Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.

OBJECTIVES: Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS: We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS: A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS: We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.

Surgical treatment of a patient with live intracranial sparganosis for 17 years.

BACKGROUND: The incidence of sparganosis, especially intracranial live sparganosis is very low in China. Due to the lack of typical clinical manifestations, it is difficult to make a clear preoperative diagnosis of the disease, which often leads to delays the disease and serious consequences. CASE PRESENTATION: A 23-year-old man presented with a 17-year history of intermittent seizures and right extremity numbness and weakness. Magnetic resonance imaging (MRI) showed patchy, nodular and line-like enhancement. Enzyme-linked immunosorbent assay (ELISA) detected positive antibodies to Spirometra mansoni in peripheral blood and cerebrospinal fluid (CSF). In addition, during the operation, an ivory-colored live sparganosis was removed under the precise positioning of neuronavigation, and the patient was diagnosed with cerebral sparganosis. The patient began praziquantel and sodium valproate treatment after the operation, and was followed up for 3 months. There was no recurrence of epilepsy, and the weakness and numbness of the right limb improved. CONCLUSION: Nonspecific clinical manifestations often make the diagnosis of cerebral sparganosis difficult, and a comprehensive diagnosis should be made based on epidemiological history, clinical manifestations, ELISA results and imaging findings. Surgery is the preferred method for the treatment of cerebral sparganosis, and more satisfactory results can be achieved under the precise positioning of neuronavigation.

LncRNA 4344 promotes NLRP3-related neuroinflammation and cognitive impairment by targeting miR-138-5p.

OBJECTIVE: Cognitive impairment is a common neurological disease of which NLRP3-related neuroinflammation has been demonstrated to be an essential mediator. Previous studies have indicated that long non-coding RNAs (lncRNAs) are critical for the development of neurological disorders. However, the roles and functions of lncRNA 4344 in neuroinflammation during cognitive impairment are unknown and need to be further elucidated. METHODS: Lipopolysaccharide (LPS)-induced rat cognitive impairment and rat microglia (RM) cell inflammation models were established in vitro and in vivo. The Morris water maze test was used to evaluate the cognitive behavior of the rats. Gene expression was assessed using real-time quantitative polymerase chain reaction, and protein levels using enzyme-linked immunosorbent assay, or western blot analysis. The targeting relationship between lncRNA 4344, miR-138-5p, and NLRP3 was identified using bioinformatics analysis and a dual-luciferase reporter gene assay. Hematoxylin-Eosin and Nissl stainings, terminal deoxynucleotidyl transferase dUTP nick end labeling, or immunofluorescence staining assays were performed to detect pathological changes, neuronal apoptosis, or positive cells in hippocampal tissues, respectively. RESULTS: The expression levels of lncRNA 4344 and NLRP3 were upregulated in the hippocampal tissues of LPS-treated rats and RM cells, and showed a strong positive correlation between each other. LncRNA 4344 overexpression further enhanced the expression of NLRP3 and its downstream genes (caspase-1, IL-1ß, and IL-18), as well as neuronal apoptosis in LPS-stimulated RM cells, whereas lncRNA 4344 silencing attenuated the inflammatory injuries. Moreover, miR-138-5p was the direct target of lncRNA 4344 and was downregulated in the RM cell inflammation model. We also found that miR-138-5p directly reduced the expression of NLRP3 and its downstream genes. Subsequently, the results of the animal experiments showed that the lncRNA 4344/miR-138-5p/NLRP3 axis plays an essential role in regulating the cognitive behavior, pathological changes and apoptosis of hippocampal neurons, expression of inflammation-related factors (NLRP3, caspase-1, IL-1ß, and IL-18), and microglial activation in LPS-induced cognitive impairment rats. CONCLUSION: Our results demonstrated for the first time that lncRNA 4344 regulates NLRP3-related neuroinflammation and cognitive impairment by targeting miR-138-5p, providing a possible target for the treatment of diseases characterized by a cognitive deficit.

