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.

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.

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.

[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.

[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.