Background: Elderly patients with multimorbidity are at higher risk of greater healthcare costs and poor outcomes due to decreased physical function. The aim of this study was to investigate the impact of infection on healthcare costs and poor outcomes in elderly hospitalized patients with multimorbidity. Methods: We retrospectively enrolled 264 patients who met the inclusion criteria from the department of geriatrics of a large public hospital in Shanghai, China between January 2020 and December 2020. Patients were divided into two groups based on whether they had infection [infection present on admission (IPOA) or healthcare-associated infection(HAI)]. We recorded the basic information and follow-up information of all patients. The follow-up information included 30-day and 1-year all-cause readmission and mortality. Then we analyzed the association between infection and healthcare costs and clinical outcomes. Results: Among 264 subjects, 47.73 % of them achieved IPOA or HAI. The 30-day poor outcomes rate was 45.45 %, and the 1-year poor outcomes rate was 78.41 %. Compared with subjects without infection, the number of drugs and the disease burden were greater in subjects with infection(P < 0.001). Subjects with infection had longer length of hospital stay(P < 0.001) and had greater healthcare cost(P < 0.001). Moreover, subjects with infection had higher poor outcomes rates of 30-day and 1-year(P < 0.001). Infection could predict greater total cost [odds ratio (OR): 1.32, 95 % CI: 1.18,1.49,P < 0.001], nursing cost(OR: 11.45, 95 % CI: 3.49,37.63,P < 0.001), and medicine cost (OR: 2.37, 95 % CI: 1.70,3.31,P < 0.001). In addition, infection was also independently associated with the 30-day poor outcomes rate(OR:3.07, 95%CI: 1.80,5.24,P < 0.001), but we found no association between infection and 1-year poor outcomes rate(OR:1.43, 95 % CI:0.73,2.79,P = 0.300) after adjustment. Conclusions: Infection was a risk factor for higher healthcare cost and 30-day poor outcome rate in elderly hospitalized patients with multimorbidity.
BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Quality of Life , Umbilical Cord , Humans , Female , Male , Double-Blind Method , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/adverse effects , Aged , Mesenchymal Stem Cells/cytology , Umbilical Cord/cytology , Frailty/therapy , Middle Aged , Aging/physiology , Aged, 80 and over , Treatment Outcome
Organosilane compounds are widely used in both organic synthesis and materials science. Particularly, 1,2-disilylated and gem-disilylated alkenes, characterized by a carbon-carbon double bond and multiple silyl groups, exhibit significant potential for subsequently diverse transformations. The versatility of these compounds renders them highly promising for applications in materials, enabling them to be valuable and versatile building blocks in organic synthesis. This review provides a comprehensive summary of methods for the preparation of cis/trans-1,2-disilylated and gem-disilylated alkenes. Despite notable advancements in this field, certain limitations persist, including challenges related to regioselectivity in the incorporation and chemoselectivity in the transformation of two nearly identical silyl groups. The primary objective of this review is to outline synthetic methodologies for the generation of these alkenes through disilylation reactions, employing silicon reagents, specifically disilanes, hydrosilanes, and silylborane reagents. The review places particular emphasis on investigating the practical applications of the C-Si bond of disilylalkenes and delves into an in-depth discussion of reaction mechanisms, particularly those reactions involving the activation of Si-Si, Si-H, and Si-B bonds, as well as the C-Si bond formation.
Organochlorides are a crucial class of electrophiles in organic synthesis. Here, we present a protocol for the cross-electrophile coupling of aryl chlorides with unactivated alkyl chlorides, facilitated by an iron/B2pin2 catalytic system. We describe steps for the coupling of aryl chlorides with alkyl chlorides, followed by purification of products. This protocol can produce alkylated products with up to 81% yield. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.
