Objective The contractions of abdominal muscle during voluntary urination is a motor control task,Which aims to explore the central activity characteristics of this action with functional near-infrared spectroscopy(fNIRS).Methods A total of 19 healthy subjects aged 18 years or older were recruited to undergo fNIRS testing twice,performing repetitive abdominal muscle contractions in the no-urine and strong-urine states.Brain activity under the corresponding no-abdominal muscle-contraction task was used as a baseline to analyze the cortical activities specific to abdominal muscle contractions in these two different states.Re-sults Abdominal muscle contractions during the strong desire to urinate primarily activated the bilateral pre-motor/supplementary motor area(BA6),bilateral dorsolateral prefrontal cortex(BA9/46),bilateral frontal pole area(BA10),the anterior portion of the right inferior frontal gyrus(BA47),the right middle temporal gyrus(BA21),the right primary motor cortex(BA4),and the left primary somatosensory cortex(BA1/2/3)in conjunction with the left inferior frontal of pars triangularis Broca's area(BA45)(P<0.05).In contrast,abdominal muscle contractions with no desire to urinate primarily activated the bilateral pre-motor/supplementary motor area(BA6)(P<0.05),the right primary motor cortex(BA4),the right primary somatosensory cortex(BA1/2/3),the right infe-rior frontal of pars triangularis Broca's area(BA45),and the right supramarginal gyrus part of Wernicke's area(BA40)(P<0.05).Compared to the strong urination state,stronger activation of the bilateral premotor/assistive motor area(BA6)was present in the non-urination state(P<0.05).Compared to the non-urination state,stronger activation of the left dorsolateral prefrontal cortex(BA46)was present in the strong urination state(P<0.05).Conclusion The primary somatosensory cortex,primary motor cortex,and pre-motor/supplementary motor area are jointly involved in the regulation of voluntary urination-associated random abdominal muscle contractions.And further activation of the prefrontal cortex can be induced during abdominal muscle contractions in the strong urination state,suggesting that the prefrontal cortex plays a positive role in facilitating abdominal muscle movements and ini-tiating urination following the perception of urinary awareness.
Cognitive impairment is common in hemodialysis patients, possibly due to inadequate cerebral blood flow during hemodialysis. No effective non-pharmacological interventions are available. This study investigates the impact of hemodialysis-induced cerebral hypoxia on cognitive decline in hemodialysis patients and the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-pharmacological intervention. A randomized controlled trial with 36 participants showed that cognitive performance and cerebral oxygenation in the dorsolateral prefrontal cortex (DLPFC) significantly declined in the sham group. In contrast, taVNS improved cognitive function by increasing cerebral oxygenation, with significant correlations to reaction times and MoCA scores. The study suggests that Hemodialysis-induced cerebral hypoxia may contribute to persistent cognitive decline in MHD patients. However, taVNS could be an effective intervention to prevent cognitive impairment in hemodialysis patients by alleviating cerebral hypoxia.
BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear.ObjectivesThis study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms.MethodsIn this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention.ResultsThe VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV.ConclusionThe combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.
Background: Stroke survivors exhibit persistent abnormal gait patterns, particularly in diminished walking ability and stability, limiting mobility and increasing the risk of falling. The purpose of the study was to determine the effects of repetitive transcranial magnetic stimulation (rTMS) coupled with cycling exercise on walking ability and stability in patients with stroke and explore the potential mechanisms underlying motor cortex recovery. Methods: In this double-blinded randomized pilot trial, 32 stroke patients were randomly separated into the real-rTMS group (RG, receiving rTMS during active cycling exercise) and the sham-rTMS group (SG, receiving sham rTMS during active cycling exercise). Participants completed 10 exercise sessions (5 times per week). Lower extremity function was measured using the Fugl-Meyer assessment of lower extremity (FMA-LE), and functional balance ability was measured by the Berg balance scale (BBS). The 2-min walk test (2MWT) and standing balance test were employed to evaluate walking and balance ability. Motor evoked potentials (MEPs) were measured to evaluate cortical excitability. The above assessments were administered at baseline and after the intervention. Additionally, the cycling exercise performance was recorded after the initial and final exercise sessions to evaluate the motor control during exercise. Results: The RG showed significant improvements in lower extremity function (FMA-LE) and functional balance ability (BBS) compared to the SG at postintervention. The walking and balance abilities, as well as the motor asymmetry of cycling exercise, significantly improved in RG. Additionally, participants in RG exhibited a higher elicitation rate of ipsilesional MEPs than that in SG. The improvements in motor asymmetry of cycling exercise in RG were significantly associated with increases in FMA-LE scores and walking ability. Conclusion: The combination of rTMS and cycling exercise effectively improves walking ability and walking stability in patients with stroke, which may be related to the excitability modulation of the motor cortex induced by rTMS. Trial Registration: Clinical Trial Registry identifier: ChiCTR2400079360.
