Effects of the Left M1 iTBS on Brain Semantic Network Plasticity in Patients with Post-Stroke Aphasia: A Preliminary Study.

BACKGROUND: The left primary motor area (M1) stimulation has recently been revealed to promote post-stroke aphasia (PSA) recovery, of which a plausible mechanism might be the semantic and/or the mirror neuron system reorganization, but the direct evidence is still scarce. The aim of this study was to explore the functional connectivity (FC) alterations induced by the left M1 intermittent theta burst stimulation (iTBS), a new transcranial magnetic stimulation paradigm, in the semantic and mirror neuron systems of PSA patients. METHODS: Sixteen PSA patients accepted the left M1 iTBS and underwent a resting-state functional magnetic resonance image (fMRI) scanning before and immediately after the first session of iTBS, of which six underwent another fMRI scanning after twenty sessions of iTBS. Three brain networks covering the semantic and the mirror neuron systems were constructed using the fMRI data, and the FC alterations following one-session iTBS were investigated in the networks. Additional seed-based FC analyses were conducted to explore the longitudinal FC patterns changes during the course of multi-session iTBS. The Aphasia quotient of the Chinese version of the western aphasia battery (WAB-AQ) was used to assess the severity of the language impairments of the participants. The relationship between the longitudinal WAB-AQ and network FC changes was analyzed by Spearman's correlation coefficients in the multi-session iTBS sub-group. RESULTS: Decreased FCs were noted in the bilateral semantic rather than in the mirror neuron networks following one-session of iTBS (p < 0.05, network based statistical corrected). Longitudinal seed-based FC analyses revealed changing FC ranges along the multi-session iTBS course, extending beyond the semantic networks. No significant relationship was found between the longitudinal WAB-AQ and network FC changes in the multi-session iTBS sub-group. CONCLUSIONS: The left M1 iTBS might induce FC changes in the semantic system of PSA patients. CLINICAL TRIAL REGISTRATION: This research was registered on the Chinese Clinical Trial Registry website (http://www.chictr.org.cn/index.aspx), and the registration number is ChiCTR2100041936.

Resting-state functional connectivity for determining outcomes in upper extremity function after stroke: A functional near-infrared spectroscopy study.

Objective: Functional near-infrared spectroscopy (fNIRS) is a non-invasive and promising tool to map the brain functional networks in stroke recovery. Our study mainly aimed to use fNIRS to detect the different patterns of resting-state functional connectivity (RSFC) in subacute stroke patients with different degrees of upper extremity motor impairment defined by Fugl-Meyer motor assessment of upper extremity (FMA-UE). The second aim was to investigate the association between FMA-UE scores and fNIRS-RSFC among different regions of interest (ROIs) in stroke patients. Methods: Forty-nine subacute (2 weeks-6 months) stroke patients with subcortical lesions were enrolled and were classified into three groups based on FMA-UE scores: mild impairment (n = 17), moderate impairment (n = 13), and severe impairment (n = 19). All patients received FMA-UE assessment and 10-min resting-state fNIRS monitoring. The fNIRS signals were recorded over seven ROIs: bilateral dorsolateral prefrontal cortex (DLPFC), middle prefrontal cortex (MPFC), bilateral primary motor cortex (M1), and bilateral primary somatosensory cortex (S1). Functional connectivity (FC) was calculated by correlation coefficients between each channel and each ROI pair. To reveal the comprehensive differences in FC among three groups, we compared FC on the group level and ROI level. In addition, to determine the associations between FMA-UE scores and RSFC among different ROIs, Spearman's correlation analyses were performed with a significance threshold of p < 0.05. For easy comparison, we defined the left hemisphere as the ipsilesional hemisphere and flipped the lesional right hemisphere in MATLAB R2013b. Results: For the group-level comparison, the one-way ANOVA and post-hoc t-tests (mild vs. moderate; mild vs. severe; moderate vs. severe) showed that there was a significant difference among three groups (F = 3.42, p = 0.04) and the group-averaged FC in the mild group (0.64 ± 0.14) was significantly higher than that in the severe group (0.53 ± 0.14, p = 0.013). However, there were no significant differences between the mild and moderate group (MD ± SE = 0.05 ± 0.05, p = 0.35) and between the moderate and severe group (MD ± SE = 0.07 ± 0.05, p = 0.16). For the ROI-level comparison, the severe group had significantly lower FC of ipsilesional DLPFC-ipsilesional M1 [p = 0.015, false discovery rate (FDR)-corrected] and ipsilesional DLPFC-contralesional M1 (p = 0.035, FDR-corrected) than those in the mild group. Moreover, the result of Spearman's correlation analyses showed that there were significant correlations between FMA-UE scores and FC of the ipsilesional DLPFC-ipsilesional M1 (r = 0.430, p = 0.002), ipsilesional DLPFC-contralesional M1 (r = 0.388, p = 0.006), ipsilesional DLPFC-MPFC (r = 0.365, p = 0.01), and ipsilesional DLPFC-contralesional DLPFC (r = 0.330, p = 0.021). Conclusion: Our findings indicate that different degrees of post-stroke upper extremity impairment reflect different RSFC patterns, mainly in the connection between DLPFC and bilateral M1. The association between FMA-UE scores and the FC of ipsilesional DLPFC-associated ROIs suggests that the ipsilesional DLPFC may play an important role in motor-related plasticity. These findings can help us better understand the neurophysiological mechanisms of upper extremity motor impairment and recovery in subacute stroke patients from different perspectives. Furthermore, it sheds light on the ipsilesional DLPFC-bilateral M1 as a possible neuromodulation target.