Chlorides , Iron , Nickel , Molecular Structure , Catalysis
Background and purpose: Functional dyspepsia (FD) is a prevalent global disorder of the upper digestive tract characterized by functional impairment. It often coexists with anxiety/depression, significantly impairing occupational productivity and overall quality of life. This study aimed to identify emerging patterns and prominent themes within FD and anxiety/depression research through bibliometric analysis to help explore new innovative avenues for investigating this type of FD. Methods: A comprehensive review of literature encompassing FD and anxiety/depression was conducted using the Science Citation Index Extension of the Web of Science Core Collection from 2003 to 2023. Information extracted comprised "Full Record and Cited References." Bibliometric analysis of relevant publications, including country, institution, author, journal, citations, and keywords, was conducted using CiteSpace, VOSviewer, and Bibliometrix package in R and Excel. Results: Studies related to FD and anxiety/depression have demonstrated an ascending trajectory since 2003. Our bibliometric analysis identified 338 studies published by 2023. NEUROGASTROENTEROLOGY AND MOTILITY emerged as the most prolific journal, while GASTROENTEROLOGY retained pre-eminence within the top 10 published journals. China emerged as the most prolific country, with two institutions within the top 10 in terms of volume of publications. The Mayo Clinic stood as the foremost institution in terms of publication volume, with the Chengdu University of Traditional Chinese Medicine exhibiting robust collaborative engagement. Eminent author influence was attributed to Talley NJ of Newcastle University, Australia. Clusters of extensively cited papers and prevalent keywords delineate the status and trend of FD and anxiety/depression research. This encompasses FD, anxiety, depression, sleep disorders, and functional gastrointestinal disorders. Furthermore, the timeline view map or trend-term analysis suggested that duodenal low-grade inflammation ("duodenal eosinophilia" and "mast cells") might be a new concern associated with FD and anxiety/depression. Conclusion: Employing bibliometric analysis, this study revealed prevalent focal areas and new trends within FD and anxiety/depression research. These insights serve as valuable guidance for scholars seeking to delve into new research avenues.
Background: The single risk factors of pancreatic cancer (PC) has been extensively studied. We aimed to synthesize results from such studies to identify and estimate multiple independent risk factors of PC. Methods: Articles published up to Feb 28, 2020 in English or Chinese reporting risk factors of PC were reviewed. The fixed-effects model with 95% confidence interval (CI) were used to calculate the pooled Odds Ratio (OR). Data were analyzed using RevMan 5.3. Results: PC was significantly associated with smoking (OR: 1.76, 95% CI: 1.61-1.92, P < 0.00001, I2 = 6%), diabetes (OR: 2.69, 95% CI: 2.52-2.88, P < 0.00001, I2 = 0%), family history of PC (OR: 2.58, 95% CI: 2.13-3.11, P < 0.00001, I2 = 0%), and chronic pancreatitis (OR: 5.84, 95% CI: 3.63-9.41, P < 0.00001, I2 = 0%). Conclusion: Smoking, diabetes, family history of PC, and chronic pancreatitis were independent risk factors for PC. These independent risk factors have an important role in identifying high-risk groups, which is of great significance to reduce the incidence of PC and improve the quality of life and prognosis of patients.
Background: There is a high incidence rate of age-related hearing loss. Severe hearing loss may increase the prevalence of mental illness, cognitive impairment, and even the risk of all-cause death. Purpose: Construction of the three-level and two-stage screening mode for age-related hearing loss of the community and to evaluate its effectiveness. Materials and Methods: A total of 401 participants (aged 60 years or older) from five typical communities were enrolled in the study. The risk factors assessment of age-related hearing loss was completed by using a cross-sectional survey and receiver operating characteristic (ROC) curve. Multiple screening method was adopted and verified by serial and parallel tests, respectively. Based on research data, incorporate risk factors assessment, the Hearing Handicap Inventory for the Elderly Screening Version (HHIE-s) and pure tone audiometry (PTA) were used to construct the screening mode. Results: Multiple screening series testing and multiple screening parallel testing, including risk factors assessment, HHIE-s, and PTA, were used for verification: the sensitivity, specificity, and Kappa index were 70.5% and 9.2%, 95.0% and 71.6%, 0.26 and 0.63, respectively. Finally, the three-level and two-stage screening mode for age-related hearing loss was established. "Three-level" was defined as the risk factors assessment/HHIE-s (high-risk population), PTA (suspect population), and comprehensive hearing loss assessment (confirmed population). "Two-stage" was defined as the population screening by general practitioner in the community and target screening by otolaryngologist of the tertiary hospitals. Conclusion: The three-level and two-stage screening mode for age-related hearing loss consists of the following framework: from population screening to target screening, from suspicious diagnosis to accurate diagnosis, from primary health care to tertiary hospitals. The study objective is to structure a new secondary prevention and treatment mode for age-related hearing loss with primary health care as the core, so as to help the front-end management of healthy aging.
