Impact of infection on healthcare costs and clinical outcomes in elderly hospitalized patients with multimorbidity.

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.

Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty: a phase I/II randomized, double-blind, placebo-controlled study.

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 .

Influencing factors of kinesiophobia among stroke patients with hemiplegia: A mixed methods study.

OBJECTIVES: There is a scarcity of data regarding the effects of kinesiophobia on stroke patients with hemiplegia. Therefore, this paper aims to evaluate the level of kinesiophobia experienced by stroke patients with hemiplegia in China, examine the elements that influence it, and investigate the unique psychological experience of kinesiophobia combined with a qualitative study. METHODS: This mixed study was conducted in two steps. Four approved scales were used to evaluate a total of 163 patients: (i) Tampa Scale of Kinesiophobia, (ii) Pain Catastrophizing Scale, (iii) Self-Efficacy for Exercise Scale, and (iv) Hospital Anxiety and Depression Scale. A multivariate linear regression model was used to evaluate the predictors of kinesiophobia in stroke patients with hemiplegia. Subsequently, semi-structured interviews with 15 stroke patients with hemiplegia were conducted using an objective sampling method, and the Colaizzi 7-step analysis process was utilized to analyze the interview data. RESULTS: A total of 163 stroke patients with hemiplegia were included in this study, of them, 47.9% reported kinesiophobia. Multiple linear regression revealed that the influencing factors of kinesiophobia in stroke patients with hemiplegia were a history of falls, exaggeration, helplessness, anxiety, depression, and low exercise self-efficacy (P<0.05). The qualitative research focuses on two main topics: personal adoption of negative coping styles and insufficient external support. CONCLUSION: Our study showed that the kinesiophobia in stroke patients with hemiplegia was high, with several factors influencing their kinesiophobia. Some of these factors are modifiable and should be considered when formulating kinesiophobia intervention strategies for stroke patients with hemiplegia.

Global trends in research related to functional dyspepsia and anxiety or depression over the past two decades: a bibliometric analysis.

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.

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia.

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.

Lifestyle-based oxidative balance score and its association with cardiometabolic health of the community-dwelling elderly: A cross-sectional secondary analysis.

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.

Suicidal ideation and suicide attempts in psychiatric patients during the COVID-19: A systematic review and meta-analysis.

Current suicidal ideation and suicide attempts among psychiatric patients during the COVID-19 pandemic were studied through systematic review and meta-analysis. We searched the following electronic databases using the relevant search terms: Medline, Embase, PubMed and Web of Science, with the search time as of January 31,2022. Forest plots were obtained using Stata statistical software and a random-effects model was used to conduct a meta-analysis of the prevalence of suicidal ideation. We found 21 eligible studies, 11 of which provided suitable data for meta-analysis. 10 studies explored current suicidal ideation and reported a pooled prevalence of 20.4% (95%CI 14.0-26.8). Six studies examined suicide attempts, with a pooled prevalence of 11.4% (95%CI 6.2-16.6). The prevalence of suicidal ideation and suicide attempts varied by the study method used and by the study sites. This work highlights the need for real-time monitoring of suicidal ideation and suicide in psychiatric patients during the covid-19 pandemic r to inform clinical practice and help identify research questions for future epidemiological studies.

Geriatric Health Care During the COVID-19 Pandemic: Managing the Health Crisis.

COVID-19 pandemic significantly threatens the health and well-being of older adults. Aging-related changes, including multimorbidity, weakened immunity and frailty, may make older people more susceptible to severe infection and place them at higher risk of morbidity and mortality from COVID-19. Various quarantine measures have been implemented to control the spread of COVID-19. Nevertheless, such social distancing has disrupted routine health care practices, such as accessibility of medical services and long-term continuous care services. The medical management of older adults with multimorbidity is significantly afflicted by COVID-19. Older persons with frailty or multiple chronic disease may poorly adapt to the altered health care system, having detrimental consequences on their physical and mental health. COVID-19 pandemic has posed great challenges to the health of older adults. We highlighted the difficulties and obstacles of older adults during this unprecedented time. Also, we provided potential strategies and recommendations for actions to mitigate the COVID-19 pandemic threats. Certain strategies like community primary health care, medication delivery and home care support are adopted by many health facilities and caregivers, whereas other services such as internet hospital and virtual medical care are promoted to be accessible in many regions. However, guidelines and policies based on high-quality data are still needed for better health promotion of older groups with increasing resilience during the COVID-19 pandemic.

Stigma and unhealthy psychological characteristics in patients with acromegaly: A cross-sectional study and identification of the associated factors.

