BACKGROUND:Breast cancer, which is the most prevalent form of cancer among women globally, encompasses various subtypes that demand distinct treatment approaches. The tumor microenvironment and immune response are of crucial significance in the development and progression of breast cancer. Nevertheless, there has been scant evidence concerning the genes within breast cancer - specific immune cells. METHODS:We utilized summary data-based Mendelian randomization (SMR) to identify genes associated with breast cancer by utilizing expression quantitative trait loci (eQTL) datasets for 14 different immune cell types and genome-wide association studies (GWAS) for overall breast cancer and its subtypes. Furthermore, colocalization analysis was carried out to evaluate whether the observed association in SMR analyses is influenced by the same causal variant. Replication analysis and bulk RNA sequencing (bulkRNA-seq) analysis were employed to validate promising immune genes as potential drug targets. RESULTS:After correcting for the rate of false discovery, we discovered a total of 17 genes in 9 immune cell types that were significantly associated with overall breast cancer and its subtypes. The genes KCNN4, L3MBTL3, ZBTB38, MDM4, and TNFSF10 were identified in overall breast cancer and its subtypes. Colocalization analyses provided robust evidence in support of these associations. Notably, the KCNN4 gene in non-classical MONOcytes (MONOnc) was further validated through replication analysis and bulkRNA-seq analysis. CONCLUSION:In summary, our research has revealed a repertoire of genes within diverse immune cells associated with breast cancer. KCNN4 gene in non-classical MONOcytes (MONOnc) exhibited a negative association with overall breast cancer and its subtypes, which was identified as a potential drug target for breast cancer, opening up new avenues for therapeutic interventions.

There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD. By utilizing data sets of expression quantitative trait loci (eQTL) for 14 different immune cell types and large-scale AD genome-wide association study (GWAS), we employed SMR to identify key genes associated with AD within specific immune cells. Sensitivity analyses, including F-statistic, colocalization, and assessment of horizontal pleiotropy, were further conducted to validate the discovered genes. In addition, replication analyses were performed in AD GWAS from the FinnGen consortium. Finally, we further identified existing drugs that target or interact with the druggable genes and reviewed the studies about the associations between these drugs and AD. SMR analysis revealed 342 genes associated with AD across 14 immune cell types. Further sensitivity analyses identified nine genes, CTSH, FCER1G, FNBP4, HLA-E, JAZF1, KNOP1, PLEKHA1, RP11-960L18.1, and ZNF638 that had significant associations with AD across nine specific immune cell types. JAZF1, KNOP1 and PLEKHA1 were replicated in an independent analysis using the GWAS data. The review on gene-related drugs also supported these findings. Our research suggests that the expression of the genes JAZF1, KNOP1, and PLEKHA1 in specific immune cell types is related to the risk of AD.

BACKGROUND:Peroxiredoxin 2 (Prx2), an intracellular protein that regulates redox reactions, released from red blood cells is involved in inflammatory brain injury after intracerebral hemorrhage (ICH). Toll-like receptor 4 (TLR4) may be crucial in this process. This study investigated the role of the Prx2-TLR4 inflammatory axis in brain injury following experimental ICH in mice.METHODS:First, C57BL/6 mice received an intracaudate injection of autologous arterial blood or saline and their brains were harvested on day 1 to measure Prx2 levels. Second, mice received an intracaudate injection of either recombinant mouse Prx2 or saline. Third, the mice were co-injected with autologous arterial blood and conoidin A, a Prx2 inhibitor, or vehicle. Fourth, the mice received a Prx2 injection and were treated with TAK-242, a TLR4 antagonist, or saline (intraperitoneally). Behavioral tests, magnetic resonance imaging, western blot, immunohistochemistry/immunofluorescence staining, and RNA sequencing (RNA-seq) were performed.RESULTS:Brain Prx2 levels were elevated after autologous arterial blood injection. Intracaudate injection of Prx2 caused brain swelling, microglial activation, neutrophil infiltration, neuronal death, and neurological deficits. Co-injection of conoidin A attenuated autologous arterial blood-induced brain injury. TLR4 was expressed on the surface of microglia/macrophages and neutrophils and participated in Prx2-induced inflammation. TAK-242 treatment attenuated Prx2-induced inflammation and neurological deficits.CONCLUSIONS:Prx2 can cause brain injury following ICH through the TLR4 pathway, revealing the Prx2-TLR4 inflammatory axis as a potential therapeutic target.