Diagnostic accuracy of stroke volume variation for predicting fluid responsiveness in children undergoing cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Stroke volume variation appears to be reliable for predicting fluid responsiveness in adults, and its predictive value in pediatric patients has been recently reported. However, its predictive value in children undergoing cardiac surgery is unclear. METHODS: A review and meta-analysis were performed on the diagnostic utility of stroke volume variation for predicting fluid responsiveness in children undergoing cardiac surgery. All relevant articles for prospective research assessing the value of stroke volume variation were searched in the Embase, MEDLINE (PubMed), and Cochrane databases through March 2020. The primary outcome was the accuracy of stroke volume variation for predicting fluid responsiveness in children. The combined data were analyzed by a meta-analysis. Publication quality was assessed using the QUADAS (quality assessment for studies of diagnostic accuracy, maximum score) standard guidelines. RESULTS: Six articles were included in the meta-analysis, following the search strategy. A total of 251 children were included from 6 prospective studies. Fluid therapy for all patients used crystalloids or colloids. The results of the analysis revealed a pooled diagnostic odds ratio of 8.23 (95% CI: 3.07-22.11), pooled sensitivity of 0.73 (95% CI: 0.64-0.80), and pooled specificity of 0.66 (95% CI: 0.58-0.74). Additionally, the overall area of the summary receiver operating characteristic curve was 0.78. There was significant moderate heterogeneity in these studies (p < .05, I2  = 42.1%) due to thresholds. CONCLUSIONS: There was some heterogeneity due to thresholds in the included studies. An evaluation of stroke volume variation may represent a reliable predictor of fluid responsiveness in children undergoing cardiac surgery. After operative cardiac output optimization, the possible impact of goal-directed fluid treatment depending on stroke volume variation on the perioperative outcome in the children population should subsequently be assessed.

The correlation of intraoperative hypotension and postoperative cognitive impairment: a meta-analysis of randomized controlled trials.

BACKGROUND: There is no consensus on whether intraoperative hypotension is associated with postoperative cognitive impairment. Hence, we performed a meta-analysis to evaluate the correlation of intraoperative hypotension and the incidence of postoperative delirium (POD) or postoperative cognitive dysfunction (POCD). METHODS: We searched PubMed, Embase, and Cochrane Library databases to find randomized controlled trials (RCTs) in which reported the relationship between intraoperative hypotension and POD or POCD. The retrieval time is up to January 2020, without language restrictions. Quality assessment of the eligible studies was conducted by two researchers independently with the Cochrane evaluation system. RESULTS: We analyzed five eligible RCTs. Based on the relative mean arterial pressure (MAP), participants were divided into low-target and high-target groups. For the incidence of POD, there were two studies with 99 participants in the low-target group and 94 participants in the high-target pressure group. For the incidence of POCD, there were four studies involved 360 participants in the low-target group and 341 participants in the high-target group, with a study assessed both POD and POCD. No significant difference between the low-target and the high-target group was observed in the incidence of POD (RR = 3.30, 95% CI 0.80 to 13.54, P = 0.10), or POCD (RR = 1.26, 95% CI 0.76 to 2.08, P = 0.37). Furthermore, it also demonstrates that intraoperative hypotension prolonged the length of ICU stay, but did not increased the mortality, the length of hospital stay, and mechanical ventilation (MV) time. CONCLUSIONS: There is no significant correlation between intraoperative hypotension and the incidence of POD or POCD.

Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn.

Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.

(-)-menthol increases excitatory transmission by activating both TRPM8 and TRPA1 channels in mouse spinal lamina II layer.

(-)-menthol, a major form of menthol, is one of the most commonly used chemicals. Many studies have demonstrated that (-)-menthol produces analgesic action through peripheral mechanisms which are mainly mediated by activation of TRPM8. Moreover, intrathecal injection of menthol induces analgesia as well. However, the central actions and mechanisms of (-)-menthol remain unclear. Here, we have investigated the action of (-)-menthol on excitatory synaptic transmission in spinal lamina II layer which plays a pivotal role in modulating nociceptive transmission from the periphery by using patch-clamp technique in mice spinal cord. We found that (-)-menthol increased miniature excitatory postsynaptic current frequency. The frequency increases which (-)-menthol induced were in a dose-dependent manner (EC50: 0.1079 mM). However, neither genetic knockout nor pharmacological inhibition of TRPM8 could block (-)-menthol-induced effects entirely. Furthermore, this increase was also impaired by TRPA1 antagonist HC030031, but abolished utterly by co-application of TRPM8 and TRPA1 antagonist. Our results indicate that (-)-menthol increases the excitatory synaptic transmission by activating either TRPA1 or TRPM8 channels in spinal lamina II layer.

