The relationship between NLR, LDL-C/HDL-C, NHR and coronary artery disease.

OBJECTIVE: Chronic inflammation and dyslipidemia are key risk factors for atherosclerotic cardiovascular diseases. We retrospectively explored the association between the neutrophil to lymphocyte ratio (NLR), the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C), and the neutrophil to HDL-C ratio (NHR), and the severity of coronary lesions in patients with acute coronary syndrome (ACS). METHOD: In June 2023, we selected 1210 patients who were diagnosed with ACS based on chest pain from January 2017 to December 2022. Of these, 1100 patients with abnormal coronary angiography were categorized into the experimental group, and 110 patients with normal coronary angiography were classified as the control group. We collected routine blood tests, lipid profiles, and coronary angiography results at admission (before coronary angiography). Patients were then stratified into a control group (Gensini score = 0) and an experimental group (Gensini score = 0) based on the Gensini score. The experimental group was further divided into a low score group (Gensini score < 69) and a high score group (Gensini score ≥ 69). RESULT: 1. Statistically significant differences were observed between the control and experimental groups in terms of gender, age, body mass index (BMI), hypertension, diabetes, smoking history, and counts of neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), red cell distribution width (RDW), total cholesterol (TC), HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR (P<0.05). Furthermore, differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, TC, triglyceride (TG), HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR were significant between the low and high score groups (P<0.05). 2. NEU, LYM, MON, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR showed significant correlations with the Gensini score (r>0.2, P<0.05), with NLR and LDL-C/HDL-C showing the strongest correlations (r = 0.822, P = 0.000). 3. The Receiver Operating Characteristic (ROC) curve indicated that the combination of NLR and LDL-C/HDL-C had superior sensitivity and specificity in predicting the severity of coronary lesions, with a significant difference (P<0.05). The sensitivity was 87.1%, the specificity was 90.9%, and the cut-off point was 2.04. 4. A predictive model was developed based on the ratio of NLR and LDL-C/HDL-C to the Gensini score. The final model score was calculated as 6.803 + 7.029NLR + 13.079LDL-C/HDL-C (R2 = 0.708). CONCLUSION: Compared to NLR, LDL-C/HDL-C, and NHR, the combined NLR and LDL-C/HDL-C ratio is a more accurate marker for assessing the severity of coronary artery disease in ACS patients. Its convenience and effectiveness make it a promising tool for early assessment, timely risk stratification, and appropriate clinical intervention, ultimately improving clinical outcomes for ACS patients.

The de novo missense mutation F224S in GABRB2, identified in epileptic encephalopathy and developmental delay, impairs GABAAR function.

Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABAAR) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the ß2 subunit of GABAAR. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABAAR channel function, we conducted transient expression experiments using GABAAR subunits in HEK293T cells. The GABAARs containing mutant ß2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABAAR containing the ß2 (F224S) subunit was significantly smaller compared to the wild type GABAAR. We propose that GABRB2 variant F224S is pathogenic and GABAARs containing this ß2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy.

MaMYBR30, a Novel 1R-MYB, Plays Important Roles in Plant Development and Abiotic Stress Resistance.

The V-myb myeloblastosis viral oncogene homolog (MYB) family participate in various bioprocesses including development and abiotic stress responses. In the present study, we first report a 1R SHAQKYF-class MYB, MaMYBR30, in mulberry. Subcellular localization and sequence analysis indicated MaMYBR30 is located in the nucleus and belongs to a CCA-like subgroup with a conserved SHAQKYF motif. Expression profile analysis showed that MaMYBR30 is expressed in leaves and can be induced by drought and salt stress. The down-regulation of MaMYBR30 using virus-induced gene silence (VIGS) in mulberry and the overexpression of MaMYBR30 in Arabidopsis were induced to explore the function of MaMYBR30. The functional characterization of MaMYBR30 in vivo indicated that MaMYBR30 can positively regulate the resistance of mulberry to drought while negatively regulating the resistance of mulberry to salt stress. In addition, MaMYBR30 also affects flower development and reproductive growth, especially after exposure to salt stress. Weighted gene co-expression network analysis (WGCNA) primarily revealed the possible genes and signal pathways that are regulated by MaMYBR30. Our results also imply that complex molecular mechanisms mediated by MaMYBR30, including crosstalk of ion toxicity, phytohormone signal transduction, flowering development, and epigenetic modification, need to be further explored in the future.