(1) Assess the prevalence of postoperative insomnia; (2) identify the risk factors for postoperative insomnia before exposure to surgery; (3) explore the impact of postoperative insomnia on rehabilitation. A study was conducted with 132 participants aged ≥ 65 undergoing spine interbody fusion. We collected the basic demographic data, Numeric Rating Scales (NRS), Pittsburgh Sleep Quality Index (PSQI), Geriatric Depression Scale (GDS), and Beck Anxiety Inventory (BAI). We measured Quality of Recovery 40 (QoR-40), GDS, BAI, NRS, and PSQI on the first and third nights post-surgery, followed by QoR-40 and NRS assessments two weeks after surgery. The cases of postoperative insomnia on the first and third nights and after two weeks were 81 (61.36 https://www.chictr.org.cn/bin/project/edit?pid=170201 ; #ChiCTR2200059827).

AimsTo evaluate the potential causal effect of glycemic traits on lung cancer and investigate the impact of antihyperglycemic agent-target genes on lung cancer risk.MethodsGenetic variants associated with glycemic traits, antihyperglycemic agent-target genes, and lung cancer were extracted from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and the International Lung Cancer Consortium (ILCCO), respectively. Mendelian randomization (MR) analyses were performed to examine the associations of glycemic traits and antihyperglycemic agent-target genes with lung cancer. Mediation analysis was conducted to explore whether overweight operated as a mediator between antihyperglycemic agents and lung cancer outcomes.ResultsGenetically determined glycated hemoglobin A1c levels were associated with squamous cell lung cancer (OR = 1.78; 95% CI, 1.08-2.92; p = 0.023). The PRKAB1 gene (the target of metformin) was associated with a lower risk of developing lung adenocarcinoma (OR = 0.85; 95% CI, 0.76-0.96; p = 0.006). Further mediation analyses did not support overweight as a mediator between PRKAB1 activation and lung adenocarcinoma.ConclusionOur analyses suggest an association of genetically determined abnormal glycemic traits with squamous cell lung cancer. The potential association between PRKAB1 activation and a reduced risk of developing lung adenocarcinoma appears to be independent of the anti-obesity effects of metformin, suggesting that PRKAB1 activation may have a direct protective effect on lung adenocarcinoma development.

Background and Objective. Approximately 50% of acute ischemic stroke (AIS) patients who achieve complete recanalization after endovascular therapy (EVT) experience unfavorable outcomes that are potentially partially attributed to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet treatment. This study aimed to evaluate the effect of periprocedural tirofiban on AIS patients who achieved complete recanalization with EVT. Methods. Anterior circulation large-vessel occlusion stroke patients who achieved complete recanalization after EVT were retrospectively analyzed. Patients were dichotomized into tirofiban and nontirofiban groups and compared. Propensity score matching (PSM) was used to balance baseline confounders. 3-month functional independence (modified Rankin scale: 0–2), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), arterial reocclusion, in-hospital mortality, and 3-month mortality were evaluated. Results. This study included 303 patients with 118 and 185 in the nontirofiban and tirofiban groups, respectively. After PSM, 85 couples with balanced baseline characteristics were generated. 49 (57.6%) and 36 patients (42.4%) in the tirofiban and nontirofiban groups achieved functional independence at 3 months with a significant difference (risk ratio: 1.361, 95% confidence interval: 1.001–1.852, P=0.046 ). However, there was no significant difference between the tirofiban and nontirofiban groups in terms of the other outcomes (all P>0.05 ). Conclusions. In anterior circulation, large-vessel occlusion AIS patients who achieved complete recanalization with EVT, periprocedural tirofiban may improve the functional outcomes and does not appear to increase the rate of ICH and sICH.

