A new canthinone glycoside isolated from the root barks of Ailanthus altissima with NO inhibitory activity.

One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.

Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart-brain axis.

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.

Cross-frequency modulation of postural fluctuations and scalp EEG in older adults: error amplification feedback for rapid balance adjustments.

Virtual error amplification (VEA) in visual feedback enhances attentive control over postural stability, although the neural mechanisms are still debated. This study investigated the distinct cortical control of unsteady stance in older adults using VEA through cross-frequency modulation of postural fluctuations and scalp EEG. Thirty-seven community-dwelling older adults (68.1 ± 3.6 years) maintained an upright stance on a stabilometer while receiving either VEA or real error feedback. Along with postural fluctuation dynamics, phase-amplitude coupling (PAC) and amplitude-amplitude coupling (AAC) were analyzed for postural fluctuations under 2 Hz and EEG sub-bands (theta, alpha, and beta). The results revealed a higher mean frequency of the postural fluctuation phase (p = .005) and a greater root mean square of the postural fluctuation amplitude (p = .003) with VEA compared to the control condition. VEA also reduced PAC between the postural fluctuation phase and beta-band EEG in the left frontal (p = .009), sensorimotor (p = .002), and occipital (p = .018) areas. Conversely, VEA increased the AAC of posture fluctuation amplitude and beta-band EEG in FP2 (p = .027). Neither theta nor alpha band PAC or AAC were affected by VEA. VEA optimizes postural strategies in older adults during stabilometer stance by enhancing visuospatial attentive control of postural responses and facilitating the transition of motor states against postural perturbations through a disinhibitory process. Incorporating VEA into virtual reality technology is advocated as a valuable strategy for optimizing therapeutic interventions in postural therapy, particularly to mitigate the risk of falls among older adults.

Effects of landscape pattern on water quality at multi-spatial scales in Wuding River Basin, China.

Urbanization and agricultural land use have led to water quality deterioration. Studies have been conducted on the relationship between landscape patterns and river water quality; however, the Wuding River Basin (WDRB), which is a complex ecosystem structure, is facing resource problems in river basins. Thus, the multi-scale effects of landscape patterns on river water quality in the WDRB must be quantified. This study explored the spatial and seasonal effects of land use distribution on river water quality. Using the data of 22 samples and land use images from the WDRB for 2022, we quantitatively described the correlation between river water quality and land use at spatial and seasonal scales. Stepwise multiple linear regression (SMLR) and redundancy analyses (RDA) were used to quantitatively screen and compare the relationships between land use structure, landscape patterns, and water quality at different spatial scales. The results showed that the sub-watershed scale is the best spatial scale model that explains the relationship between land use and water quality. With the gradual narrowing of the spatial scale range, cultivated land, grassland, and construction land had strong water quality interpretation abilities. The influence of land use type on water quality parameter variables was more distinct in rainy season than in the dry season. Therefore, in the layout of watershed management, reasonably adjusting the proportion relationship of vegetation and artificial building land in the sub-basin scale and basin scope can realize the effective control of water quality optimization.

Transformation of A1/A2 Astrocytes Participates in Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning via Inhibiting NDRG2.

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia-reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10+/GFAP+ cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10+/GFAP+ cells yet increased C3d expression and the number of C3d+/GFAP+ cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d+/GFAP+ cells increased, while S100A10 expression and the number of S100A10+/GFAP+ cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression.

A Silver Lining of Neuropathic Pain: Predicting Favorable Functional Outcome in Spinal Cord Injury.

Background: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear. Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters. Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized ß=11.47, 95% CI (4.95,17.99), P<0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized ß=15.67, 95% CI (8.94,22.41), P<0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia). Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.

Primary motor hand area corticospinal excitability indicates overall functional recovery after spinal cord injury.

Background: After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. Methods: A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. Results: The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0-6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. Conclusion: The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.

Stimulation enhancement effect of the combination of exoskeleton-assisted hand rehabilitation and fingertip haptic stimulation.