BACKGROUND: Stigma, besides aggravating the damage caused by the disease, may also lead to unhealthy characteristics in patients and unhealthy situations in society. Individuals with acromegaly disease may suffer from stigma concerns, and the associated factors remain largely unknown. Therefore, the present cross-sectional study aimed to investigate the levels of perceived stigma in patients with acromegaly and explore the associated factors. METHODS: A total of 138 patients with acromegaly were evaluated for having stigma using five previously validated scales: (i) the Stigma Scale for Chronic Illness, (ii) the Hamilton Anxiety Scale, (iii) the Rosenberg Self-Esteem Scale, (iv) the Body Image Concern scale, and (v) the Acromegaly Quality of Life scale. The potential determinants of stigma were evaluated using the univariate statistical analysis. A multivariate linear regression model was adopted to assess the predictors of stigma in patients with acromegaly. Pearson's correlation analysis was performed to analyze the relationship between stigma and the quality of life of the patients. RESULTS: Among the 138 respondents, 102 provided consent for participation.The evaluated patients exhibited critically high levels of perceived stigma. The multiple regression analysis revealed high BMI, serious body image concerns, inferiority complex personality, and critical levels of anxiety as the potential predictors of stigma in patients with acromegaly. The overall stigma and internalized stigma were significantly correlated with QoL in these patients. CONCLUSION: The patients with acromegaly exhibited critically high levels of perceived stigma, which led to psychological distress and disruptions in their daily lives. This finding highlights the importance of addressing the stigma concerns and the necessity for providing additional support to these patients in this regard during follow-up sessions. Further research should focus on developing intervention strategies to decrease the levels of perceived stigma in patients with acromegaly to promote their quality of life and for the psychosocial rehabilitation of these patients.

Application of mesenchymal stem cell therapy for aging frailty: from mechanisms to therapeutics.

Aging frailty is a complex geriatric syndrome that becomes more prevalent with advancing age. It constitutes a major health problem due to frequent adverse outcomes. Frailty is characterized by disruption of physiological homeostasis and progressive decline of health status. Multiple factors contribute to development of frailty with advancing age, including genome instability, DNA damage, epigenetic alternations, stem cell exhaustion, among others. These interrelated factors comprehensively result in loss of tissue homeostasis and diminished reserve capacity in frailty. Therefore, the aged organism gradually represents symptoms of frailty with decline in physiological functions of organs. Notably, the brain, cardiovascular system, skeletal muscle, and endocrine system are intrinsically interrelated to frailty. The patients with frailty may display the diminished reserves capacity of organ systems. Due to the complex pathophysiology, no specific treatments have been approved for prevention of this syndrome. At such, effective strategies for intervening in pathogenic process to improve health status of frail patients are highly needed. Recent progress in cell-based therapy has greatly contributed to the amelioration of degenerative diseases related to age. Mesenchymal stem cells (MSCs) can exert regenerative effects and possess anti-inflammatory properties. Transplantation of MSCs represents as a promising therapeutic strategy to address the pathophysiologic problems of frail syndrome. Currently, MSC therapy have undergone the phase I and II trials in human subjects that have endorsed the safety and efficacy of MSCs for aging frailty. However, despite these positive results, caution is still needed with regard to potential to form tumors, and further large-scale studies are warranted to confirm the therapeutic efficacy of MSC therapy.

Transplantation of Mesenchymal Stem Cells: A Potential Adjuvant Therapy for COVID-19.

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.

Effect of upregulation of DD3 on early detection and prognosis in prostate cancer.

BACKGROUND: Expression of prostate cancer antigen 3 (PCA3 OR DD3) in the blood has been reported to be significantly higher in prostate cancer (PCa) than in benign prostate hyperplasia (BPH). To confirm whether DD3 expression is significantly different between PCa and BPH tissues, DD3 expression was tested in the blood both preoperatively and postoperatively and in the paired tissues of PCa patients. METHODS: Expression levels of DD3 mRNA in the blood of patients who did not undergo surgery (PCa, n=102; BPH, n=53), those underwent surgery (preoperative, n=35; postoperative, n=35), and in PCa tissue specimens (tumor, n=41; adjacent normal, n=21) were determined by real-time quantitative PCR. Sensitivity and specificity for DD3 in PCa patients were validated by receiver operating characteristic (ROC) curve analysis. RESULTS: Our data suggest that expression level of DD3 in blood samples was significantly higher in PCa patients than in BPH patients (P=0.005). Expression of DD3 mRNA was also significantly elevated in PCa tissues compared with adjacent normal tissues (P=0.013). The increase in DD3 expression in PCa patients was further validated using a dataset from The Cancer Genome Atlas (n=549). Postoperative DD3 expression decreased following surgical intervention (P<0.001). Moreover, low DD3 expression was associated with improved overall survival (OS). Using gene set enrichment analysis, DD3 expression was correlated with specific PCa target genes including carcinogenesis-related and cancer proliferation-related genes. CONCLUSIONS: This study demonstrated that expression of DD3 was upregulated in blood and PCa tumor tissues and was associated with prognosis. The oncogenic role of DD3 was further validated in the TCGA database, indicating that DD3 is a potential therapeutic target for PCa. Furthermore, this study suggests that DD3 expression could be considered as a prognostic biomarker for PCa.