This study aimed to investigate the impact of abdominal aortic occlusion (AAO)-induced injury on the kidney, lower limb muscles, heart, and brain in mice, and the potential protective effects of hypoxic postconditioning (HyC). The experimental design employed an abdominal aortic occlusion (AAO) model, and involved three groups of mice: sham, AAO, and AAO+HyC. Ten minutes after the AAO model, mice were subjected to hypoxic treatment lowering oxygen concentration to 5% within 45 minutes, and then returned to a normal oxygen environment. Hematoxylin-eosin (HE) stain was used for Histopathological examinations, and Quantibody Mouse Array was used for detecting apoptosis and inflammation-related protein expression. Histopathological examinations showed that HyC mitigated pathological damage to proximal organs (kidneys and lower limb muscles), distal organs (heart and brain), and reduced inflammatory cell infiltration. Expression of apoptosis-and inflammation-related proteins in brain and heart tissues were also evaluated. HyC significantly increased cellular inhibitor of apoptosis 2 (cIAP2) in the brain and Bcl-2 and insulin-like growth factor 2 (IGF-2) in the heart. Additionally, HyC regulated the expression of several inflammation-related factors in both brain and heart tissues. Although further investigation is needed, particularly in human subjects, this study highlights the potential of HyC as a promising therapeutic strategy for reducing AAO-associated organ damage.

BACKGROUND: Hemorrhagic shock (HS) causes severe organ damage, worsened by high-altitude conditions with lower oxygen and temperatures. Existing research lacks specific insights on brain and heart damage under these conditions. This study hypothesizes that high-altitude and cold (HAC) environments exacerbate HS-induced damage in the brain and heart, aiming to improve treatment strategies. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley (SD) rats (200–250 g of weight) were randomly assigned into sham, HS + normal, HS + HAC (4,000 m), and HS + HAC (6,000 m). The HS model was established in SD rats (35% loss of total blood volume), and histopathological injuries of the brain and heart were detected using hematoxylin and eosin staining, Sirius red staining, and immunohistochemistry. Apoptosis of the brain and heart tissues was detected by terminal transferase-mediated dUTP nick end labeling (TUNEL) immunofluorescence staining. To determine the levels of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (Mcp-1), BCL2-associated X (BAX), and myeloid cell leukemia-1 (Mcl-1) protein, western blotting assay was used. RESULTS: The HAC environment induced pathological damage to the brain and heart and aggravated the degree of cardiac fibrosis in HS rats. However, it did not cause apoptosis of the brain and heart. In addition, it upregulated TNF-α, IFN-γ, Mcp-1, and BAX protein levels, but downregulated Mcl-1 protein levels (P < 0.05). CONCLUSIONS: The HAC environment aggravated the degree of brain and heart damage in HS rats, which may be related to neuron nucleus pyknosis, myocardial fibrosis, and inflammatory and apoptosis activation.

Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data-based Mendelian randomization (SMR) along with multi-single nucleotide polymorphism (SNP)-based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene-trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.

Insomnia, often associated with anxiety and depression, is a prevalent sleep disorder. Biofeedback (BFB) treatment can help patients gain voluntary control over physiological events such as by utilizing electroencephalography (EEG) and electromyography (EMG) power. Previous studies have rarely predicted biofeedback efficacy by measuring the changes in relative EEG power; therefore, we investigated the clinical efficacy of biofeedback for insomnia and its potential neural mechanisms. We administered biofeedback to 82 patients with insomnia, of whom 68 completed 10 sessions and 14 completed 20 sessions. The average age of the participants was 49.38 ± 12.78 years, with 26 men and 56 women. Each biofeedback session consisted of 5 min of EMG and 30 min of EEG feedback, with 2 min of data recorded before and after the session. Sessions were conducted every other day, and four scale measures were taken before the first, fifth, and tenth sessions and after the twentieth session. After 20 sessions of biofeedback treatment, scores on the Pittsburgh Sleep Quality Index (PSQI) were significantly reduced compared with those before treatment (−5.5 ± 1.43,t = −3.85, p = 0.006), and scores on the Beck Depression Inventory (BDI-II) (−7.15 ± 2.43, t = −2.94, p = 0.012) and the State-Trait Anxiety Inventory (STAI) (STAI-S: −12.36 ± 3.40, t = −3.63, p = 0.003; and STAI-T: −9.86 ± 2.38, t = −4.41, p = 0.001) were significantly lower after treatment than before treatment. Beta and theta power were significantly reduced after treatment, compared with before treatment (F = 6.25, p = 0.014; and F = 11.91, p = 0.001). Alpha power was increased after treatment, compared with before treatment, but the difference was not prominently significant (p > 0.05). EMG activity was significantly decreased after treatment, compared with before treatment (F = 2.11, p = 0.015). Our findings suggest that BFB treatment based on alpha power and prefrontal EMG relieves insomnia as well as anxiety and depression and may be associated with increased alpha power, decreased beta and theta power, and decreased EMG power.

