disease, pain, fire needling therapy, acupuncture, pilot randomized controlled trial

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

BACKGROUND: Humeral avulsion of the glenohumeral ligament (HAGL) lesions are an uncommon cause of anterior glenohumeral instability and may occur in isolation or combination with other pathologies. As HAGL lesions are difficult to detect via magnetic resonance imaging (MRI) and arthroscopy, they can remain unrecognized and result in continued glenohumeral instability. PURPOSE: To compare patients with anterior shoulder instability from a large multicenter cohort with and without a diagnosis of a HAGL lesion and identify preoperative physical examination findings, patient-reported outcomes, imaging findings, and surgical management trends associated with HAGL lesions. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with anterior glenohumeral instability who underwent surgical management between 2012 and 2020 at 11 orthopaedic centers were enrolled. Patients with HAGL lesions identified intraoperatively were compared with patients without HAGL lesions. Preoperative characteristics, physical examinations, imaging findings, intraoperative findings, and surgical procedures were collected. The Student t test, Kruskal-Wallis H test, Fisher exact test, and chi-square test were used to compare groups. RESULTS: A total of 21 HAGL lesions were identified in 915 (2.3%) patients; approximately one-third (28.6%) of all lesions were visualized intraoperatively but not identified on preoperative MRI. Baseline characteristics did not differ between study cohorts. Compared with non-HAGL patients, HAGL patients were less likely to have a Hill-Sachs lesion (54.7% vs 28.6%; P = .03) or an anterior labral tear (87.2% vs 66.7%; P = .01) on preoperative MRI and demonstrated increased external rotation when their affected arm was positioned at 90° of abduction (85° vs 90°; P = .03). Additionally, HAGL lesions were independently associated with an increased risk of undergoing an open stabilization surgery (odds ratio, 74.6 [95% CI, 25.2-221.1]; P < .001). CONCLUSION: Approximately one-third of HAGL lesions were missed on preoperative MRI. HAGL patients were less likely to exhibit preoperative imaging findings associated with anterior shoulder instability, such as Hill-Sachs lesions or anterior labral pathology. These patients underwent open procedures more frequently than patients without HAGL lesions.

Juan Li,1,&ast; Shu Wang,2,&ast; Chaoping Ma,1,&ast; Ning Ning,3,&ast; Yingying Huang,1,4,&ast; Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Rui Shen,1,2,&ast; Kebin Cheng,3,&ast; Guanyi Li,1 Zhendong Pan,4 Xijier Qiaolongbatu,1 Yuting Wang,1 Cui Ma,1 Xucong Huang,1 Li Wang,1 Wenjing Li,1 Yuanyuan Wang,2 Lili Jing,1 Guorong Fan,2 Zhenghua Wu2 1School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 4Department of Clinical Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghua Wu, Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-159-0161-7923, Email wuzhenghua@sjtu.edu.cnPurpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME.Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms.Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO’s ME-inhibitory effects.Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME. Keywords: Alisma orientale, macular edema, network pharmacology, zebrafish, TNF-&#x03B1

Simin Liu,1,&ast; Zhiyuan Tian,2 Taiming Zhang,3 Jirong Zhang,3 Yanlei Huo,1,&ast; Chao Ma1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Zibo Ninth People’s Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Medical Imaging, People’s Hospital of Shuangjiang Autonomous Country, Lincang, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of China, Tel +86 21-66302075, Email mc_7419@hotmail.comObjective: To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, brand name, Yunke) on bone metastases (BM).Procedures: In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, 99Tc+SnCl2 and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed.Results: In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38.Conclusion: Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.Keywords: 99Tc-MDP, bone metastases, molecular mechanisms, RM-1, prostate cancer

Ming Cheng,1,2 Cong Ma,1– 3 Hong-Duo Chen,1,2 Yan Wu,1,2 Xue-Gang Xu1,2 1Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China; 2Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China; 3Department of Dermatology and Sexually Transmitted Diseases, The First Hospital of Inner Mongolia University for Nationalities, Tongliao, 028000, People’s Republic of ChinaCorrespondence: Xue-Gang Xu; Yan Wu, Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China, Email xuxuegang2749290@163.com; jlwuyan@126.comAbstract: Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth.Keywords: exosome, hair follicle, alopecia

