BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Freezing of gait(FOG)is a confirmed disabling gait disorder in Parkinson disease(PD).Resting-state functional MRI(rs-fMRI)can reflect brain functional connectivity(FC)under resting-state,hence being helpful to reveal the pathophysiological mechanisms of FOG.The processes of rs-MRI brain networks for PD complicated with FOG were reviewed in this article.

BACKGROUND: Epilepsy accounts for a significant portion of the global disease burden. However, little is known about the disease burden of epilepsy in China and its provinces. METHODS: We assessed the burden of epilepsy in China and its provinces, municipalities, and autonomous regions from 1990 to 2019. Burden was measured as incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs), by age, sex, year, and province. We used the Socio-Demographic Index (SDI) to determine the association between the provincial development level and age-standardized DALY rates of epilepsy from 1990 to 2019. RESULTS: In 2019, epilepsy caused 1367.51 thousand (95% uncertainty interval [UI]: 979.92-1837.61 thousand) DALYs, and the age-standardized DALY rate was 99.77 (95% UI: 71.33-133.52)/100,000. The age-standardized incidence and prevalence rates for epilepsy in China were 24.65/100,000 and 219.69/100,000, increased by 45.00% (95% UI: 8.03-98.74%) and 35.72% (95% UI: 0.47-86.19%) compared with that in 1990, respectively. From 1990 to 2019, the proportion of DALY caused by epilepsy in the age group under 25 years steadily decreased. The proportion of DALYs caused by epilepsy in people aged 50 years and over increased from 9.45% and 10.22% in 1990 to 29.01% and 32.72% for male and female individuals in 2019, respectively. The highest age-standardized mortality rates were seen in Tibet (4.26 [95% UI: 1.43-5.66]/100,000), Qinghai (1.80 [95% UI: 1.15-2.36]/100,000), and Yunnan (1.30 [95% UI: 0.88-1.62]/100,000), and the lowest mortality rates were in Guangdong (0.48 [95% UI: 0.39-0.64]/100,000), Zhejiang (0.56 [95% UI: 0.44-0.70]/100,000), and Shanghai (0.57 [95% UI: 0.41-0.73]/100,000). The age-standardized DALY rates across the country and in provinces, municipalities, and autonomous regions generally decreased as their SDI increased. CONCLUSIONS The disease burden of epilepsy is still heavy in China, especially in the western provinces. The incidence and prevalence of epilepsy increased between 1990 and 2019, and the burden of epilepsy in the elderly increases gradually. This study provides evidence on epilepsy prevention and care of different regions in China.
Aged ; Humans ; Male ; Female ; Middle Aged ; Adult ; Global Burden of Disease ; China/epidemiology* ; Quality-Adjusted Life Years ; Cost of Illness ; Epilepsy/epidemiology* ; Prevalence

Objective: To construct a scientific behavioral research of pasta matrix reaching task (PMRT) and comprehensively evaluate sensory-motor dysfunction caused by brain injury. Methods: Twenty-one SD rats were subjected to 14-days pasta matrix grasping training and then were randomly divided into model group (11 rats) and sham group (6 rats). Motor cortex ischemia was induced by injection of endothelin-1 in SD rats. The number of pasta grabed by the injured forelimb and the location in matrix were evaluated daily 7 days after surgery. The infarct volume was measured by Nissl staining at the 7 days, 14 days, and 28 days after stroke. Results: The number of pasta obtained by rats was reduced from (33.43±1.02) to (20.57±0.57) at 7 days post stroke in model group, and then increased to (26.85±0.98) at 28 days post stroke, although there was a significant difference between sham group(32.33±1.45) and ischemic group (t=3.198, P<0.05). The frequency of retrieval from each slot of the pasta matrix represented that sham group demonstrated a significant gain in performance in the antero quadrant of the matrix compared to ischemic rats by the fourth week after stroke.The stroke volume was decreased from (37.82±1.17)mm³ at 7 days post-stroke to (24.35±0.38)mm³ at 28 days post-stroke, indicating brain recovery from ischemic injury. Conclusion The pasta matrix reaching task can function as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies and focused rehabilitative training after stroke.

