Analysis of vasoactive and oxidative stress indicators for evaluating the efficacy of continuous positive airway pressure, and relation of vasoactive and oxidative stress indicators and cardiac function in obstructive sleep Apnea Syndrome patients.

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a breathing disorder during sleep. The work was to evaluate the relationship between vasoactive and oxidative stress indicators and cardiac function in Obstructive Sleep Apnea Syndrome (OSAS) patients. Methods: OSAS patients (n=120) were treated with CPAP from May 2021 to June 2022. According to the clinical efficacy, the patients were divided into effective and ineffective groups. Vasoactive factors and oxidative stress indices were compared between the two groups to evaluate their clinical efficacy. The changes in cardiac function indices in the two groups were tested, and the correlation between vasoactive factors and oxidative stress indices and cardiac function was analysed. Results: The effective rate of CPAP was 63.33% (76/120). Ang II, ET-1, and MDA levels were lower, and the SOD level was higher in the effective group than in the ineffective group after treatment. The AUC of the four indicators was all greater than 0.75. LPWT and IVST values of the effective group were lower than the ineffective group. A positive correlation was identified between the levels of Ang II, ET-1, and MDA with LPWT, between levels of ET-1 and MDA with IVST, and a negative correlation between SOD with LPWT and IVST. Conclusions: CPAP treatment can effectively improve vascular activity and reduce the oxidative stress response in OSAS patients, and the combined detection of vasoactive factors and oxidative stress indicators is valuable for evaluating the efficacy of CPAP and is related to the cardiac function of patients.

HSF1 inhibits microglia activation to attenuate neuroinflammation via regulating miR-214-3p and NFATc2 in Parkinson's disease.

Parkinson's disease (PD) is characterized by microglia activation that leads to neuroinflammation. Heat shock transcription factor 1 (HSF1) is known to exert neuroprotective effects on neurodegenerative diseases. This study sought to analyse the role and mechanism of HSF1 in PD-induced neuroinflammation. The PD mouse models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animal behaviour capacities and neuronal damage were assessed via behavioural tests, tyrosine hydroxylase (TH) staining, and immunofluorescence. Levels of HSF1, miR-214-3p, nuclear factor of activated T cells 2 (NFATc2), and neuroinflammatory factors were detected via RT-qPCR, Western blotting, and ELISA.Binding relationships between HSF1 and miR-214-3p, miR-214-3p, and NFATc2 were tested via dual-luciferase or chromatin immunoprecipitation assays. Functional rescue experiments were designed to confirm the roles of miR-214-3p and NFATc2. HSF1 expression in brain tissues was downregulated upon MPTP treatment. HSF1 overexpression reduced motor deficits and loss of dopaminergic neurons, increased TH-positive neurons, and repressed neuroinflammation and micro-glia activation. Mechanically, HSF1 bound to the miR-214-3p promoter to increase its expression and inhibited NFATc2 transcription. miR-214-3p downregulation or NFATc2 overexpression reversed the inhibition of HSF1 overexpression on neuroinflammation and microglia activation. Overall, our findings unveiled the therapeutic role of HSF1 in PD-induced neuroinflammation and microglia activation via regulating miR-214-3p and NFATc2.

IRAK-M deficiency exacerbates dopaminergic neuronal damage in a mouse model of sub-acute Parkinson's disease.