Age-Related Differences in Stepping Reactions to a Balance Perturbation: A Functional Near-Infrared Spectroscopy and Surface Electromyography Study.

We sought to investigate age-related differences in stepping reactions to a sudden balance perturbation, focusing on muscle activity and cortical activation. A total of 18 older healthy adults (older group, OG) and 16 young healthy adults (young group, YG) were recruited into this study. A cable-pull instrument was used to induce a forward perturbation at the waist level among participants, who were required to take the right step to maintain their postural balance. The seven right lower-limb muscle activities during periods of compensatory postural adjustments (CPAs) were recorded by surface electromyography. At the same time, the signals of channels located in the prefrontal, temporal and parietal lobes were recorded by functional near-infrared spectroscopy (fNIRS) during the whole process. Integral electromyograms of the right peroneus muscle, gluteus medius, and lateral gastrocnemius muscles showed greater activity for the OG in the CPA periods. Two channels belonging to the right pre-frontal (PFC) and pre-motor cortex (PMC) revealed lower activation in the OG compared with the YG. These findings can help us to better understand the differences at the peripheral and central levels and may provide some suggestions for future neuromodulation techniques and other clinical treatments.

Contralaterally controlled neuromuscular electrical stimulation-induced changes in functional connectivity in patients with stroke assessed using functional near-infrared spectroscopy.

Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is an innovative therapy in stroke rehabilitation which has been verified in clinical studies. However, the underlying mechanism of CCNMES are yet to be comprehensively revealed. The main purpose of this study was to apply functional near-infrared spectroscopy (fNIRS) to compare CCNMES-related changes in functional connectivity (FC) within a cortical network after stroke with those induced by neuromuscular electrical stimulation (NMES) when performing wrist extension with hemiplegic upper extremity. Thirty-one stroke patients with right hemisphere lesion were randomly assigned to CCNMES (n = 16) or NMES (n = 15) groups. Patients in both groups received two tasks: 10-min rest and 10-min electrical stimulation task. In each task, the cerebral oxygenation signals in the prefrontal cortex (PFC), bilateral primary motor cortex (M1), and primary sensory cortex (S1) were measured by a 35-channel fNIRS. Compared with NMES, FC between ipsilesional M1 and contralesional M1/S1 were significantly strengthened during CCNMES. Additionally, significantly higher coupling strengths between ipsilesional PFC and contralesional M1/S1 were observed in the CCNMES group. Our findings suggest that CCNMES promotes the regulatory functions of ipsilesional prefrontal and motor areas as well as contralesional sensorimotor areas within the functional network in patients with stroke.

Capturing Neuroplastic Changes after iTBS in Patients with Post-Stroke Aphasia: A Pilot fMRI Study.