Introduction: Providing stimulation enhancements to existing hand rehabilitation training methods may help stroke survivors achieve better treatment outcomes. This paper presents a comparison study to explore the stimulation enhancement effects of the combination of exoskeleton-assisted hand rehabilitation and fingertip haptic stimulation by analyzing behavioral data and event-related potentials. Methods: The stimulation effects of the touch sensations created by a water bottle and that created by cutaneous fingertip stimulation with pneumatic actuators are also investigated. Fingertip haptic stimulation was combined with exoskeleton-assisted hand rehabilitation while the haptic stimulation was synchronized with the motion of our hand exoskeleton. In the experiments, three experimental modes, including exoskeleton-assisted grasping motion without haptic stimulation (Mode 1), exoskeleton-assisted grasping motion with haptic stimulation (Mode 2), and exoskeleton-assisted grasping motion with a water bottle (Mode 3), were compared. Results: The behavioral analysis results showed that the change of experimental modes had no significant effect on the recognition accuracy of stimulation levels (p = 0.658), while regarding the response time, exoskeleton-assisted grasping motion with haptic stimulation was the same as grasping a water bottle (p = 0.441) but significantly different from that without haptic stimulation (p = 0.006). The analysis of event-related potentials showed that the primary motor cortex, premotor cortex, and primary somatosensory areas of the brain were more activated when both the hand motion assistance and fingertip haptic feedback were provided using our proposed method (P300 amplitude 9.46 µV). Compared to only applying exoskeleton-assisted hand motion, the P300 amplitude was significantly improved by providing both exoskeleton-assisted hand motion and fingertip haptic stimulation (p = 0.006), but no significant differences were found between any other two modes (Mode 2 vs. Mode 3: p = 0.227, Mode 1 vs. Mode 3: p = 0.918). Different modes did not significantly affect the P300 latency (p = 0.102). Stimulation intensity had no effect on the P300 amplitude (p = 0.295, 0.414, 0.867) and latency (p = 0.417, 0.197, 0.607). Discussion: Thus, we conclude that combining exoskeleton-assisted hand motion and fingertip haptic stimulation provided stronger stimulation on the motor cortex and somatosensory cortex of the brain simultaneously; the stimulation effects of the touch sensations created by a water bottle and that created by cutaneous fingertip stimulation with pneumatic actuators are similar.

Monomeric and dimeric guaianolide sesquiterpenoids with hypoglycemic activity from Achillea alpina.

Three new monomeric (1-3) and two newdimeric guaianolides (4 and 5), along with three known analogues (6-8) were isolated from the aerial part of Achillea alpina L. Compounds 1-3 were three novel 1,10-seco-guaianolides, while 4 and 5 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures were elucidated by analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their hypoglycemic activity with a glucose consumption model in palmitic acid (PA)-induced HepG2-insulin resistance (IR) cells, and compound 1 showed the most promising activity. A mechanistic study revealed that compound 1 appeared to mediate hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.

Two new guaianolide-type sesquiterpenoids with NO inhibitory activity from Chrysanthemum indicum.

Two new guaianolide-type sesquiterpenoids chrysanthemulides K and L (1 and 2), together with six known analogues (3-8), were isolated from an CH2Cl2 extract of the aerial parts of Chrysanthemum indicum. The structures of new compounds 1 and 2 were established by extensive spectroscopic analysis, including UV, IR, MS, NMR and computational electronic circular dichroism (ECD) methods. Inhibitory effects of all compounds on nitric oxide production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 1-8 displayed NO production inhibitory activity with IC50 values ranged from 3.5 to 34.3 µM.

Online Monitoring Technology of Metal Powder Bed Fusion Processes: A Review.

Metal powder bed fusion (PBF) is an advanced metal additive manufacturing (AM) technology. Compared with traditional manufacturing techniques, PBF has a higher degree of design freedom. Currently, although PBF has received extensive attention in fields with high-quality standards such as aerospace and automotive, there are some disadvantages, namely poor process quality and insufficient stability, which make it difficult to apply the technology to the manufacture of critical components. In order to surmount these limitations, it is necessary to monitor the process. Online monitoring technology can detect defects in time and provide certain feedback control, so it can greatly enhance the stability of the process, thereby ensuring its quality of the process. This paper presents the current status of online monitoring technology of the metal PBF process from the aspects of powder recoating monitoring, powder bed inspection, building process monitoring, and melt layer detection. Some of the current limitations and future trends are then highlighted. The combination of these four-part monitoring methods can make the quality of PBF parts highly assured. We unanimously believe that this article can be helpful for future research on PBF process monitoring.

Adaptations of postural sway dynamics and cortical response to unstable stance with stroboscopic vision in older adults.

