Depression, anxiety, stress and other mental health conditions of personnel undergoing hospital isolation during the COVID-19 pandemic and influencing factors.

Objective: To understand the depression, anxiety, stress and other mental health conditions of personnel undergoing hospital isolation during the COVID-19 pandemic and the influencing factors. Methods: This was retrospective study. A total of 120 personnel undergoing Baoding No.1 Hospital isolation who completed the questionnaires were included from June 10, 2021 to February 07, 2022. The Patient Health Questionnaire-9(PHQ-9), the Generalized Anxiety Scale (GAD7) and psychological stress measurement table (PSTR) were used for psychological problem screening for personnel undergoing hospital isolation. Results: The incidence of depression was the lowest, while that of stress was the highest. The difference in the incidence of depression, anxiety and stress among personnel undergoing hospital isolation with different gender, age, income statuses, marital statuses and attitude towards isolation was statistically significant (p< 0.05), while the difference in the incidence of these problems among personnel with different degree of education was not statistically significant(p> 0.05). Multivariate Logistic regression analysis showed that age, gender, marital status, economic status and attitude towards isolation are factors associated with stress. Economic status and attitude towards isolation are factors associated with depression. A high economic level is a protective factor against depression, while a negative attitude is a risk factor for depression. Conclusion: During the COVID-19 pandemic, anxiety, depression and stress increased to different extents in personnel undergoing hospital isolation, especially in females with poor economic conditions and poor attitudes towards isolation. Therefore, necessary psychological counseling and social support should be provided to these people.

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis.

OBJECTIVE: Isolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. METHODS: Consecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. RESULTS: A total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). CONCLUSIONS: Standard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.

Phenylacetyl glutamine (PAGln) enhances cardiomyocyte death after myocardial infarction through ß1 adrenergic receptor.

This study aims to explore the roles of phenylacetyl glutamine (PAGln) on myocardial infarction (MI) pathogenesis. Here, using targeted metabolomics analysis, it was found that the plasma metabolite PAGln was upregulated in coronary artery disease (CAD) patients and MI mice and could be an independent risk factor for CAD. In vivo and in vitro functional experiments revealed that PAGln pretreatment enhanced MI-induced myocardial injury and cardiac fibrosis, as evident by the increased infarct size, cardiomyocyte death, and the upregulated expression of cardiac fibrosis markers (Col1a1 and α-SMA). Combined with RNA-sequencing analysis and G protein-coupled receptor (GPCR) inhibitor, we found that the GPCR signaling activation is essential for PAGln-mediated effects on cardiomyocyte death. Furthermore, drug affinity responsive target stability and cellular thermal shift assay demonstrated that PAGln could interact with ß1-adrenergic receptor (AR). Moreover, ß1-AR blocker treatment indeed extended the cardiac remodeling after PAGln-enhanced MI. These results suggest that PAGln might be a potential therapeutic target for extending the cardiac remodeling window in MI patients that signals via ß1-AR.

Comparison of rivaroxaban-based dual antithrombotic and antiplatelet therapies for symptomatic patients with lower-extremity peripheral artery disease post-revascularization: a retrospective cohort study.

Background: Patients with symptomatic lower-extremity peripheral artery disease (LE-PAD) are prone to serious cardiovascular and limb events. Few studies have evaluated the effect of rivaroxaban-based dual antithrombotic therapy in high-risk patients with LE-PAD in Asian populations. Objectives: To investigate the efficacy and safety of rivaroxaban-based dual antithrombotic therapy in symptomatic patients with LE-PAD. Design: Retrospective cohort study. Methods: This study included patients with LE-PAD treated at the Nanjing Drum Tower Hospital from 1 January 2018 to 31 December 2021. These participants were divided into antiplatelet (APT) or antiplatelet therapy combined with rivaroxaban (RAPT) groups. The efficacy outcomes in this study were the occurrence of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, or death from cardiovascular causes, and major adverse limb events (MALE), including urgent revascularization, acute limb ischemia, and major amputation. The safety outcomes included major and clinically relevant non-major (CRNM) bleeding. Patients were followed up until the time of death or the end of the study (31 March 2023). Results: We included 1144 patients with LE-PAD (APT: 502 patients; RAPT: 642 patients). The RAPT group had a lower risk of primary composite efficacy outcomes [hazard ratio (HR): 0.40] and a nonsignificant increase in major bleeding risk (HR: 2.33) than the APT group. The RATP group also had a significantly lower risk of secondary efficacy outcomes, including ischemic stroke (HR: 0.41), myocardial infarction (HR: 0.31), cardiovascular death (HR: 0.40), and MALE (HR: 0.65), than the APT group. The CRNM bleeding incidence varied between the two groups (HR: 3.96). Moreover, no significant interactions were observed between the subgroups and treatment groups in the composite efficacy analysis. Conclusion: Rivaroxaban-based dual antithrombotic therapy significantly reduced the occurrence of MACE in patients with LE-PAD without increasing major bleeding events. High-risk patients benefited from the dual antithrombotic therapy.