Exercise Attenuate Diaphragm Atrophy in COPD Mice via Inhibiting the RhoA/ROCK Signaling.

Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear. Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1ß, TNF-α, and RhoA/ROCK were determined by Western blotting. Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably. Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.

Effect of obstructive sleep apnea on postoperative delirium: a system review and meta-analysis.

PURPOSE: To investigate the impact of obstructive sleep apnea (OSA) on postoperative delirium (PD), and evaluate the effectiveness of positive airway pressure (PAP) therapy on PD among OSA patients. METHODS: We systematically searched Embase, Cochrane Library and PubMed databases from their establishment to November 27, 2022. A random-effects approach was employed to determine aggregated results. Subgroup and sensitivity analyses were carried out to investigate heterogeneity. RESULTS: Sixteen eligible studies were included in the analysis. Thirteen studies revealed that OSA significantly elevated the likelihood of developing PD (OR = 1.71; 95%CI = 1.17 to 2.49; p = 0.005). Subgroup analysis according to delirium assessment scales showed that OSA did not exhibit an association with the incidence of PD assessed by the Confusion Assessment Method-Intensive Care Unit (OR = 1.14; 95%CI = 0.77 to 1.67; p = 0.51) but enhanced the likelihood of developing PD evaluated with other measurement scales (OR = 2.15; 95%CI = 1.44 to 3.19; p = 0.0002). Three additional studies explored the impact of PAP treatment on PD among OSA individuals, indicating no significant reduction in PD incidence with PAP use (OR = 0.58; 95%CI = 0.13 to 2.47; p = 0.46). CONCLUSIONS: OSA may not be a risk factor for PD in critically ill patients in the intensive care unit, but may increase the likelihood of developing PD among individuals receiving regular care in the ward postoperatively. The efficacy of PAP therapy in decreasing PD incidence among OSA patients remains debatable.

Enhancement of colour formation of fermented sausages by overexpression of nitric oxide synthase in Staphylococcus vitulinus under hydrogen peroxide stress.

This study used hydrogen peroxide (H2O2) treatment to overexpress the gene of nitric oxide synthase (nos) in Staphylococcus vitulinus, which was then inoculated into fermented sausages to observe its effect on colour development. The results showed that a low concentration of H2O2 (50 mM) could up-regulate the expression of nos by increasing the oxidative stress level of S. vitulinus. At 2 h after treatment, the expression of nos in S. vitulinus was the highest (P < 0.05), and the relative enzyme activity was increased to about 1.5 times that of the untreated. The growth of S. vitulinus was not substantially affected by 50-mM H2O2 treatment (P > 0.05). When H2O2-treated S. vitulinus was inoculated into fermented sausages, the content of nitrosomyoglobin was increased, and the a*-value (indicating redness) was not significantly different from that in the group treated with nitrite (P > 0.05). This study provides a potential method to enhance the ability of S. vitulinus for colourising fermented sausage by inducing the overexpression of nos.

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.

Effects of ultrasound-assisted dry-curing on water holding capacity and tenderness of reduced­sodium pork by modifying salt-soluble proteins.

This study investigated the effects of ultrasound-assisted dry-curing (UADC) on water holding capacity (WHC) and tenderness of pork at different powers and times, and the mechanism was discussed by considering the functional and structural properties of salt-soluble proteins (SSP). The results showed the application of appropriate UADC treatments (300 W, 60 min) have disruptively affected the muscle structure and decreased the size of the SSP particles (P < 0.05), resulting in the increased concentration of active sulfhydryl and surface hydrophobicity (P < 0.05). These modifications facilitated the dissociation of the myofibrillar structure and the dissolution of more connected proteins, which in turn improved the WHC and tenderness of the pork (P < 0.05). Nevertheless, extended periods of high-power UADC treatments negatively affected the WHC and tenderness of dry-cured pork (P < 0.05). In general, using SSP modified by UADC provides a novel strategy for enhancing the WHC and tenderness of dry-cured products.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: the role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates procellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Lung transcriptomics reveals the underlying mechanism by which aerobic training enhances pulmonary function in chronic obstructive pulmonary disease.