Intermittent theta-burst stimulation (iTBS) is a high-efficiency transcranial magnetic stimulation (TMS) paradigm that has been applied to post-stroke aphasia (PSA). However, its efficacy mechanisms have not been clarified. This study aimed to explore the immediate effects of iTBS of the primary motor cortex (M1) of the affected hemisphere, on the functional activities and connectivity of the brains of PSA patients. A total of 16 patients with aphasia after stroke received iTBS with 800 pulses for 300 s. All patients underwent motor, language, and cognitive assessments and resting-state functional MRI scans immediately before and after the iTBS intervention. Regional, seed-based connectivity, and graph-based measures were used to test the immediate functional effects of the iTBS intervention, including the fractional amplitude of low-frequency fluctuation (fALFF), degree centrality (DC), and functional connectivity (FC) of the left M1 area throughout the whole brain. The results showed that after one session of iTBS intervention, the fALFF, DC, and FC values changed significantly in the patients' brains. Specifically, the DC values were significantly higher in the right middle frontal gyrus and parts of the left parietal lobe (p < 0.05), while fALFF values were significantly lower in the right medial frontal lobe and parts of the left intracalcarine cortex (p < 0.05), and the strength of the functional connectivity between the left M1 area and the left superior frontal gyrus was reduced (p < 0.05). Our findings provided preliminary evidences that the iTBS on the ipsilesional M1 could induce neural activity and functional connectivity changes in the motor, language, and other brain regions in patients with PSA, which may promote neuroplasticity and functional recovery.

Associations between Upper Extremity Motor Function and Aphasia after Stroke: A Multicenter Cross-Sectional Study.

METHODS: Patients with stroke were compared and correlated from overall and three periods (1-3 months, 4-6 months, and >6 months). Fugl-Meyer assessment for the upper extremity (FMA-UE) and action research and arm test (ARAT) were used to compare the UE motor status between patients with PSA and without PSA through a cross-sectional study among 435 patients. Then, the correlations between the evaluation scale scores of UE motor status and language function of patients with PSA were analyzed in various dimensions, and the language subfunction most closely related to UE motor function was analyzed by multiple linear regression analysis. RESULTS: We found that the scores of FMA-UE and ARAT in patients with PSA were 14 points ((CI) 10 to 18, p < 0.001) and 11 points lower ((CI) 8 to 13, p < 0.001), respectively, than those without PSA. Their FMA-UE (r = 0.70, p < 0.001) and ARAT (r = 0.62, p < 0.001) scores were positively correlated with language function. Regression analysis demonstrated that spontaneous speech ability may account for UE motor function (R 2 = 0.51, p < 0.001; R 2 = 0.42, p < 0.001). Consistent results were also obtained from the analyses within the three time subgroups. CONCLUSION: Stroke patients with PSA have worse UE motor performance. UE motor status and language function showed positive correlations, in which spontaneous speech ability significantly accounts for the associations.

[Yin-yang balance penetrating acupuncture combined with rehabilitation training on upper limb spasticity in stroke hemiplegia].

OBJECTIVE: To compare the therapeutic effect of yin-yang balance penetrating acupuncture combined with rehabilitation training and single rehabilitation training on upper limb spasticity in patients with stroke hemiplegia. METHODS: A total of 60 patients with upper limb spasticity of stroke hemiplegia were randomized into an observation group and a control group, 30 cases in each one. On the basis of conventional western medication, rehabilitation training was adopted in the control group. On the basis of treatment in the control group, yin-yang balance penetrating acupuncture was applied from Jianyu (LI 15) to Binao (LI 14), Quchi (LI 11) to Shaohai (HT 3), Yanglingquan (GB 34) to Yinlingquan (SP 9), Xuanzhong (GB 39) to Sanyinjiao (SP 6), etc. of the affected side in the observation group. The treatment was given once a day, 5 days were as one course, with a 2-day interval between two courses, 4 courses were required in both groups. The classification of modified Ashworth spasticity scale (MAS), surface integrated electromyogram (iEMG) of affected upper limb and the scores of National Institute of Health stroke scale (NIHSS), Fugl-Meyer assessment (FMA) of upper limb and modified Barthel index (MBI) before and after treatment were observed, the therapeutic effect was evaluated in both groups. RESULTS: ①After treatment, the MAS classification reduced in both groups (P<0.05), the cases of grade 0 to Ⅰ+ in the observation group were more than those in the control group (P<0.05); iEMG values of the maximum isometric voluntary contraction of affected usculus biceps brachii, musculus triceps brachii, musculus flexor carpi, musculus extensor carpi, extensor digitorum, aductor pollicis brevis were increased in both groups (P<0.05), and the variations of iEMG of above muscles on the affected side in the observation group were larger than those in the control group (P<0.05). ②After treatment, the scores of NIHSS were decreased (P<0.05), the scores of FMA, MBI were increased in both groups (P<0.05), and the variations of NIHSS, FMA and MBI scores were larger than those in the control group (P<0.05). ③The total effective rate was 93.3% (28/30) in the observation group, which was superior to 70.0% (21/30) in the control group (P<0.05). CONCLUSION: Yin-yang balance penetrating acupuncture combined with rehabilitation training can improve upper limb spasticity, heighten the motor function of upper limb and daily self care in patients with stroke hemiplegia, its therapeutic effect is superior to single rehabilitation training.

