Synthesis and biological activity evaluation of podophyllotoxin-linked bile acid derivatives as potential anti-liver cancer agents.

Podophyllotoxin's undifferentiated cytotoxicity and poor selectivity limit its clinical application. To improve above disadvantages, conjugation of bile acids with podophyllotoxin could improve cell line selectivity of liver cancer to achieve clinical translation further. Enlightened by the bile acids' moiety magic characters, thirty podophyllotoxin-linked bile acid derivatives had been designed and synthesized. The cytotoxicity of these compounds in vitro was evaluated on HepG2, HCT-116, A549 and MDCK cell lines. After conjunction with bile acids, most of the derivatives (IC50 = 0.066-0.831 µM) were more potent against above three types of tumor cells than Etoposide (VP-16, IC50 = 4.319-41.080 µM) and exhibited similar antitumor activity compared with doxorubicin (DOX, IC50 = 0.230-0.745 µM). Moreover, structure-activity relationship displayed the length of the linker chain between podophyllotoxin and bile acids affected the cytotoxicity. Especially, compound 23 exhibited strong activity against HepG2 cell lines (IC50 = 0.188 ± 0.01 µM) than MDCK cell lines (IC50 = 4.780 ± 0.50 µM) and its SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4. Further antitumor mechanism studies showed that compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest. In particular, compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model. The current research displayed that introduction of bile acids contributed to improve selectivity and activity to cell, and compound 23 could be a promising anti-tumor candidate.

Tetrahydropalmatine triggers angiogenesis via regulation of arginine biosynthesis.

Over a short span of two decades, the central role of angiogenesis in the treatment of wound healing, diverse cancers, nerve defect, vascular injury and several ophthalmic diseases has become evident. Tetrahydropalmatine, as the index component of Corydalis yanhusuo W. T. Wang, is inseparable from protecting cardiovascular system, yet its role in angiogenesis has been poorly characterized. We have demonstrated the binding potential of THP and VEGFR2 using molecular docking based on the clinical experience of traditional Chinese medicine in the pretest study. Here, we identified tetrahydropalmatine (THP) as one proangiogenic trigger via regulation of arginine biosynthesis by pharmacological assays and DESI-MSI/GC-MS based metabolomics. First, the proangiogenic effects of THP were evaluated by quail chorioallantoic membrane test in vivo and multiple models of endothelial cells in vitro. According to virtual screening, the main mechanisms of THP (2/5 of the top terms with smaller p-value) were metabolic pathways. Hence, metabolomics was applied for the main mechanisms of THP and results showed the considerable metabolite difference in arginine biosynthesis (p < 0.05) altered by THP. Finally, correlated indicators were deteced using targeted metabolomics and pharmacological assays for validation, and results suggested the efficacy of THP on citrulline to arginine flux, arginine biosynthesis, and endothelial VEGFR2 expression sequentially, leading to the promotion of angiogenesis. Overall, this manuscript identified THP as the proangiogenic trigger with the potential to develop as pharmacological agents for unmet clinical needs.

Neural correlates of different behavioral response to transcranial direct current stimulation between patients in the unresponsive wakefulness syndrome and minimally conscious state.

In this study, we used event-related potential (ERP) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to study the neural correlates of different behavioral response to transcranial direct current stimulation (tDCS) between patients in unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Thirteen patients (eight in UWS and five in MCS) underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC). Before tDCS, all the patients and six age-matched healthy subjects underwent a cerebral FDG-PET scan and ERP test. The coma recovery scale-revised (CRS-R) results revealed that after tDCS, a significant improvement was observed only in the MCS group. The ERP results supported that MCS patients preserved more high-order cortical information processing capacities. The residual brain metabolism in the left DLPFC in MCS patients supported that a residual brain activity in the stimulated area was necessary for a behavioral response to tDCS. Our study also demonstrated that the cerebral metabolic rates of glucose (CMRgl) ratios in intrinsic network were correlated significantly with CRS-R in MCS patients. In addition, the right prefrontal region might be another potential therapeutic target for MCS patients.

Betulinic Acid-Nitrogen Heterocyclic Derivatives: Design, Synthesis, and Antitumor Evaluation in Vitro.

Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21 BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) assay. The majority of these derivatives showed much stronger cytotoxic activity than BA. Remarkably, the most potent compound 7e (the half maximal inhibitory concentration (IC50) of which was 2.05 ± 0.66 µM) was 12-fold more toxic in vitro than BA-treated Hela. Furthermore, multiple fluorescent staining techniques and flow cytometry collectively revealed that compound 7e could induce the early apoptosis of Hela cells. Structure-activity relationships were also briefly discussed. The present study highlighted the importance of introducing nitrogen heterocyclic rings into betulinic acid in the discovery and development of novel antitumor agents.

