Screening for optimal parameters for modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats.

Pharyngeal electrical stimulation (PES), a novel noninvasive peripheral nerve stimulation technique, can effectively improve neurogenic dysphagia and increase the safety and effectiveness of swallowing in the clinic. However, the lack of animal models for dysphagia has limited the mechanistic research on PES, which affects its wide application. Therefore, determining optimal parameters for PES in rats is needed to enable mechanistic studies. Modified PES (mPES), which has different waves and pulse widths from PES, was used; in previous studies mPES was found to have a neurological mechanism like that of PES. A poststroke dysphagia (PSD) model was established, and rats with dysphagia were grouped into three different intensities (0.1 mA, 0.5 mA, and 1 mA) for the selection of optimal intensity and three different frequencies (1 Hz, 2 Hz, and 5 Hz) for the selection of optimal frequency based on a stimulation duration of 10 min in the clinic. A Videofluroscopic Swallow Screen (VFSS) was used to assess swallowing function in rats before and after mPES treatment. The results showed that the 1 mA group had better swallowing function (p < 0.05) than the model group. Compared with the model group, the 1 Hz and 5 Hz groups had the same improvement in swallowing function (p < 0.05). However, the increase in excitatory signals in the sensorimotor cortex was more pronounced in the 5 Hz group than in the other frequency stimulation groups (p < 0.05). Combining the clinical findings with the above results, we concluded that the optimal stimulation parameter for mPES in rats is "frequency: 5 Hz, current intensity: 1 mA for 10 min/day", which provides a basis for future basic experimental studies of mPES in animals.

Effect of electroacupuncture stimulation of "Sibai"(ST2) and "Quanliao"(SI18) on excitatory neurons of sensorimotor cortex in mice. / 电针"四白"和"颧髎"æ¿€æ´»å°é¼ èº¯ä½“æ„Ÿè§‰è¿åŠ¨çš®å±‚çš„å ´å¥‹æ€§ç¥žç»å ƒ.

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.

Pyramidal and parvalbumin neurons modulate the process of electroacupuncture stimulation for stroke rehabilitation.

Electroacupuncture (EA) stimulation has been shown to be beneficial in stroke rehabilitation; however, little is known about the neurological mechanism by which this peripheral stimulation approach treats for stroke. This study showed that both pyramidal and parvalbumin (PV) neuronal activity increased in the contralesional primary motor cortex forelimb motor area (M1FL) after ischemic stroke induced by focal unilateral occlusion in the M1FL. EA stimulation reduced pyramidal neuronal activity and increased PV neuronal activity. These results were obtained by a combination of fiber photometry recordings, in vivo and in vitro electrophysiological recordings, and immunofluorescence. Moreover, EA was found to regulate the expression/function of N-methyl-D-aspartate receptors (NMDARs) altered by stroke pathology. In summary, our findings suggest that EA could restore disturbed neuronal activity through the regulation of the activity of pyramidal and PV neurons. Furthermore, NMDARs we shown to play an important role in EA-mediated improvements in sensorimotor ability during stroke rehabilitation.

Evaluation of Clinical Efficacy of Acupuncture and Moxibustion for Asthma: Systematic Review and Meta-Analysis.

Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).

Toe stimulation improves tactile perception of the genitals.

The human body is represented in a topographic pattern in the primary somatosensory cortex (S1), and genital representation is displaced below the toe representation. However, the relationship between the representation of the genitals and toe in S1 remains unclear. In this study, tactile stimulation was applied to the big toe in healthy subjects to observe changes in tactile acuity in the unstimulated genital area, abdomen, and metacarpal dorsal. Then tactile stimulation was applied to the right abdomen and metacarpal dorsal to observe changes in tactile acuity in bilateral genitals. The results revealed that tactile stimulation of the big toe led to a reduction in the 2-point discrimination threshold (2PDT) not only in the stimulated big toe but also in the bilateral unstimulated genitals, whereas the bilateral abdomen and metacarpal dorsal threshold remained unchanged. On the other hand, tactile stimulation of the abdomen and metacarpal dorsal did not elicit 2-point discrimination threshold changes in the bilateral genitals. Cortical and subcortical mechanisms have been proposed to account for the findings. One explanation involves the intracortical interaction between 2 adjacent representations. Another possible explanation is that the information content of a specific body part is broadly distributed across the S1. Moreover, exploring the links between human behaviors and changes in the cerebral cortex is of significant importance.