Emerging evidence has proved that inflammatory responses aggravate the pathological progression of Parkinson's disease. This study aimed to identify the role of Interleukin-1 receptor-associated kinase-M (IRAK-M) as an important negative regulator of innate immunity, in the pathological progression of Parkinson's disease. In the present study, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection was administered to prepare the acute and sub-acute Parkinson's disease mouse models. Western blot analysis was utilized to examine the protein expressions of tyrosine hydroxylase and IRAK-M. The mRNA expression levels of IRAK-M, interleukin (IL)-6, IL-ß, and cyclooxygenase-2 were evaluated via using reverse transcription quantitative PCR (RT-qPCR). The expression of tyrosine hydroxylase-positive neurons in corpus striatum and substantia nigra pars compacta (SNc) tissues was detected using immunohistochemistry. The results showed that the protein and mRNA levels of IRAK-M were considerably upregulated in corpus striatum and SNc tissues in the sub-acute Parkinson's disease model. Furthermore, IRAK-M knockout significantly enhanced the MPTP-induced loss of tyrosine hydroxylase-positive fibers in corpus striatum and tyrosine hydroxylase-positive neurons in SNc, and intensified the effect of MPTP on the activation of microglial cells and the expression of inflammatory cytokines. In addition, sub-acute Parkinson's disease mice with IRAK-M deletion exhibited worse motor abilities than those of wild-type littermates. Overall, the present study suggested that IRAK-M reduces dopaminergic neuron damage in sub-acute Parkinson's disease by suppressing inflammation, which may provide a new therapeutic target for Parkinson's disease treatment.

Effects of schedule exercise therapy on chronic insomnia.

Schedule exercise therapy (SET) is a novel nonpharmacological intervention for the treatment of chronic insomnia disorder (CID). The aim of this study was to explore the effects of SET on CID. Methods: One hundred and eighteen CID were recruited and randomized into medication (MED) or medication combined with SET (MSET) groups. Over 12 observational weeks, sleep and mood status were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS). At the end of the observational period, the rates of clinically effective hypnotic use were calculated. At 12 weeks, the PSQI progressively decreased for all subjects combined (P < .001) as well as ISI (P < .001), ESS (P < .001), SDS (P < .001), and SAS (P < .001). The decreases in PSQI (P < .05), ISI (P < .05), SDS (P < .01), and SAS (P < .05) in the MSET group were significantly larger than those in the MED group, but not the same as those in the ESS group (P > .05). At the trial endpoint, the clinically effective rate was significantly higher (P < .05) and the hypnotic usage rate was lower (P < .05) in the MSET group than in the MED group. SET may be an effective treatment for insomnia in patients with CID.

Risk factors for COVID-19 progression and mortality in hospitalized patients without pre-existing comorbidities.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49-75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. METHODS: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. RESULTS: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00-56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. CONCLUSIONS: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.

[Analysis of clinical characteristics and risk factors in patients with benign paroxysmal positional vertigo].

〓 Objective: To analyze the clinical characteristics of patients with benign paroxysmal positional vertigo, summarize experience for diagnosis and treatment activities and to explore the risk factors related to the onset of BPPV and provide reference for early intervention to reduce the risk factor exposure of BPPV. Methods:One hundred and twelve patients with BPPV were included in the study, and clinical data including age, gender, onset symptoms and duration, past medical history and family history were analyzed. A One-way ANOVA was performed on 16 variables using age, gender, diabetes, hyperuric acid, hyperlipidemia, osteoporosis, hypertension, coronary heart disease, stroke, Meniere's disease, suppurative otitis media, vestibular neuronitis, sudden deafness, head injury, ear nose/maxillofacial surgery and autoimmune thyroiditis. The statistically significant parameters of the one-way ANOVA were included in the multivariate regression analysis to explore the independent risk factors for BPPV. Results:Seventy-six cases（67.86%） of BPPV patients were primary BPPV, 36 cases（32.14%） were secondary BPPV（P<0.01）. The gender composition（male, female）, ears involvement（unilateral, bilateral） and semicircular canal involvement（posterior semicircular canal, horizontal semicircular canal, anterior semicircular canal, mixed type） were different between the two groups（P<0.05）. During the follow-up period, 34（30.36%） patients relapsed, of which 19（25.00%） were the primary patients and 15（41.67%） were the secondary patients（P<0.01）. Diabetes（P=0.004）, osteoporosis（P=0.017）, hypertension（P=0.013）, stroke（P=0.005） and suppurative otitis media（P=0.031） were related to the onset of BPPV. Conclusion:BPPV patients are mainly primary, while the secondary patients are more likely to relapse after being cured. Diabetes, osteoporosis, hypertension, stroke and suppurative otitis media are independent risk factors for the onset of BPPV.

Case report: narcolepsy type 2 due to temporal lobe glioma.