Objective To explore the neurobehavioral mechanism of cross-education phenomenon and asymmetry in the up-per limb based on functional near-infrared spectroscopy(fNIRS).Methods A total of 17 healthy subjects recruited by Sir Run Run Hospital of Nanjing Medical University from November 2023 to January 2024 were selected in a randomized cross-over trial.Pur-due pegboard training with the contralateral upper limb of unilateral limb was taken as the contralateral training,and the number of Purdue pegboard plug-ins completed within a limited time as the task performance.fNIRS was used to collect the cerebral hemody-namic changes of healthy right-handed individuals after contralateral training when the left and right hand performed operational ac-tivities and record the behavioral data,and compare the cerebral cortex activation and behavioral performance of the left and right hands before and after contralateral training.Results After contralateral training,the performance of the left hand was significantly better than that before training(t=-8.865,P<0.010),while the performance of the right hand did not change after training(t=-1.689,P=0.606).In addition,the left pre-motor and supplementary motor area(CH 29),right pre-motor and supplementary motor area(CH 16,CH 17)and right primary motor cortex(CH 09)were more significantly activated after contralateral training when subjects per-formed the Purdue pegboard task with left hand(P<0.05).However,the right pre-motor and supplementary motor area(CH 19),right primary somatosensory cortex(CH 08)and right primary motor cortex(CH 10)showed a decreasing trend in the activation after contralateral training when subjects performed the Purdue pegboard task with right hand(P<0.05).Conclusion Cross-educa-tion of the upper limbs is asymmetrical,indicating that the non-dominant hand experiences greater benefits compared to the domi-nant hand.Cross-education may be attributed to enhance the cortical activation of the bilateral pre-motor and supplementary motor area(pSMA)to improve the task performance of the non-training limb.
Cancer stem cells (CSCs) are known to contribute to the progression of colorectal cancer (CRC). However, understanding of the molecular mechanisms and key factors involved in CRC is still insufficient to identify therapeutic targets against colorectal CSCs. In an effort to identify such mechanisms, we conducted bioinformatics analyses to evaluate the expression patterns in tumor and normal colorectal tissues, leading us to focus on the role of the ZNF217/Notch1 axis in mediating stem cell properties in CRC. Our findings revealed that ZNF217 overexpression activated self-renewal ability, expression of colorectal CSC markers, and Notch signaling in CRC. Dual-luciferase reporter assay suggested a role for ZNF217 in targeting Notch1 to activate Notch signaling. We observed that the promotional effects of Notch signaling, as well as CSC markers, under ZNF217 overexpression were attenuated after Notch1 knockdown. In addition to in vitro data, our in vivo results confirmed the inhibitory effect of sulforaphane on the tumorigenicity of CSCs, depicted the suppressive role of sulforaphane on colorectal CSCs mediated by the ZNF217/Notch1 axis, thereby providing new targetable vulnerabilities and therapeutic strategies for CRC.