Changxiu Ma,1 Ying Zhang,1 Tingchao Tian,2 Ling Zheng,1 Jing Ye,1 Hui Liu,1 Dahai Zhao1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huoqiu First People’s Hospital, Huoqiu, 237400, People’s Republic of ChinaCorrespondence: Dahai Zhao, Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Tel +86-13721027959, Email zhaodahai@ahmu.edu.cnPurpose: To explore the role of the mean apnea–hypopnea duration (MAD) and apnea–hypopnea duration per hour (HAD) in hypoxemia and evaluate whether they can effectively predict the occurrence of hypoxemia among adults with OSA.Patients and Methods: A total of 144 participants underwent basic information gathering and polysomnography (PSG). Logistic regression models were conducted to evaluate the best index in terms of hypoxemia. To construct the prediction model for hypoxemia, we randomly divided the participants into the training set (70%) and the validation set (30%).Results: The participants with hypoxemia tend to have higher levels of obesity, diabetes, AHI, MAD, and HAD compared with non-hypoxemia. The most relevant indicator of blood oxygen concentration is HAD (r = 0.73) among HAD, MAD, and apnea–hypopnea index (AHI). The fitness of HAD on hypoxemia showed the best. In the stage of establishing the prediction model, the area under the curve (AUC) values of both the training set and the validation set are 0.95. The increased HAD would elevate the risk of hypoxemia [odds ratio (OR): 1.30, 95% confidence interval (CI): 1.13– 1.49].Conclusion: The potential role of HAD in predicting hypoxemia underscores the significance of leveraging comprehensive measures of respiratory disturbances during sleep to enhance the clinical management and prognostication of individuals with sleep-related breathing disorders.Keywords: mean apnea–hypopnea duration, obstructive sleep apnea, apnea–hypopnea duration per hour, polysomnography, apnea–hypopnea index

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li5,6 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 6Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86-371-66278091, Email gmchao219@163.comAbstract: Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients’ visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.Keywords: melatonin, fundus degeneration, oxidative stress, inflammation, anti-apoptotic

PURPOSE OF REVIEW: Periprosthetic infection after shoulder arthroplasty is relatively uncommon though associated with severe long-term morbidity when encountered. The purpose of the review is to summarize the recent literature regarding the definition, clinical evaluation, prevention, and management of prosthetic joint infection after reverse shoulder arthroplasty. RECENT FINDINGS: The landmark report generated at the 2018 International Consensus Meeting on Musculoskeletal Infection has provided a framework for diagnosis, prevention, and management of periprosthetic infections after shoulder arthroplasty. Shoulder specific literature with validated interventions to reduce prosthetic joint infection is limited; however existing literature from retrospective studies and from total hip and knee arthroplasty allows us to make relative guidelines. One and two-stage revisions seem to demonstrate similar outcomes; however, no controlled comparative studies exist limiting the ability to make definitive recommendations between the two options. We report on recent literature regarding the current diagnostic, preventative, and treatment options for periprosthetic infection after shoulder arthroplasty. Much of the literature does not distinguish between anatomic and reverse shoulder arthroplasty, and further high-level shoulder specific studies are needed to answer questions generated from this review.