Niemann-Pick disease type C (NPC) is an autosomal recessive hereditary disease in which sphingomyelin and cholesterol are deposited in various organs of the body. The clinical manifestations of NPC include neurologic symptoms and cataplexy; other symptoms related to sleep have seldom been reported. One previous study described various sleep disorders including chronic insomnia, obstructive sleep apnea, restless legs syndrome, and rapid eye movement sleep behavior disorder, thus suggesting that sleep disorders in patients with NPC are more prevalent than previously thought and warrant close attention. Here, we describe sleep disorders in 2 patients with NPC and discuss the clinical characteristics and, for the first time, discuss potential pathogenic mechanisms underlying sleep disorders in such patients.

Vascular cognitive impairment (VCI) due to chronic cerebral hypoperfusion (CCH), is the second leading cause of dementia. Although synaptic impairment plays a critical role in VCI, its exact mechanism remains unknown. Our previous research revealed that remote ischemic conditioning (RIC) could alleviate cognitive decline resulting from CCH, however, its effects on synaptic impairment remain unclear. In this study, we confirmed that RIC alleviated both cognitive decline and its associated synaptic dysfunction caused by CCH. RNA sequencing revealed that CCH increased in miR-218a-5p expression, which was decreased by RIC. Elevated miR-218a-5p levels limited the benefits of RIC, however, inhibiting miR-218a-5p in hippocampal CA1 neurons rescued synaptic dysfunction. Additionally, we found that SHANK2 is a downstream target of miR-218a-5p, and inhibiting SHANK2 expression reduced the alleviation caused by hypoxic conditioning in synaptic impairment in vitro. In conclusion, our results suggested that RIC alleviated synaptic impairment via the miR-218a-5p/SHANK2 pathway, which could be a potential biomarker or therapeutic target for cognitive impairment caused by CCH.

Background: The presence of mild deficit is the most common reason for nonuse of intravenous alteplase in ischemic stroke. We analyzed within a national prospective cohort on whether patients with minor stroke can benefit from intravenous alteplase.Methods: This observational study included patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score 0 to 5 at admission. The short-term outcomes at discharge and 3-month were analyzed including the modified Rankin Scale score, gait speed, Montreal Cognitive Assessment, Patient Health Questionnaire-9, General Anxiety Disorder-7 and Stroke Impact Scale-16. Multivariate regression models were performed to evaluate the association between intravenous thrombolysis and clinical outcomes.Results: A total of 1876 consecutive patients were included in the current analyses with 102 patients (5.4%) received alteplase and 1774 patients (94.5%) were in non-alteplase group. We found that 10.9% patients presented unfavorable functional outcome with a mRS >= 2 at 3-month. Patients with alteplase treatment had a more favorable outcome in SIS-16 at discharge (OR, 5.45; 95% CI, 2.22-8.68) and 3-month after stroke (OR, 2.34; 95% CI, 0.17-4.50). There was an association of alteplase with better gait speed in the restricted sample of age >60 (OR,0.14; 95% CI, 0.02-0.25), while an unfavorable effect was found in anxiety (OR, 2.23; 95% CI, 2.23, 0.91-3.55) and depression (OR, 1.54; 95% CI, 0.17-2.91) in female.Conclusion: Alteplase showed a suggestive benefit in function and motor outcomes in patients with low NIHSS score of 0-5. Meanwhile, female seemed more inclined to post-stroke emotional problems after alteplase treatment, which should be further explored in the future.