BACKGROUND: Aerobic training is the primary method of rehabilitation for improving respiratory function in patients with chronic obstructive pulmonary disease (COPD) in remission. However, the mechanism underlying this improvement is not yet fully understood. The use of transcriptomics in rehabilitation medicine offers a promising strategy for uncovering the ways in which exercise training improves respiratory dysfunction in COPD patients. In this study, lung tissue was analyzed using transcriptomics to investigate the relationship between exercise and lung changes. METHODS: Mice were exposed to cigarette smoke for 24 weeks, followed by nine weeks of moderate-intensity treadmill exercise, with a control group for comparison. Pulmonary function and structure were assessed at the end of the intervention and RNA sequencing was performed on the lung tissue. RESULTS: Exercise training was found to improve airway resistance and lung ventilation indices in individuals exposed to cigarette smoke. However, the effect of this treatment on damaged alveoli was weak. The pair-to-pair comparison revealed numerous differentially expressed genes, that were closely linked to inflammation and metabolism. CONCLUSIONS: Further research is necessary to confirm the cause-and-effect relationship between the identified biomarkers and the improvement in pulmonary function, as this was not examined in the present study.

Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice.

Epilepsy is a brain disorder affecting up to 1 in 26 individuals. Despite its clinical importance, the molecular mechanisms of epileptogenesis are still far from clarified. Our previous study showed that disruption of Clock in excitatory neurons alters cortical circuits and leads to generation of focal epilepsy. In this study, a GAD-Cre;Clockflox/flox mouse line with conditional Clock gene knockout in inhibitory neurons was established. We observed that seizure latency was prolonged, the severity and mortality of pilocarpine-induced seizure were significantly reduced, and memory was improved in GAD-Cre;Clockflox/flox mice. We hypothesize that mice with CLOCK knockout in inhibitory neurons have increased threshold for seizure, opposite from mice with CLOCK knockout in excitatory neurons. Further investigation showed Clock knockout in inhibitory neurons upregulated the basal protein level of ARC, a synaptic plasticity-associated immediate-early gene product, likely through the BDNF-ERK pathway. Altered basal levels of ARC may play an important role in epileptogenesis after Clock deletion in inhibitory neurons. Although sEPSCs and intrinsic properties of layer 5 pyramidal neurons in the somatosensory cortex exhibit no changes, the spine density increased in apical dendrite of pyramidal neurons in CLOCK knockout group. Our results suggest an underlying mechanism by which the circadian protein CLOCK in inhibitory neurons participates in neuronal activity and regulates the predisposition to epilepsy.

A Case of Severe Rhabdomyolysis, Acute Myocardial Damage and Multi-Organ Dysfunction Syndrome in a Patient with Novel Coronavirus Pneumonia.

In recent years, healthcare systems worldwide have faced the challenge of the severe COVID-19 pandemic. However, cases of severe rhabdomyolysis, acute myocardial damage, and multiple organ dysfunction syndrome (MODS) caused by COVID-19 are currently rare. This report presents a case of severe rhabdomyolysis, acute myocardial damage, and MODS caused by COVID-19. The patient was treated at The University of Hong Kong-Shenzhen Hospital. The purpose of this report is to aid clinicians in quickly identifying and treating similar cases, ultimately improving patient outcomes.

Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats.

Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo. We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis.

FGF9 is required for Purkinje cell development and function in the cerebellum.

Fibroblast growth factor 9 (FGF9) is a member of the fibroblast growth factor family, which is widely expressed in the central nervous system (CNS). It has been reported that deletion of FGF9 leads to defects in cerebellum development, including Purkinje cell defect. However, it is not clear how FGF9 regulating cerebellar development remains to be determined. Our results showed that in addition to disrupt Bergmann fiber scaffold formation and granule neuron migration, deletion of neuronal FGF9 led to ataxia defects. It affected development and function of Purkinje cells, and also changed the action potential threshold and excitation frequency. Mechanistically, depletion of FGF9 significantly changed neurotransmitter contents in Purkinje cells and led to preferential increase in inflammation, even downregulation in ERK signaling. Together, the data demonstrate that neuronal FGF9 is required for the development and function of Purkinje cells in the cerebellum. Insufficient FGF9 during cerebellum development will cause ataxia defects.

L-ascorbyl-2-phosphate alleviates white matter injury caused by chronic hypoxia through the PRMT5/P53/NF-κB pathway.