PurposeTo use T1ρ and T2 magnetic resonance imaging to evaluate the effect of leukocyte-poor platelet-rich plasma (LP-PRP) injections on knee cartilage health and to correlate structural changes with patient-reported outcome measurements.MethodsTen patients with symptomatic unilateral mild-to-moderate knee osteoarthritis (Kellgren-Lawrence Grade 1-2) underwent T1ρ and T2 magnetic resonance imaging of both the symptomatic and contralateral knee before injection and 6 months after injection with LP-PRP. Patient-reported outcome questionnaires (Knee Osteoarthritis Outcome Score and International Knee Documentation Committee) that evaluate the domains of pain, symptoms, activities of daily living, sports function, and quality of life were completed at baseline, 3 months, 6 months, and 12 months after injection. T1ρ and T2 relaxation times, which are correlated with the proteoglycan and collagen concentration of cartilage, were measured in compartments with and without chondral lesions.ResultsTen patients were prospectively enrolled (9 female, 1 male) with a mean age of 52.9 years (range, 42-68) years and mean body mass index of 23.2 ± 1.9. Significant increases in Knee Osteoarthritis Outcome Score for all subscales and International Knee Documentation Committee scores were observed 3 months after injection and the improvements were sustained at 12 months. T1ρ and T2 values of compartments with chondral lesions were observed to significantly decrease by 6.0% (P = .036) and 7.1% (P = .017) 6 months after LP-PRP injection, respectively. No significant associations between T1ρ and T2 relaxation times and improvement in patient-reported outcomes were observed.ConclusionsPatients undergoing LP-PRP injections for the treatment of mild-to-moderate knee osteoarthritis had increased proteoglycan and collagen deposition in the cartilage of affected compartments by 6 months after injection. Patient-reported outcomes scores improved 3 months after injection and were sustained through 1 year after injection, but these improvements were not associated with the changes in proteoglycan and collagen deposition in knee cartilage.Level of evidenceLevel II, prospective cohort study.

BACKGROUND: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction. PURPOSE: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patients outcome at 6-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx Activity Rating Scale. Patients were followed up at 6 years and asked to complete the identical set of outcome instruments. Regression analysis assessed the meniscal and articular cartilage pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction. RESULTS: An overall 1234 patients were enrolled (716 males, 58%; median age, 26 years). Surgeons reported the pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (43%), lateral femoral condyle (29%), medial tibial plateau (11%), lateral tibial plateau (17%), patella (30%), and trochlea (21%). Six-year follow-up was obtained on 79% of the sample (980/1234). Meniscal pathology and articular cartilage pathology (medial femoral condyle, lateral femoral condyle, lateral tibial plateau, trochlea, and patella) were significant drivers of poorer patient-reported outcomes at 6 years (IKDC, KOOS, WOMAC, and Marx). The most consistent factors driving outcomes were having a medial meniscal excision (either before or at the time of revision surgery) and patellofemoral articular cartilage pathology. Six-year Marx activity levels were negatively affected by having either a repair/excision of the medial meniscus (odds ratio range, 1.45-1.72; P≤ .04) or grade 3-4 patellar chondrosis (odds ratio, 1.72; P = .04). Meniscal pathology occurring before the index revision surgery negatively affected scores on all KOOS subscales except for sports/recreation (P < .05). Articular cartilage pathology significantly impaired all KOOS subscale scores (P < .05). Lower baseline outcome scores, higher body mass index, being a smoker, and incurring subsequent surgery all significantly increased the odds of reporting poorer clinical outcomes at 6 years. CONCLUSION: Meniscal and chondral pathology at the time of revision ACL reconstruction has continued significant detrimental effects on patient-reported outcomes at 6 years after revision surgery.

Chenlu Ma,1 Wen Zhang,1 Shu Da,2 Huan Zhang,3 Xichao Zhang1 1Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China; 2School of Psychology, Nanjing Normal University, Nanjing, 210024, People’s Republic of China; 3Academy of Global Innovation & Governance, University of International Business and Economics, Beijing, 100029, People’s Republic of ChinaCorrespondence: Xichao Zhang, Faculty of Psychology, Beijing Normal University, No. 19 XinJieKouWai Street, HaiDian District, Beijing, 100875, People’s Republic of China, Email xchzhang@bnu.edu.cnPurpose: Environmental uncertainty has reached unprecedented levels in recent years. While there is substantial knowledge about the connection between environmental uncertainty and organizational outcomes, limited attention has been devoted to investigating its impact on employees’ depression and anxiety symptoms. Grounded in job demands-resources theory, this study aims to explore the relationship between environmental uncertainty and employees’ depression and anxiety symptoms, and it further investigates the mediating role of work pressure and the moderating role of union practices.Methods: In September 2022, we undertook a cross-sectional survey study, gathering data from 1081 employees across various enterprises situated in Liaoning, China. Throughout this timeframe, notable global occurrences heightened the awareness of environmental uncertainty. Following the exclusion of participants who did not provide information on the main variables, the final valid sample comprised 940 employees. To test all hypotheses, a series of confirmatory factor analyses and path-analytic procedures were conducted using Mplus 7.0.Results: Our results confirm that environmental uncertainty, as a high job demand, increases employees’ work pressure, thereby elevating rates of anxiety and depression; the indirect relationship between environmental uncertainty and employees’ anxiety and depression through work pressure is stronger when union practices are lower.Conclusion: Our findings indicate the detrimental impact of environmental uncertainty on employees’ mental health, and highlight the roles of work pressure and union practices. In light of this, organizations should take steps to mitigate employees’ perceptions of environmental uncertainty and establish mental health programs, in cooperation with union practices, to protect employees’ mental well-being.Keywords: environmental uncertainty, anxiety, depression, union practices, work pressure