Association between ambulatory blood pressure variability and frailty among older hypertensive patients.

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.

Mutations in m6A consensus motifs are suppressed in the m6A modified genes in human cancer cells.

N6-methyladenosine (m6A) is the most prevalent type of RNA modification. METTL3 in the methyltransferase complex is the core enzyme responsible for methylation. METTL3 selectively catalyzes the adenosines centered in the RRAC motif. Functional studies established that m6A could enhance the translation efficiency (TE) of modified genes by recruiting reader protein YTHDF1 and other initiation factors. We downloaded the m6A peaks in HeLa cells from a previous study and defined the m6A modified genes and sites. Ancestral mutations in the genic region fixed in the HeLa cell samples were defined using their mRNA-Seq data and the alignment between human and mouse genomes. Furthermore, in the small interfering (si)-METTL3 sample, the calculated TE foldchange of all genes was compared to that in the negative control. The TE of m6A genes was globally down-regulated in si-METTL3 versus control compared to the non-m6A genes. In m6A modified genes, RRAC motif mutations were suppressed compared to mutations in non-motif regions or non-m6A genes. Among the m6A genes, a fraction RRAC motif mutations negatively correlated with the TE foldchange (si-METTL3 versus control). The TE of m6A modified genes was enhanced in HeLa cells. RRAC motif mutations could potentially prevent methylation of adenosines and consequently abolish the enhanced translation. Such mutations in the RRAC motif might be deleterious. Accordingly, we observed lower fractions of mutations in RRAC motifs than in other regions. This prevention of mutations in the RRAC motif could be a strategy adopted by cancer cells to maintain the elevated translation of particular genes.

miR-199a-5p is involved in doxorubicin resistance of non-small cell lung cancer (NSCLC) cells.

Non-small cell lung cancer (NSCLC) is one of the prevalent and deadly cancers worldwide. Chemotherapy resistance is one of the most challenging problems for NSCLC and other cancer treatment. Recent study suggested that miRNAs are involved in therapeutic functions of chemotherapy during cancer treatment. Our present study established doxorubicin (Dox) resistant NSCLC A549 and H460 cells (named A549Dox/R and H460 Dox/R). We found that miR-199a-5p was significantly down regulated in Dox resistant cells. Over expression of miR-199a-5p can increase the Dox sensitivity of resistant cells. Among various targets of miR-199a-5p, chemoresistance can increase the expression of ABCC1 and HIF-1α. Gain and loss of function studies confirmed that both ABCC1 and HIF-1α were involved in the chemoresistance of NSCLC cells. Collectively, our data showed that miR-199a-5p regulated expression of ABCC1 and HIF-1α were involved in Dox resistance of NSCLC.

Gut microbiota in atherosclerosis: focus on trimethylamine N-oxide.

The increasing prevalence of cardiovascular diseases cannot adequately be explained by traditional risk factors. Recently, accumulating evidence has suggested that gut microbiota-derived numerous metabolites are contributors to atherosclerotic events. Among them, the role of trimethylamine N-oxide (TMAO) in promoting atherosclerosis has gained attention. TMAO is reported to exert the proatherogenic effects by impacting on the traditional risk factors of atherosclerosis and is associated with high risk of cardiovascular events. Besides that, TMAO is involved in the complex pathological processes of atherosclerotic lesion formation, such as endothelial dysfunction, platelet activation and thrombus generation. In light of these promising findings, TMAO may serve as a potential target for atherosclerosis prevention and treatment, which is conceptually novel, when compared with existing traditional treatments. It is likely that regulating TMAO production and associated gut microbiota may become a promising strategy for the anti-atherosclerosis therapy.

Association of Blood Pressure Variability and Intima-Media Thickness With White Matter Hyperintensities in Hypertensive Patients.