Background: Serious cardiovascular and limb events are common adverse effects in patients with symptomatic lower-extremity peripheral artery disease (LE-PAD).Few studies have reported the benefits of dual antithrombotic therapy with rivaroxaban in patients with high risk of LE-PAD in Asian populations. Methods: We collected data from in-patients with LE-PAD from January 1, 2018 to December 31, 2021.Depending on the antithrombotic medication administered, we classified the patients into antiplatelet therapy (e.g., aspirin and clopidogrel; APT group) and antiplatelet therapy combined with rivaroxaban (RAPT group) groups.The primary efficacy outcome was major adverse cardiovascular events (MACE), which was a composite of myocardial infarction, ischemic stroke or death from cardiovascular causes. The primary safety outcome was major bleeding.Secondary clinical outcomes included myocardial infarction, ischemic stroke, death from cardiovascular causes, clinically relevant non-major (CRNM) bleeding, and major adverse limb events (MALE), including urgent revascularization, acute limb ischemia, and major amputation.Follow-up continued until death or the end of the study (March 31, 2023). Results: The RAPT group had a lower risk of primary composite efficacy outcome and a non-significant increase in the risk of major bleeding than the APT group.The risk of secondary efficacy was significantly lower in the RAPT group than in the APT groups. The incidence of CRNM bleeding varied between the two groups.The subgroups and treatment groups had no significant interactions with the risk of composite efficacy outcomes. Conclusions: Rivaroxaban-based dual antithrombotic therapy has a clear therapeutic advantage over single antiplatelet therapy in Asian populations and does not increase the risk of major bleeding.Rivaroxaban-based combination therapy reduces the risk of serious adverse cardiovascular and limb events with an acceptable safety profile.

Comparison of rivaroxaban-based dual antithrombotic and antiplatelet therapies for symptomatic patients with lower-extremity peripheral artery disease post-revascularization: a retrospective cohort study.

Efficacy and Safety of Anticoagulant Therapy Versus Antiplatelet Therapy in Acute Ischemic Stroke Patients with Atrial Fibrillation.

The efficacy and safety of anticoagulant therapy in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) remain uncertain. This study enrolled 431 AIS and AF patients from Nanjing Drum Tower Hospital between January 2019 and December 2021 and followed for 365 days to determine the associations between anticoagulants and clinical outcomes by assessing modified Rankin Scale (mRS) score, recurrent ischemic stroke/systemic embolism (IS/SE), all-cause mortality, intracranial hemorrhage (ICH) and major bleeding. Final analysis included 400 eligible patients and divided them into antiplatelet group (n = 191) and anticoagulant group (n = 209). Anticoagulant therapy was associated with excellent (mRS 0-1; adjusted odds ratio (aOR), 2.63; 95% confidence interval (CI), 1.61-4.30) and favorable functional outcomes (mRS 0-2; aOR, 2.82; 95% CI, 1.69-4.70) and lower risk of all-cause mortality (adjusted hazard ratio (aHR), 0.35; 95% CI, 0.21-0.57), ICH (aHR, 0.45; 95% CI, 0.23-0.87) and major bleeding (aHR, 0.51; 95% CI, 0.28-0.94), without increasing the risk of recurrent IS/SE (aHR, 0.75; 95% CI, 0.45-1.24). In conclusion, anticoagulant therapy may be a more effective and safer option than antiplatelet therapy for AIS patients with AF.