Advances in the study of endocannabinoid receptors in experimental acupuncture analgesia. / å† æºæ€§å¤§éº»ç´ å—ä½“åœ¨é’ˆåˆºé•‡ç—›æœºåˆ¶ä¸­çš„ç ”ç©¶è¿›å±•.

The endocannabinoid system, an important biological network for maintaining and balancing various functions of the human body, is involved in many physiological functions such as pain, emotion, learning and memory, etc. Among which the endocannabinoid receptors ï¼»including type I (CB1) and type II (CB2) receptorsï¼½ play an important role in the regulation of pain and have become an important target in the mechanism research of acupuncture analgesia. CB1 is mainly distributed in the central nervous system, including the spinal cord, cerebral cortex, amygdala, insular cortex, and basal ganglia, etc. CB2 is mainly distributed in peripheral immune tissues, such as spleen, bone, skin, etc. In the central and peripheral nervous systems, acupuncture can activate CB1 and CB2 receptors respectively, which is involved in the transmission of central nociceptive signals and related transmitters as well as the peri-pheral pro-nociceptive inflammatory response, thereby alleviating the nociceptive hypersensitivity in animal models. In this paper, we systematically summarize the roles of the above mechanisms in different types of animal models (inflammatory pain, neuropathological pain, visceral pain, etc.), so as to provide new ideas for the study of the underlying mechanisms of acupuncture analgesia.

Role of TRPV1 in electroacupuncture-mediated signal to the primary sensory cortex during regulation of the swallowing function.

AIMS: Electroacupuncture (EA) at the Lianquan (CV23) could alleviate swallowing dysfunction. However, current knowledge of its neural modulation focused on the brain, with little evidence from the periphery. Transient receptor potential channel vanilloid subfamily 1 (TRPV1) is an ion channel predominantly expressed in sensory neurons, and acupuncture can trigger calcium ion (Ca2+ ) wave propagation through active TRPV1 to deliver signals. The present study aimed to investigate whether TRPV1 mediated the signal of EA to the primary sensory cortex (S1) during regulation of swallowing function. METHODS: Blood perfusion was evaluated by laser speckle contrast imaging (LSCI), and neuronal activity was evaluated by fiber calcium recording and c-Fos staining. The expression of TRPV1 was detected by RNA-seq analysis, immunofluorescence, and ELISA. In addition, the swallowing function was assessed by in vivo EMG recording and water consumption test. RESULTS: EA treatment potentiated blood perfusion and neuronal activity in the S1, and this potentiation was absent after injecting lidocaine near CV23. TRPV1 near CV23 was upregulated by EA-CV23. The blood perfusion at CV23 was decreased in the TRPV1 hypofunction mice, while the blood perfusion and the neuronal activity of the S1 showed no obvious change. These findings were also present in post-stroke dysphagia (PSD) mice. CONCLUSION: The TRPV1 at CV23 after EA treatment might play a key role in mediating local blood perfusion but was not involved in transferring EA signals to the central nervous system (CNS). These findings collectively suggested that TRPV1 may be one of the important regulators involved in the mechanism of EA treatment for improving swallowing function in PSD.

Participation of the nucleus tractus solitarius in the therapeutic effect of electroacupuncture on post-stroke dysphagia through the primary motor cortex.