Flexors activity of affected upper extremity in stroke patients during different standing conditions and their relationships with clinical scales: a cross-sectional study.

Purpose: To explore the flexors activity of affected upper extremity in stroke patients during different standing conditions and their relationships with clinical scales.Materials and methods: Sixteen stroke patientswere recruited, all subjects stood on balance equipment with four different standing postures. The electromyogram (EMG) simultaneously recorded the muscle activity of bilateral biceps brachii, triceps brachii, flexor carpi radialis and extensor carpi radialis and their integrated electromyogram were figured out the contraction rate of elbow flexors(biceps brachii/triceps brachii) and wrist flexors(flexor carpi radialis/extensor carpi radialis). All subjects were assessed using Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Berg Balance Scale (BBS), Barthel Index (BI) and Modified Ashworth Scale (MAS).Results: The contraction rate of affected elbow flexors in the condition of feet together on soft surface was significantly higher than that in the condition of feet separatedon hard surface (P < 0.05). The contraction rate of affected elbow flexors in four standing conditions tended to increase, all the values of which were greater than numerical value1. The difference in the contraction rate of elbow flexor between the affected side and the unaffected side was statistically significant (P < 0.05). No correlation was observed between the contraction rate of the elbow flexor and the results of MAS, FMA-UE, BBS and BI regardless of the standing conditions.Conclusions: The contraction rates of elbowflexor in the affected side increase with the difficulty in different standing postures,and it may be a good index to reflect the changes of muscle tone in postural control.

Clinical value of iodine 131I metuximab infusion combined with TACE for treatment of patients with post-intervention relapse of mid or advanced stage hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of iodine[131I] metuximab infusion combined with transcatheter arterial chemoembolization (TACE) for treating cases of post-intervention relapse of mid or advanced stage hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Sixty patients who were diagnosed between March 2009 and June 2010 with relapse of mid or advanced stage HCC following previous intervention with various standard clinical methods were recruited for study. The patients were randomly and equally divided into a control treatment group (CG; receiving TACE therapy alone) and an experimental treatment group (TG; receiving TACE combined with iodine [131I] metuximab injection). For all patients, licartin was first perfused into the tumor feeding artery and then the TACE procedure was performed 20 min later. Liver function markers and routine blood parameters, including alpha-fetoprotein (AFP) and clotting time, were examined at one week and one month after the treatment. Enhanced computed tomography or magnetic resonance imaging of the liver was performed at one month after treatment and thereafter on a bi-monthly follow-up schedule. The World Health Organization's tumor evaluation standard was used to assess the therapeutic effects in each group. Results of laboratory tests (pre- and post-treatment), reported complications, and side-effects were evaluated for their contributions to time of tumor progression (TTP) and survival time.</p><p><b>RESULTS</b>Patients in the TG and CG groups had similar blood cell counts at pre-operative and 1-week postoperative time points. The TG group showed a significantly reduced level of AFP following treatment, but it was not significantly different from the level in the CG group. The TG group did however show significantly different levels of liver functional parameters (all P less than 0.05) and significantly higher TTP (4.84+/-4.11 vs. CG: 2.54+/-2.08 months; t = -2.13, P less than 0.05) and average survival time (7.05 vs. 5.15 months; x2 = 4.24, P = 0.039). The rates of partial response (PR), slight remission (MR), unchanged status (SD) and progressive disease (PD) were 16.7%, 37.5%, 25.0% and 20.8% in the TG group, and 8.7%, 17.4%, 21.7% and 52.2% in the CG group. The therapeutic effect rate (CR + PR + MR) and reaction rate (CR + PR + MR + SD) was significantly different between the two groups (P = 0.048). No serious adverse effects were reported.</p><p><b>CONCLUSION</b>TACE combined with iodine [131I] metuximab injection is a safe and effective procedure for prolonging the survival and TTP of patients with HCC relapse following prior therapeutic intervention.</p>