Presbycusis , Aged , Humans , Cross-Sectional Studies , Surveys and Questionnaires , China/epidemiology , Presbycusis/diagnosis , Presbycusis/epidemiology , Audiometry, Pure-Tone
Objective: Hospital-associated venous thromboembolism (VTE) is a major cause of unintended death in hospitalized patients. Standardized and reasonable prevention measures may reduce its occurrence effectively. This study aims to analyze the consistency of VTE risk assessment by physicians and nurses and its potential causes. Methods: A total of 897 patients admitted to Shanghai East Hospital from December 2021 to March 2022 were recruited. The VTE assessment scores of physicians and nurses and the activities of daily living (ADL) scores within the first 24 h of admission were collected for each patient. Cohen's Kappa values were calculated to assess the inter-rater consistency of these scores. Results: VTE scores were fairly consistent between doctors and nurses in both surgical (Kappa = 0.30, 95% CI: 0.25-0.34) and non-surgical (Kappa = 0.35, 95% CI: 0.31-0.38) departments. There was moderate agreement in VTE risk assessment between doctors and nurses in surgical departments (Kappa = 0.50, 95% CI: 0.38-0.62) while fair agreement in VTE risk assessment between doctors and nurses in non-surgical departments (Kappa = 0.32, 95% CI: 0.26-0.40). The assessment of the mobility impairment component was fairly consistent between doctors and nurses in the non-surgical departments (Kappa = 0.31, 95% CI: 0.25-0.37). Conclusion: Due to the poor consistency of VTE risk assessment between doctors and nurses, it is necessary to provide systematic training and develop a standardized assessment process for healthcare professionals to construct a scientific and effective VTE prevention and treatment system.
Background: Along with acceleration of population aging, the increasing prevalence of sarcopenia has posed a heavy burden on families as well as society. In this context, it is of great significance to diagnose and intervene sarcopenia as early as possible. Recent evidence has indicated the role of cuproptosis in the development of sarcopenia. In this study, we aimed to seek the key cuproptosis-related genes that can be used for identification and intervention of sarcopenia. Methods: The GSE111016 dataset was retrieved from GEO. The 31 cuproptosis-related genes (CRGs) were obtained from previous published studies. The differentially expressed genes (DEGs) and Weighed gene co-expression network analysis (WGCNA) were subsequently analyzed. The core hub genes were acquired by the intersection of DEGs, WGCNA and CRGs. Through logistic regression analysis, we established a diagnostic model of sarcopenia based on the selected biomarkers and was validated in muscle samples from GSE111006 and GSE167186. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed on these genes. Furthermore, the gene set enrichment analysis (GSEA), and immune cell infiltration were also conducted on the identified core genes. Finally, we screened the potential drugs targeting the potential biomarkers of sarcopenia. Results: A total of 902 DEGs and WGCNA containing 1,281 significant genes were preliminarily selected. Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia. The predictive model was established and validated with high AUC values. KEGG pathway and Gene Ontology biological analysis indicated these core genes may play a crucial role in energy metabolism in mitochondria, oxidation process, and aging-related degenerative diseases. In addition, the immune cells may be involved in the development of sarcopenia through mitochondrial metabolism. Finally, metformin was identified as a promising strategy of sarcopenia treatment via targeting NDUFC1. Conclusion: The four cuproptosis-related genes PDHA1, DLAT, PDHB and NDUFC1 may be the diagnostic biomarkers for sarcopenia, and metformin holds great potential to be developed as a therapy for sarcopenia. These outcomes provide new insights for better understanding of sarcopenia and innovative therapeutic approaches.
The development of aryl alkyl sulfides as dichotomous electrophiles for site-selective silylation via C-S bond cleavage has been achieved. Iron-catalyzed selective cleavage of C(aryl)-S bonds can occur in the presence of ß-diketimine ligands, and the cleavage of C(alkyl)-S bonds can be achieved by t-BuONa without the use of transition metals, resulting in the corresponding silylated products in moderate to excellent yields. Mechanistic studies suggest that Fe-Si species may undergo metathesis reactions during the cleavage of C(aryl)-S bonds, while silyl radicals are involved during the cleavage of C(alkyl)-S bonds.
