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Fengyu Liu,1,2,&ast; Huajing Chang,1,&ast; Xiaojun Liu1,3 1School of Public Health, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2School of Public Health, National Key Laboratory of Health Technology Assessment (National Health Commission of the People’s Republic of China), Global Health Institute, Fudan University, Shanghai, People’s Republic of China; 3School of Health Management, Provincial Research Center for Healthcare Reform and Development of Fujian, Health Research Institute, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Liu, School of Health Management, Fujian Medical University, No. 1 Xuefu North Road, University New District, Fuzhou City, Fujian Province, 350122, People’s Republic of China, Tel + 86 591-22869579, Email xiaojun_liu@fjmu.edu.cnBackground: Non-adherence or partial adherence is the main reason for poor therapeutic effect of hypertension. This paper aims to assess adherence behaviors and related factors among elderly hypertensive patients in China.Methods: Participants aged ≥ 60 years, with hypertension, and with complete data in 2018 interviews of the China Health and Retirement Longitudinal Study (CHARLS) were included. The adherence behaviors included medication, blood pressure monitoring and the combined adherence behaviors. Referring to the social-ecological theory, correlates of adherence behaviors were divided into three layers, namely demographic characteristics, health behaviors, living environment and retirement. Univariate and multivariable logistic regression models were performed to identify factors of adherence behaviors.Results: The prevalence of medication adherence (76.58%) was higher than that of blood pressure monitoring adherence (20.08%), and the full adherence rate was 18.53%. Self-rated health status, smoking status, living area, and health education status were detected to be associated with medication adherence and blood pressure monitoring adherence (all p < 0.05). Gender, sleep duration, health examination, and physical exercise were also detected to be associated with blood pressure monitoring adherence (all p < 0.05). Self-rated health status and health education status were detected to be associated with partially and fully adherence, while age, living area, and life satisfaction were detected to be associated with partially adherence, smoking status, sleep duration, health examination, and pension reliance were detected to be associated with fully adherence (all p < 0.05).Conclusion: Our study reveals the poor adherence behaviors of elderly hypertensive patients in China. This is most evident among those who were male, 60– 69 years old, living in rural areas, self-reported being healthier, those without health examination and health education. Targeting these vulnerable populations, we suggest to strengthen health education, increase the publicity of basic public health services and enhance the self-management ability of hypertensive patients.Keywords: medication adherence, blood pressure monitoring, hypertension, behavior, elderly

Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone, but no regenerative therapy exist. Previously, we showed that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) via fibrin-based bio-glue facilitate meniscus healing by inducing recruitment and stepwise differentiation of synovial mesenchymal stem/progenitor cells. Here, we first explored the potential of genipin, a natural crosslinker, to enhance fibrin-based glue's mechanical and degradation properties. In parallel, we identified the harmful effects of lubricin on meniscus healing and investigated the mechanism of lubricin deposition on the injured meniscus surface. We found that the pre-deposition of hyaluronic acid (HA) on the torn meniscus surface mediates lubricin deposition. Then we implemented chemical modifications with heparin conjugation and CD44 on our bioactive glue to achieve strong initial bonding and integration of lubricin pre-coated meniscal tissues. Our data suggested that heparin conjugation significantly enhances lubricin-coated meniscal tissues. Similarly, CD44, exhibiting a strong binding affinity to lubricin and hyaluronic acid (HA), further improved the integrated healing of HA/lubricin pre-coated meniscus injuries. These findings may represent an important foundation for developing a translational bio-active glue guiding the regenerative healing of meniscus injuries.