Noninvasive Brain Stimulation for Motor Dysfunction After Incomplete Spinal Cord Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to examine the effectiveness of noninvasive brain stimulation on motor dysfunction after incomplete spinal cord injury. METHODS: The PubMed, Embase, and Cochrane Library were searched from the inception dates to April 30, 2022. Randomized controlled trials comparing the effects of noninvasive brain stimulation and sham stimulation on motor dysfunction in patients with incomplete spinal cord injury were included. Two reviewers performed the data extraction and assessed study quality using Cochrane Collaboration's Tool. The primary outcomes involved upper limb function, lower limb function, spasticity, and activities of daily living. They were analyzed using meta-analysis method and the results were reported as standardized mean difference with 95% confidence interval. RESULTS: Fourteen studies involving 225 patients were included. Noninvasive brain stimulation reduced spasticity at the end of intervention (standardized mean difference = -0.68, 95% confidence interval = -1.32 to -0.03, P = 0.04) and 1-wk follow-up (standardized mean difference = -0.82, 95% confidence interval = -1.48 to -0.16, P = 0.02), but no beneficial effect at 1-mo follow-up (standardized mean difference = -0.32, 95% confidence interval = -1.06 to 0.42, P = 0.39). In addition, noninvasive brain stimulation also increased lower limb muscle strength at 1-mo follow-up (standardized mean difference = 0.69, 95% confidence interval = 0.11 to 1.28, P = 0.02). Other main outcomes were similar between groups. CONCLUSIONS: Noninvasive brain stimulation can reduce spasticity, and the favorable effect can sustain for 1 wk after intervention. In addition, noninvasive brain stimulation can increase lower limb muscle strength at 1-mo follow-up.

Predictors of deep-vein thrombosis for acute stroke at admission to a rehabilitation unit: A retrospective study.

Background: Deep-vein thrombosis (DVT) is a common complication of acute stroke (AS). Only limited studies have discussed DVT in patients with AS at admission to a rehabilitation unit. The purpose of this study is to identify the predictors of DVT in AS patients admitted to a rehabilitation unit in China. Methods: We retrospectively reviewed the medical records of all patients with AS admitted within 14 days of stroke onset between July 2019 and June 2022 at the Department of Rehabilitation Medicine, Xuanwu Hospital, Capital Medical University, China. Ultrasonography was used to diagnose DVT in all patients within 3 days after rehabilitation admission. Univariate and binary logistic regression analyses were performed to determine the risk factors for DVT. Results: Overall, 234 cases were identified and the incidence rate of DVT among AS patients was 13.2% (31/234). The univariate analysis showed that age, drinking, lower limb muscle strength, Brunnstrom Assessment (BRS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Barthel Index (BI) scale, serum albumin (Alb), and D-dimer were statistically significant factors. Age (OR = 1.037, 95% CI = 1.000-1.075, p < 0.05), BBS (OR = 0.952, 95% CI = 0.913-0.993, p < 0.05), and D-dimer (OR = 1.446, 95% CI = 1.130-1.849, p < 0.05) were demonstrated as independent risk factors for DVT. Conclusion: Older age, lower BBS, and higher D-dimer levels at rehabilitation admission were independent risk factors for DVT. Therefore, ultrasonography should be performed for those patients with these three significant factors before implementing rehabilitation therapy.

Recombinant pseudorabies virus (PRV) expressing stabilized E2 of classical swine fever virus (CSFV) protects against both PRV and CSFV.

Pseudorabies (PR) and classical swine fever (CSF) are economically important infectious diseases of pigs. Most pig farms in China are immunized against these two diseases. Here, we describe a stabilized E2 protein as an immunogen inserted into the PRV genome as a bivalent live virus-vectored vaccine. The E2 protein has 48 variant sites, there are 2-5 candidate amino acids per variant site, and the relative energy contribution of each amino acid to E2 energy was calculated. Combined substitutions of amino acids at the neighbor variant site (neighbor substitution) were performed to obtain the E2 protein sequence with the lowest energy (stabilized E2). Multiple amino acid substitutions at 48 variant sites were performed, and the results were consistent with neighbor substitutions. The stabilized E2 sequence was obtained, and its energy decreased by 22 Rosetta Energy Units (REUs) compared with the original sequence. After the recombinant PRV expressing stabilized E2 of CSFV was constructed, the secretion efficiency of stabilized E2 was increased by 2.97 times, and the thermal stability was increased by 10.5 times. Immunization of mice resulted in a 2-fold increase in antibody production, and a balanced antibody level against subtype 1.1 and subtype 2.1d E2 was achieved. In rabbits immunized, the lethal challenge of PRV-ZJ and the fever response induced by CSFV could be prevented simultaneously. These findings suggest that rPRV-muta/287aaE2 is a promising bivalent vaccine against CSFV and PRV infections.

