A regulatory miRNA-mRNA network is associated with transplantation response in acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a life-threatening complication characterized by rapid decline in renal function, which frequently occurs after transplantation surgery. However, the molecular mechanism underlying the development of post-transplant (post-Tx) AKI still remains unknown. An increasing number of studies have demonstrated that certain microRNAs (miRNAs) exert crucial functions in AKI. The present study sought to elucidate the molecular mechanisms in post-Tx AKI by constructing a regulatory miRNA-mRNA network. RESULTS: Based on two datasets (GSE53771 and GSE53769), three key modules, which contained 55 mRNAs, 76 mRNAs, and 151 miRNAs, were identified by performing weighted gene co-expression network analysis (WGCNA). The miRDIP v4.1 was applied to predict the interactions of key module mRNAs and miRNAs, and the miRNA-mRNA pairs with confidence of more than 0.2 were selected to construct a regulatory miRNA-mRNA network by Cytoscape. The miRNA-mRNA network consisted of 82 nodes (48 mRNAs and 34 miRNAs) and 125 edges. Two miRNAs (miR-203a-3p and miR-205-5p) and ERBB4 with higher node degrees compared with other nodes might play a central role in post-Tx AKI. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that this network was mainly involved in kidney-/renal-related functions and PI3K-Akt/HIF-1/Ras/MAPK signaling pathways. CONCLUSION: We constructed a regulatory miRNA-mRNA network to provide novel insights into post-Tx AKI development, which might help discover new biomarkers or therapeutic drugs for enhancing the ability for early prediction and intervention and decreasing mortality rate of AKI after transplantation.

The role of SARC-F scale in predicting progression risk of COVID-19 in elderly patients: a prospective cohort study in Wuhan.

BACKGROUND: Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. METHOD: A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. RESULT: Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p < 0.001). After adjustment for demographic and clinical factors, higher risk sarcopenia was associated with a higher hazard of severe condition [hazard ratio = 2.87 (95% CI, 1.33-6.16)]. CONCLUSION: We found that COVID-19 patients with higher sarcopenia risk were more likely to develop severe condition. A clinician-friendly assessment of sarcopenia could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.

[Prevalence of Sarcopenia and Associated Factors in Community-dwelling Elderly Populations in Chengdu China].

OBJECTIVE: To determine the prevalence of sarcopenia in community-dwelling elderly populations in Chengdu and its associated risk factors. METHODS: A total of 947 community dwelling residents aged ≥60 yr. in Chengdu participated in this study. Their appendicular skeletal muscle mass was measured through bioelectrical impedance analyses. Sarcopenia was defined using the diagnostic algorithm recommended by the Asia Working Group (AWGS) for Sarcopenia. Data in relation to the demographic characteristics, chronic diseases and life style of the participants were obtained through a questionnaire survey, which included the 15-item geriatric depression scale (GDS-15) and the mini nutritional assessment (MNA). RESULTS: Overall, 10.5% of the elderly participants were identified with sarcopenia: 8.4% in men and 12.5% in women. The prevalence of sarcopenia increased with age: 2.3% in the 60-64 yr., 5.6% in the 65-74 yr., 19.7% in the ≥75 yr.. Age [odds ratio (OR)=1.109, 95% confldence interval (CI):1.054-1.168], smoking (OR=3.482, 95%CI:1.356-8.938) and Malnorishment (OR=5.598, 95%CI:2.677-11.709) are significant predictors of sarcopenia after adjustment for potential confounders. CONCLUSION: Approximately 10% community-dwelling elderly in Chengdu have sarcopenis. Age, smoking, malnutrition are risk factors of sarcopenia.

[Localization Establishment of an Interdisciplinary Intervention Model to Prevent Post-Operative Delirium in Older Patients Based on 'Hospital Elder Life Program'].