Background/Objectives: The use of neuraxial anesthesia versus general anesthesia for hip fracture surgery remains an active area of research, with recent studies demonstrating mixed findings supporting neuraxial over general anesthesia. The benefits of neuraxial anesthesia have been documented in associated surgeries, including total joint arthroplasty. However, racial disparities in the administration of neuraxial anesthesia have been identified in numerous procedures. We aimed to examine the association of race/ethnicity with neuraxial anesthesia use and the effect of neuraxial anesthesia on length of stay, non-home discharge, 30-day severe adverse events, and rates of readmission among patients undergoing isolated hip and femoral shaft fracture operations. Methods: The American College of Surgeons National Quality Improvement Program database was queried for isolated hip or femoral shaft fractures from 2015 to 2019. Stepwise logistic regression was performed to assess the relationship between race/ethnicity and neuraxial anesthesia use. Within each sex–race stratum, neuraxial anesthesia recipients were propensity-matched to general anesthesia recipients in a 1:2 ratio. Logistic regression and negative binomial regression were performed on the propensity-matched cohort. Results: A total of 12,004 neuraxial and 64,250 general anesthesia hip and femoral shaft fracture patients were identified. Compared to White patients, Black and Hispanic patients were between 0.64 and 0.61 times less likely to receive neuraxial anesthesia over general anesthesia, respectively (p < 0.05). 11,993 patients who received neuraxial anesthesia were propensity matched to 23,946 patients who received general anesthesia. Propensity-matched logistic regressions found that neuraxial anesthesia was associated with decreased length of stay, 30-day severe adverse events, and acute rehab/skilled nursing facility discharge for White patients (p < 0.05 for all), but only decreased length of stay in Black and Hispanic patients (p = 0.01 and p = 0.02, respectively). Conclusions: Notable disparities exist in the administration of neuraxial anesthesia for isolated hip and femoral shaft fracture patients. Hispanic and Black race/ethnicity in particular influences provision of neuraxial anesthesia. Further research is required to understand the degree of effect modification and root causes of regional anesthesia access and benefits for this high-volume patient population.

Abstract Background: Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19. Objective: To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED. Material and methods: Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of

Background Cardiac rehabilitation (CR) is an evidence‐based, guideline‐recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in‐center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology‐based, multicomponent health equity‐focused intervention as an alternative to traditional in‐center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone. Methods The mTECH‐Rehab (Impact of a Mobile Technology Enabled Corrie CR Program) trial will randomize 200 patients who either have a diagnosis of type 1 myocardial infarction or who undergo coronary artery bypass grafting surgery, percutaneous coronary intervention, heart valve repair, or replacement presenting to 4 hospitals in a large academic health system in Maryland, United States, to the Corrie Hybrid CR program combined with usual care CR (intervention group) or usual care CR alone (control group) in a parallel arm, randomized controlled trial. The Corrie Hybrid CR program leverages 5 components: (1) a patient‐facing mobile application that encourages behavior change, patient empowerment, and engagement with guideline‐directed therapy; (2) Food and Drug Administration‐approved smart devices that collect health metrics; (3) 2 upfront in‐center CR sessions to facilitate personalization, self‐efficacy, and evaluation for the safety of home exercise, followed by a combination of in‐center and home‐based sessions per participant preference; (4) a clinician dashboard to track health data; and (5) weekly virtual coaching sessions delivered over 12 weeks for education, encouragement, and risk factor modification. The primary outcome is the mean difference between the intervention versus control groups in distance walked on the 6‐minute walk test (ie, functional capacity) at 12 weeks post randomization. Key secondary and exploratory outcomes include improvement in a composite cardiovascular health metric, CR engagement, quality of life, health factors (including low‐density lipoprotein‐cholesterol, hemoglobin A1c, weight, diet, smoking cessation, blood pressure), and psychosocial factors. Approval for the study was granted by the local institutional review board. Results of the trial will be published once data collection and analysis have been completed. Conclusions The Corrie Hybrid CR program has the potential to improve functional status, cardiovascular health, and CR engagement and advance equity in access to cardiac rehabilitation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05238103.