High expression of the classical swine fever virus (CSFV) envelope protein E2 by a single amino acid mutation and its embedded in the pseudorabies virus (PRV) vector for immunization.

Pseudorabies (PR) and classical swine fever (CSF) are economically important infectious diseases in pigs. Most pig farms in China are vaccinated against these two diseases. Gene-deleted pseudorabies virus (PRV) can be used to develop promising and economical multivalent live attenuated viral vector vaccines. It has been reported that recombinant PRV can express a truncated E2 protein (1-338 aa), but it has not been reported that recombinant PRV can express a full-length E2 protein. We constructed nine groups of E2 proteins with different expression forms and found that the E2 protein could be expressed in vitro only when the transmembrane region of E2 was removed and the signal peptide was added. Analysis of the transmembrane region of E2 revealed that the high hydrophobicity of the E2 transmembrane region was the main reason for its inability to express. By mutating an amino acid to reduce the hydrophobicity of the transmembrane region, it was found that the full-length mutant of E2 (E2FL-muta3 or E2FL-muta4) could be expressed. The expressed full-length mutant E2 could also localize to the cell membrane. Mice immunized with a PRV vector vaccine expressing E2FL-muta3 or E2FL-muta4 developed specific cellular immunity to the E2 protein and stimulated higher levels of E2 antibody than mice immunized with a PRV vector expressing truncated E2. After immunizing the rabbits, the lethal challenge by PRV-ZJ2013 and the febrile response elicited by CSFV were simultaneously prevented. These results suggest that rPRV-dTK/gE-E2FL-muta4 is a promising bivalent vaccine against CSFV and PRV infections.

Study on the occurrence and neural bases of hemispatial neglect with different reference frames.

OBJECTIVES: To study the distributions and the neural correlates of left hemispatial neglect with different reference frames. DESIGN: Data were collected from patients with right brain injury who participated in a case series. SETTING: Hospital departments of rehabilitation and neurology. PARTICIPANTS: Right brain-damaged patients (N=110). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The frequency of left hemispatial neglect with different reference frames was investigated, and the respective brain lesions were displayed and analyzed. RESULTS: Not all subjects finished predesigned neglect tests because of their condition: 8 of the 55 neglect patients were unable to complete the test for classification. Thirty (63.83%) of 47 subjects with neglect displayed both allocentric and egocentric neglect, while 17 subjects showed pure egocentric neglect. The lesions in the inferior frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus (STG), middle temporal gyrus (MTG), insula, and surrounding white matters were more frequent in the neglect group than in the control group. Compared with the egocentric neglect group, the lesions in the right STG, MTG, lenticular nucleus, and the surrounding white matter were damaged more frequently in the group displaying both allocentric and egocentric neglect. CONCLUSIONS: More than half of the subjects with left neglect after right brain injury have both egocentric and allocentric neglect. The right inferior frontal gyrus, precentral gyrus, postcentral gyrus, STG, MTG, insula, and the surrounding white matter are associated with left hemispatial neglect. Left allocentric neglect is associated with the right STG, MTG, and lenticular nucleus.

Multidimensional review of cognitive impairment after spinal cord injury.

Cognitive impairment is highly prevalent in the population with spinal cord injury (SCI) and exerts a significant impact on functional independence and quality of life in this population. A number of neuroscientists have conducted preliminary investigations of cognitive deficits after SCI, but achieved marginally contradictory results due to some limitations such as the heterogeneity in the sample population, sample size, types of tests utilized, study design, and time since SCI. Therefore, this review mainly focuses on the characteristics, assessments, potential causality and treatment of cognitive impairment for better understanding such deficits in the SCI population.

Self-Assembled Nanoparticles of Natural Phytochemicals (Berberine and 3,4,5-Methoxycinnamic Acid) Originated from Traditional Chinese Medicine for Inhibiting Multidrug-Resistant Staphylococcus aureus.