BACKGROUND: Post-stroke dysphagia (PSD), a common and serious disease, affects the quality of life of many patients and their families. Electroacupuncture (EA) has been commonly used effectively in the treatment of PSD, but the therapeutic mechanism is still under exploration at present. We aim to investigate the effect of the nucleus tractus solitarus (NTS) on the treatment of PSD by EA at Lianquan (CV23) through the primary motor cortex (M1). METHODS: C57 male mice were used to construct a PSD mouse model using photothrombotic technique, and the swallowing function was evaluated by electromyography (EMG) recording. C-Fos-positive neurons and types of neurons in the NTS were detected by immunofluorescence. Optogenetics and chemical genetics were used to regulate the NTS, and the firing rate of neurons was recorded via multichannel recording. RESULTS: The results showed that most of the activated neurons in the NTS were excitatory neurons, and multichannel recording indicated that the activity levels of both pyramidal neurons and interneurons in the NTS were regulated by M1. This process was involved in the EA treatment. Furthermore, while chemogenetic inhibition of the NTS reduced the EMG signal associated with the swallowing response induced by activation of M1 in PSD mice, EA rescued this signal. CONCLUSION: Overall, the NTS was shown to participate in the regulation of PSD by EA at CV23 through M1.

Effects of electroacupuncture preconditioning on microglial cells and serum inflammatory factors in the early stage of ischemic stroke. / ç”µé’ˆé¢„å¤„ç†å¯¹ç¼ºè¡€æ€§ä¸­é£Žå°é¼ æ—©æœŸå°èƒ¶è´¨ç»†èƒžåŠè¡€æ¸ ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To investigate the effects on the motor function, cortex blood flow perfusion, microglial cells, and the contents of serum inflammatory factors, i.e. interleukin-1ß (IL-1ß), transforming growth factor-ß (TGF-ß), and interleukin-10 (IL-10) after electroacupuncture (EA) preconditioning at "Baihui" (GV20) and "Dazhui" (GV14) in the mice with ischemic stroke, so as to explore the mechanism of EA preconditioning for improving motor function after ischemic stroke. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, and EA preconditioning group (EA group), with 15 mice in each group. A photothrombotic method was used to induce the model of unilateral ischemic stroke and motor impairment. The mice in the EA group received EA preconditioning, 20 min each time, once daily for 7 consecutive days before modeling. The motor function of mice was evaluated by the grid-walking test and cylinder test before and after modeling. Laser speckle blood flow video monitoring system was employed to assess the cerebral blood flow perfusion in the primary motor cortex of mice. The contents of IL-1ß, TGF-ß, and IL-10 in the serum were measured by ELISA, and the expressions of microglial cell and M2 subtype cell marker in the primary motor cortex were detected using immunofluorescence staining. RESULTS: After modeling, compared with the sham-operation group, the grid error rate and the dragging rate of the affected limb were increased (P<0.01)；the utilization rate of the affected limb and percentage of the blood perfusion in the affected cortex to healthy side were decreased (P<0.01)；the contents of serum IL-1ß, TGF-ß, and IL-10 were increased (P<0.01, P<0.05)；and the microglia in the primary motor cortex on the affected side showed ameboid, the fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA1) and CD206 was increased (P<0.01) in the model group. In the EA group, when compared with the model group, the grid error rate and the dragging rate of affected limb were decreased (P<0.01)；the utilization rate of affected limb and the percentage of blood perfusion were increased (P<0.05)；the content of serum IL-1ß was decreased (P<0.01), while the contents of TGF-ß and IL-10 were increased (P<0.01)；and the microglia in the primary motor cortex on the affected side got more round and were distributed more densely, the fluorescence intensity of IBA1 and CD206 was increased (P<0.01). CONCLUSIONS: Electroacupuncture preconditioning at "GV20" and "GV14" can up-regulate the expression of microglial cells, especially the M2 subtype cell marker, and increase the contents of the anti-inflammatory factors and decrease that of the pro-inflammatory factors in the serum, thereby alleviate the inflammatory reaction.

The Role of Perineuronal Nets in the Contralateral Hemisphere in the Electroacupuncture-Mediated Rehabilitation of Poststroke Dysphagia Mice.