目的:进行上肢改良多方向伸展测试(modified multi-directional reach test,mMDRT)的内部一致性研究,并提供一种可能的数据处理方法,为mMDRT在平衡评估中的应用提供基础.方法:应用mMDRT评估健康大学生青年平衡能力,将各方向数据进行内部一致性检验,并分析人体形态学偏倚的影响,进行数据标准化.结果:mMDRT内部一致性良好,各方向最大伸展距离均为高度相关.上肢综合长度与mMDRT各方向数据均高度相关,将最大伸展距离进行标准化处理,转换为个体上肢综合长的倍数,可一定程度上消除人体形态学偏倚的影响.结论:mMDRT内部一致性良好,在其进一步运用时需注意人体形态学偏倚造成的影响.
Gastric cancer is one of the deadliest malignant tumors, and half of the patients develop recurrences or metastasis within 5 years after eradication therapy. Cancer stem cells (CSCs) are considered to be important in this progress. The sonic hedgehog (SHH) pathway plays an important role in the maintenance of gastric CSCs characteristics. The p63 proteins are vital transcription factors belonging to the p53 family, while their functions in regulating CSCs remain unclear. The preventive effects of dietary diallyl trisulfide (DATS) against human gastric cancer have been verified. However, whether DATS can target gastric CSCs are poorly understood. Here, we investigated the role of ?Np63/SHH pathway in gastric CSCs and the inhibitory effect of DATS on gastric CSCs via ?Np63/SHH pathway. We found that ?Np63 was upregulated in serum-free medium cultured gastric tumorspheres compared with the parental cells. Overexpression of ANp63 elevated the self renewal capacity and CSC markers' levels in gastric sphere-forming cells. Furthermore, we found that ?Np63 directly bound to the promoter region of Gli1, the key transcriptional factor of SHH pathway, to enhance its expression and to activate SHH pathway. In addition, it was revealed that DATS effectively inhibited gastric CSC properties both in vitro and in vivo settings. Activation of SHH pathway attenuated the suppressive effects of DATS on the stemness of gastric cancer. Moreover, DATS suppression of gastric CSC properties was also diminished by ?Np63 upregulation through SHH pathway activation. These findings illustrated the role of ?Np63/SHH pathway in DATS inhibition of gastric cancer stemness. Taken together, the present study suggested for the first time that DATS inhibited gastric CSCs properties by ?Np63/SHH pathway.
目的:探索经颅直流电刺激(transcranial direct current stimulation,tDCS)改善维持性血液透析(maintenance he-modialysis,MHD)患者注意力和执行力,降低跌倒风险的作用.方法:本研究招募MHD患者36例,采用随机数字表法将患者随机分为对照组(n=18)和治疗组(n=18).治疗组患者在每次透析期间使用tDCS治疗20min,每周3次,共2周的治疗,对照组进行假刺激.两组患者在治疗前后均采用蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)评估认知功能,使用无线APDM运动监测惯性传感器系统采集步态时空参数(步速、步幅、转弯时间、转弯角度及转弯峰值角速度)观察行为学的变化.结果:治疗前两组患者各项测试得分均无显著差异(P>0.05).治疗后治疗组患者的MoCA总分显著提高(P<0.05),其中MoCA量表的视空间与执行力、注意力、定向得分显著升高(P<0.05).治疗组转弯角度和转弯峰值角速度的差值较对照组显著提高(P<0.05).多元线性逐步回归分析结果表明,MHD患者治疗后的转弯峰值角速度与MoCA总分和tDCS干预有关,标准回归系数分别为0.581、0.402(P<0.05).结论:tDCS显著改善了 MHD患者的注意力和执行力,步行中转弯角度及转弯峰值角速度的提高与认知功能的改善有关.