The global death and disability burden associated with a high BMI in children and adolescents, 1990-2019.

Objective: Exploring changing trends in the burden caused by overweight and obesity among children and adolescents from 1990 to 2019 at the global, regional, and national levels, based on data from the Global Burden of Disease study (GBD) 2019. Methods: The annual number and rate of deaths and disability-adjusted life years (DALYs) associated with a high BMI among children and adolescents at global, regional, and national levels by age groups, sexes, and the sociodemographic index from 1990 to 2019 were collected from the GBD study 2019. Change percentage for number, and the estimated annual percentage changes (EAPCs) for rate were calculated to determine the temporal trends. Results: From 1990 to 2019, global high BMI-related deaths decreased by 34% but DALYs increased by 48%. Death rates in females were higher than in males, although both showed decreasing trends. For the rate of DALYs, both sexes showed increasing trends, but since 1999, the rate in males has surpassed that in females. A high BMI had the greatest impact on children under 5 years of age, and the burden in other age groups continued to increase. Regionally, High-income Asia Pacific experienced the fastest decrease in death rate (EAPC=-9.57), and East Asia saw the fastest increase in the DALYs rate (EAPC= 3.47). Globally, as age increases, the proportion of disease burden attributed to a high BMI in females generally increases. Conclusions: Our findings emphasize the urgent need to improve efforts to prevent children and adolescents becoming overweight and obese.

Dexmedetomidine enhances Mitophagy via PINK1 to alleviate hippocampal neuronal Pyroptosis and improve postoperative cognitive dysfunction in elderly rat.

Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis.

Relationship between systemic immune inflammation index and mortality among US adults with different diabetic status: Evidence from NHANES 1999-2018.

OBJECTIVE: To investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database. STUDY DESIGN AND SETTING: Adults with follow-up data in the NHANES 1999-2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data. According to the quartiles of SII, population were divided into four groups (Q1-Q4). Mortality data was determined by linking NHANES survey participants to the National Death Index records, which collect mortality data and determine their vital status. Cox regression models were also performed to explore the hazard ratio (HR) and the corresponding 95 % confidence interval (95 % CI) of SII related with all-cause and CVDs mortality. In addition, restricted cubic spline was used to explore the nonlinear relationship between SII and mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of our results. RESULTS: In this study, there were 45,454 participants were enrolled (50.43 % females), with a mean age of 47.35 ± 0.19 years. Among of which, 7971 were diabetes patients and 3281 were pre-diabetes. With the mean 9.89 ± 0.08 follow-up years, there were 6935 (15.26 %) deaths occurred. Of which, 1795 deaths were caused by CVDs. The age-adjusted death rates were higher in participants with high SII levels compared to those with low SII levels. Cox regression analysis, after adjusting for covariates, revealed that SII levels were associated with an increased risk of all-cause mortality (HR, 1.02; 95 % CI, 1.02-1.03, P < 0.0001) and CVDs mortality (HR, 1.05; 95 % CI, 1.02-1.08, P = 0.002) in the fully adjusted Model. Moreover, there was a slight increase in HR values with the progression of diabetes status. Restricted cubic spline analysis demonstrated a "U-shaped" relationship between SII and all-cause mortality in diabetic, pre-diabetic and non-diabetic populations (all the P for nonlinear < 0.001). In addition, the relationship between SII and CVDs mortality was also nonlinear in both the pre-diabetic and non-diabetic populations (both P < 0.001). However, there was a linear relationship between SII and cardiovascular mortality in individuals with diabetes (P = 0.528). CONCLUSION: The SII is closely associated with the risk of all-cause and cardiovascular mortality. These associations vary among individuals with different diabetic states. Therefore, monitoring systemic inflammation and SII values is crucial in mitigating the risk of mortality.