Abstract Insomnia is the most prevalent clinical sleep disorder and is usually accompanied by some affective symptoms. As traditional interventions for insomnia have certain limitations, novel interventions such as biofeedback therapy can be of great clinical significance. Here, we aimed to explore the clinical efficacy of biofeedback for insomnia and its potential mechanisms of action. We recruited 82 patients with insomnia from the insomnia clinic at the Xuanwu Hospital. Electroencephalography (EEG) and electromyography (EMG) biofeedback training was conducted for 30 minutes. EEG data of two minutes were also recorded each before and after training. Intervention was performed once every alternate day and included 10 biofeedback treatments session and measured three times before, after fifth, and after tenth biofeedback treatment session. Scores on the Pittsburgh Sleep Quality Index (PSQI) scale after one trial of biofeedback treatment were significantly lower than those before treatment (p < 0.001) and continued to lower after subsequent trials (p < 0.001). Specifically, patients experienced a significant reduction in insomnia, an easier transition to natural sleep, a shorter time to fall asleep, fewer awakenings during sleep, and a much better quality of sleep. Additionally, the scores on the Beck Depression Inventory Scale (BDI) and State-Trait Anxiety Scale (S-STAI, and T-STAI) after treatment were significantly lower than those before treatment (p < 0.001). Our findings suggest that biofeedback therapy is effective in relieving insomnia symptoms for insomnia patients and biofeedback therapy likely relaxes the patients’ minds (reflected by the alpha wave) and muscles (reflected by frontal EMG) and reduces alertness states (reflected by beta waves), which finally promotes deep sleep (reflected by the theta wave).

Purpose:Narcolepsy is a rare debilitating disorder for which multiple novel pharmacological options have been approved as treatment for the past few years. The current study systematically updates the comparative efficacy and detailed safety analysis of approved wake-promoting agents in narcolepsy.Methods:Randomized controlled trials (RCTs) were searched for diagnosed narcolepsy with approved interventions. Efficacy outcomes included the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS), Clinical Global Impression of Change (CGI-C), and Patient Global Impression of Change (PGI-C). Safety outcomes including overall adverse event (AE) risk were measured. The study was registered at PROSPERO (CRD 42022334915).Results:The final analysis included 17 RCTs with five drug treatments: modafinil/armodafinil, sodium oxybate, pitolisant, solriamfetol, and lower-sodium oxybate (LXB). For efficacy measures, interventions included in each outcome were effective compared with placebo. Furthermore, the magnitude of solriamfetol effect on MWT (9.11 minutes; 95% CI=7.05-11.16), ESS (-4.79; 95% CI=-6.56 to -3.01), and PGI-C (9.39; 95% CI= 2.37-37.19), and LXB effect on CGI-C (9.67; 95% CI=2.73-34.26) was greater than that of other treatments included in each outcome compared with placebo. For safety measures, all interventions had an acceptable safety profile with LXB having least risk for overall AEs (0.56; 95% CI=0.20-1.53), serious AEs (0.33; 95% CI=0.09-1.20), AEs leading to treatment discontinuation (0.11; 95% CI=0.01-2.04), and all-cause discontinuation (0.04; 95% CI=0.00-0.67) compared to placebo. Placebo had the lowest risk for exploratory AEs.Conclusion:All approved interventions were effective in controlling the symptoms of narcolepsy at varying degrees with an acceptable safety profile.

