BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

Focal choroidal excavation(FCE)is an elusive clinical sign characterized by a localized structural depression in the choroid. It has been increasingly recognized with the widespread use of optical coherence tomography(OCT), though its pathogenesis remains incompletely understood and may involve congenital developmental anomalies or acquired factors(such as inflammation or tumor compression). Studies indicate that FCE can occur independently or secondary to various chorioretinal diseases(e.g., central serous chorioretinopathy, choroidal osteoma, age-related macular degeneration, etc.). Clinically, it has also been observed that FCE may be associated with the development of choroidal neovascularization(CNV). Potential mechanisms linking FCE and CNV include: 1)mechanical traction-hypoxia-signaling pathway activation; 2)disruption of the retinal pigment epithelium(RPE)-Bruch's membrane-choroid complex barrier; 3)structural collapse induced by inflammatory scar contraction. Anti-vascular endothelial growth factor(VEGF)therapy is currently the mainstay of treatment for CNV secondary to FCE. By reviewing relevant domestic and international literature, this paper seeks to elucidate the possible pathological relationship between FCE and CNV, with the goal of facilitating early identification of high-risk patients and optimizing anti-VEGF treatment strategies. It also highlights the limitations of current research(such as sample heterogeneity and lack of histological validation of typing criteria), and suggests future directions, such as multicenter studies and molecular mechanism investigations, to support the development of personalized diagnostic and therapeutic approaches.

The rules of acupoint selection and treatment were identified and discovered from the collected ancient acupuncture-moxibustion prescriptions recorded the earliest for epigastric pain. The database of ancient acupuncture-moxibustion prescriptions for epigastric pain was set up using Excel2016 software. After the disease term, etiology, pathogenesis, symptoms and acupoints were normalized, the underlying multi-dimensional correlation among the elements of acupuncture-moxibustion was explored, using the frequency statistics and the association rule of Apriori algorithm. In the ancient time, in treatment with acupuncture-moxibustion therapy for epigastric pain, the acupoints of the high use frequency were sequenced as Zhongwan (CV12), Shangwan (CV13), Zusanli (ST36), Neiguan (PC6), Gongsun (SP4), Pishu (BL20) and Weishu (BL21). The common combinations of acupoints included the pairs of back-shu points, the combination of back-shu points and front-mu points, the combination of front-mu points and yuan-source points and the combination of back-shu points and the lower he-sea points. The highly involved acupoints were those from the conception vessel, pericardium meridian, spleen meridian, stomach meridian and bladder meridian; and they were commonly distributed on the abdomen, the yin parts of the foot and the arm, the yang part of the leg and on the back. Regarding the etiologies such as parasites, food retention, masses, qi stagnation and stomach cold, Zhongwan (CV12) and Shangwan (CV13) were coordinated; and Sanyinjiao (SP6) and Daling (PC7) were highly associated with masses. Besides cold injury, parasites and masses, for the epigastric pain caused by other factors of etiology (qi stagnation, stomach cold and food retention), moxibustion therapy was greatly applicable. For epigastric pain combined with qi reversion in the lower abdominal region, Qichong (ST30), Sanyinjiao (SP6), Tianshu (ST25) and Zusanli (ST36) must be selected. Dadu (SP2) and Taibai (SP3) must be used if the distention in the chest and abdomen accompanied; and Zhongzhu (TE3) be used if back pain involved. Zusanli (ST36) was commonly selected for hiccups. For the other accompanied symptoms, Zhongwan (CV12) was used, which is consistent with the acupoint selection of main symptoms. On the trunk, moxibustion was generally used at Weishu (BL21), Pishu (BL20), Geshu (BL17), Zhongwan (CV12), Juque (CV14) and Qihai (CV6), except Shangwan (CV13). Among the acupoints below the elbows and knees, moxibustion was commonly applicable at Zusanli (ST36), and acupuncture was often used at Gongsun (SP4) and Daling (PC7).
Acupuncture Points ; Humans ; Moxibustion/history* ; History, Ancient ; Acupuncture Therapy/history* ; Data Mining ; Abdominal Pain/history*

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.

Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.

Background The occurrences of occupational stress and sleep disorders are closely related. As a high-risk group of occupational stress, the sleep quality of locomotive engineers is of great significance for road traffic safety. Objective To explore the direction and degree of occupational stress affecting the sleep quality among locomotive engineers, and to analyze potential mediating and moderating roles of response strategy and overcommitment in the relationship. Methods From July 1st to July 31st, 2022, a total of 6219 locomotive engineers from three locomotive depots of China Railway Lanzhou Group Corporation were selected. We conducted an online survey on occupational stress, overcommitment, response strategy and sleep quality using the Effort-Reward Imbalance, Personal Resources Questionnaire, and Pittsburgh Sleep Quality Index. Single factor analysis and correlation analysis were conducted using SPSS 25.0 software, mediation and moderation models were constructed using the Process V3.3 macro program plugin, and Harman's single factor test was used for common method bias testing. Results A total of 6219 questionnaires were distributed, and 5738 valid questionnaires were collected, with an effective response rate of 92.27%. The average locomotive engineers' occupational stress score (1.22±0.29), overcommitment score (16.38±3.55), response strategy score (50.00±10.00), and sleep quality score (11.51±3.95) were calculated. The Pearson correlation analysis results showed that occupational stress was positively correlated with overcommitment and sleep quality (r=0.435, 0.321, P<0.01), and negatively correlated with response strategy (r=−0.286, P<0.01); overcommitment was positively correlated with sleep quality (r=0.367, P<0.01), and negatively correlated with response strategy (r=−0.210, P<0.01); there was a negative correlation between response strategy and sleep quality (r=−0.244, P<0.01). Occupational stress positively associated with sleep quality in locomotive engineers (b=3.658, t=21.177, P<0.001); response strategy exhibited a partial mediating role between occupational stress and sleep quality, with an effect size of 0.581, accounting for 15.88% of the total effect; overcommitment presented a significant moderating effect in the first half of the mediating process of "occupational stress-response strategy-sleep quality" (P<0.001). Conclusion Occupational stress has an impact on the sleep quality of locomotive engineers through the mediating effect of response strategy, and the first half of this mediating pathway is moderated by overcommitment.

