Remimazolam-based anesthesia in a patient with hypertrophic obstructive cardiomyopathy undergoing radical colorectal cancer surgery: A case report.

BACKGROUND: The goal of anesthesia in patients with hypertrophic obstructive cardiomyopathy (HOCM) is to reduce the risk of left ventricular outflow tract obstruction triggered by anesthetics. Remimazolam is a newly developed anesthetic that has been reported to have superior hemodynamic stability. There have been no reports on the completion of non-cardiac surgery with remimazolam in patients with HOCM. METHODS: Here we report the case of a 49-year-old man diagnosed with hypertrophic obstructive cardiomyopathy who underwent resection of colon cancer with remimazolam and remifentanil anesthesia. A bolus 0.3 mg/kg remimazolam was administered for anesthesia induction, and then adjusted to 2 mg/kg/h to maintain anesthesia. Set the pain threshold index to 50 to auto-control the infusion speed of remifentanil. RESULTS: No hypotension occurred during anesthesia, and norepinephrine was not administered. After conversion to open surgery, the patient's blood pressure elevated and reduced with urapidil and esmolol. CONCLUSION: In this patient with HOCM, remimazolam and remifentanil provided adequate anesthesia for induction and maintenance to complete the right hemicolectomy.

Predicting ICU readmission risks in intracerebral hemorrhage patients: Insights from machine learning models using MIMIC databases.

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke subtype characterized by high mortality and complex post-event complications. Research has extensively covered the acute phase of ICH; however, ICU readmission determinants remain less explored. Utilizing the MIMIC-III and MIMIC-IV databases, this investigation develops machine learning (ML) models to anticipate ICU readmissions in ICH patients. METHODS: Retrospective data from 2242 ICH patients were evaluated using ICD-9 codes. Recursive feature elimination with cross-validation (RFECV) discerned significant predictors of ICU readmissions. Four ML models-AdaBoost, RandomForest, LightGBM, and XGBoost-underwent development and rigorous validation. SHapley Additive exPlanations (SHAP) elucidated the effect of distinct features on model outcomes. RESULTS: ICU readmission rates were 9.6% for MIMIC-III and 10.6% for MIMIC-IV. The LightGBM model, with an AUC of 0.736 (95% CI: 0.668-0.801), surpassed other models in validation datasets. SHAP analysis revealed hydrocephalus, sex, neutrophils, Glasgow Coma Scale (GCS), specific oxygen saturation (SpO2) levels, and creatinine as significant predictors of readmission. CONCLUSION: The LightGBM model demonstrates considerable potential in predicting ICU readmissions for ICH patients, highlighting the importance of certain clinical predictors. This research contributes to optimizing patient care and ICU resource management. Further prospective studies are warranted to corroborate and enhance these predictive insights for clinical utilization.

Mitochondrial dysfunction: A fatal blow in depression.

Mitochondria maintain the normal physiological function of nerve cells by producing sufficient cellular energy and performing crucial roles in maintaining the metabolic balance through intracellular Ca2+ homeostasis, oxidative stress, and axonal development. Depression is a prevalent psychiatric disorder with an unclear pathophysiology. Damage to the hippocampal neurons is a key component of the plasticity regulation of synapses and plays a critical role in the mechanism of depression. There is evidence suggesting that mitochondrial dysfunction is associated with synaptic impairment. The maintenance of mitochondrial homeostasis includes quantitative maintenance and quality control of mitochondria. Mitochondrial biogenesis produces new and healthy mitochondria, and mitochondrial dynamics cooperates with mitophagy to remove damaged mitochondria. These processes maintain mitochondrial population stability and exert neuroprotective effects against early depression. In contrast, mitochondrial dysfunction is observed in various brain regions of patients with major depressive disorders. The accumulation of defective mitochondria accelerates cellular nerve dysfunction. In addition, impaired mitochondria aggravate alterations in the brain microenvironment, promoting neuroinflammation and energy depletion, thereby exacerbating the development of depression. This review summarizes the influence of mitochondrial dysfunction and the underlying molecular pathways on the pathogenesis of depression. Additionally, we discuss the maintenance of mitochondrial homeostasis as a potential therapeutic strategy for depression.

Cropland displacement contributed 60% of the increase in carbon emissions of grain transport in China over 1990-2015.

Rapid urbanization and population growth have increased the need for grain transportation in China, as more grain is being consumed and croplands have been moved away from cities. Increased grain transportation has, in turn, led to higher energy consumption and carbon emissions. Here we undertook a model-based approach to estimate the carbon emissions associated with grain transportation in the country between 1990 and 2015. We found that emissions more than tripled, from 5.68 million tons of CO2 emission equivalent in 1990 to 17.69 million tons in 2015. Grain production displacement contributed more than 60% of the increase in carbon emissions associated with grain transport over the study period, whereas changes in grain consumption and population growth contributed 31.7% and 16.6%, respectively. Infrastructure development, such as newly built highways and railways in western China, helped offset 0.54 million tons of CO2 emission equivalent from grain transport. These findings shed light on the life cycle environmental impact within food supply chains.