Short-term antithrombotic strategies after left atrial appendage occlusion: a systematic review and network meta-analysis.

Background: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a stroke prevention strategy in patients with nonvalvular atrial fibrillation (NVAF), and these patients were required to receive antithrombotic therapy post-procedure. However, the optimal antithrombotic strategy after LAAO remains controversial. This study explored the safety and efficacy of different antithrombotic strategies after LAAO through a network comparison method. Methods: We systematically searched the MEDLINE, Embase, and Cochrane Library databases for studies that reported the interested efficacy and safety outcomes (stroke, device-related thrombus (DRT), and major bleeding) of different antithrombotic strategies [DAPT (dual antiplatelet therapy), DOACs (direct oral anticoagulants), and VKA (vitamin k antagonist)] in patients who had experienced LAAO. Pairwise comparisons and network meta-analysis were performed for the interested outcomes. Risk ratios (RRs) with their confidence intervals (CIs) were calculated using a random-effects model. The rank of the different strategies was calculated using the surface under the cumulative ranking curve (SUCRA). Results: Finally, 10 observational studies involving 1,674 patients were included. There was no significant difference in stroke, DRT, and major bleeding among the different antithrombotic strategies (DAPT, DOACs, and VKA). Furthermore, DAPT ranked the worst in terms of stroke (SUCRA: 19.8%), DRT (SUCRA: 3.6%), and major bleeding (SUCRA: 6.6%). VKA appeared to be superior to DOACs in terms of stroke (SUCRA: 74.9% vs. 55.3%) and DRT (SUCRA: 82.3% vs. 64.1%) while being slightly inferior to DOACs in terms of major bleeding (SUCRA: 71.0% vs. 72.4%). Conclusion: No significant difference was found among patients receiving DAPT, DOACs, and VKA in terms of stroke, DRT, and major bleeding events after LAAO. The SUCRA indicated that DAPT was ranked the worst among all antithrombotic strategies due to the higher risk of stroke, DRT, and major bleeding events, while VKAs were ranked the preferred antithrombotic strategy. However, DOACs are worthy of consideration due to their advantage of convenience.

LRRK2 Gly2019Ser Mutation Promotes ER Stress via Interacting with THBS1/TGF-ß1 in Parkinson's Disease.

The gene mutations of LRRK2, which encodes leucine-rich repeat kinase 2 (LRRK2), are associated with one of the most prevalent monogenic forms of Parkinson's disease (PD). However, the potential effectors of the Gly2019Ser (G2019S) mutation remain unknown. In this study, the authors investigate the effects of LRRK2 G2019S on endoplasmic reticulum (ER) stress in induced pluripotent stem cell (iPSC)-induced dopamine neurons and explore potential therapeutic targets in mice model. These findings demonstrate that LRRK2 G2019S significantly promotes ER stress in neurons and mice. Interestingly, inhibiting LRRK2 activity can ameliorate ER stress induced by the mutation. Moreover, LRRK2 mutation can induce ER stress by directly interacting with thrombospondin-1/transforming growth factor beta1 (THBS1/TGF-ß1). Inhibition of LRRK2 kinase activity can effectively suppress ER stress and the expression of THBS1/TGF-ß1. Knocking down THBS1 can rescue ER stress by interacting with TGF-ß1 and behavior burden caused by the LRRK2 mutation, while suppression of TGF-ß1 has a similar effect. Overall, it is demonstrated that the LRRK2 mutation promotes ER stress by directly interacting with THBS1/TGF-ß1, leading to neural death in PD. These findings provide valuable insights into the pathogenesis of PD, highlighting potential diagnostic markers and therapeutic targets.

Facial nerve in skullbase tumors: imaging and clinical relevance.

Facial nerve, the 7th cranial nerve, is a mixed nerve composed of sensory and motor fibers, and its main branch is situated in the cerebellopontine angle. Facial nerve dysfunction is a debilitating phenomenon that can occur in skullbase tumors and Bell's pals. Recovery of the facial nerve dysfunction after surgery for skullbase tumors can be disappointing, but is usually favorable in Bell's palsy. Advances in magnetic resonance imaging (MRI) allow to visualize the facial nerve and its course in the cerebellopontine angle, also when a large tumor is present and compresses the nerve. Here, we describe the anatomical, neurochemical and clinical aspects of the facial nerve and highlight the recent progress in visualizing the facial nerve with MRI.