Abstract Objective: Insomniais the most prevalent clinical sleep disorder and is usually accompanied by some affective symptoms. To some extent, traditional interventions for insomnia remain some shortcomings. Hence, exploring potential novel interventions for insomnia is of great clinical significance. Recently, the biofeedback therapy (i.e. the electroencephalography EEG and electromyography EMG feedback) has been regarded as a new method for the treatment of insomnia following medication and physical therapy, where EEG information is fed back to the subject for the purpose of self-regulation of EEG activity. We aimed to explore the clinical efficacy of biofeedback for insomnia and its potential mechanisms. Methods: We recruited 82 patients with insomnia from the insomnia clinic of Xuanwu Hospital in this research. The EEG and EMG biofeedback training were conducted for 30 minutes. The EEG data of two minutes were also recorded each before and after the training section. The intervention was performed once every other day and included 10 times treatments in total. The Becker Depression Scale(BDI), state anxiety (S-STAI) and trait anxiety (T-STAI) of Spielberger State-Trait Anxiety Inventory (STAI), and Pittsburgh Sleep Quality Index(PQRI) scales were administered three times before treatment and after 1 treatment session, respectively. Results: Results showed that the scores of the PQRI scale after 1 trial of biofeedback treatmentwere significantly lower than those before treatment (p < 0.001). Furthermore, the score of the PQRI following 10 trials of biofeedback treatments were significantly lower than values following 5 trials of treatments (p < 0.001). More specifically, patients experienced a significant reduction in insomnia, an easier transition to natural sleep, a shorter time to fall asleep, fewer awakenings during sleep, and a much better quality of sleep. In addition, the scores of the BDI, S-STAI, and T-STAI scales after the treatments were significantly lower than those before the treatments (p<0.001), indicating that the patient's anxiety and depression were relieved. For the physiological results, compared with the baseline level, the patient's prefrontal EMG decreased, EEG alpha waves increased, and EEG beta and theta waves decreased after the biofeedback therapy. Conclusion: Our findings suggest that Biofeedback therapy is effective to relieve insomnia symptoms for insomnia patients. The potential mechanism of the biofeedback therapy might be that the therapy relaxes the patients’ mind (reflected by the alpha wave) and muscles (reflected by EMG), and reduces alertness states (reflected by Beta wave), which finally promotes the deep sleep (reflected by the Theta wave).

(1) Background: The purpose of this study was to investigate the efficacy and safety of transcutaneous vagus nerve stimulation (t-VNS) in the treatment of primary insomnia. (2) Methods: This is a single center, randomized, double-blind study. A total of 30 patients diagnosed with primary insomnia were randomly divided into two groups to receive 20 Hz t-VNS in either the auricular concha area (treatment group) or periauricular area (control group), twice a day for 20 min during a one-month study period. The effective rate of treatment, defined as a ≥50% reduction of the Pittsburgh Sleep Index Scale (PSQI) after treatment, was compared between the two groups as the primary outcome. Response rate (defined as ≥10% change in the PSQI score), and changes in the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were also assessed. (3) Results: After one month of treatment, the PSQI score of the treatment group decreased significantly (p = 0.001). The effective rate of the treatment group (73% vs. 27%, p = 0.027) was significantly higher than that of the control group. No statistical differences in changes of HAMA and HAMD scores were detected between the two groups. There were no complications in all patients. (4) Conclusion: T-VNS appeared to be a safe and effective treatment for primary insomnia.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

To investigate the effectiveness of alpha activity neurofeedback training over the parietal lobe in GAD patients.

Cognitive impairment is closely associated with the slowing of glucose metabolism in the brain. Glucose transport, a rate-limiting step of glucose metabolism, plays a key role in this phenomenon. Previous studies have reported that limb remote ischemic conditioning (LRIC) improves cognitive performance in rats with chronic cerebral hypoperfusion (CCH). Here, we determined whether LRIC could ameliorate cognitive impairment in rats with CCH by regulating glucose transport. A total of 170 male Sprague-Dawley rats were used. Animals subjected to permanent double carotid artery occlusion (2VO) were assigned to the control or LRIC treatment group. LRIC was applied beginning 3 days after the 2VO surgery. We found that LRIC can improve learning and memory; decrease the ratio of ADP/ATP; increase glucose content; upregulate the expression of pAMPKα, GLUT1 and GLUT3; and increase the number of GLUT1 and GLUT3 transporters in cerebral cortical neurons. The expression of GLUT1 and GLUT3 in the cortex displayed a strong correlation with learning and memory. Pearson correlation analysis showed that the levels of GLUT1 and GLUT3 are correlated with neurological function scores. All of these beneficial effects of LRIC were ablated by application of the AMPK inhibitor, dorsomorphin. In summary, LRIC ameliorated cognitive impairment in rats with CCH by regulating glucose transport via the AMPK/GLUT signaling pathway. We conclude that AMPK-mediated glucose transport plays a key role in LRIC. These data also suggest that supplemental activation of glucose transport after CCH may provide a clinically applicable intervention for improving cognitive impairment.