Sulfides , Transition Elements , Catalysis , Iron , Ligands
Background: Cardiometabolic diseases, the main disease burden in older adults, are largely caused by oxidative stress resulting from lifestyle factors. This study investigated the relationship between lifestyle-based oxidative balance scores and cardiometabolic health among the community-dwelling elderly. Methods: This work conducted a secondary analysis of previous cross-sectional research data and constructed a lifestyle-based oxidative balance score (LOBS) including 4 components (higher scores were considered more antioxidant). Linear regression models and logistic regression models were used to evaluate the associations with cardiometabolic biomarkers and the number of cardiometabolic risk factors. Besides, we investigated whether these associations differed by covariates. Results: A total of 710 individuals (60.99% female, median age 70.0 years) were recruited. The inverse associations of LOBS with SBP and TG and the positive association with HDLC were statistically significant in both linear and logistic regression models. In contrast, an inverse association of LOBS with DBP was significant only in the linear regression model (all P < 0.05). The associations of LOBS with TG and HDLC were not affected by age, gender, or socioeconomic level. A significant inverse association was observed between LOBS and the number of cardiometabolic risk factors. Compared with the lowest LOBS, the ORs for more cardiometabolic risk factors in the second and third intervals were 0.577 (0.422, 0.788) and 0.460 (0.301, 0.703) (both P < 0.001). Conclusion: In summary, this study shows that antioxidant-predominant lifestyle exposure yields a better cardiometabolic health status. We recommend that general practitioners should offer comprehensive healthy lifestyle management to community-dwelling elderly.
We present a protocol for the eco-friendly synthesis of aryl and alkyl boronic esters from aryl and alkyl carboxylic acids. We describe steps for aryl and alkyl carboxylates preparation. We further detail procedures for the synthesis of borylated products using aryl and alkyl carboxylates through iron-catalyzed decarbonylation at 100°C-130°C, followed by purification of the crude products by flash column chromatography. For complete details on the use and execution of this protocol, please refer to Wen et al. (2022).1.
Carboxylic Acids , Iron , Carboxylic Acids/chemistry , Molecular Structure , Catalysis , Esters/chemistry
Organoboron and organosilane compounds are widely used in organic synthesis and pharmaceuticals. In addition, the C-F bond functionalization is a useful tool for the construction of carbon-carbon and carbon-heteroatom bonds. In particular, the late-stage functionalization of bioactive molecules through defluoroborylation and defluorosilylation reactions will provide good opportunities for the development and diversification of new medicinal compounds. Thus, this feature article summarized the methods for the defluorosilylation and defluoroborylation of unreactive monofluoroarenes and gem-difluoroalkenes from 2000 to 2021, which might create some new ideas and will be helpful for further research in this field. These defluoroborylation and defluorosilylation strategies can be applied to synthesize silylated arenes, borylated arenes, silylated fluoroalkenes, and borylated fluoroalkenes, thus providing impressive advantages over traditional methods for the synthesis of organoboron and organosilane compounds in terms of divergent structures.
The first iron-catalyzed defluorosilylation of unactivated gem-difluoroalkenes was developed, delivering gem-disilylated alkenes and (E)-silylated alkenes with excellent efficiency. This protocol features good functional group compatibility and excellent regio- and stereoselectivity, enabling the late-stage silylation of biologically relevant compounds, thus providing good opportunities for applications in medicinal chemistry. Preliminary mechanistic studies and DFT calculations reveal that a nucleophilic addition and elimination of the second C-F bond might be involved in the disilylation catalytic system, demonstrating unusual reactivity characteristics of iron catalysis.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen for coronavirus disease-2019 (COVID-19), which has posed an increasing serious public health threat. However, still there are no approved antiviral agents or vaccines available yet. Mesenchymal stem cells (MSCs) are emerging as a novel promising adjuvant therapy for the attenuation of COVID-19 based on its putative pathogenesis. MSCs may exert anti-inflammatory, immunomodulatory, anti-apoptotic, as well as regenerative effects through a series of mechanisms. Remarkably, MSCs may be resistant to virus infection, which is fundamental for the treatment of COVID-19. The beneficial therapeutic effects of MSCs have been preliminarily proved to be safe and efficacious for the treatment of COVID-19 in current clinical trials. This work aims to review the beneficial effects of MSCs in treating ALI/ARDS, which provides novel insight into the potential therapeutic strategies against COVID-19. However, further research is warranted regarding both safety and efficacy of MSCs.