BACKGROUND: Postoperative delirium is a significant complication in elderly patients. The occurrence of delirium may increase the related physical and psychological risks, delay the length of hospital stays, and even lead to death. According to the current evidence-based model, the application of interdisciplinary intervention may effectively prevent delirium, shorten the length of hospital stays, and save costs. PURPOSE: To establish a culturally appropriate interdisciplinary intervention model for preventing postoperative delirium in older Chinese patients. METHODS: The authors adapted the original version of the Hospital Elder Life Program (HELP©) from the Hebrew Senior Life Institute for Aging Research of Harvard University by localizing the content using additional medical resources and translating the modified instrument into Chinese. Furthermore, the final version of this interdisciplinary intervention model for postoperative delirium was developed in accordance with the "guideline of delirium: diagnosis, prevention and management produced by the National Institute for Health and Clinical Excellence in 2010" and the "clinical practice guideline for postoperative delirium in older adults" produced by American geriatrics society in 2014. Finally, the translated instrument was revised and improved using discussions, consultations, and pilot study. RESULTS: The abovementioned procedure generated an interdisciplinary intervention model for preventing postoperative delirium that is applicable to the Chinese medical environment. The content addresses personnel structure and assignment of responsibility; details of interdisciplinary intervention protocols and implementation procedures; and required personnel training. CONCLUSIONS: The revised model is expected to decrease the occurrence of post-operative delirium and other complications in elderly patients, to help them maintain and improve their function, to shorten the length of their hospital stays, and to facilitate recovery.

Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss.

Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.

The association between systemic inflammatory markers and sarcopenia: Results from the West China Health and Aging Trend Study (WCHAT).

BACKGROUND: Increased evidence suggests chronic inflammation is significant in the progression of sarcopenia in older adults. In this study, we aimed to compare the level of systemic inflammation markers (White blood cells, neutrophils, lymphocytes, platelets and their derived ratios) between sarcopenic and non-sarcopenic individuals and investigate the association of these inflammatory markers with sarcopenia. METHODS: This cross-sectional study included 4224 adults (1514 men and 2710 women) from the West China Health and Aging Trend (WCHAT) study. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia (AWGS). The value of systemic inflammatory markers was based on laboratory data. Multiple logistic regression analysis was used to explore the association between inflammatory markers and sarcopenia after adjusting for covariates. RESULTS: Among 4224 participants (mean age 62.3 ±â€¯8.2 years, 64.2 % women), 814 (19.3 %) were diagnosed as sarcopenia. After adjusting for potential confounders, logistic regression analysis indicated that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were significantly associated with sarcopenia. Participants in the highest NLR, PLR and SII value group had higher odds for sarcopenia than those in the lowest value group (OR [95 %CI]: 1.233 [1.002,1.517], 1.455 [1.177,1.799] and 1.268 [1.029,1.561], respectively). CONCLUSIONS: Higher NLR, PLR, and SII level are associated with an increased prevalence of sarcopenia in middle-aged and older adults. Since these systemic inflammatory markers are inexpensive and can be obtained easily from routine blood tests, regular follow-up of NLR, PLR and SII may be an effective strategy in sarcopenia screening and management.

The association of sleep quality and sleep duration with nutritional status in older adults: Findings from the WCHAT study.

OBJECTIVE: To identify the associations between sleep quality, sleep duration and nutritional status in older adults. METHODS: Data from a total of 6792 community-dwellings adults aged 50 and over from the baseline of the West China Health and Aging Trend (WCHAT) study were analyzed. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI scores >5 were categorized as poor sleep quality. Duration of sleep was classified as <6 h, 6-7 h, 7-8 h, 8-9 h and ≥9 h. The Mini Nutritional Assessment Short Form (MNA-SF) was used to assess nutritional status and a score <12 was identified as indicating a risk of malnutrition. Logistic regression models were used to explore the associations. RESULTS: Of 6792 participants (mean age 62.4 ±â€¯8.3 years, 62.5 % women), 1831 (27.0 %) were at risk of malnutrition. The prevalence of poor sleep quality was 47.1 %. In the logistic regression model adjusted for potential confounders, poor sleep quality was significantly associated with a risk of malnutrition (OR = 1.62, 95 %CI = 1.44, 1.82). Sleep durations of less than 6 h and of more than 9 h were shown to increase the odds of malnutrition risk (OR = 1.42, 95 %CI = 1.16, 1.73 and OR = 1.24, 95 %CI = 1.05, 1.47, respectively). CONCLUSIONS: Sleep disorders were significantly associated with malnutrition risk among older adults. Our results highlight the importance of good sleep quality and enough sleep in order to maintain good nutritional status in older adults.