Keyan Hu,1,2,&ast; Xueying Liu,1,&ast; Hongfeng Chang,1 Yi Zhang,1 Hui Zhou,3 Lei Liu,1 Xin Zhang,1 Ziying Jiao,4 Bing Shen,4 Qiu Zhang1 1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, 471003, People’s Republic of China; 3Institute of Brain Diseases and Cognition, School of Medicine, Xiamen University, Xiamen, Fujian, 361000, People’s Republic of China; 4School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu Zhang, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Tel/Fax +86-551-62923631, Email zhangqiu@ahmu.edu.cn Bing Shen, Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People’s Republic of China, Tel +86-551-65161132, Fax +86-551-65161126, Email shenbing@ahmu.edu.cnIntroduction: Diabetes foot ulcer (DFU) is a serious complication of diabetes characterized with chronic foot ulceration, poor wound healing (WH), and persistent inflammation. MiR-221-3p, as microRNA, has been shown to accelerate WH in previous study, but the underlying mechanisms are poorly understood.Methods: In this study, we aimed to determine how miR-221-3p influences WH by targeting THBS1. The effect of miRNA-221-3p on wound healing of diabetes by epidermal injection of miRNA-221-3p agomir. In vitro generated human immortalized keratinocytes (HaCaT cells) were transfected with miR-mimics and negative control with high glucose treatment. The effects of miRNA-221-3p on cell apoptosis and angiogenesis using cell apoptosis assay and the tube formation assay, respectively. Direct target interaction of miR-221-3p and predicted target sites in 3’UTR of THBS1 were examined by luciferase reporter gene assay. Breeding miRNA-221 knockout mice for experimental verification.Results: We found that miRNA-221-3p overexpression at the wound edge of normal mice and diabetes mice can promote WH. As contrast, WH of miR-221 knockout mice delayed with increased epithelial apoptosis and reduced angiogenesis in the dermis. miR-221-3p was found to inhibit apoptosis in HaCaT cells, and enhanced angiogenesis in human umbilical vein endothelial cells (HUVECs) that were co-cultured. Bioinformatics analysis as well as the dual-luciferase reporter assay revealed miR-221-3p to target 3ʹ untranslated region of THBS1.Conclusion: Our findings suggested miR-221-3p might exert an essential impact on diabetes WH via inhibition of THBS1 and lack of miR-221-3p possibly results in impaired healing in chronic wounds of type 2 diabetes. Therefore, developing medicine such as chemically modified analogs of miR-221-3p in future could benefit patients with DFU.Keywords: diabetes, wound healing, microRNA, keratinocyte

Qianming Bai,1– 3,&ast; Hong Lv,1– 3,&ast; Longlong Bao,1– 3,&ast; Yu Yang,1– 3 Xin Zhang,4 Heng Chang,1– 3 Tian Xue,1– 3 Min Ren,1– 3 Xiaoli Zhu,1– 3 Xiaoyan Zhou,1– 3,&ast; Wentao Yang1– 3,&ast; 1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Fudan University Zhongshan Hospital, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wentao Yang; Xiaoyan Zhou, Department of Pathology, Fudan University Shanghai Cancer Centre, 270 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-18017312353 ; +86-18017312385, Email yangwt2000@163.com; xyzhou100@163.comPurpose: To investigate the HER2 status and clinicopathological features in invasive breast cancer with HER2 ≥ 4.0 and < 6.0, which has always been controversial.Methods: Forty breast cancer cases with HER2 ≥ 4.0 and < 6.0 by fluorescence in situ hybridization (FISH) were collected and classified into two groups based on the HRE2/CEP17 ratio (Group A: ≥ 2.0, n=22; Group B: < 2.0, n=18). Clinicopathological characteristics, HER2 status, risk classification, and molecular typing were further analyzed and compared by 21-Gene expression assay and MammaPrint plus BluePrint test.Results: The majority of cases in both groups were invasive carcinoma (NOS), with histological grade II, HR+, Ki-67 ≥ 20%, HER2 2+, and a high risk of recurrence, although younger patients and lymph node metastases were more common in Group A. Surprisingly, all HR+ breast cancers in both groups were classified as luminal-type, HR− cases were all basal-type or unknown, and the index of HER2 in all cases was < 0.000 using the BluePrint test, which indicated that HER2 status should be negative. Furthermore, the level of HER2 mRNA expression in all cases of both groups was < 10.7, which was defined as HER2 negative by the 21-Gene expression assay. In addition, 10 patients of Group A received anti-HER2 neoadjuvant therapy; only one patient with HR- achieved Grade 5 based on the Miller-Payne system, whereas none of the patients achieved pathological complete response (pCR) based on the Residual Cancer Burden system.Conclusion: Group A breast cancer, which has always been unquestionably diagnosed as HER2 amplification, was more likely to be HER2 negative and derived less benefit from anti-HER2 neoadjuvant chemotherapy. Group A breast cancer should be distinguished from classical HER2-positive breast cancers when assessing HER2 FISH, and a larger cohort of Group A patients should be included in further studies.Graphical Abstract: Keywords: breast cancer, HER2, FISH, 21-gene expression assay, MammaPrint plus BluePrint