BACKGROUND: In the field of antibacterial, nanomaterials are favored by researchers because of their unique advantages. Medicinal plants, especially traditional Chinese medicine, are considered to be an important source of new chemicals with potential therapeutic effects, as well as an important source for the discovery of new antibiotics. MRSA is endangering people's lives as a kind of multidrug-resistant Staphylococcus aureus, which is resistant to tetracycline, amoxicillin, norfloxacin and other first-line antibiotics. It is a hotspot to find good anti-drug-resistant bacteriae, nature-originated nanomaterials with good biocompatibility. OBJECTIVE: We reported the formation of phytochemical nanoparticles (NPs) by the self-assembly of berberine (BBR) and 3,4,5-methoxycinnamic acid (3,4,5-TCA) from Chinese herb medicine, which had good antibacterial activity against MRSA. METHODS AND RESULTS: We found that NPs had good antibacterial activity against MRSA; especially, its antibacterial activity was better than first-line amoxicillin, norfloxacin and its self-assembling precursors on MRSA. When the concentration reached 0.1 µmol/mL, the inhibition rate of NPs reached 94.62%, which was higher than that of BBR and the other two antibiotics (p < 0.001). It was observed by Field-Emission Scanning Electron Microscopy (FESEM) that NPs could directly adhere to the bacterial surface, which might be an important aspect of the antibacterial activity of NPs. Meanwhile, we further analyzed that the self-assembly was formed by hydrogen bonds and π-π stacking through Ultraviolet-Visible (UV-vis), Fourier Transform Infrared Spectroscopy (FTIR), hydrogen Nuclear Magnetic Spectrum (1H NMR), and powder X-ray Diffraction (pXRD). NPs' morphology was observed by FESEM and TEM. The particle size and surface charge were characterized by Dynamic Light Scattering (DLS); and the surface charge was -31.6 mv, which proved that the synthesized NPs were stable. CONCLUSION: We successfully constructed a naturally self-assembled nanoparticle, originating from traditional Chinese medicine, which had a good antibacterial activity for MRSA. It is a promising way to obtain natural nanoparticles from medicinal plants and apply them to antibacterial therapy.

2-[4-tert-Butyl-5-(2-chloro-benz-yl)-1,3-thia-zol-2-yl]isoindoline-1,3-dione.

In the title compound, C(22)H(19)ClN(2)O(2)S, the dihedral angle between the phenyl-ene ring and the phthalimide ring system is 4.4 (1)°. There is no hydrogen bonding or π-π stacking in the crystal structure.

A novel long-acting oxyntomodulin analogue eliminates diabetes and obesity in mice.

Oxyntomodulin (OXM) was identified as a glucagon (GCG) receptor (GCGR) and glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) dual agonist to suppress appetite, increase energy expenditure, and induce body weight loss in obese humans. However, the activities of native OXM to activate GCGR and GLP-1R in vitro were much weaker than the natural ligands. To address this gap, structural modifications were adopted and novel OXM analogues were obtained through chimeric peptide sequence design. One specific analogue with enhanced and balanced GCGR/GLP-1R activations was chemically conjugated with polyethylene glycol (PEG) to achieve sustained release in vivo. This PEGylated analogue was further explored pharmacologically in db/db and diet-induced obese (DIO) mice models. Chronic weekly administration significantly induced hypoglycemic effects and body weight loss with dose dependency, along with normalized adiposity, lipid metabolism, and liver steatosis. Based on its profiles in vitro and in vivo, the analogue has the great potential to develop as a novel anti-diabetic and/or anti-obese candidate. As observed more insulin stimulation and improved insulin resistance, it may be also explored for the treatment of nonalcoholic steatohepatitis (NASH) in the future.

Exogenous 24-Epibrassinolide alleviates oxidative damage from copper stress in grape (Vitis vinifera L.) cuttings.