Nrf2: An all-rounder in depression.

The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes and diseases, such as depression. Oxidative stress can result in or aggravate a battery of pathological processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder and ferroptosis, which have been found to be involved in the development of depression. Inhibition of oxidative stress and related pathological processes can help improve depression. In this regard, the nuclear factor erythroid 2-related factor 2 (Nrf2) in the antioxidant defense system may play a pivotal role. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damages, but also directly regulate the genes related to the above pathological processes to combat the corresponding alterations. Therefore, targeting Nrf2 has great potential for the treatment of depression. Activation of Nrf2 has antidepressant effect, but the specific mechanism remains to be elucidated. This article reviews the key role of Nrf2 in depression, focusing on the possible mechanisms of Nrf2 regulating oxidative stress and related pathological processes in depression treatment. Meanwhile, we summarize some natural and synthetic compounds targeting Nrf2 in depression therapy. All the above may provide new insights into targeting Nrf2 for the treatment of depression and provide a broad basis for clinical transformation.

TFEB in Alzheimer's disease: From molecular mechanisms to therapeutic implications.

Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenerative disease worldwide. The primary pathological hallmarks of AD are the deposition of ß-amyloid plaques and neurofibrillary tangles. Autophagy, a pathway of clearing damaged organelles, macromolecular aggregates, and long-lived proteins via lysosomal degradation, has emerged as critical for proteostasis in the central nervous system (CNS). Studies have demonstrated that defective autophagy is strongly implicated in AD pathogenesis. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, enhances the expression of related genes that control autophagosome formation, lysosome function, and autophagic flux. The study of TFEB has greatly increased over the last decade, and the dysfunction of TFEB has been reported to be strongly associated with the pathogenesis of many neurodegenerative disorders, including AD. Here, we delineate the basic understanding of TFEB dysregulation involved in AD pathogenesis, highlighting the existing work that has been conducted on TFEB-mediated autophagy in neurons and other nonneuronal cells in the CNS. Additionally, we summarize the small molecule compounds that target TFEB-regulated autophagy involved in AD therapy. Our review may yield new insights into therapeutic approaches by targeting TFEB and provide a broadly applicable basis for the clinical treatment of AD.

High frequency repetitive transcranial magnetic stimulation alleviates cognitive deficits in 3xTg-AD mice by modulating the PI3K/Akt/GLT-1 axis.

OBJECTIVE: Glutamate mediated excitotoxicity, such as oxidative stress, neuroinflammation, synaptic loss and neuronal death, is ubiquitous in Alzheimer's disease (AD). Our previous study found that 15 Hz repetitive transcranial magnetic stimulation (rTMS) could reduce cortical excitability. The purpose of this study was to explore the therapeutic effect of higher frequency rTMS on 3xTg-AD model mice and further explore the mechanisms of rTMS. METHODS: First, WT and 3xTg-AD model mice received 25 Hz rTMS treatment for 21 days. The Morris water maze test was used to evaluate the cognitive function. The levels of Aß and neuroinflammation were assessed by ELISA and immunofluorescence. Oxidative stress was quantified by biochemical assay kits. Brain glucose metabolism was assessed by 18F-FDG PET. Apoptosis was assessed by western blot and TUNEL staining. Synaptic plasticity and PI3K/Akt/GLT-1 pathway related protein expression were assessed by western blot. Next, to explore the activity of PI3K/Akt in the therapeutic effect of rTMS, 3xTg-AD model mice were given LY294002 intervention and rTMS treatment for 21 days, the experimental method was the same as before. RESULTS: We found that 25 Hz rTMS could improve cognitive function of 3xTg-AD model mice, reduce hippocampal Aß1-42 levels, ameliorate oxidative stress and improve glucose metabolism. rTMS alleviated neuroinflammatory response, enhanced synaptic plasticity and reduced neuronal loss and cell apoptosis, accompanied by activation of PI3K/Akt/GLT-1 pathway. After administration of PI3K/Akt inhibitor LY294002, 25 Hz rTMS could not improve the cognitive function and reduce neuron damage of 3xTg-AD model mice, nor could it upregulate the expression of GLT-1, indicating that its therapeutic and protective effects required the involvement of PI3K/Akt/GLT-1 pathway. CONCLUSION: rTMS exerts protective role for AD through regulating multiple pathological processes. Meanwhile, this study revealed the key role of PI3K/Akt/GLT-1 pathway in the treatment of AD by rTMS, which might be a new target.

Repetitive transcranial magnetic stimulation exerts anti-inflammatory effects via modulating glial activation in mice with chronic unpredictable mild stress-induced depression.