ObjectiveTo explore the influence of electroacupuncture combined with point bloodletting and cupping for facial nerve function recovery in acute stage of idiopathic facial palsy （IFP）. MethodsEighty patients with IFP in the acute stage were randomly divided into 40 cases each in the treatment group and the control group. In the control group， oral prednisone acetate tablets were administered during the acute stage when the disease duration was less than 10 days； and electroacupuncture and flash cupping were provided during the recovery stage when the disease duration was more than 10 days， five times a week. For treatment group in acute stage， the stellate ganglion， vagus nerve stimulation point in the auricular cavity， Yifeng （TE 17） and Tinghui （GB 2） were needled on the affected side on the basis of the treatment of control group， with Yifeng and Tinghui connecting to electroacupuncture apparatus， once a day； point bloodletting and then cupping in Yifeng 2 times a week； in recovery stage， the treatment was the same as that of the control group. Both groups were treated until the 45th day from onset. The primary outcome was the Toronto facial grading system （SFGS）， and the secondary outcomes included house-brackmann （H-B） grade， facial disability index （FDI） score， and number of H-B grade-Ⅰ cases. Adverse events were recorded in both groups. ResultsThe SFGS scores of the patients in both groups were higher on the 10th， 30th and 45th days after onset of disease compared with those before the treatment （P＜0.05）； the H-B grade was lower on the 30th and 45th days after the onset of the disease compared with those before the treatment （P＜0.05）； and the facial disability index physical function （FDIP） and facial disability index social function （FDIS） scores were higher on the 30th and 45th days after onset of disease （P＜0.05）. SFGS scores of patients in the treatment group were significantly higher than those of the control group on the 30th and 45th days after onset （P＜0.05）； H-B grade was significantly lower than that of the control group on the 30th and 45th days after onset （P＜0.05）； and FDIP scores on the 45th day after onset， and FDIS scores on the 30th and 45th days after onset were significantly higher than those of the control group （P＜0.05）. At the end of treatment， 77.50% （31 cases） achieved H-B grade-Ⅰ in the treatment group， which was more than 55.00% （22 cases） in the control group （P＜0.05）. No adverse events occurred in either group. ConclusionElectroacupuncture combined with point bloodletting and cupping for IFP in acute stage can improve the recovery degree of facial nerve function， improve effectiveness， and show a high degree of safety.

Objective: To explore the effects of different positions, epoch lengths and cut points of accelerometers on the measurement of sedentary behaviour (SB), light physical activity (LPA) and moderate vigorous physical activity (MVPA) in school aged children, so as to provide a reference for optimizing the criteria of accelerometers to measure SB and physical activity in school aged children. Methods: From May 2021 to September 2022, 110 school aged children aged 8-12 years old were convenient selected from a primary school in Hangzhou, and the accelerometers were worn on the waist, back, thigh, and wrist during the school time, and the collected data were transformed into six datasets with different epoch lengths (1, 5, 10, 15, 30, and 60 s) and compared using 4 common cut points developed by Puyau, Freedson, Evenson, and Pulsford (a total of 96 combinations) for classifying the percentages of time spent in SB, LPA, and MVPA. The effects of different positions, epoch lengths and cut points and their interactions on the assessment results were analyzed using a three way repeated measures ANOVA, and the variability of multiple comparisons between groups was analyzed using a Bonferroni post hoc test. Results: Except for the interaction of cut point × position × epoch on the percentage of time spent in SB and the main effect of epoch on he percentage of time spent in MVPA were not statistically significant ( F =0.66，1.18， P >0.05), the remaining main effects and interactions of the three factors on the assessment results were all statistically significant ( F =6.28-11 662.28， P <0.01). The differences between the results of different positions were statistically significant ( F =90.98-308.79, P <0.01). The percentages of time spent in SB and MVPA decreased with the increase of epoch lengths, while the percentage of time spent in LPA increased with the increase of epoch lengths ( F =16.54- 676.35 , P <0.01). The difference between the results using different cut points measurements was statistically significant ( F = 98.14- 976.40, P <0.01). Conclusions Accelerometer methodological factors including positions, epoch lengths and cut points will affect the estimates of SB and physical activity in school aged children. Therefore, it is recommended that future studies need to optimize the applicability of accelerometer analysis methods in school aged children, and the comparisons of results between studies need to be treated with caution.