Background: Stroboscopic vision (SV), intermittent visual blocking, has recently been incorporated into postural training in rehabilitation. This study investigated interactions of postural fluctuation dynamics and cortical processing for the elderly during stabilometer stance with SV. Methods: Thirty-five healthy elderly maintained an upright stance on a stabilometer. Along with postural fluctuation dynamics, EEG relative power and EEG-EEG connectivity were used to contrast neuromechanical controls of stabilometer stance with SV and full-vision. Results: Compared with the full-vision, SV led to greater postural fluctuations with lower sample entropy and mean frequency (MF). SV also reduced regional power in the mid-frontal theta cluster, which was correlated to SV-dependent changes in the size of postural fluctuations. SV also enhanced the alpha band supra-threshold connectivity in the visual dorsal and frontal-occipital loops of the right hemisphere, and the supra-threshold connectivity from Fp2 positively related to variations in the MF of postural fluctuations. Conclusion: SV adds challenge to postural regulation on the stabilometer, with the increasing regularity of postural movements and fewer corrective attempts to achieve the postural goal. The elderly shift over-reliance on visual inputs for posture control with more non-visual awareness, considering deactivation of the dorsal visual stream and visual error processing.

Germacranolide- and guaianolide-type sesquiterpenoids from Achillea alpina L. reduce insulin resistance in palmitic acid-treated HepG2 cells via inhibition of the NLRP3 inflammasome pathway.

Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A-H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1ß,2ß:4ß,5ß-diepoxy-10ß-hydroxy-6ßH,7αH,11ßH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D-F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56-6.25 µM. Moreover, achigermalide D decreased the expression of IL-1ß and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.

Effects of Training with a Brain-Computer Interface-Controlled Robot on Rehabilitation Outcome in Patients with Subacute Stroke: A Randomized Controlled Trial.

INTRODUCTION: Stroke is always associated with a difficult functional recovery process. A brain-computer interface (BCI) is a technology which provides a direct connection between the human brain and external devices. The primary aim of this study was to determine whether training with a BCI-controlled robot can improve functions in patients with subacute stroke. METHODS: Subacute stroke patients aged 32-68 years with a course of 2 weeks to 3 months were randomly assigned to the BCI group or to the sham group for a 4-week course. The primary outcome measures were Loewenstein Occupational Therapy Cognitive Assessment (LOCTA) and Fugl-Meyer Assessment for Lower Extremity (FMA-LE). Secondary outcome measures included Fugl-Meyer Assessment for Balance (FMA-B), Functional Ambulation Category (FAC), Modified Barthel Index (MBI), serum brain-derived neurotrophic factor (BDNF) levels and motor-evoked potential (MEP). RESULTS: A total of 28 patients completed the study. Both groups showed a significant increase in mean LOCTA (sham: P < 0.001, Cohen's d =  - 2.972; BCI: P < 0.001, Cohen's d =  - 4.266) and FMA-LE (sham: P < 0.001, Cohen's d =  - 3.178; BCI: P < 0.001, Cohen's d =  - 3.063) scores. The LOCTA scores in the BCI group were 14.89% higher than in the sham group (P = 0.049, Cohen's d =  - 0.580). There were no significant differences between the two groups in terms of FMA-B (P = 0.363, Cohen's d =  - 0.252), FAC (P = 0.363), or MBI (P = 0.493, Cohen's d =  - 0.188) scores. The serum levels of BDNF were significantly higher within the BCI group (P < 0.001, Cohen's d =  - 1.167), and the MEP latency decreased by 3.75% and 4.71% in the sham and BCI groups, respectively. CONCLUSION: Training with a BCI-controlled robot combined with traditional physiotherapy promotes cognitive function recovery, and enhances motor functions of the lower extremity in patients with subacute stroke. These patients also showed increased secretion of BDNF. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR-INR-17012874.

Iridoid glycosides isolated from Nardostachys chinensis batal with NO production inhibitory activity.

Investigation into the chemical diversity of Nardostachys chinensis Batal led to the discovery of three new (1-3) and one known (4) iridoid glycosides. Their structures were established through spectroscopic methods including 1 D and 2 D NMR experiments and HRESIMS analysis. Inhibitory effects of 1-4 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and they displayed IC50 values in the range 7.8-15.2 µM.

Visual Effect on Brain Connectome That Scales Feedforward and Feedback Processes of Aged Postural System During Unstable Stance.