RATIONALE: The orexin projection system includes the lateral hypothalamus, reticular activating structure, and ventrolateral preoptic nucleus, and this system is related to the pathogenesis of narcolepsy. Here, we report a case of narcolepsy type 2 caused by hippocampal glioma of the right temporal lobe. PATIENT CONCERNS: A 44-year-old male farmer complained of excessive daytime sleepiness (EDS) over the past 3 months and more. INTERVENTIONS: The lesion of the right anteromedial temporal lobe was removed and its pathological examination was carried out. OUTCOMES: General examination showed no abnormalities of his heart, lungs, or abdomen. Neurological examination showed no positive sign. The blood routine and biochemical examination were normal. He scored 7 on the Pittsburg sleep quality index, 16 on the Epworth sleepiness scale, 52 on the self-rating anxiety scale, and 48 on the self-rating depression scale. The multiple sleep latency test data showed 2 periods of sleep-onset rapid eyes movement period across 4 successive tests; the average sleep latency was under 8 minutes, and the rapid eyes movement latency was under 7 minutes. Lesion of glioma in hippocampus area of the right anteromedial temporal lobe was confirmed through magnetic resonance imaging, magnetic resonance spectroscopy, and histological examination. After surgical removal of the glioma from the hippocampus area of the right anteromedial temporal lobe, the patient's EDS symptoms disappeared immediately. He scored 3 on the Epworth sleepiness scale. During our follow-up three months later, he remained well with no complications. DIAGNOSIS: We diagnosed the patient with narcolepsy type 2 according to the 3rd Edition of International Classification of Sleep Disorders (ICSD-3). CONCLUSION: The patient suffered from EDS and was diagnosed with narcolepsy type 2. The narcolepsy type 2 was linked to glioma of the hippocampus area. The hippocampus might be another part of regulating the sleep-arousal pathway, and the glioma secretion might interact with the orexin projection system.

A novel mutation R190H in the AT-hook 1 domain of MeCP2 identified in an atypical Rett syndrome.

BACKGROUND: Mutations in Methyl-CpG binding protein 2 (MECP2) have been identified as the disease-causing mutations in Rett Syndrome (RTT). However, no mutation in the AT-hook 1 domain of MECP2 has been reported in RTT yet. The function of AT-hook 1 domain of MECP2 has not been described either. METHODS: The clinical and radiological features of a girl with progressive hyperactivity and loss of acquired linguistic and motor functions were presented. Next generation sequencing was used to screen the causative gene. Effect of the mutant protein on histone 3 methylation was assessed in vitro experiment. RESULTS: The patient was diagnosed with an atypical RTT at the age of nine. Magnetic resonance imaging revealed a loss of whole-brain volume and abnormal myelination. Genetic analysis identified a de novo novel missense mutation of MECP2 (NM_004992, c.570G->A, p.Arg190His). This mutation is located in the AT-hook 1 domain of MeCP2 protein. Overexpression of the mutant MeCP2 in cultured neuroblastoma cells SH-SY5Y revealed increased level of dimethylated histone 3 lysine 9, a transcriptional repressor marker. CONCLUSION: A novel missense mutation in AT-hook 1 domain of MeCP2 was identified in a patient with atypical RTT. Clinical data and in vitro experiment result imply that R190H mutation in AT-hook1 may cause dysfunction of MeCP2 and be a pathogenic variant.

TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse cortical neurons.

The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups. MPP+ was then applied to all groups, with the exception of the control group, and neurons were cultured for an additional 24 h. Neuron viability was evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism underlying the protective effects of TFP5, the expression levels of p35, p25 and phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell membranes and distribute around the nucleus. CCK8 assay showed that neuronal apoptosis was dependent on MPP+ concentration and exposure time. Cell viability decreased significantly in the model group compared with the control group (55±7 vs. 100±0%; P<0.01), and increased significantly in the TFP5 group compared with the model group (98±2 vs. 55±5%; P<0.01) and Scb group (98±2 vs. 54±4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+-induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical neurons, possibly through inhibiting the MPP+-induced formation and elevated kinase activity of a cyclin-dependent kinase 5/p25 complex.