Effect of the Tailored, Family-Involved Hospital Elder Life Program on Postoperative Delirium and Function in Older Adults: A Randomized Clinical Trial.

Importance: Postoperative delirium (POD) is a common condition for older adults, contributing to their functional decline. Objective: To investigate the effectiveness of the Tailored, Family-Involved Hospital Elder Life Program (t-HELP) for preventing POD and functional decline in older patients after a noncardiac surgical procedure. Design, Setting, and Participants: A 2-arm, parallel-group, single-blind, cluster randomized clinical trial was conducted from August 24, 2015, to February 28, 2016, on 6 surgical floors (gastric, colorectal, pancreatic, biliary, thoracic, and thyroid) of West China Hospital in Chengdu, China. Eligible participants (n = 281) admitted to each of the 6 surgical floors were randomized into a nursing unit providing t-HELP (intervention group) or a nursing unit providing usual care (control group). All randomized patients were included in the intention-to-treat analyses for the primary outcome of POD incidence. Statistical analysis was performed from April 3, 2016, to December 30, 2017. Interventions: In addition to receiving usual care, all participants in the intervention group received the t-HELP protocols, which addressed each patient's risk factor profile. Besides nursing professionals, family members and paid caregivers were involved in the delivery of many of the program interventions. Main Outcomes and Measures: The primary outcome was the incidence of POD, evaluated with the Confusion Assessment Method. Secondary outcomes included the pattern of functional and cognitive changes (activities of daily living [ADLs], instrumental activities of daily living [IADLs], Short Portable Mental Status Questionnaire [SPMSQ]) from hospital admission to 30 days after discharge, and the length of hospital stay (LOS). Results: Of the 475 patients screened for eligibility, 281 (171 [60.9%] male, mean [SD] age 74.7 [5.2] years) were enrolled and randomized to receive t-HELP (n = 152) or usual care (n = 129). Postoperative delirium occurred in 4 participants (2.6%) in the intervention group and in 25 (19.4%) in the control group, with a relative risk of 0.14 (95% CI, 0.05-0.38). The number needed to treat to prevent 1 case of POD was 5.9 (95% CI, 4.2-11.1). Participants in the intervention group compared with the control group showed less decline in physical function (median [interquartile range] for ADLs: -5 [-10 to 0] vs -20 [-30 to -10]; P < .001; for IADLs: -2 [-2 to 0] vs -4 [-4 to -2]; P < .001) and cognitive function (for the SPMSQ level: 1 [0.8%] vs 8 [7.0%]; P = .009) at discharge, as well as shorter mean (SD) LOS (12.15 [3.78] days vs 16.41 [4.69] days; P < .001). Conclusions and Relevance: The findings suggest that t-HELP, with family involvement at its core, is effective in reducing POD for older patients, maintaining or improving their physical and cognitive functions, and shortening the LOS. The results of this t-HELP trial may improve generalizability and increase the implementation of this program. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-POR-15006944.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

[Abnormal expression of caspase8,bcl-2 and cytochrome C in drug resistant lung cancer cell].

OBJECTIVE: To investigate the relations between the chemotherapy resistance in lung cancer cell (LCC) A549 and the expression of apoptosis protein including caspase8, bcl-2 and cytochrome C and bcl-2 mRNA. METHODS: Bcl-2 mRNAs of sensitive A549 cell (A549S) and drug-resistant A549 cell (A549R) cultured were amplified by reverse transcription polymerase chain reaction (RT-PCR), and the expressions in the two strains were compared by AG electrophoresis, with beta-actin as control. The caspase8, bcl-2 and cytochrome C proteins in the two strains were measured and assessed by Western Blot. RESULTS: The caspase8 and cytochrome C protein expressions were higher in A459S than in A549R (P<0.05). The bcl-2 protein expression was lower in A459S than in A549R (P<0.05). But there was no significant difference between the level of bcl-2 mRNA expression in strain A549S (8.74+/-1.81) and that in strain A549R (10.29+/-2.92) (P>0.05). CONCLUSION: The upregulation of the bcl-2 protein could depress the caspase8 and cytochrome C protein expression and so might be one of the reasons for drug resistance in lung cancer cell, but the upregulation might happen at the level of translation or thereafter not at the mRNA level.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Association of serum uric acid with body mass index among long-lived Chinese.