Background and Purpose: Ambulatory blood pressure variability (ABPV), ABP, and carotid intima-media thickness (IMT) are closely associated with white matter hyperintensities (WMH), and few studies focused on establishing effective models based on ABP, ABPV, and IMT to predict the WMH burden. We aimed to evaluate the value of a predictive model based on the metrics of ABP, ABPV, and IMT, which were independently associated with the WMH burden. Methods: We retrospectively enrolled 140 hypertensive inpatients for physical examinations in Shanghai East Hospital, Tongji University School of Medicine between February 2018 and January 2019. The basic clinical information of all subjects was recorded, and we also collected the metrics of ABP, ABPV, and IMT. Patients with Fazekas scale grade ≥2 were classified into heavy burden of WMH group. Then, we analyzed the association between all characteristics and the WMH burden. Multivariate analysis was performed to assess whether the metrics of ABP, ABPV, and IMT were independently associated with WMH, and we used receiver operating characteristic (ROC) to evaluate the value of predictive model based on the metrics of ABP, ABPV, and IMT. Results: Higher WMH grade was associated with increasing age, diabetes mellitus, higher total cholesterol (TC), higher low-density lipoprotein (LDL), higher IMT, higher 24-h systolic blood pressure (SBP), higher daytime SBP, higher nocturnal SBP, 24-h and daytime standard deviation (SD) of SBP, and 24-h SBP weight SD; 24-h SBP, 24-h SBP-SD, and IMT were independently related to the burden of WMH even after adjusting for the clinical variables. In addition, we also established a model that has a higher predictive capacity using 24-h SBP, 24-h SBP-SD, and IMT in the ROC analysis to assess the WMH burden in hypertensive patients. Conclusions: Higher 24-h SBP, higher 24-h SBP-SD, and larger IMT were independently associated with a greater burden of WMH among elderly primary hypertension Asian patients. Establishing a model based on these factors might provide a new approach for enhancing the accuracy of diagnosis of WMH using metrics in 24-h ABPM and carotid ultrasound.

Tight correlation between FoxM1 and FoxP3+ Tregs in gastric cancer and their clinical significance.

The aim of the present study was to investigate the expression of Forkhead box transcription M1 (FoxM1) and Forkhead box transcription P3 (FoxP3) in gastric cancer tissues in order to reveal any correlation between FoxM1, FoxP3 and clinicopathological parameters. Their clinical significance in gastric cancer was also investigated. Immunohistochemistry was used to detect the expression of FoxM1 and FoxP3 in gastric cancer and para-cancer tissues. The clinical significance of FoxM1 and FoxP3 in gastric cancer was explored, and the association between FoxM1 and FoxP3 was further analyzed. As a result, the overexpression of FoxM1 and FoxP3 was evident in gastric cancer (P < 0.001). FoxM1 overexpression was showed to be correlated with late AJCC stage (P = 0.025), while positive tumoral FoxP3 expression was associated with deeper invasion (P = 0.020), lymph node metastasis (P = 0.019) and later AJCC stage (P = 0.024). Overexpression of FoxM1 or FoxP3 was revealed to be negative prognostic factors for survival duration (P < 0.05), whereas only FoxM1 was shown to be independently associated with prognosisin gastric cancer after multivariate analysis (P = 0.020). A significant and positive correlation between FoxM1 and FoxP3 expressions was finally confirmed (P = 0.001). This significantly positive correlation between FoxM1 and FoxP3 prompts that FoxM1 may induce immune inhibition by recruiting FoxP3+ Tregs, leading to the progression of carcinogenesis, invasion and metastasis.

[The protective effect of Astragalus membranaceus extraction on cryopreserved primary-cultured human fetal hepatocytes].

OBJECTIVE: To observe the influence of Astragalus membranaceus Extraction (AE) on the primary-cultured human fetal hepatocytes stored in liquid nitrogen and explore a new method for the cryopreservation of human hepatocytes with improved function. METHODS: Human fetal hepatocytes were harvested by two-step collagenase perfusion, and then stored in a liquid nitrogen for one month with five different cryoprotectants (I: 10% DMSO, II: 5% DMSO + 2 mg/L AE, III: 5% DMSO + 20 mg/L AE, IV: 5% DMSO + 60 mg/L AE, V: 5% DMSO + 100 mg/L AE). One month later, the cells were thawed rapidly and the viability, morphology and basic function of them were tested. RESULTS: The human fetal hepatocytes in different groups showed various levels of viability, morphological manifestation and cell function respectively. After thawing, the viability rate and flash adhering rate in group IV and V had no significant difference with group I (P > 0.05), but were higher than group II and III (P < 0.05); the cell function analysis in the group IV, the results of ALB and AST level determination, NH4Cl transformation test, were the best among the groups (P < 0.05). CONCLUSION: AE can provide protection for human fetal hepatocytes in cryopreservation, and the best performance concentration level of its is 60 mg/L; the preservation dosage of DMSO can be reduced when combined with AE in the preservation solution, which shows that AE has a synergistic effect with DMSO.