功能性近红外光谱技术(functional near-infrared spec-troscopy,fNIRS)是一种光学、无创的血流动力学神经成像技术,它可以通过将近红外光(650-950nm)照射入头部,测量出脑组织内氧合血红蛋白(oxygenated hemoglobin,HbO2)和脱氧血红蛋白(deoxyhemoglobin,Hb)的浓度变化,进而间接地测量出脑区兴奋性[1].fNIRS具有抗身体运动干扰能力强、便携不受环境限制等特点,因此研究者可以较容易地调整实验控制条件,以选择性观察大脑皮质区的兴奋情况.目前,fNIRS已经被证明是一种可靠的神经科学研究手段,国外大多数fNIRS研究都集中在认知心理行为、语言处理功能、脑功能重塑与运动学习等领域2-4].国内已有学者报道了fNIRS在社会认知神经科学以及语言言语科学中的应用[5-6]但尚缺少fNIRS应用于皮质感觉运动区的介绍.因此本文旨在对国内外针对感觉运动区皮质的近红外线成像研究进行梳理,为临床和科研中fNIRS的应用提供依据.
TEADs are critical transcription factors that participate in the Hippo pathway. Evidence indicates the promotion role of TEADs in cancer progression. However, the role of TEADs and the expression patterns in gastric cancer remains unclear. In this study, we evaluated the expression levels of TEADs in gastric cancer samples, and the clinical outcomes of patients with high TEADs expression were observed. Co-expression and interaction analysis as well as functional enrichment analysis were further conducted to determine the potential role of TEADs in gastric cancer. These results suggested TEADs may serve as the prognostic biomarkers or therapeutic targets for gastric cancer. However, more studies are warranted to verify our findings and promote the application in gastric cancer patients.
脑性瘫痪(cerebral palsy,CP),简称脑瘫,是由于脑部发育受损而引起的一组症状异质性的临床综合征,在活产儿中的患病率约为2‰-3.5‰[1].国际上将脑瘫定义为"由于在发育过程中胎儿和婴幼儿的大脑出现非进行性损伤而导致的一组持续存在的运动与姿势发育障碍症候群"[2].脑瘫是儿童运动障碍最常见的原因,平衡能力的下降会使脑瘫患儿活动时的姿势调节能力出现问题,从而难以高质量地完成功能性日常活动[3].
Cancer stem cells (CSCs) play a key role in cancer initiation, development, metastasis, and recurrence. Previously, we found that sulforaphane (SFN), a natural compound obtained from cruciferous vegetables, inhibited colorectal CSCs via the downregulation of TAp63α. However, the role of ΔNp63α, another critical isoform of p63 which has been considered to contribute to cancer progression, in SFN-mediated colorectal CSCs inhibition remains unclear. Here, we showed that ΔNp63α expression was enhanced in sphere-forming colorectal cancer cells. Overexpression of ΔNp63α promoted the properties of CSCs, while downregulation of ΔNp63α suppressed those properties. Besides, ΔNp63α was found to activate the transcription of core CSCs genes including Nanog, Oct4, and Sox2. Furthermore, in vitro and in vivo experiments illustrated the regulatory effects of SFN on ΔNp63α and colorectal CSCs. These findings suggested for the first time that ΔNp63α activated the transcription of Nanog, Oct4, Sox2 and mediated the interventional effects of SFN on colorectal CSCs, thus providing a novel mechanism by which SFN inhibits colorectal CSCs.
Cancer stem cells (CSCs) have an established role in cancer progression and therapeutic resistance. The p63 proteins are important transcription factors which belong to the p53 family, but their function and mechanism in CSCs remain elusive. Here, we investigated the role of TAp63α in colorectal CSCs and the effects of sulforaphane on TAp63α. We found that TAp63α was upregulated in spheres with stem cell properties compared to the parental cells. Overexpression of TAp63α promoted self-renewal capacity and enhanced CSC markers expression in colorectal sphere-forming cells. Furthermore, we showed that TAp63α directly bound to the promoter region of Lgr5 to enhance its expression and activate its downstream β-catenin pathway. Functional experiments revealed that sulforaphane suppressed the stemness of colorectal CSCs both in vitro and in vivo. Upregulation of TAp63α attenuated the inhibitory effect of sulforaphane on colorectal CSCs, indicating the role of TAp63α in sulforaphane suppression of the stemness in colorectal cancer. The present study elucidated for the first time that TAp63α promoted CSCs through targeting Lgr5/β-catenin axis and participated in sulforaphane inhibition of the stem cell properties in colorectal cancer.