Copper (Cu) stress is the most common abiotic stress experienced in vineyards owing to the copper-based fungicides application. Plant hormones, including 24-Epibrassinolide (EBR), may alleviate the adverse impacts of heavy metal stress on plants. We investigated the effects of EBR pretreatment on root morphological parameters, active oxygen metabolism, osmolytes contents, antioxidant enzyme activity, endogenous phytohormone contents, and ascorbate-glutathione (AsA-GSH) cycle activity of one-year-old grape (Vitis vinifera L.) cuttings under Cu stress. Pretreatment with EBR significantly enhanced root morphological parameters (total root length, root surface area, root diameter, root volume, and tip number), increased soluble protein and proline contents, and significantly decreased the contents of H2O2, O2⋅-, and malondialdehyde (MDA) in roots and leaves. EBR pretreatment increased the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase oxidase (POD), and the contents of the endogenous phytohormones abscisic acid, jasmonic acid, and salicylic acid in the leaves. In addition, EBR regulated the balance of the AsA-GSH cycle by increasing the activities of monodehydroascorbate reductase (MDHAR), glutathione peroxidase (GR), ascorbate peroxidase (APX), and dehydroascorbate reductase (DHAR), and the contents of the antioxidant ascorbate (AsA) and dehydroascorbic acid (DHA), but the contents of glutathione (GSH) and oxidized glutathione (GSSG) decreased. Among the treatments tested, pretreatment with 0.10 mg/L EBR showed the optimal performance for alleviation of Cu toxicity. The results show that exogenous brassinosteroids reduce oxidative damage and improve the tolerance of Cu stress of grapevine cuttings.

Coherence in P300 as a predictor for the recovery from disorders of consciousness.

Accurate and reliable prognostic judgments for disorders of consciousness (DOCs) can provide useful information for clinicians in the establishment of appropriate care plan, and may affect end-of-life decisions of caregivers. But until now no certain or standardized prognostic indicator has been constructed to predict the probability of awareness recovery. This study aims to assess higher-order cortical information processing in DOCs by event-related potential (ERP) and determine the value of P300 to predict the long-term prognosis. Two locked-in (LIS) patients and eighteen DOCs were evaluated with a hierarchical cognitive assessment by ERP. We used subject's own name (SON) as a deviant stimulus, 1000Hz tone and subject's derived name (SDN) as a standard stimulus in two paradigms respectively. P300 elicited by SON was used to assess the information processing. The patients' clinical outcomes were followed up at 2, 6 and 12 months after ERP recordings. The results showed that a P300 component was observed in both paradigms in two LIS patients. All of MCS and four out of nine UWS/VS showed an intact P300 in either paradigm. All of the five patients with P300 in both paradigms were finally awake after 12 months, while none of the eight patients without P300 regained consciousness. A highly significant relationship between P300 and subsequent recovery was found. The results provide evidence that P300 in the hierarchical bedside neurophysiologic oddball procedure can accurately characterize the level of cognitive preservation, and may serve as an alternative tool to predict the likelihood of recovery of DOCs.

Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of Consciousness: Combined Behavioral and Event-Related Potential Evidence.

BACKGROUND: The electrophysiological evidence supporting the therapeutic efficacy of multiple transcranial direct current stimulation (tDCS) sessions on consciousness improvement in patients with prolonged disorders of consciousness (DOCs) has not been firmly established. OBJECTIVES: To assess the effects of repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS-R) score and event-related potential (ERP). METHOD: Using a sham-controlled randomized double-blind design, 26 patients were randomly assigned to either a real [five vegetative state (VS) and eight minimally conscious state (MCS) patients] or sham (six VS and seven MCS patients) stimulation group. The patients in the real stimulation group underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 10 consecutive working days. The CRS-R score and P300 amplitude and latency in a hierarchical cognitive assessment were recorded to evaluate the consciousness level before tDCS and immediately after the 20 sessions. RESULTS: The intra-group CRS-R analysis revealed a clinically significant improvement in the MCS patients in the real stimulation group. The inter-group CRS-R analysis showed a significant difference in CRS-R between VS and MCS patients at baseline in both the real and sham stimulation groups. The intra-group ERP analysis revealed a significant increase in P300 amplitude after tDCS in the MCS patients in the real stimulation group, but no significant differences in P300 latency. For the inter-group ERP analysis, we observed significant differences regarding the presence of P300 at baseline between the VS and MCS patients in both groups. CONCLUSION: The repeated anodal tDCS of the left DLPFC could produce clinically significant improvements in MCS patients. The observed tDCS-related consciousness improvements might be related to improvements in attention resource allocation (reflected by the P300 amplitude). The findings support the use of tDCS in clinical practice and ERP might serve as an efficient electrophysiological assessment tool in patients with DOCs.

Continuous theta-burst stimulation may improve visuospatial neglect via modulating the attention network: a randomized controlled study.