AIMS: Recently numerous studies have demonstrated that neuroinflammation plays a critical role in the pathogenesis of depression. Repetitive transcranial magnetic stimulation (rTMS) has been used to treat depression for years but its mechanism is not fully elucidated. The present study was designed to investigate whether rTMS could alleviate neuroglia-associated neuro-inflammatory process in mice models of depression. METHODS: Mice were treated with chronic unpredictable mild stress (CUMS) to induce depression models and received four weeks of 15 Hz rTMS. Then the depression-like behaviors, microglia activation, the level of astrocytes, pro-inflammatory cytokines and inflammation-related signaling pathways were evaluated. RESULTS: rTMS ameliorated depression-like behaviors in CUMS-treated mice. rTMS not only markedly alleviated the activation of microglia but induced a switch of microglia polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype in the hippocampus and prefrontal cortex. Meanwhile, rTMS reversed the down-regulation of astrocytes and inhibited high levels of interleukin (IL)-6, IL-1ß and tumor necrosis factor-alpha (TNF-α) caused by CUMS in above regions. Moreover, we found that anti-inflammatory actions by rTMS were associated with the TLR4/NF-κB/NLRP3 signaling pathway. CONCLUSION: Collectively, our findings indicate that rTMS can exert anti-inflammatory actions in depression and provide new insights into the mechanism of rTMS in the treatment of depression.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment.

Grey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Hippocampal proteomic analysis reveals activation of necroptosis and ferroptosis in a mouse model of chronic unpredictable mild stress-induced depression.

Neuronal loss has been identified in depression, but its mechanisms are not fully understood. Proteomic analyses provide a novel insight to explore the potential mechanisms of such pathological alterations. In this study, mice were treated with chronic unpredictable mild stress (CUMS) for 2 months to establish depression models. The hippocampus was analyzed for proteomic patterns by mass spectrometry followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Behavioral tests showed that mice receiving CUMS showed depression-like symptoms such as anhedonia in the sucrose preference test (SPT) and behavioral despair in the forced swimming test (FST). CUMS induced anxiety-like behaviors in the open field test (OFT), but did not impair spatial learning and memory ability in the Morris water maze (MWM) test. Out of 4046 quantified proteins, 47 differentially expressed proteins were obtained between the CUMS and control groups. These proteins were functionally enriched in a series of biological processes. Among the notably enriched pathways, necroptosis and ferroptosis were significantly activated. Western blot and biochemical assay analyses identified changes in receptor-interacting protein kinase 3 (RIP3), phosphorylated mixed lineage kinase domain-like protein (p-MLKL), ferritin light chain 1 (Ftl1) and lipid peroxidation that were related to necroptosis and ferroptosis. Further, we found reduced levels of alpha-crystallin B (Cryab) and brain-derived neurotrophic factor (BDNF), which were also associated with neuronal survival. Our study highlighted that necroptosis and ferroptosis were involved in depression and partially account for neuronal loss, thereby providing potentially novel targets for the treatment of depression.

A Cross-Sectional Study of Psychological Status in Different Epidemic Areas in China After the COVID-19 Outbreak.

Background: The outbreak of coronavirus disease 2019 in Wuhan, Hubei Province, China has seriously affected people's mental health. We aimed to assess the psychological impact of the coronavirus disease 2019 on health care workers and non-health care workers in three different epidemic areas in China and to identify independent risk factors. Methods: We surveyed 1,020 non-health care workers and 480 health care workers in Wuhan, other cities in Hubei except Wuhan and other provinces in China except Hubei. Results: Health care workers in Hubei had higher levels of anxiety and depression than non-health care workers (p < 0.05), but there was no such difference in other provinces in China except Hubei (p > 0.05). Compared with other regions, health care workers in Wuhan was more anxious (p < 0.05), and this anxiety may be caused by concerns about occupational exposure and wearing protective clothing for a long time daily; health care workers in Hubei had more obvious depression (p < 0.05), which may be associated with long days participating in epidemic work and wearing protective clothing for a long time daily. Meanwhile, 62.5% of health care workers were proud of their work. The anxiety and depression of non-health care workers in Wuhan were also the most serious. Conclusions: In Wuhan, where the epidemic is most severe, levels of anxiety and depression seem to be higher, especially among health care workers. This information may help to better prepare for future events.

Nomograms to predict 2-year overall survival and advanced schistosomiasis-specific survival after discharge: a competing risk analysis.