Cheng Ma,1 Minnan Yue,2 Xiaoling Zhu1 1Department of Physical Education, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2School of Energy and Power Engineering, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Cheng Ma, Department of Physical education, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of China, Tel +86-13795365789, Email macheng@usst.edu.cnPurpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure.Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy.Results: A total of 969 students were recruited, with mean age of 18.73± 0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57± 0.95, 32.63± 4.07, and 27.06± 7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52– 2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12– 1.22, P < 0.001). A bachelor’s degree and being in the sophomore year were positively associated with knowledge (OR = 1.51– 4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43– 0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33– 2.57, P < 0.001). Father’s education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37– 0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72– 5.55, P < 0.001) were associated with practice.Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.Keywords: knowledge, attitude, practice, cross-sectional study, physical literacy

Background: Food safety plays a significant role in the management and recovery of hospitalized patients. This study has assessed knowledge, attitude, and practices of food handlers on food safety in selected tertiary hospitals in Metro Manila, Philippines.Methods: In a cross-sectional analytical design, the knowledge, attitude, and practice levels of 50 food handlers on food safety in four tertiary Metro Manila hospitals were assessed, and the relationship of knowledge, attitude, and practices with sociodemographic characteristics was investigated using a self-administered questionnaire.Results: Food handlers were shown to have fair knowledge (69.73±11.3%), positive attitude (87.8±7.6%), and good practices (84.3±7.8%) on food safety. They had good knowledge on personal hygiene (99%) and cross-contamination (89%), but had poor knowledge on foodborne diseases (42%) and storage temperatures (31%). The majority of the food handlers reported good food safety practices, food safety control, and food storage. No significant association was demonstrated between sociodemographic characteristics and knowledge, attitude, and practices of food handlers regarding food safety. A correlation was observed between attitude (p=0.4431) and practices (p=0.0013) of food handlers on food safety.Conclusion: Food handlers in hospitals in Metro Manila reported positive attitude and good practices on food safety. Improvement in quality of food services through constant and holistic training and evaluation of food handlers seems essential. The strict compliance to food safety standards should be undertaken to ensure the safety and quality of food served to people.