Association of obstructive sleep apnea symptoms with all-cause mortality and cause-specific mortality in adults with or without diabetes: A cohort study based on the NHANES.

BACKGROUND: The association between obstructive sleep apnea syndrome (OSAS) and mortality has not been extensively researched among individuals with varying diabetic status. This study aimed to compare the relationship of OSAS with all-cause and cause-specific mortality in US individuals with or without diabetes based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study included participants from the NHANES 2005-2008 and 2015-2018 cycles with follow-up information. OSAS data (OSAS.MAP10) was estimated from the questionnaire. Hazard ratios (HRs) and the 95% confidence interval (CI) of OSAS for mortality were calculated by Cox regression analysis in populations with different diabetes status. The relationships between OSAS and mortality risk were examined using survival curves and restricted cubic spline curves. RESULTS: A total of 13 761 participants with 7.68 ± 0.042 follow-up years were included. In the nondiabetic group, OSAS.MAP10 was positively associated with all-cause, cardiovascular, and cancer mortality. In individuals with prediabetes, OSAS.MAP10 was positively related to all-cause mortality (HR 1.11 [95% CI: 1.03-1.20]) and cardiovascular mortality (HR 1.17 [95% CI: 1.03-1.33]). The relationship between OSAS.MAP10 and the risk of all-cause mortality and cancer mortality exhibited L-shaped curves in diabetes patients (both with nonlinear p values <.01). Further threshold effect analysis revealed that OSAS was positively related to death risk when OSAS.MAP10 exceeded the threshold scores. CONCLUSION: The relationship between OSAS and mortality differed among participants with or without diabetes. Individualized clinical treatment plans should be developed in clinical practice to reduce the risk of death for patients with different metabolic conditions.

Changing trends of the diseases burden attributable to high BMI in Asia from 1990 to 2019: results from the global burden of disease study 2019.

OBJECTIVE: To analyse the trends of diseases burden attributed to high body mass index (BMI), including overweight and obesity, in Asia from 1990 to 2019. DESIGN: Observational study. SETTING: The data of 45 countries and regions in Asia were obtained from the Global Burden of Disease Study 2019 database. MAIN OUTCOME MEASURES: Numbers, age-standardised rate (ASR) of deaths and disability-adjusted life years (DALYs), and the corresponding estimated annual percentage changes (EAPCs), attributable to high BMI in Asia from 1990 to 2019, were analysed by regions, genders and age. We also analysed changes in the causes of deaths and DALYs that are attributable to high BMI over this period. RESULTS: In 2019, all causes deaths attributable to high BMI in Asia were 2 329 503, with increases by 265% compared with 1990. Over three decades, DALYs related to high BMI have increased by 268%. The ASRs of deaths and DALYs in Asia both showed continuous upward trends during this period (EAPC 1.39; 95% certainty interval [95% CI] 1.35 to 1.43 for deaths; EAPC 1.8; 95% CI 1.76 to 1.84 for DALYs), while both were declined in high-income areas (EAPC -2.03 and -1.26). By geographical regions, disease burden in Central Asia and West Asia have been fluctuating at high levels, but high-income Asia Pacific showed decreasing trends of ASR of deaths (EAPC -2.03) and DALYs (EAPC -1.26). Over this period, disease burden in Asia was changing from women to men, and tends to ageing. In addition, diabetes were the diseases most affected by high BMI, and cancer burden was high in middle-aged and elderly people. CONCLUSIONS: The disease burden attributed to high BMI in Asia has experienced great changes. It is necessary to promote the prevention of obesity and chronic diseases in a comprehensive manner, especially in low-income areas, men and elderly.

Secular trends of epidemiologic patterns of chronic kidney disease over three decades: an updated analysis of the Global Burden of Disease Study 2019.