BACKGROUND: The prognosis of patients with advanced schistosomiasis is poor. Pre-existing prognosis studies did not differentiate the causes of the deaths. The objectives were to evaluate the 2-year overall survival (OS) and advanced schistosomiasis-specific survival (ASS) in patients with advanced schistosomiasis after discharge through competing risk analysis and to build predictive nomograms. METHODS: Data was extracted from a previously constructed database from Hubei province. Patients were enrolled from September 2014 to January 2015, with follow up to January 2017. OS and ASS were primary outcome measures. Nomograms for estimating 2-year OS and ASS rates after discharge were established based on univariate and multivariate Cox regression model and Fine and Gray's model. Their predictive performances were evaluated using C-index and validated in both internal and external validation cohorts. RESULTS: The training cohort included 1487 patients with advanced schistosomiasis. Two-year mortality rate of the training cohort was 8.27% (123/1487). Competing events accounted for 26.83% (33/123). Older age, splemomegaly clinical classification, abnormal serum DBil, AST, ALP and positive HBsAg were significantly associated with 2-year OS. Older age, splemomegaly clinical classification, abnormal serum AST, ALP and positive HBsAg were significantly associated with 2-year ASS. The established nomograms were well calibrated, and had good discriminative ability, with a C-index of 0.813 (95% CI 0.803-0.823) for 2-year OS prediction and 0.834 (95% CI 0.824-0.844) for 2-year ASS prediction. Their predictive performances were well validated in both internal and external validation cohorts. CONCLUSION: The effective predictors of 2-year OS and ASS were discovered through competing risk analysis. The nomograms could be used as convenient predictive tools in clinical practice to guide follow-up and aid accurate prognostic assessment.

Neuroprotective efficacy of different levels of high-frequency repetitive transcranial magnetic stimulation in mice with CUMS-induced depression: Involvement of the p11/BDNF/Homer1a signaling pathway.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is widely used to treat depression. However, the underlying mechanism has not been identified, and there is uncertainty regarding the optimal choice of stimulus parameters, especially stimulus frequency. Our previous study in mice demonstrated that 10-Hz HF-rTMS ameliorated depression by inducing expression of Homer1a and reducing excitability of cortical pyramidal cells. The aims of this study were to compare the effects of 15-Hz and 25-Hz HF-rTMS in a model of chronic unpredictable mild stress (CUMS)-induced depression and investigate its possible molecular mechanism. Male C57BL/6J mice were treated with CUMS for 28 days followed by 15-Hz and 25-Hz rTMS for 4 weeks. The sucrose preference, open field, forced swimming, and tail suspension tests were used to evaluate depression-like behaviors. Immunostaining was performed to measure neuronal loss and neurogenesis. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of synapse-related proteins and the effects of HF-rTMS on the signaling pathway were examined using Western blot. The results showed that both 15-Hz and 25-Hz rTMS had significant antidepressant effects; 15-Hz rTMS seemed to be more effective than 25-Hz rTMS in preventing neuronal loss and promoting neurogenesis, while 25-Hz rTMS was superior to 15-Hz rTMS in facilitating synaptic plasticity. We also found that 15-Hz and 25-Hz rTMS markedly increased expression of p11, BDNF, Homer1a, and p-trkB proteins. These findings suggest that 15-Hz and 25-Hz HF-rTMS could exert neuroprotective effects to different degrees via multiple perspectives, which at least in part involve the p11/BDNF/Homer1a pathway.

Dysfunctional Architecture Underlies White Matter Hyperintensities with and without Cognitive Impairment.

BACKGROUND: White matter hyperintensities (WMH) are common in older adults and are associated with cognitive decline. However, little is known about the functional changes underlying cognitive decline in WMH subjects. OBJECTIVES: To investigate whole-brain functional connectivity (FC) underpinnings of cognitive decline in WMH subjects using univariate and multivariate analyses. METHODS: Twenty-three WMH subjects with mild cognitive impairment (WMH-MCI), 43 WMH subjects with no cognitive impairment (WMH-nCI), and 55 healthy controls underwent resting-state functional MRI scans. Whole-brain FC was calculated using the fine-grained human Brainnetome Atlas, followed by performance of between-group comparisons and FC-cognition correlation analysis. A multivariate analysis using support vector machine (SVM) was performed to classify WMH-MCI and WMH-nCI subjects based on FC. RESULTS: Both the WMH-MCI and WMH-nCI subjects exhibited characteristic impaired FC patterns. Markedly reduced FC involving subcortical nuclei and cortical hub regions of cognitive networks, especially the cingulate cortex, was identified in the WMH-MCI patients. In the WMH-MCI group, several connections involving the cingulate cortex were associated with cognitive decline. The exploratory mediation analyses indicated that FC alterations could partially explain the association between WMH and cognition. Furthermore, an SVM classifier based on FC distinguished WMH-MCI and WMH-nCI subjects with 78.8% accuracy. Connections that contributed most to the classification showed a similar distribution as the connections identified in the univariate analysis. CONCLUSIONS: This study provides a new window into the pathophysiology of cognitive impairment in WMH subjects and offer a novel and potential approach for early detection of the cognitive impairment in WMH subjects at the individual level.