BackgroundMild to moderate glenohumeral joint osteoarthritis is a common finding among patients who are evaluated for rotator cuff tears. However, the impact of preoperative shoulder joint degeneration on patient-reported outcomes after rotator cuff repair (RCR) is not well-established.PurposeTo apply the magnetic resonance imaging (MRI)-based Shoulder Osteoarthritis Severity (SOAS) score to the evaluation of patients undergoing RCR and determine the relationship between preoperative shoulder pathology present on MRI and postoperative Patient-Reported Outcomes Measurement Information System-Upper Extremity (PROMIS-UE) scores.Study designCase-control study; Level of evidence, 3.MethodsSeventy-one MRI scans corresponding to 71 patients were analyzed by 2 independent reviewers and scored using the SOAS criteria. Intraclass correlation coefficients were calculated for total SOAS score as well as for each subscore. Spearman correlations were calculated between averaged SOAS scores, patient characteristics, and PROMIS-UE scores. Linear regression analysis was performed between the independent variables of patient age, sex, body mass index, and significant SOAS score components determined by univariate analysis with the dependent variable of PROMIS-UE score. Significance was defined as P < .05 for univariate analyses and < .0125 for multivariate analyses using the Bonferroni correction.ResultsThe mean PROMIS-UE score of this cohort was 51.5 ± 7.4, while the mean total SOAS score was 21.5 ± 8.4. There was a negative correlation between total SOAS score and postoperative PROMIS-UE score (r = -0.24; P = .040). Both cartilage wear (r = -0.33; P = .0045) and acromioclavicular joint degeneration (r = -0.24; P = .048) individually demonstrated negative correlations with PROMIS-UE score. When a multivariate linear regression with Bonferroni correction was applied to the significant variables identified in univariate analysis along with patient characteristics, none were independently correlated with PROMIS-UE score.ConclusionIn this cohort of patients undergoing RCR, increasing preoperative total SOAS score was predictive of lower postoperative PROMIS-UE scores. SOAS subscores with the strongest negative correlations with PROMIS-UE scores included cartilage wear and acromioclavicular joint degeneration. The cartilage subscore was negatively correlated with PROMIS-UE scores independent of patient factors in multivariate analysis.

Surgical treatment options for proximal humeral fractures include hemiarthroplasty (HA), reverse shoulder arthroplasty (RSA), and open reduction and internal fixation (ORIF). The objectives of this study were to analyze the trends in surgical treatment of proximal humeral fractures across a decade and to compare complications, reoperation rates, and readmission rates between ORIF and RSA.MethodsThe PearlDiver MUExtr Database was used to identify patients with proximal humeral fractures who were treated with ORIF, HA, or RSA between 2010 and 2019 and analyze yearly trends. Complications, revision procedures, demographic characteristics, comorbidities, and emergency room visits and hospital readmissions within 90 days of the surgical procedure were compared between ORIF and RSA cohorts for patients who had at least 2-year follow-up data.ResultsIn this study, 384,158 patients with proximal humeral fractures were identified in the 10-year period between 2010 and 2019. There was a significant increase in the frequency of RSA and a decrease in the frequency of ORIF and HA over time (p < 0.0001). Compared with patients who underwent ORIF or HA, patients who underwent RSA were more likely to be older (p < 0.0001), to be female, and to have a higher Charlson Comorbidity Index. Patients who underwent ORIF had higher complication rates (23.03% compared with 18.62%; p < 0.0001) and higher reoperation rates (20.3% compared with 10.3%; p < 0.0001) than patients who underwent RSA. Patients who underwent RSA had higher emergency room visit rates (20.0% compared with 16.7%; p < 0.001) and hospital readmission rates (12.9% compared with 7.3%; p < 0.0001) within 90 days of the surgical procedure compared with patients who underwent ORIF.ConclusionsThere has been an increasing trend in RSA utilization for the surgical treatment of proximal humeral fractures, along with a decreasing trend in HA and ORIF, over time. Patients who underwent ORIF for a proximal humeral fracture had higher complication and reoperation rates compared with patients who underwent RSA. Patients who underwent RSA had higher emergency room visit and hospital readmission rates within 90 days of the surgical procedure compared with patients who underwent ORIF, which may be attributable to the RSA cohort being older and having more comorbidities.Level of evidenceTherapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

BackgroundRecurrent shoulder instability is an orthopedic problem with potentially long-term functional ramifications. Although arthroscopic stabilization has become increasingly utilized over open stabilization, optimal surgical intervention to minimize recurrent instability remains controversial.MethodsThe PearlDiver Mariner database was queried for all cases of open and arthroscopic shoulder stabilization from 2010 to 2019. Utilization trends were aggregated after identifying cohorts of 107,210 and 13,217 patients who respectively underwent arthroscopic or open stabilization using Current Procedural Terminology codes. Subsets from those cohorts with laterality-specific International Classification of Diseases, Tenth Revision codes for shoulder instability were used to evaluate 2-year rates of recurrent instability (presence of shoulder dislocation or revision open or arthroscopic stabilization). Linear regression and chi-squared analysis were used to analyze utilization trends and to compare recurrent instability.ResultsArthroscopic stabilization comprised 90% of all stabilization procedures with annual utilization continuing to increase into 2019. Latarjet utilization increased from 15% to 42% of all open stabilization procedures while open Bankart repair utilization decreased from 56% to 35%. The rate of recurrent instability was 10.2% after arthroscopic stabilization and 12.3% after open stabilization (P = .01). Rates of redislocation (4.0% vs. 2.6%, P