OBJECTIVES: To assess the characteristics of the global death burden imposed by chronic kidney disease (CKD) and the attributable risk factors from 1990 to 2019 to help inform a framework for policy discussions, resource allocation and research priorities. DESIGN: A population-based observational study. SETTING: The death data and relative risk factors were obtained from the Global Burden of Disease (GBD) Study 2019 database. MAIN OUTCOME MEASURES: Based on the GBD database, we estimated the death burden attributable to CKD stratified by sociodemographic index (SDI), geographic location, sex, age group, time period and risk factors from 1990 to 2019. RESULTS: Over three decade study period, the global number of CKD-related deaths increased from 0.60 million (95% uncertainty interval (UI): 0.57-0.63 million) in 1990 to 1.43 million (95% UI: 1.31-1.52 million) in 2019. The age-standardised death rate (ASDR) of CKD, among all causes, increased from 15th in 1990 to 10th in 2019. Globally, the ASDR in males was higher than that in females. CKD-related deaths mainly occurred in those aged over 50 years, especially in regions with higher SDIs. The ASDR was negatively related to SDI (ρ=-0.603, p<0.0001). Among risk factors, metabolic risk factors, especially systolic blood pressure, fasting plasma glucose and body mass index, were the main contributors to CKD-related deaths. Although the high-temperature-related death burden was low, the trend increased sharply in lower SDI regions. CONCLUSIONS: CKD-related deaths continue to increase, with the majority occurring in elderly adults. The CKD-related death burden is higher in males than in females. Additionally, the increasing high-temperature-related death burdens in lower SDI regions should receive social attention.

The Presence, Location, and Degree of Late Gadolinium Enhancement in Relation to Myocardial Dysfunction and Poor Prognosis in Patients with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) typically develop myocardial fibrosis. No studies have investigated the clinical significance of the presence, location, and degree of fibrosis in SLE patients. Seventy-four SLE patients were included. Thirty-seven non-autoimmune disease patients and thirty-seven healthy individuals were included as controls. Myocardial fibrosis was evaluated at cardiac magnetic resonance via a qualitative and quantitative assessment of late gadolinium enhancement (LGE). Myocardial function was measured via speckle-tracking echocardiography. All patients were followed up for the occurrence of major adverse cardiac events (MACE). The presence, locations, and degrees of LGE disturbed regional and global myocardial function. The presence of LGE, left ventricular free-wall LGE (LVFW LGE), and severe LGE were all independent predictors of MACE in SLE patients [LGE presence HR: 3.746 (1.434-9.79), p = 0.007; LVFW LGE HR: 2.395 (1.023-5.606), p = 0.044; severe LGE HR: 3.739 (1.241-11.266), p = 0.019]. LGE combined with SLE-related organ damage identified patients at high risk of MACE (p < 0.001). In conclusion, the presence, degree, and location of LGE were associated with myocardial dysfunction. The presence, location, and degree of LGE had the potential to independently predict poor prognosis and improve risk stratification in SLE patients.

LncRNA-mRNA Expression Profiles and Functional Networks Associated with Cognitive Impairment in Folate-deficient Mice.

BACKGROUND: Cognitive impairment is a common neurocognitive disorder that affects the health of millions of people worldwide, related to folate deficiency. OBJECTIVE: The present study aimed to investigate the lncRNA-mRNA functional networks associated with cognitive impairment in folate-deficient mice and elucidate their possible molecular mechanisms. METHODS: We downloaded the gene expression profile (GSE148126) of lncRNAs and mRNAs from NCBI Gene Expression Omnibus (GEO) database. Four groups of mouse hippocampi were analyzed, including 4 months (4mo) and 18 months (18mo) of folic acid (FA) deficiency/supplementation. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified using gplots and heatmap packages. The functions of the DEmRNAs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The hub genes were identified by CytoHubba plugins of Cytoscape, and protein-protein interaction (PPI) network of deregulated mRNAs was performed using the STRING database. Finally, lncRNA-mRNA co-expression and competitive endogenous RNA (ceRNA) network analyses were constructed. RESULTS: In total, we screened 67 lncRNAs with 211 mRNAs, and 89 lncRNAs with 229 mRNAs were differentially expressed in 4mo_FA and 18mo_FA deficient mice, respectively. GO analyses indicated that DEmRNAs were highly related to terms involved in binding and biological regulation. KEGG pathway analyses demonstrated that these genes were significantly enriched for renin secretion, pancreatic secretion, and AMPK signaling pathways in the 18mo_FA deficiency group. Subsequently, the top 5 hub genes were screened from the PPI network, which may be key genes with the progression of folate deficiency. Upon the lncRNA-mRNA co-expression network analysis, we identified the top 10 lncRNAs having the maximum number of connections with related mRNAs. Finally, a ceRNA network was constructed for DE lncRNAs and DEmRNAs, and several pivotal miRNAs were predicted. CONCLUSIONS: This study identified the lncRNA-mRNA expression profiles and functional networks associated with cognitive impairment in folate-deficient mice by bioinformatics analysis, which provided support for the possible mechanisms and therapy for this disease.