Clinical efficacy of malignant obstructive jaundice treated by domestic biliary metallic stent insertion / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of implanted biliary metallic stents in the management of malignant obstructive jaundice (MOJ).</p><p><b>METHODS</b>Percutaneous transhepatic cholangiography and stent insertion were performed in 241 consecutive patients to treat malignant biliary obstruction between December 1998 and February 2009. The study end point was patient death. All patients were followed-up until death or until February 2010. The therapeutic efficacy was determined by statistical analysis of life span and pre- and post-operative laboratory indices.</p><p><b>RESULTS</b>All 241 patients were successfully stented. The level of bilirubin descended obviously within four weeks of implantation (P less than 0.05), and the early mortality rate was 4.56% (11/241). Two-hundred-and-two patients were followed-up (range: 8-193 weeks post-transplantation) and showed a median survival of 43.55 weeks. The survival rates at 13, 26, 39 and 52 weeks post-transplantation were 87%, 66%, 56%, and 41%, respectively. The stent patency rates at 13, 26, 39 and 52 weeks post-transplantation were 70%, 46%, 36% and 24%, respectively; the mean stent patency was 27.57 weeks. Cox regression analysis identified the strong predictors of improved survival as an initial bilirubin level of less than 221 mumol/L (P = 0.01) and a stent-induced bilirubin reduction of more than 50% (P = 0.002).</p><p><b>CONCLUSION</b>Transhepatic metallic biliary stenting is a safe and effective therapeutic intervention for malignant biliary obstruction. Significant periods of survival and palliation of jaundice can be achieved with this method. Hyperbilirubinemia and a stent-induced bilirubin reduction of less than 50% are independent predictive factors for the survival of MOJ patients.</p>

Investigation of the toxic effect of cadmium on Candida humicola and Bacillus subtilis using a microcalorimetric method.

In this study, the technique of microcalorimetry based on heat-output by aerobic bacterial respiration was explored to evaluate the toxic effect of cadmium on Candida humicola, Bacillus subtilis, singularly or in a mixture of both. Power-time curves of the growth metabolism of C. humicola and B. subtilis and the effect of Cd(2+) were studied using the TAM III (the third generation thermal activity monitor) multi-channel microcalorimetric system, isothermal mode, at 28 degrees C. The differences in shape of the power-time curves and the thermodynamic and kinetic characteristics of microorganisms growth were compared. The effect of cadmium added into microorganism would significantly reduce the life cycle and change the thermal effect of microbial metabolic process with different concentrations of Cd(2+). The experimental results revealed that at the same concentration, the sequence of inhibitory ratio (I) and maximum thermal power (P(max)) of the Cd(2+) was: mixed microorganisms>C. humicola>B. subtilis. The sequence of total thermal effect (Q(total)) and growth rate constant (k) is mixed microorganisms>B. subtilis>C. humicola. These results are important to further studies of the physiology and pharmacology of C. humicola and B. subtilis and may support the theory of restoring contaminated soil.

[Lipid peroxidation affects serum T and Bcl-2 expression in the testis of aging male rats].

OBJECTIVE: To investigate the effect of lipid peroxidation on testosterone (T) in the serum and bcl-2 expression in the Leydig cells of aging male rats. METHODS: The D-galactose-induced subacute aging male rat model was established and 20 SD rats were randomly divided into two groups of equal number: a D-galactose (D) group and a control (C) group. The activity of superoxide dismutase(SOD) and the level of malondialdehyde (MDA) were examined by spectro-absorptiometer, the expression of bcl-2 by immunohistochemical method, and the concentration of serum T by radio-immunity technique. RESULTS: (1) The activity of SOD in the testis of the D group was (116 +/- 18.09) U/ mg x prot, significantly lower than in the C group [(156 +/- 31.02) U/mg x prot (P < 0.01)]. (2) The level of MDA in the testis of the D group was (1.77 +/- 0.41) nmol/mg x prot, significantly higher than in the C group [(1.19 +/- 0.15) nmol/mg x prot (P < 0.05)]. (3) Serum T in the D group was (2.39 +/- 0.90) nmol/L, significantly lower than in the C group [(8.95 +/- 2.53) nmol/L (P < 0.01)]. (4) The expressions of bcl-2 in the leydig cells of the D and C groups were (35.1 +/- 3.6)% and (49.6 +/- 7.4)% respectively, with statistical difference between them (P < 0.01). CONCLUSION: Lipid peroxidation affects the concentration of serum T and the expression of bcl-2 in the Leydig cells of aging male rats.