Renzhe Tang,1,&ast; Chong Li,2,&ast; Dongmei Di,1 Lin Zhou,2 Yongxiang Qian,1 Chaohua Qiang,3 Chao Ma,1 Rui Zhou,1 Bin Wang,1 Min Wang1 1Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 2Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 3Department of Echocardiography, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wang; Bin Wang, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, No. 185 of Juqian Street, Changzhou, Jiangsu Province, 213003, People’s Republic of China, Email wangmin80808@163.com; wangbin1987@suda.edu.cnObjective: Obstructive sleep apnea (OSA) is a disorder characterized by disruption in breathing and hypoventilation. In parallel, metabolic syndrome (MetS) mainly co-occur with OSA, however, their association has not been fully elucidated. Therefore, this study aimed to reveal the relationship between OSA and MetS using data from the National Health And Nutrition Examination Survey (NHANES) database and pooled data from Genome-Wide Association Studies (GWAS).Material and Methods: Data from the National Health and Nutrition Examination Survey and pooled data from genome-wide association analysis (GWAS) were used univariate and multivariate logistic regression analyses were carried out to evaluate the correlation between OSA and MetS, and multivariate logistic regression models were utilized for adjusting for potential confounders. Two-sample Mendelian randomization (MR) was used to assess the causal relationship between OSA and MetS. The variance-weighted inverse method was employed as the main method of analysis.Results: A positive relationship of OSA with Mets was evidenced by multivariate logistic regression analysis, and OSA was associated with higher incidence rates of all-cause and cardiovascular mortality. OSA is strongly associated with abdominal obesity, hypertension, hyperglycemia, high triglycerides, and low HDL. Furthermore, except for hypertriglyceridemia, MR analysis indicated that genetically driven OSA was causally associated with a higher risk of MetS.Conclusion: The positive relationship of OSA with Mets was revealed, and higher incidence rates of all-cause mortality and cardiovascular mortality were noted to be correlated with OSA. MR analysis further confirmed the causal relationship of OSA with MetS and cardiovascular disease.Keywords: obstructive sleep apnea, metabolic syndrome, cardiovascular disease, NHANES, Mendelian randomization

Yanjuan Song,1 Jing Hu,2 Chunlian Ma,3– 5 Hua Liu,3– 5 Zhanghua Li,6 Yi Yang3– 5 1Graduate School, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 2Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 3Fitness Monitoring and Chronic Disease Intervention Research Center, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 4College of Sports Medicine, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 5Hubei Key Laboratory of Exercise Training and Monitoring, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 6Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Yi Yang, Fitness Monitoring and Chronic Disease Intervention research center, Wuhan Sports University, Wuhan, Hubei Province, 430079, People’s Republic of China, Tel +86 139 7129 3990, Email yangyi999999@foxmail.com Zhanghua Li, Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, 430074, People’s Republic of China, Tel +86 189 7161 0121, Email lizhanghua_123@163.comAbstract: The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos’ biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.Keywords: inflammation, macrophage-derived exosomes, biological functions, inflammation modulation, engineering strategies

Jinhui Bu,1,2,&ast; Zhenfei Wang,2,&ast; Chao Ma,1,2 Juan Gao,2 Guangpu Liu,2 Libo Pang,2 Bo He,1 Minghui Dong,1 Quan Zhang,1 Yan Lei,1 Long Xu,2 Sen Huang,1 Yuming Li,3 Guangwang Liu1,2 1Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 3Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Yuming Li, Tel +1-8573524988, Fax +1-8572188459, Email yuming.li@childrens.harvard.edu; Guangwang Liu, Tel +86-18012018238, Fax +86-51683956400, Email guangwangliu@163.comObjective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients.Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3).Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = − 10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = − 0.13, sig < 0.05).Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.Keywords: spinal endoscopy, residual mass, remodeling of fibrous annulus, contrast medium