Depression and the risk factors for isolated infectious disease fever patients in the hospital during the COVID-19.

Objectives: To compare and analyze the incidence of anxiety and depression of infectious disease fever patients in hospitalized isolation and home isolation during the COVID-19 pandemic, as well as the risk factors for the negative emotions of hospitalized isolation patients. Methods: Forty isolated infectious disease fever patients in Baoding No.1 Hospital were randomly selected as the study group, and the other 40 isolated infectious disease fever patients at home were randomly selected as the control group from March 2020 to August 2020. The scores and prevalence of depression and anxiety between the two groups were compared and analyzed. The logistic regression analysis was used to judge and analyze the negative psychological factors of hospitalized isolation patients such as depression and anxiety. Result: The HAMA and HAMD-17 scores of study group are significantly higher than those of control group (HAMA, p=0.00; HAMD-17, p=0.01). The prevalence of anxiety and depression in the study group was significantly higher than that in the control group (p=0.03, p=0.04). The gender (p=0.002), economic status (p=0.004) and isolation attitude (p=0.023) are the related factors of anxiety, among which economic status is the protective factor, while women and resistant attitude are the risk factors. Economic status (p=0.003) and isolation attitude (p=0.001) are the related factors of depression, among which economic status is the protective factor, and resistant attitude is the risk factor. Conclusion: The prevalence and severity of anxiety and depression in hospitalized isolation patients due to infectious disease fever are significantly higher than those of home isolation patients. The focus groups are women, with bad economic status and poor isolation attitude. Necessary psychological counseling and social support should be provided to these groups to reduce negative emotions and increase the experience of isolated patients.

Warfarin anticoagulation management during the COVID-19 pandemic: The role of internet clinic and machine learning.

Background: Patients who received warfarin require constant monitoring by hospital staff. However, social distancing and stay-at-home orders, which were universally adopted strategies to avoid the spread of COVID-19, led to unprecedented challenges. This study aimed to optimize warfarin treatment during the COVID-19 pandemic by determining the role of the Internet clinic and developing a machine learning (ML) model to predict anticoagulation quality. Methods: This retrospective study enrolled patients who received warfarin treatment in the hospital anticoagulation clinic (HAC) and "Internet + Anticoagulation clinic" (IAC) of the Nanjing Drum Tower Hospital between January 2020 and September 2021. The primary outcome was the anticoagulation quality of patients, which was evaluated by both the time in therapeutic range (TTR) and international normalized ratio (INR) variability. Anticoagulation quality and incidence of adverse events were compared between HAC and IAC. Furthermore, five ML algorithms were used to develop the anticoagulation quality prediction model, and the SHAP method was introduced to rank the feature importance. Results: Totally, 241 patients were included, comprising 145 patients in the HAC group and 96 patients in the IAC group. In the HAC group and IAC group, 73.1 and 69.8% (p = 0.576) of patients achieved good anticoagulation quality, with the average TTR being 79.9 ± 20.0% and 80.6 ± 21.1%, respectively. There was no significant difference in the incidence of adverse events between the two groups. Evaluating the five ML models using the test set, the accuracy of the XGBoost model was 0.767, and the area under the receiver operating characteristic curve was 0.808, which showed the best performance. The results of the SHAP method revealed that age, education, hypertension, aspirin, and amiodarone were the top five important features associated with poor anticoagulation quality. Conclusion: The IAC contributed to a novel management method for patients who received warfarin during the COVID-19 pandemic, as effective as HAC and with a low risk of virus transmission. The XGBoost model could accurately select patients at a high risk of poor anticoagulation quality, who could benefit from active intervention.

The Analysis of the Effect of Blood Transfusion on Changes of Blood Platelet Parameters in Patients with Leukemia Treated with Chemotherapy.