Acupuncture at Lianquan (CV23) acupoint has been shown to improve swallowing function in poststroke dysphagia (PSD). This improvement is supposed to be associated with the regulation of neuronal activity in the contralateral primary motor cortex (M1), while the underlying mechanism still needs to be elucidated. Perineuronal nets (PNNs) are well-known to be involved in the regulation of neuronal activity. Thus, we here aimed to detect the role of PNNs in the contralateral M1 hemisphere in the electroacupuncture (EA)-mediated effect in male mice. The results were obtained from a combination of methods, including in vitro slice electrophysiological recording, in vivo electrophysiological recording, and immunofluorescent staining in male mice. These results showed a decrease of the excitatory postsynaptic currents (sEPSCs) and no alteration of the inhibitory postsynaptic currents (sIPSCs) in the GABAergic neurons and the tonic inhibition in the excitatory neurons in the contralateral M1 after stroke induction, and EA recovered the impaired sEPSCs in the GABAergic neurons. We further found that the effect of EA-induced increase of c-Fos expression, enhancement of spike firing, potentiation of sEPSCs in the excitatory neurons, and improvement of swallowing function were all blocked by the removal of PNNs in the contralateral M1. In conclusion, the PNNs in the contralateral M1 was suggested to be participated in stroke pathogenesis and might be associated with the EA-mediated swallowing function rehabilitation of PSD in male mice. Our study provides insight into how PNNs might be involved in the mechanism of EA treatment for stroke rehabilitation.

Electroacupuncture Exerts Analgesic Effects by Restoring Hyperactivity via Cannabinoid Type 1 Receptors in the Anterior Cingulate Cortex in Chronic Inflammatory Pain.

As one of the commonly used therapies for pain-related diseases in clinical practice, electroacupuncture (EA) has been proven to be effective. In chronic pain, neurons in the anterior cingulate cortex (ACC) have been reported to be hyperactive, while the mechanism by which cannabinoid type 1 receptors (CB1Rs) in the ACC are involved in EA-mediated analgesic mechanisms remains to be elucidated. In this study, we investigated the potential central mechanism of EA analgesia. A combination of techniques was used to detect the expression and function of CB1R, including quantitative real-time PCR (q-PCR), western blot (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and in vivo multichannel optical fibre recording, and neuronal activity was examined by in vivo two-photon imaging and in vivo electrophysiological recording. We found that the hyperactivity of pyramidal neurons in the ACC during chronic inflammatory pain is associated with impairment of the endocannabinoid system. EA at the Zusanli acupoint (ST36) can reduce the hyperactivity of pyramidal neurons and exert analgesic effects by increasing the endocannabinoid ligands anandamide (AEA), 2-arachidonoylglycerol (2-AG) and CB1R. More importantly, CB1R in the ACC is one of the necessary conditions for the EA-mediated analgesia effect, which may be related to the negative regulation of the N-methyl-D-aspartate receptor (NMDAR) by the activation of CB1R downregulating NR1 subunits of NMDAR (NR1) via histidine triad nucleotide-binding protein 1 (HINT1). Our study suggested that the endocannabinoid system in the ACC plays an important role in acupuncture analgesia and provides evidence for a central mechanism of EA-mediated analgesia.

Study on after-effect of electroacupuncture with different time intervals on corticospinal excitability in primary motor cortex. / ä¸åŒé—´éš”æ—¶é—´ç”µé’ˆå¯¹åˆçº§è¿åŠ¨çš®å±‚çš®è´¨è„Šé«“å ´å¥‹æ€§çš„åŽæ•ˆåº”ç ”ç©¶.

OBJECTIVES: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. METHODS: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). RESULTS: The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). CONCLUSIONS: Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Research status and hotspots in the surgical treatment of tremor in Parkinson's disease from 2002 to 2022: a bibliometric and visualization analysis.