BACKGROUND: Visuospatial neglect (VSN) is devastating and common after stroke, and is thought to involve functional disturbance of the attention network. Non-invasive theta-burst stimulation (TBS) may help restore the normal function of attention network, therefore facilitating recovery from VSN. OBJECTIVE: This study investigated the effects of continuous TBS on resting-state functional connectivity (RSFC) in the attention network, and behavioral performances of patients with VSN after stroke. METHODS: Twelve patients were randomly assigned to receive 10-day cTBS of the left posterior parietal cortex delivered at 80% (the cTBS group), or 40% (the active control group) of the resting motor threshold. Both groups received daily visual scanning training and motor function treatment. Resting-state functional MRI (fMRI) and behavioral tests including line bisection test and star cancelation test were conducted at baseline and after the treatment. RESULTS: At baseline, the two groups showed comparable results in the resting-state fMRI experiments and behavioral tests. After treatment, the cTBS group showed lower functional connectivity between right temporoparietal junction (TPJ) and right anterior insula, and between right superior temporal sulcus and right anterior insula, as compared with the active control group; both groups showed improvement in the behavioral tests, with the cTBS group showing larger changes from baseline than the active control group. CONCLUSION: cTBS of the left posterior parietal cortex in patients with VSN may induce changes in inter-regional RSFC in the right ventral attention network. These changes may be associated with improved recovery of behavioral deficits after behavioral training. The TPJ and superior temporal sulcus may play crucial roles in recovery from VSN.

Intermittent θ burst stimulation modulates resting-state functional connectivity in the attention network and promotes behavioral recovery in patients with visual spatial neglect.

Functional connectivity changes in the attention network are viewed as a physiological signature of visual spatial neglect (VSN). The left dorsal lateral prefrontal cortex (LDLPFC) is known to initiate and monitor top-down attentional control and dynamically adjust behavioral performance. This study aimed to investigate whether increasing the activity of the LDLPFC through intermittent θ burst stimulation (iTBS) could modulate the resting-state functional connectivity in the attention network and facilitate recovery from VSN. Patients with right hemisphere stroke and VSN were randomly assigned to two groups matched for clinical characteristics and given a 10-day treatment. On each day, all patients underwent visual scanning training and motor function training and received iTBS over the LDLPFC either at 80% resting motor threshold (RMT) or at 40% RMT before the trainings. MRI, the line bisection test, and the star cancelation test were performed before and after treatment. Patients who received iTBS at 80% RMT showed a large-scale reduction in the resting-state functional connectivity extent, largely in the right attention network, and more significant improvement of behavioral performance compared with patients who received iTBS at 40% RMT. These results support that the LDLPFC potentially plays a key role in the modulation of attention networks in neglect. Increasing the activity of the LDPLPFC through iTBS can facilitate recovery from VSN in patients with stroke.

Electrophysiological correlates of processing subject's own name.

To understand the neurological mechanisms associated with the perception of subject's own name (SON) and provide a reference for assessing residual cognitive functions in patients with disorders of consciousness, event-related potentials were recorded in 16 healthy volunteers. Compared with event-related potentials elicited by tone stimuli, SON elicited larger MMN and P300. The amplitudes and latencies of MMN and P300 induced by subject's derived name (SDN) were similar to those induced by SON. Discriminating SON from SDN resulted in longer MMN and P300 latencies. These data showed that the SDN had similar quality as SON and might provide a useful reference for quantitatively evaluating disorders of consciousness.

Long-term effects of continuous theta-burst stimulation in visuospatial neglect.

OBJECTIVE: To investigate whether the efficacy of continuous theta-burst stimulation (cTBS) for improving visuospatial neglect can be enhanced by providing more days of stimulation and more stimulation trains per day. METHODS: In a prospective study, right-handed patients with right hemisphere stroke and visuospatial neglect were randomized to cTBS or sham cTBS treatment for 2 weeks and were followed up for 4 weeks. The cTBS group received active cTBS over the posterior parietal cortex of the unaffected hemisphere, combined with conventional rehabilitation therapy. Changes in scores for two paper-pencil tests for visuospatial neglect (star cancellation and line bisection) were evaluated. RESULTS: In each group, 10 patients completed follow up. Compared with the sham group, star cancellation test scores in the cTBS group were improved by 37.03% at the end of treatment and by 47.21% after 4 weeks' follow up, and the line bisection score improved by 21.37% at the end of treatment and by 35.99% after 4 weeks' follow up. CONCLUSIONS: These results suggest that the efficacy of cTBS in visuospatial neglect can be enhanced and prolonged by increasing the days of stimulation and the number of stimulation trains per day over the left posterior parietal cortex.