Yi Yao,1,&ast; Juan Li,2,&ast; Wenwu Sun,1,&ast; Chaoping Ma,2,&ast; Ning Ning,1 Jiaoyan Li,1 Tongtian Ni,1 Menglu Gui,1 Ying Chen,1 Bing Zhao,1 Jiyuan Zhang,2 Jiyue Zhu,3 Chengjin Gao,2 Huiqiu Sheng,1 Enqiang Mao1 1Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 2Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiu Sheng, Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China, Tel +86-15801971839, Email shenghq803@163.com Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +86-18221088783, Email gaochengjin@xinhuamed.com.cnPurpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis.Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported.Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31– 4.46; p< 0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25– 1.70; p< 0.001; Model 2: RR 1.35; CI 1.14– 1.60; p< 0.001; Model 3: RR 1.18; CI 1.02– 1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis.Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.Keywords: sepsis, low T3 syndrome, nonthyroidal illness syndrome, thyroid function, disseminated intravascular coagulation

Yongsheng Sun,1 ChengJiang Liu,2 Nianping Zhang,3 Debing Yang,4 Cungen Ma,5 Xi Zhang61Department of Neurology and Psychiatry, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 2Department of General Medicine, Affiliated Anqing First People’s Hospital of Anhui Medical University, Anhui, 246000, People’s Republic of China; 3Department of Internal Medicine, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 4Department of Anatomy, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 5Neurobiology Research Center, Shanxi University of Traditional Chinese Medicine, Jinzhong, 030619, People’s Republic of China; 6Department of Neurology, Second Medical Center, General Hospital of the Chinese People’s Liberation Army, Beijing, 100000, People’s Republic of ChinaCorrespondence: Cungen Ma; Xi Zhang, Email macungen2001@163.com; zhangxiplagh@sina.comObjective: The common chronic non-communicable diseases and epidemiological characteristics of the forsaken elders over 60 in Guangling and Tianzhen were investigated and analyzed to provide reference for health resource allocation, hospital capacity establishing and health management of the forsaken elders in county-level regions.Materials and Methods: The data of 10,331 resident elderly over 60 in Guangling and Tianzhen of Datong Civil Affairs Bureau in the management system for disabled and semi-disabled elderly was collected. The gender, age, main diagnosis and coding of diseases, common chronic non-communicable diseases, and system diseases of the respondents were retrospectively analyzed.Results: The prevalence of the forsaken elders aged over 60 in Guangling and Tianzhen were different. Hypertension, arthritis, type 2 diabetes, hyperlipidemia and cerebral infarction are the top five common chronic non infectious diseases in Guangling, Tianzhen and the two counties. Among the top five common diseases in Guangling, Tianzhen and the two counties, arthritis or rheumatism, hypertension, diabetes or elevated blood sugar were found, which were different in the 60– 65, 66– 70, 71– 75 and 76– 80 groups, with the prevalence increasing with age. The top five diseases in Guangling, Tianzhen and the two counties were consistent, while the ranking changed slightly. The proportion of circulatory diseases, musculoskeletal diseases, connective tissue diseases and endocrine/nutritional and metabolic diseases in 60– 65, 66– 70 and 71– 75 groups increased with age, and was much higher than that in other groups.Conclusion: The prevalence and disease spectrum order of common chronic non-communicable diseases and systemic diseases in Guangling and Tianzhen are diverse, also in gender and age groups. As China’s county-level local administrative divisions have relatively independent administrative autonomy, medical and health resources can be better configured according to the information mined, accurately maintaining and promoting residents’ health. It is suggested to explore the disease management mechanism with county-level administrative divisions as database management units under the background of big data, so as to implement the interconnection and sharing of information among health-related departments in county-level regions.Keywords: chronic non-communicable diseases, system diseases, administrative division, disease spectrum, the forsaken elders