Older adults with degenerative declines in sensory systems depend strongly on visual input for postural control. By connecting advanced neural imaging and a postural control model, this study investigated the visual effect on the brain functional network that regulates feedback and feedforward processes of the postural system in older adults under somatosensory perturbations. Thirty-six older adults conducted bilateral stance on a foam surface in the eyes-open (EO) and eyes-closed (EC) conditions while their center of pressure (COP) and scalp EEG were recorded. The stochastic COP trajectory was modeled with non-linear stabilogram diffusion analysis (SDA) to characterize shifts in postural control in a continuum of feedback and feedforward processes. The EEG network was analyzed with the phase-lag index (PLI) and minimum spanning tree (MST). The results indicated that visual input rebalanced feedforward and feedback processes for postural sway, resulting in a greater critical point of displacement (CD), short-term effective diffusion coefficients (Ds) and short-term exponent (Hs), but the smaller critical point of time (CT) and long-term exponent (Hl) for the EC state. The EC network demonstrated stronger frontoparietal-occipital connectivity but weaker fronto-tempo-motor connectivity of the theta (4-7 Hz), alpha (8-12 Hz), and beta (13-35 Hz) bands than did the EO network. MST analysis revealed generally greater leaf fraction and maximal betweenness centrality (BCmax) and kappa of the EC network, as compared with those of the EO network. In contrast, the EC network exhibited a smaller diameter and average eccentricity than those of the EO network. The modulation of long-term negative feedback gain of the aged postural system with visual occlusion was positively correlated with leaf fraction, BCmax, and kappa, but negatively correlated with the diameter and average eccentricity for all EEG sub-bands. In conclusion, the aged brain functional network in older adults is tuned to visual information for modulating long-term negative feedback of the postural system under somatosensory perturbations.

LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels.

BACKGROUND: Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. METHODS: sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and ß-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0-35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. RESULTS: We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. CONCLUSIONS: LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

Nomogram for predicting the overall survival of the patients with oesophageal signet ring cell carcinoma.

BACKGROUND: The purpose of this study was to explore the prognostic factors of oesophageal signet ring cell (SRC) carcinoma and to construct a nomogram for predicting the outcome of SRC carcinoma of oesophagus. METHODS: A total of 968 cases of oesophageal SRC carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Cases were divided into training cohort and validation cohort. Univariate and multivariable Cox analyses was performed to select the predictors of overall survival (OS for the nomogram. The performance of nomogram was validated with Harrell's concordance index (C-index), calibration curves and decision curve analysis (DCA). RESULTS: The 1- and 5-year OS in the training cohort were 0.446 and 0.146, respectively, and the 1- and 5-year OS in the validation cohort were 0.459 and 0.138. The independent prognostic factors for establishing the nomogram were marital status, invasion of the surrounding tissue, lymph node metastasis, distant metastasis, surgery and chemotherapy. The Harrell's c-index value of the training cohort and validation cohort were 0.723 and 0.708. In the calibration curves, the predicted survival probability and the actual survival probability have a considerable consistency. DCA indicated the favourable potential clinical utility of the nomogram. CONCLUSIONS: A nomogram to predict the OS of patients with oesophageal SRC carcinoma was established. The validation of the nomogram fully demonstrates its great performance.

Analgesic Effects of Navigated Repetitive Transcranial Magnetic Stimulation in Patients With Acute Central Poststroke Pain.

INTRODUCTION: Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke. METHODS: We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. RESULTS: Significant treatment-time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P < 0.001, Cohen's d = 1.302) (P = 0.003, Cohen's d = 0.771), and this effect lasted until the third week (P = 0.001, Cohen's d = 0.860) (P = 0.027, Cohen's d = 0.550). The HAM-A and HAM-D scores did not change in the rTMS group when compared with the sham group (P = 0.341, Cohen's d = 0.224) (P = 0.356, Cohen's d = 0.217). The serum BDNF levels were significantly higher in the treated group (P = 0.048, Cohen's d = -0.487), and the resting motor threshold (RMT) decreased by 163.65%. CONCLUSION: Our findings indicate that rTMS applied over the upper extremity area of the motor cortex can effectively alleviate acute CPSP, possibly by influencing cortical excitability and serum BDNF secretion. TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of China: Reg. No. ChiCTR-INR-17012880.