Glutaminolysis and CD4+ T-cell metabolism in autoimmunity: From pathogenesis to therapy prospects.

The recent increase in the pathogenesis of autoimmune diseases revealed the critical role of T cells. Investigation into immunometabolism has drawn attention to metabolic processes other than glycometabolism. In rapidly dividing immune cells, including T lymphocytes, the consumption of glutamine is similar to or higher than that of glucose even though glucose is abundant. In addition to contributing to many processes critical for cellular integrity and function, glutamine, as the most abundant amino acid, was recently regarded as an immunomodulatory nutrient. A better understanding of the biological regulation of glutaminolysis in T cells will provide a new perspective for the treatment of autoimmune diseases. In this review, we summarized the current knowledge of glutamine catabolism in CD4+ T-cell subsets of autoimmunity. We also focused on potential treatments targeting glutaminolysis in patients with autoimmune diseases. Knowledge of immunometabolism is constantly evolving, and glutamine metabolism may be a potential therapeutic target for autoimmune disease therapy.

Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2019.

Background: With the increase in the aging population worldwide, Alzheimer's disease has become a rapidly increasing public health concern. Monitoring the dementia disease burden will support health development strategies by providing scientific data. Methods: Based on the data obtained from the 2019 Global Burden of Disease (GBD) database, the numbers and age-standardized rates (ASRs) of incidence, prevalence, death, and disability-adjusted life-years (DALYs) of Alzheimer's disease and other dementias from 1990 to 2019 were analyzed. Calculated estimated annual percentage changes (EAPCs) and Joinpoint regression analyses were performed to evaluate the trends during this period. We also evaluated the correlations between the epidemiology and the sociodemographic index (SDI), an indicator to evaluate the level of social development in a country or region considering the education rate, economic situation, and total fertility rate. Results: From 1990 to 2019, the incidence and prevalence of Alzheimer's disease and other dementias increased by 147.95 and 160.84%, respectively. The ASR of incidence, prevalence, death, and DALYs in both men and women consistently increased over the study period. All the ASRs in women were consistently higher than those in men, but the increases were more pronounced in men. In addition, the ASRs of incidence, prevalence, and DALYs were positively correlated with the SDI. Moreover, the proportion of patients over 70 years old with dementia was also positively correlated with the SDI level. Smoking was a major risk factor for the disease burden of dementia in men, while obesity was the major risk factor for women. Conclusion: From 1990 to 2019, the Alzheimer's disease burden increased worldwide. This trend was more serious in high-SDI areas, especially among elderly populations in high-SDI areas, who should receive additional attention. Policy-makers should take steps to reverse this situation. Notably, women were at a higher risk for the disease, but the risk in men showed a faster increase. We should give attention to the aging population, attach importance to interventions targeting dementia risk factors, and formulate action plans to address the increasing incidence of dementia.

Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation.

Mechanical damage is one of the predisposing factors of inflammation, and it runs through the entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic inflammatory diseases. The mechanism of how mechanical forces induce inflammation is not fully understood. Piezo1 is a newly discovered mechanically sensitive ion channel. The Piezo1 channel opens in response to mechanical stimuli, transducing mechanical signals into an inflammatory cascade in the cell leading to tissue inflammation. A large amount of evidence shows that Piezo1 plays a vital role in the occurrence and progression of chronic inflammatory diseases. This mini-review briefly presents new evidence that Piezo1 responds to different mechanical stresses to trigger inflammation in various tissues. The discovery of Piezo1 provides new insights for the treatment of chronic inflammatory diseases related to mechanical stress. Inhibiting the transduction of damaging mechanical signals into inflammatory signals can inhibit inflammation and improve the outcome of inflammation at an early stage. The pharmacology of Piezo1 has shown bright prospects. The development of tissue-specific Piezo1 drugs for clinical use may be a new target for treating chronic inflammation.