Objective: This study aims to investigate the research status and hotspots of surgical treatment for tremor in Parkinson's disease (PD) from 2002 to 2022, utilizing bibliometric and visual analysis. Additionally, it aims to offer insights into future research trends in this field. Methods: This study collected publications on the surgical treatment of tremor in PD from 2002 to 2022 using the Web of Science (WOS) database. CiteSpace, VOSviewer, and Scimago Graphica were employed to quantify the number of publications and analyze the bibliographic information networks, including the contributions of countries/cities, authors, keywords, and co-cited references. Results: A total of 2,815 publications were included in the study, revealing that 541 scientific institutions experienced an increase in publications from 2002 to 2022. Michael Okun emerged as the most productive author, and the United States emerged as the leading hub for research. The study identified 772 keywords. Noteworthy citation bursts and long-term activity were observed in pallidotomy, bilateral stimulation, and focused ultrasound thalamotomy. The top 10 highly co-cited references comprised eight deep brain stimulation (DBS) studies (including two follow-up studies and six randomized controlled trials), one randomized controlled trial on focused ultrasound, and one consensus on tremor. Conclusion: This study uses an in-depth and systematic bibliometric and visualization analysis to visualize the evolution of research and identify emerging hotspots. The identified hotspots are as follows: Firstly, DBS has received significant attention and widespread recognition as a surgical treatment for tremor in PD. Secondly, there are various key aspects to consider in DBS, such as operative indications, operative targets, and surgical protocols. Lastly, magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a promising treatment option in the surgical management of tremor in Parkinson's disease. This research also provides insights into the phenomenon of these hotspots, offering valuable prompts and reminders for further research.

A two-branch trade-off neural network for balanced scoring sleep stages on multiple cohorts.

Introduction: Automatic sleep staging is a classification process with severe class imbalance and suffers from instability of scoring stage N1. Decreased accuracy in classifying stage N1 significantly impacts the staging of individuals with sleep disorders. We aim to achieve automatic sleep staging with expert-level performance in both N1 stage and overall scoring. Methods: A neural network model combines an attention-based convolutional neural network and a classifier with two branches is developed. A transitive training strategy is employed to balance universal feature learning and contextual referencing. Parameter optimization and benchmark comparisons are conducted using a large-scale dataset, followed by evaluation on seven datasets in five cohorts. Results: The proposed model achieves an accuracy of 88.16%, Cohen's kappa of 0.836, and MF1 score of 0.818 on the SHHS1 test set, also with comparable performance to human scorers in scoring stage N1. Incorporating multiple cohort data improves its performance. Notably, the model maintains high performance when applied to unseen datasets and patients with neurological or psychiatric disorders. Discussion: The proposed algorithm demonstrates strong performance and generalizablility, and its direct transferability is noteworthy among similar studies on automated sleep staging. It is publicly available, which is conducive to expanding access to sleep-related analysis, especially those associated with neurological or psychiatric disorders.

Identifying promising GSK3ß inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations.

Glycogen synthase kinase-3 (GSK3ß), a serine/threonine protein kinase, has been discovered as a novel target for anticancer drugs. Although GSK3ß is involved in multiple pathways linked to the etiology of various cancers, no specific GSK3ß inhibitor has been authorized for cancer therapy. Most of its inhibitors have toxicity effects therefore, there is a need to develop safe and more potent inhibitors. In this study, a library of 4,222 anti-cancer compounds underwent rigorous computational screening to identify potential candidates for targeting the binding pocket of GSK3ß. The screening process involved various stages, including docking-based virtual screening, physicochemical and ADMET analysis, and molecular dynamics simulations. Ultimately, two hit compounds, BMS-754807 and GSK429286A, were identified as having high binding affinities to GSK3ß. BMS-754807 and GSK429286A exhibited binding affinities of -11.9, and -9.8 kcal/mol, respectively, which were greater than that of the positive control (-7.6 kcal/mol). Further, molecular dynamics simulations for 100 ns were employed to optimize the interaction between the compounds and GSK3ß, and the simulations demonstrated that the interaction was stable and consistent throughout the study. These hits were also anticipated to have good drug-like properties. Finally, this study suggests that BMS-754807 and GSK429286A may undergo experimental validation to evaluate their potential as cancer treatments in clinical settings.

Efficacy and underlying mechanisms of acupuncture therapy for PTSD: evidence from animal and clinical studies.