Objective: To study and analyze the effect of blood transfusion on the change of blood platelet parameters in patients with leukemia treated with chemotherapy. Methods: Ninety-eight patients with leukemia treated with chemotherapy in the First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to January 2022 were selected to observe the changes of platelet parameters before and after blood transfusion. Results: There was significant difference between pre-transfusion and post-transfusion indexes (platelet count, mean platelet volume, and hematocrit) (P < 0.05). After binary logistic regression analysis, the use of antibiotics (OR = 2.235), blood transfusion history (OR = 3.086), abnormal white blood cell count (OR = 1.134), and frozen plasma transfusion (OR = 3.121) were the main factors of blood platelet parameters after transfusion in leukemia patients (P < 0.05). Conclusion: Blood transfusion is beneficial to improve blood platelet parameters and prevent bleeding in patients with leukemia treated with chemotherapy. Attention should be paid to patients with risk factors for poor response to blood platelet transfusion and early intervention.

Outcome of anticoagulation with rivaroxaban in patients with non-retrieved inferior vena cava filters for the prevention of filter thrombosis: a retrospective cohort study.

BACKGROUND: Non-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF. METHODS: The study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death. RESULTS: A total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable. CONCLUSIONS: It is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.

Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions.

The intracellular aggregation of α-synuclein in neurons/glia is considered to be a key step in the pathogenesis of synucleinopathy [including Parkinson's disease (PD), dementia with Lewy body (DLB), multiple system atrophy (MSA), etc.]. Increasing evidence indicates that the initial pathological α-synuclein aggregates can replicate themselves and propagate in a "seeding" manner to multiple areas of the brain and even to peripheral tissue, which makes it the most important biomarker for the diagnosis of synucleinopathies in recent years. The amplification and propagation capabilities of α-synuclein aggregates are very similar to those of prion-like diseases, which are based on the inherent self-recruitment capabilities of existing misfolded proteins. In vitro, the rapid recruitment process can be reproduced in a simplified model by adding a small amount of α-synuclein pre-formed fibrils to the monomer solution as fibril seeds, which may partially reveal the properties of α-synuclein aggregates. In this study, we explored the elongation rate of α-synuclein pre-formed fibrils under a quiescent incubation condition (rather than shaking/agitating). By using the ThT fluorescence assay, we compared and quantified the elongation fluorescence curves to explore the factors that affect fibril elongation. These factors include proteins' concentration, temperature, NaCl strength, SDS, temperature pretreatment, and so on. Our work further describes the elongation of α-synuclein fibrils under quiescent incubation conditions. This may have important implications for the in vitro amplification and preservation of α-synuclein aggregates to further understand the prion-like transmission mechanism of PD.

MiR-9-5p Inhibits the MMP+-Induced Neuron Apoptosis through Regulating SCRIB/ß-Catenin Signaling in Parkinson's Disease.

The pathogenesis of Parkinson's disease remains unclear that there is no cure for Parkinson's disease yet. The abnormal expressions of certain miRNA are closely related to the occurrence and progression of Parkinson's disease. Here, we demonstrate that miR-9-5p inhibits the dopaminergic neuron apoptosis via the regulation of ß-catenin signaling which directly targets SCRIB, a tumor suppressor gene. Besides, miR-9-5p improved the motor function of mice with Parkinson's disease. The results of this study suggest that miR-9-5p might be a potential therapeutic target against Parkinson's disease.

The Use of Oral Anticoagulation Is Not Associated With a Reduced Risk of Mortality in Patients With COVID-19: A Systematic Review and Meta-Analysis of Cohort Studies.

Background: Hypercoagulability and thromboembolic events are associated with poor prognosis in coronavirus disease 2019 (COVID-19) patients. Whether chronic oral anticoagulation (OAC) improve the prognosis is yet controversial. The present study aimed to investigate the association between the chronic OAC and clinical outcomes in COVID-19 patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were comprehensively searched to identify studies that evaluated OAC for COVID-19 until 24 July 2021. Random-effects model meta-analyses were performed to pool the relative risk (RR) and 95% confidence interval (CI) of all-cause mortality and intensive care unit (ICU) admission as primary and secondary outcomes, respectively. According to the type of oral anticoagulants [direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs)], subgroup and interaction analyses were performed to compare DOACs and VKAs. Meta-regression was performed to explore the potential confounders on all-cause mortality. Results: A total of 12 studies involving 30,646 patients met the inclusion criteria. The results confirmed that chronic OAC did not reduce the risk of all-cause mortality (RR: 0.92; 95% CI 0.82-1.03; p = 0.165) or ICU admission (RR: 0.65; 95% CI 0.40-1.04; p = 0.073) in patients with COVID-19 compared to those without OAC. The chronic use of DOACs did not reduce the risk of all-cause mortality compared to VKAs (P interaction = 0.497) in subgroup and interaction analyses. The meta-regression failed to detect any potential confounding on all-cause mortality. Conclusion: COVID-19 patients with chronic OAC were not associated with a lower risk of all-cause mortality and ICU admission compared to those without OAC, and the results were consistent across DOACs and VKA subgroups. Systematic Review Registration: clinicaltrials.gov, identifier CRD42021269764.