Frailty and hypertension often coexist and are increasingly prevalent with advancing age. Although hypertension is independently associated with frailty, whether high blood pressure variability affecting frailty is unclear. In this retrospective study, we consecutively enrolled elderly patients with essential hypertension undergoing 24-hour ABPM. The frailty was assessed by a 38-item frailty index. The parameters of blood pressure variability of ABPM, including ARV, coefficient of CV, SD, and weighed SD were calculated. Ordinal logistic regression was used to investigate the association between blood pressure variability and frailty. A total of 242 hypertensive patients were recruited and divided into the frail group, pre-frail group, and non-frail group. The overall magnitudes of BP variability, assessed by ARV, CV, SD, and weighed SD, were significantly greater in patients with frailty than those with pre-frailty and non-frailty. With adjustment for covariates, ARV of 24-hour, diurnal, and nocturnal SBP were independently associated with frailty (24 hours, OR: 2.48, 95% CI: 2.01-3.07; daytime, OR: 1.83, 95% CI: 1.60-2.10; nighttime, OR: 1.19, 95% CI: 1.12-1.27). The CV of 24-hour, diurnal, and nocturnal SBP was independently associated with frailty in the study (24 hours, OR: 1.2, 95% CI: 1.05-3.07; daytime, OR: 1.19, 95% CI: 1.05-1.34; nighttime, OR: 1.13, 95% CI: 1.03-1.24). For SD and weighed SD, only 24-hour systolic SD was independent risk factor associated with frailty (OR: 1.12, 95% CI: 1.01-1.23). The greater blood pressure variability of SBP, particular ARV and CV, were independent risk factors associated with higher-order frailty status. Longitudinal studies are needed to investigate the causality associations between hypertension and frailty.
Frailty , Hypertension , Aged , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Diabetes Mellitus, Type 2 , Female , Frail Elderly , Frailty/diagnosis , Frailty/epidemiology , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Longitudinal Studies , Male , Middle Aged , Retrospective Studies
Herein we describe an iron-catalyzed borylation of alkenyl and aryl carbamates through the activation of a C-O bond. This protocol exhibits high efficiency, a broad substrate scope, and the late-stage borylation of biorelevant compounds, thus providing potential applications in medicinal chemistry. Moreover, this method enables orthogonal transformations of phenol derivatives and also offers good opportunities for the synthesis of multisubstituted arenes. Preliminary mechanistic studies suggest that a FeII/FeIII catalytic cycle via a radical pathway might be involved in the reaction.
Herein, we report the iron-catalyzed borylation of aryl ethers and aryl amines via cleavage of C-O and C-N bonds. This protocol does not require the use of Grignard reagents and displays a broad substrate scope, which allows the late-stage borylation. It also provides facile access to multisubstituted arenes through C-H functionalization using 2-pyridyloxy as the directing group.
The iron-catalyzed construction of Csp2-Si bonds via unreactive C-O bonds possesses a challenging topic in organic chemistry. Herein we report an iron-catalyzed silylation of aryl and alkenyl carbamates via C-O bond activation. This protocol features high efficiency and a broad substrate scope, enabling the late-stage silylation of biorelevant compounds and thus providing a good method to access valuable motifs in medicinal chemistry. Moreover, this protocol enables orthogonal transformations of phenol derivatives and also allows for the synthesis of multisubstituted arenes through the carbamate group as the directing group.
Tumor-derived extracellular vesicles (EVs) and their contents are involved in the development of human malignancies. Circular RNAs (circRNAs), enriched in EVs, can regulate diverse cellular processes by acting as microRNA (miRNA) sponges or through other mechanisms. In the present study, we explored the potential roles of circRNAs in EVs in the development of pancreatic ductal adenocarcinoma (PDAC). First, plasma was obtained from patients with PDAC (n = 8) and healthy volunteers (n = 8), and EVs were isolated by the ultracentrifugation method. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size and form of the isolated EVs. The circRNA expression profiles of EVs were investigated by high-throughput whole transcriptome sequencing. We then further validated the accuracy of the circRNA sequencing data by quantitative real-time PCR analysis using plasma samples and PC cell lines, and subsequently performed bioinformatics analysis to reveal the potential functional roles of the differentially expressed circRNAs and to construct a circRNA-miRNA interaction network to predict the target miRNAs of these circRNAs. Our work provides novel targets for further studies concerning the pathogenesis of PDAC.
Carcinoma, Pancreatic Ductal/genetics , Extracellular Vesicles/genetics , RNA, Circular/genetics , Adenocarcinoma/blood , Adenocarcinoma/genetics , Adult , Carcinoma, Pancreatic Ductal/blood , Cell Line, Tumor , Computational Biology/methods , Female , Gene Expression Profiling/methods , Humans , Male , MicroRNAs/genetics , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/genetics , RNA, Circular/analysis , RNA, Circular/blood , Real-Time Polymerase Chain Reaction/methods , Transcriptome/genetics , Pancreatic Neoplasms