White matter injury (WMI) is one of the most serious complications associated with preterm births. Damage to oligodendrocytes, which are the key cells involved in WMI pathogenesis, can directly lead to myelin abnormalities. L-ascorbyl-2-phosphate (AS-2P) is a stable form of vitamin C. This study aimed to explore the protective effects of AS-2P against chronic hypoxia-induced WMI, and elucidate the underlying mechanisms. An in vivo chronic hypoxia model and in vitro oxygen-glucose deprivation (OGD) model were established to explore the effects of AS-2P on WMI using immunofluorescence, immunohistochemistry, western blotting, real-time quantitative polymerase chain reaction, Morris water maze test, novel object recognition test, beaming-walking test, electron microscopy, and flow cytometry. The results showed that AS-2P resulted in the increased expression of MBP, Olig2, PDGFRα and CC1, improved thickness and density of the myelin sheath, and reduced TNF-α expression and microglial cell infiltration to alleviate inflammation in the brain after chronic hypoxia. Moreover, AS-2P improved the memory, learning and motor abilities of the mice with WMI. These protective effects of AS-2P may involve the upregulation of protein arginine methyltransferase 5 (PRMT5) and downregulation of P53 and NF-κB. In conclusion, our study demonstrated that AS-2P attenuated chronic hypoxia-induced WMI in vivo and OGD-induced oligodendrocyte injury in vitro possibly by regulating the PRMT5/P53/NF-κB pathway, suggesting that AS-2P may be a potential therapeutic option for WMI.

Effectiveness of mandibular advancement devices in the treatment of obstructive sleep apnea and the impact of different body positions on treatment： A systematic review and meta-analysis.

OBJECTIVE: The meta-analysis aimed to evaluate the efficacy of mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA) and explore the effect of different positions on MAD for OSA. METHODS: The Embase, PubMed, Medline, and Cochrane Library databases were searched for relevant studies evaluating the effect of MAD on the treatment of OSA from database inception to November 2022. The Bayesian random-effects mode was used to calculate the pooled outcome. Subgroup analysis and sensitivity analysis were applied to investigate the heterogeneity. RESULTS: A total of 6 studies enrolling 643 patients were eligible for further analysis. MAD treatment led to improvements in total apnea-hypopnea index (AHI) for both positional OSA(POSA) and Non-POSA groups, but there was no significant difference in the effect of MAD on Non-POSA and POSA (MD = -1.46,95%CI [-4.89,1.97], P = 0.40). In the supine position, AHI improvement after MAD treatment in POSA group was more than that in Non-POSA group by 15 events/hour in average (MD = 14.82, 95%CI [11.43,18.22], P＜0.00001), while in the non-supine position, the change of AHI in Non-POSA group was significantly better than that in POSA group by approximately 8 events/hour (MD = -7.55,95%CI[-10.73,-4.38],p < 0.00001). CONCLUSION: MAD is more suitable for POSA compared to Non-POSA in patients with habitual sleep in the supine or supine predominant position. While for patients with habitual sleep in the non-supine position, MAD is an effective treatment option for Non-POSA.

microRNA profilings identify plasma biomarkers and targets associated with pediatric epilepsy patients.

BACKGROUND: Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. METHODS: miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride-pilocarpine. RESULTS: We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls (p < 0.01), of which miR-27a-3p exhibited a very low p value (p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased (p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. CONCLUSIONS: MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. IMPACT: A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children. Plasma miR-27a-3p was one of the miRNAs with a low p value. GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p. miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.

Neonatal di-(2-ethylhexyl)phthalate exposure induces permanent alterations in secretory CRH neuron characteristics in the hypothalamus paraventricular region of adult male rats.

Corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) play a critical role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis. Early-life exposure to di-(2-ethylhexyl) phthalate (DEHP) has been associated with an increased risk of developing psychiatric disorders in adulthood. The present work was designed to explore the impact of neonatal exposure to DEHP on adult PVN CRH neuronal activity. DEHP or vehicle was given to male rat pups from PND16 to PND22. Then, anxiety-like behaviors, serum corticosterone and testosterone, immunohistochemistry, western blotting, fluorescence in situ hybridization and acute ex vivo slice electrophysiological recordings were used to evaluate the influence of DEHP on adult PVN secretory CRH neurons. Neonatal DEHP-exposed rats exhibited enhanced anxiety-like behaviors in adults, with an increase in CORT. Secretory CRH neurons showed higher spontaneous firing activity but could be inhibited by GABAAR blockers. CRH neurons displayed fewer firing spikes, prolonged first-spike latency, depolarizing shifts in GABA reversal potential and strengthened GABAergic inputs, as indicated by increases in the frequency and amplitude of sIPSCs. Enhancement of GABAergic transmission was accompanied by upregulated expression of GAD67 and downregulated expression of GABABR1, KCC2 and GAT1. These findings suggest that neonatal exposure to DEHP permanently altered the characteristics of secretory CRH neurons in the PVN, which may contribute to the development of psychiatric disorders later in life.

Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Numerous randomized controlled trials (RCTs) have reported the benefits of external diaphragm pacing combined with conventional rehabilitation therapies (EDP-CRTs) on pulmonary function and exercise capacity in patients with chronic obstructive pulmonary disease (COPD). However, evidence-based regarding its effects remains unclear. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effects of EDP-CRTs versus CRTs on patients with COPD. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: We performed a systematic review and meta-analysis, searching PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus, China Biology Medicine Disc, Chinese National Knowledge Infrastructure, Wan-Fang Database, and Chinese Scientific Journal Database from inception to 10 September 2023. RCTs investigating the effects of EDP-CRTs versus CRTs on COPD patients were included. The primary outcome was pulmonary function, including forced expiratory volume in 1 s (FEV1), the percentage of predicted values of FEV1 (FEV1%pred), and FEV1/forced vital capacity (FVC)%. Secondary outcomes included arterial blood gas analysis [the partial pressure of arterial oxygen (PaO2) and the partial pressure of arterial carbon dioxide (PaCO2)]; dyspnea [modified Medical Research Council Dyspnea Scale (mMRC)]; exercise capacity [6-min walking distance (6MWD)]; and quality of life [COPD assessment test (CAT)]. RevMan 5.3 software was used for meta-analysis. The quality of the included studies was assessed using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2.0). The certainty of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: In total, 13 studies/981 participants were included. The pooled results revealed significant benefits of EDP-CRTs versus CRTs on the FEV1 [standardized mean difference (SMD) = 1.07, 95% confidence interval (CI) = 0.58-1.56], FEV1%pred [weighted mean difference (WMD) = 6.67, 95% CI = 5.69-7.64], the FEV1/FVC% (SMD = 1.24, 95% CI = 0.48-2.00), PaO2 (SMD = 1.29, 95% CI = 0.74-1.84), PaCO2 (SMD = -1.88, 95% CI = -2.71 to -1.04), mMRC (WMD = -0.55, 95% CI = -0.65 to -0.45), 6MWD (SMD = 1.63, 95% CI = 0.85-2.42), and CAT (WMD = -1.75, 95% CI = -3.16 to -0.35), respectively. Planned subgroup analysis suggested that EDP-CRTs had a better effect on FEV1, FEV1/FVC%, 6MWD, and CAT in the duration of 2-4 weeks. CONCLUSION: EDP-CRTs have better effects on pulmonary function, PaCO2, dyspnea, exercise capacity, and quality of life in COPD patients than CRTs, and the duration to achieve the most effective treatment is 2-4 weeks. TRIAL REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (No. CRD42022355964).

Effects of pulmonary-based Qigong exercise in stable patients with chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: Physical exercise training is the central component of pulmonary rehabilitation. This study aimed to further investigate the rehabilitative effects of pulmonary-based Qigong exercise (PQE) in stable patients with chronic obstructive pulmonary disease (COPD). METHODS: In this randomized, assessor-blinded clinical trial, 44 participants with stable COPD were randomly assigned to 2 groups in a 1:1 ratio. Participants in the control group received usual care for 3 months. Participants in the intervention group received usual care combined with PQE (60 min each time, 2 times per day, 7 days per week, for 3 months). The outcome included exercise capacity, lung function test, skeletal muscle strength, dyspnea, and quality of life were measured before and after intervention. RESULTS: A total of 37 participants completed the trial. Compared to the control group, after 3 months of PQE, the mean change in exercise capacity, skeletal muscle strength, and quality of life were statistically significant (P < 0.05, for each), but no significant differences were observed in lung function (except for the forced expiratory volume in one second) and dyspnea (P > 0.05, for each). CONCLUSION: The findings of study suggest that the proposed program of 3 months of PQE intervention has significant improvement in exercise capacity, skeletal muscle strength, and quality of life of COPD-stable patients. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Trial ID: ChiCTR-1800017405 on 28 July 2018; available at https://www.chictr.org.cn/showproj.html?proj=28343 ).