Positive impacts of e-aid cognitive behavioural therapy on the sleep quality and mood of nurses on site during the COVID-19 pandemic.

OBJECTIVE: To investigate the positive impact of e-aid cognitive behavioural therapy on the sleep quality, anxiety, and depression of nurses on site during the COVID-19 pandemic. METHODS: Nurses on site at the Tianjin Medical University General Hospital Airport Site experiencing insomnia, anxiety and depression during the COVID-19 prevention and control period, from February 2020 to April 2021, were selected and divided into either an e-aid cognitive behavioural therapy (eCBT-I) group or a control group using a randomized grouping method. The eCBT-I group was given standard eCBT-I for 6 weeks; the control group did not get any intervention. The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) were used to evaluate the sleep quality of the subjects. The Generalized Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire (PHQ-9) were used to assess the subjects' anxiety and depression. Changes in sleep quality, anxiety and depression before and after treatment were compared between the two groups. RESULTS: Of 118 nurses randomized, the PSQI and ISI scores within the eCBT-I group (n=60) were significantly lower after treatment (5.9 ± 3.9, 6.7 ± 4.5) than before treatment (10.4 ± 3.5, 12.4 ± 4.7) (p <0.05). Compared to the scores of the control group (n=58) (9.1 ± 3.9, 10.6 ± 4.1), the PSQI and ISI scores in the eCBT-I group (5.9 ± 3.9, 6.7 ± 4.5) were lower after treatment (p <0.05). The GAD-7 and PHQ-9 scores in the eCBT-I group were all lower after treatment (3.7±3.4, 4.2±4.1) than before treatment (6.7±4.9, 7.7±5.1) (p <0.05). Compared with subjects in the control group (7.1±5.6, 7.3±5.1), subjects in the eCBT-I group (3.7±3.4, 4.2±4.1) had lower scores on the GAD-7 and PHQ-9 scales after treatment (p <0.05). CONCLUSION: eCBT-I improved the sleep quality of frontline nurses during the COVID-19 prevention and control period and relieved anxiety and depression.

Combined Effect of MTHFR C677T and PAI-1 4G/5G Polymorphisms on the Risk of Venous Thromboembolism in Chinese Lung Cancer Patients.

Venous thromboembolism (VTE) is a common and potentially fatal complication in cancer patients. Although several genetic risk factors related to thrombophilia have been identified, their contributions for the occurrence of VTE in cancer patients have conflicting results. The aim of this study was to evaluated the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G in lung cancer patients, with and without VTE, and the combined effect on the risk of VTE. 92 lung cancer patients diagnosed with VTE (VTE group) and 122 lung cancer patients without VTE (non-VTE group) were enrolled in the study. The gene polymorphisms were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism. Gene mutation of factor V Leiden was not detected both in non-VTE group and VTE group. The frequency of MTHFR C677T homozygous mutation in VTE group was 25.00%, higher than that in the non-VTE group without statistical difference. It was found that the PAI-1 4G4G genotype is associated with a higher risk of VTE (OR: 2.62, 95%CI: 1.19-5.75). Interestingly, the interaction between MTHFR C677T and PAI-1 4G/5G polymorphisms showed that the coexistence of the 2 homozygous mutation could further increase the risk of VTE. In conclusion, PAI-1 4G/5G polymorphism may be an increased risk factor for VTE among lung cancer patients in Chinese population. The homozygous MTHFR C677T mutation may be not a risk factor for VTE but increases the risk, accompanied with PAI-1 4G5G genotype.

Stress increases MHC-I expression in dopaminergic neurons and induces autoimmune activation in Parkinson's disease.