As a major public health problem, posttraumatic stress disorder (PTSD) has a substantial impact on individuals and society. The total excess economic burden of PTSD in the US is estimated to be more than $232.2 billion a year. Acupuncture is widely used in patients with PTSD, and an increasing number of studies have been undertaken to assess the efficacy and underlying mechanisms of acupuncture for the treatment of individuals with PTSD. However, there has not yet been a review that simultaneously elucidates the therapeutic efficacy and biological mechanisms of acupuncture. We wished to examine the efficacy and underlying mechanisms of acupuncture for the treatment of individuals with PTSD. We conducted this review in three sections as follows: a meta-analysis, an acupoint analysis, and mechanism research. PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI), WanFang Database, China Biology Medicine Database (CBM), Chinese Science and Technology Journals Database (VIP), and other databases were searched from 1 January 2012 to 27 November 2022. Based on the included studies, we first determined whether acupuncture is more effective than psychological treatment or pharmacological treatment for treating and improving the quality of life of individuals with PTSD by meta-analysis. Second, the most commonly used acupoints and parameters of acupuncture were summarized based on animal and clinical studies. Third, we attempt to summarize the current mechanisms of acupuncture in the treatment of PTSD. Finally, 56 acupoint analyses, eight meta-analyses, and 33 mechanistic studies were included. Acupuncture outperformed pharmacotherapy treatment in improving symptom scores by CAPS, HAMA, HAMD, PCL-C, and SCL-90 somatization for PTSD and outperformed psychotherapy treatment in improving symptom scores by CAPS PCL-C and HAMD, according to the meta-analysis. GV20 was the most frequently used acupuncture point in clinical studies and animal studies, with a 78.6% application rate. Acupuncture may be effective in treating PTSD by regulating the structure and components of several brain areas, regulating the neuroendocrine system, and involving signaling pathways. In conclusion, this finding indicates that acupuncture has promising potential for treating PTSD.

Activation of POMC neurons to adiponectin participating in EA-mediated improvement of high-fat diet IR mice.

Background: Insulin resistance (IR) is one of the common pathological manifestations of metabolic-related diseases, and the prevalence of relevant diseases is high. Acupuncture is beneficial to IR patients, but the central mechanism underlying this treatment remains unclear. This study provides mechanistic insights into how electroacupuncture (EA) improves IR through the response of Pro-opiomelanocortin (POMC) neurons to adiponectin (Adipo). Methods: Glucose tolerance tests (GTT), Insulin tolerance tests (ITT) and fasting blood glucose (FBG) were detected by glucometer. Serum insulin, Adipo and skeletal muscle adiponectin receptor 1 (AdipoR1) protein levels were examined by ELISA. Homeostasis model assessment estimated insulin resistance (HOMA-IR) was calculated using the following formula: HOMA-IR = fasting insulin (FINS) (mU/L) × FBG (mmol/L)/22.5. The expression levels of AdipoR1 and Adipo mRNA in skeletal muscle were detected by real-time PCR quantification. The co-marking of c-Fos/AdipoR1 and POMC neurons were investigated using immunofluorescence. Spontaneous excitatory postsynaptic currents (sEPSCs) of POMC neurons and the response of POMC neurons to Adipo were detected via electrophysiology. Results: EA significantly ameliorated HFD-induced impairment of GTT, ITT, FBG, and HOMA-IR which was correlated with recovery of the expression level of AdipoR1 and Adipo in skeletal muscle. The improved response of POMC neurons to Adipo in the hypothalamus may be a key factor in correcting abnormal glucose tolerance and improving IR. Conclusion: This study demonstrates that EA can ameliorate HFD-induced impaired glucose tolerance through improved response of POMC neurons to Adipo in the hypothalamus, providing insight into the central mechanism of improving IR through EA.

[Discussion on "sugar needle - comfortable acupuncture and moxibustion"].

The cases of feeling comfort during acupuncture and moxibustion treatment in literature were summarized and its biological basis was explored. A simple classification of comfort was made, and the importance of obtaining comfort in acupuncture treatment was pointed out. Considering the pursuit of less pain and harmlessness in modern clinical treatment, sugar needle should be advocated and popularized in current clinical practice of acupuncture and moxibustion.

DDTC-Cu(I) based metal-organic framework (MOF) for targeted melanoma therapy by inducing SLC7A11/GPX4-mediated ferroptosis.

Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.