Susu Feng,1 Lin Guo,1 Sijing Wang,1 Lijuan Chen,1 Hang Chang,2 Bo Hang,2,3 Jianhua Mao,2 Antoine M Snijders,2 Yibing Lu,1 Dafa Ding1 1Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; 3Department of Biomaterials, Berkeley-Nanjing Research Center, Nanjing, People’s Republic of ChinaCorrespondence: Dafa Ding, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, People’s Republic of China, Tel +86 15850514014, Email dingdafa@njmu.edu.cnAim: We aimed to identify the ability of serum bile acids (BAs) and unsaturated fatty acids (UFAs) profiles to predict the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients.Methods: We first used univariate and multivariate analysis to compare 15 serum BA and 11 UFA levels in healthy control (HC) group (n = 82), T2DM patients with DR (n = 58) and T2DM patients without DR (n = 60). Forty T2DM patients were considered for validation. Then, the receiver operating characteristic curve (ROC) and decision curve analysis were used to assess the diagnostic value and clinical benefit of serum biomarkers alone, clinical variables alone or in combination, and the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to further assess whether the addition of biomarkers significantly improved the predictive ability of the model.Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of serum BAs and UFAs separated the three cohorts including HC, T2DM patients with or without DR. The difference in serum BA and UFA profiles of T2DM patients with or without DR was mainly manifested in the three metabolites of taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and arachidonic acid (AA). Together, they had an AUC of 0.785 (0.918 for validation cohort) for predicting DR in T2DM patients. After adjusting for numerous confounding factors, TLCA, TUDCA, and AA were independent predictors that differentiated T2DM with or without DR. The results of AUC, IDI, and NRI demonstrated that adding these three biomarkers to a model with clinical variables statistically increased their predictive value and were replicated in our independent validation cohort.Conclusion: These findings highlight the association of three metabolites, TLCA, TUDCA and AA, with DR and may indicate their potential value in the pathogenesis of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, serum bile acid, unsaturated fatty acid

Growing evidence suggests that the gut microbiome (GM) plays a critical role in health and disease. However, the contribution of GM to psychiatric disorders, especially anxiety, remains unclear. We used the Collaborative Cross (CC) mouse population-based model to identify anxiety associated host genetic and GM factors. Anxiety-like behavior of 445 mice across 30 CC strains was measured using the light/dark box assay and documented by video. A custom tracking system was developed to quantify seven anxiety-related phenotypes based on video. Mice were assigned to a low or high anxiety group by consensus clustering using seven anxiety-related phenotypes. Genome-wide association analysis (GWAS) identified 141 genes (264 SNPs) significantly enriched for anxiety and depression related functions. In the same CC cohort, we measured GM composition and identified five families that differ between high and low anxiety mice. Anxiety level was predicted with 79% accuracy and an AUC of 0.81. Mediation analyses revealed that the genetic contribution to anxiety was partially mediated by the GM. Our findings indicate that GM partially mediates and coordinates the effects of genetics on anxiety.

The global burden of colorectal cancer (CRC) is expected to continuously increase. Through research performed in the past decades, the effects of various environmental factors on CRC development have been well identified. Diet, the gut microbiota and their metabolites are key environmental factors that profoundly affect CRC development. Major microbial metabolites with a relevance for CRC prevention and pathogenesis include dietary fiber-derived short-chain fatty acids, bile acid derivatives, indole metabolites, polyamines, trimethylamine-N-oxide, formate, and hydrogen sulfide. These metabolites regulate various cell types in the intestine, leading to an altered intestinal barrier, immunity, chronic inflammation, and tumorigenesis. The physical, chemical, and metabolic properties of these metabolites along with their distinct functions to trigger host receptors appear to largely determine their effects in regulating CRC development. In this review, we will discuss the current advances in our understanding of the major CRC-regulating microbial metabolites, focusing on their production and interactive effects on immune responses and tumorigenesis in the colon.