The expression of major histocompatibility complex class I (MHC-I), a key antigen-presenting protein, can be induced in dopaminergic neurons in the substantia nigra, thus indicating its possible involvement in the occurrence and development of Parkinson's disease. However, it remains unclear whether oxidative stress induces Parkinson's disease through the MHC-I pathway. In the present study, polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. The findings revealed that MHC-I was expressed in both models. To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells, immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8 (CD8)+ T cell infiltration in the substantia nigra of MPTP-treated mice. The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+ T cells. Moreover, in MPTP-induced Parkinson's disease model mice, the genetic knockdown of endogenous MHC-I, which was caused by injecting specific adenovirus into the substantia nigra, led to a significant reduction in CD8+ T cell infiltration and alleviated dopaminergic neuronal death. To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation, the expression of PTEN-induced kinase 1 (PINK1) was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA (siRNA), and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells. Taken together, MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation, thus rendering dopaminergic neurons susceptible to immune cells and degeneration. This may be one of the mechanisms of oxidative stress-induced Parkinson's disease, and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation. All animal experiments were approved by the Southern Medical University Ethics Committee (No. 81802040, approved on February 25, 2018).

Meta-analysis of postoperative antithrombotic therapy after left atrial appendage occlusion.

OBJECTIVE: This meta-analysis explored the safety and effectiveness of different anticoagulant regimens after left atrial appendage occlusion (LAAO). METHODS: Databases, such as PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library, were searched to identify eligible studies according to the inclusion criteria. The incidences of events, including device-related thrombus (DRT) formation, stroke, systemic thromboembolism, bleeding, cardiovascular mortality, and all-cause mortality, were analyzed using R version 3.2.3. RESULTS: The screening retrieved 32 studies, including 36 study groups and 4,474 patients. The incidence of outcomes after LAAO was calculated via meta-analysis. In the subgroup analysis, the rates of DRT formation, cardiovascular mortality, and all-cause mortality were significantly different among different antithrombotic methods. Single antiplatelet therapy was associated with the highest rate of adverse events, followed by dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and new oral anticoagulants (NOACs) carried lower rates of adverse events. CONCLUSIONS: Anticoagulant therapy had better safety and efficacy than antiplatelet therapy. Thus, for patients with nonabsolute anticoagulant contraindications, anticoagulant therapy rather than DAPT should be actively selected. NOACs displayed potential for further development, and these treatments might represent alternatives to VKAs in the future.

Tristetraprolin destabilizes NOX2 mRNA and protects dopaminergic neurons from oxidative damage in Parkinson's disease.

Tristetraprolin (TTP), an RNA-binding protein encoded by the ZFP36 gene, is vital for neural differentiation; however, its involvement in neurodegenerative diseases such as Parkinson's disease (PD) remains unclear. To explore the role of TTP in PD, an in vitro 1-methyl-4-phenylpyridinium (MPP+ ) cell model and an in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of PD were used. Transfection of small interfering (si)-TTP RNA upregulated pro-oxidative NOX2 expression and ROS formation, downregulated anti-oxidative GSH and SOD activity；si-TTP upregulated pro-apoptotic cleaved-caspase-3 expression, and downregulated antiapoptotic Bcl-2 expression; while overexpression (OE)-TTP lentivirus caused opposite effects. Through database prediction, luciferase experiment, RNA immunoprecipitation (RIP), and mRNA stability analysis, we evaluated the potential binding sites of TTP to 3'-untranslated regions (3'-UTR) of NOX2 mRNA. TTP affected the NOX2 luciferase activity by binding to two sites in the NOX2 3'-UTR. RIP-qPCR confirmed TTP binding to both sites, with a higher affinity for site-2. In addition, TTP reduced the NOX2 mRNA stability. si-NOX2 and antioxidant N-acetyl cysteine (NAC) reversed si-TTP-induced cell apoptosis. In MPTP-treated mice, TTP expression increased and was co-located with dopaminergic neurons. TTP also inhibited NOX2 and decreased the oxidative stress in vivo. In conclusion, TTP protects against dopaminergic oxidative injury by promoting NOX2 mRNA degradation in the MPP+ /MPTP model of PD, suggesting that TTP could be a potential therapeutic target for regulating the oxidative stress in PD.