OBJECTIVES: To examine the individual association between BMI and level of serum uric acid (SUA) among the very elderly Chinese population. METHODS: A survey was conducted on 870 long-lived subjects (aged ≥90years). Subjects were divided into four groups according to quartile of BMI (<16.6, 16.6-18.9, 18.9-21.1, ≥21.1kg/m(2)) and to classification criteria of underweight, normal weight, overweight and obesity in BMI (<18.5, 18.5-23.0, 23.0-27.5, ≥27.5kg/m(2), respectively). Subjects were also divided into hyperuricemia and normal SUA groups. RESULTS: The sample included 661 unrelated Chinese. The mean age was 93.52±3.29years (range 90-108years). The mean level of BMI was 19.16±3.47kg/m(2) and mean SUA was 318.72±87.01. Compared to individuals without hyperuricemia, high level of SUA was associated with a higher level of BMI in both genders (p<0.001). According to the both BMI classification criteria, the group with higher BMI had higher level of SUA (p<0.001). Pearson correlation showed that SUA was significantly correlated with BMI (with coefficients r=0.235, 0.140, in men and women, respectively). Unadjusted and adjusted multiple logistic regressions showed that odds ratios for hyperuricemia were associated with BMI according to quartile of BMI. CONCLUSIONS: We found that among long-lived Chinese subjects, higher levels of SUA may be associated with higher BMI.

Pro12Ala polymorphism in PPAR-gamma2 and dementia in Chinese nonagenarians/centenarians.

We examined the existence of a relationship between polymorphism and dementia in subjects aged 90 years and above. The sample included 732 unrelated Chinese nonagenarians/centenarians (aged 90-108 years, mean age 93.68 years; 67.5% women). The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism. Cognitive function was measured with 30-item mini-mental state examination. The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala, 9.1% Pro12Ala, and 90.9% Pro12Pro. The prevalence rates of dementia were 64.9% in the whole sample (45.0% for men and 74.5% for women). In both men and women, between subjects with and without 12Ala carriers, there was no significant difference in cognitive function scores and also no significant difference in prevalence of dementia; there was no significant difference in frequency of 12Ala carriers between subjects with and without dementia. Multiple logistic regression was performed by adjusting clinical factors that are thought to be associated with cognitive function or with 12Ala carriers. We found that 12Ala is not a risk factor for dementia. We found that Pro12Ala polymorphism in PPAR-gamma2 was not directly correlated with dementia among Chinese nonagenarians and centenarians.

Chronic diseases and risk for depression in old age: a meta-analysis of published literature.

OBJECTIVE: We assessed the relationship between chronic diseases and risk for depression in old age. METHOD: MEDLINE, EMBASE, The Cochrane Library database were used to identify potential studies. All of the clinical studies that obtained data on the association between chronic diseases and risk of depression among individuals aged 55 years or older were identified and included in this review. The studies were classified into cross-sectional and longitudinal subsets. The quantitative meta-analysis of cross-sectional studies and that of longitudinal studies were preformed, respectively. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: Since all but one study found in the search was for individuals 60 years of age or over, we assessed and report on results for this larger group only. 24 cross-sectional and 7 prospective longitudinal studies were included in this review. The quantitative meta-analysis showed that, among chronic diseases, stroke, loss of hearing, loss of vision, cardiac disease or chronic lung disease had both a significant OR and RR for increased depression in old age; arthritis, hypertension or diabetes had a significant OR but an un-significant RR for increased depression in old age; and gastrointestinal disease had neither a significant OR nor a significant RR for increased depression in old age. CONCLUSIONS: We concluded here that in old age, the associations of depression with some chronic diseases were definite; among these chronic diseases, stroke, loss of hearing, loss of vision, cardiac disease and chronic lung disease were risk factors for increased depression, but it should be further investigated whether arthritis, hypertension and diabetes were risk factors for increased depression or not.