CB2R Activation Regulates TFEB-Mediated Autophagy and Affects Lipid Metabolism and Inflammation of Astrocytes in POCD.

Evidence suggests that the accumulation of lipid drots (LDs) accelerates damage to mitochondria and increases the release of inflammatory factors. These have been implicated as a mechanism underlying neurodegenerative diseases or tumors and aging-related diseases such as postoperative cognitive dysfunction (POCD), nevertheless, accumulation of lipid droplets has not been extensively studied in the central nervous system (CNS). Here, we found that after surgery, there was activation of astrocytes and lipid accumulation in the hippocampus. However, cannabinoid receptor type II (CB2R) activation significantly reduced lipid accumulation in astrocytes and change the expression of genes related to lipid metabolism. CB2R reduces the release of the inflammatory factors interleukin-1 beta (IL-1ß) and interleukin 6 (IL-6) in peripheral serum and simultaneously improves cognitive ability in mice with POCD. Further research on mechanisms indicates that CB2R activation promotes the nuclear entry of the bHLH-leucine zipper transcription factor, the transcription factor EB (TFEB), and which is a master transcription factor of the autophagy-lysosomal pathway, also reduces TFEB-S211 phosphorylation. When CB2R promotes TFEB into the nucleus, TFEB binds at two sites within promoter region of PGC1α, promoting PGC1α transcription and accelerating downstream lipid metabolism. The aforementioned process leads to autophagy activation and decreases cellular lipid content. This study uncovers a new mechanism allowing CB2R to regulate lipid metabolism and inflammation in POCD.

Predictive Value of Echocardiographic Strain for Myocardial Fibrosis and Adverse Outcomes in Autoimmune Diseases.

Background: Myocardial fibrosis is an important pathophysiologic mechanism of cardiac involvement that leads to increased mortality in patients with autoimmune diseases (AIDs). The aim of this study was to evaluate the association between myocardial strain from speckle-tracking echocardiography (STE) and fibrosis on cardiovascular magnetic resonance (CMR) and to further explore their prognostic implications in patients with AIDs. Methods: We prospectively included 102 AIDs patients with clinically suspected cardiac involvement and 102 age- and sex-matched healthy individuals. Patients underwent CMR for evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) and T1 mapping. A semiquantitative evaluation based on the extent of LGE was used to calculate the total (tLGEs) and segmental (sLGEs) LGE score. Global longitudinal strain (GLS) was evaluated by STE in all subjects. All patients were regularly followed up every 6 months. The primary endpoint was the composite incidence of all-cause death and cardiovascular hospitalization. Results: Compared to healthy controls, AIDs patients had impaired GLS (-17.9 ± 5.1% vs. -21.2 ± 2.5%, p < 0.001). LGE was detected in 70% of patients. Patients with LGE presented worse GLS (-17.1 ± 5.3% vs. -19.6 ± 4.1%, p = 0.018) than those without LGE. On multivariate logistic analysis, GLS ≥ -15% was an independent predictor of LGE presence (OR = 4.98, 95%CI 1.35-18.33, p = 0.016). Moreover, a marked and stepwise impairment of segmental longitudinal strain (-19.3 ± 6.6 vs. -14.9 ± 6.5 vs. -8.9 ± 6.3, p < 0.001) was observed as sLGEs increased. During a median follow-up time of 25 months, 6 patients died, and 14 patients were hospitalized for cardiovascular reasons. Both GLS ≥ -15% (HR 3.56, 95%CI 1.28-9.86, p = 0.015) and tLGEs ≥ 6 (HR 4.13, 95%CI 1.43-11.92, p = 0.009) were independently associated with the primary endpoint. Conclusions: In AIDs patients, impaired myocardial strain on STE could reflect the presence and extent of myocardial fibrosis and provide incremental prognostic value in addition to LGE in the prediction of adverse outcomes.