Objective To discuss the clinical effects of forward lateral malleolus perforator flap in the repair of skin and soft tissue defect of ankle or dorsal foot.Methods From November,2014 to June,2017,16 cases of skin and soft tissue defect in ankle or dorsal foot had been repaired,which were 11 males and 5 females,aged from 25to 58 years old(average,32.5 years).The rotation points were on proximal 5 cm of the lateral malleolus in 11 cases and on the level of tarsal sinus in 5 cases.The largest flap was 10.0 cm×18.0 cm and the smallest flap was 6.0 cm×4.0 cm.The color,thickness,texture,sensation,appearance,donor site shape and functional were followed-up after operation.Results All the 16 patients were followed-up from 1 to 24 months.The distal flap appeared dark in 1 case 2 days after operation,and blood supply was improved after stitches;One case was superficial necrosis and healed after dressing.All the flaps had good appearance and texture,no pigmentation,scar contracture,and so on.Conclusion The forward lateral malleolus perforator flaps have perforator constantly and the color,thickness are similar with the receiving areas,the rotation point could on proximal 5 cm of the lateral malleolus and on the level of tarsal sinus,which is a good method to repair skin and soft tissue defect of ankle or dorsal foot.

Objective: To evaluate theresult of Screwless Scarf osteotomy for the treatment of moderate to severe hallux valgus. Methods: From January 2016 to May 2017, 13 patients with 15 feet underwent Screwless (without internal fixation) Scarf osteotomy for the treatment of moderate to severe hallux valgus.The hallux valgus angle (HVA) and intermetatarsal angle(IMA) were compared before and after surgery.Clinical outcomes were assessed by American Orthopedic Foot and Ankle Society (AOFAS) scoring. Results: The mean follow-up was 6 months in all the patients(range, 2-12 months). HVA was decreased by 25.7°(form 38.8°preoperative to 13.1°postoperative). IMA was decreased by 9.6°(form 18.3°preoperative to 8.7°postoperative). AOFAS sore was increase by 39.7 points (45.7 points preoperative to 85.4 points). The incidence of excellence was 86.7%. Conclusions Satisfactory clinical outcomes can be achieved by screwless Scarf osteotomy for moderate or severe hallux valgus.However, strict indications and sufficient surgical skills are crucial.

Objective To evaluate the imaging changes of the arterial wall and lumen at the site of intracranial large artery lesions with high-resolution magnetic resonance imaging (HR-MRI) before and after Wingspan stent implantation.Methods From December 2013 to December 2014,9 patients with symptomatic intracranial arterial stenosis (stenosis rate:70%-99%) admitted to the Department of Interventional Neuroradiology,Xuanwu Hospital,Capital Medical University were enrolled retrospectively.The sites of the lesions included middle cerebral arteries,basilar artery,and intracranial segment of vertebral artery.Head 3D HR-MRI technique was used to analyze and compare the changes of the tube-wall enhancement areas in the lesion sites through image registration and matching.The consistency of stenosis rates measured by HR-MRI and DSA was compared through Pearson correlation analysis and Bland-Altman Plot.Results The success rate of technique was 100% without related complications.(1) After Wingspan stent implantation,the gadolinium enhancement in the vascular walls of the stenosis sites was decreased significantly compared with that before procedure.The area of enhancement decreased was 87±16% after stent implantation compared with before implantation,and the difference was statistically significant (t=2.325,P=0.049).(2) Before stent implantation,the mean stenosis rates of the HR-MRI and DSA measurements were 82±6% and 82±8% respectively,and the difference was not statistically significant (t=0.051,P=0.961);after procedure,the mean stenosis rates of HR-MRI and DSA measurements were 16±12% and 21±12% respectively,and the difference was not statistically significant (t=1.345,P=0.216).(3) The Pearson correlation coefficients of HR-MRI and DSA for stenosis rate measurement before and after stent implantation were 0.347 (P=0.361) and 0.545 (P=0.129) respectively.Bland-Altman statistical images showed that most of the data points were within the consistency limit (x-±1.96 s).Conclusions As an in vivo noninvasive imaging means,HR-MRI can be used to assess the changes of vascular walls of the lesion sites,the vascular lumen,and the original plaques after the intracranial stent release.It can also be used to evaluate the reconstruction of intracranial arterial walls.

Objective To investigate the impacts of pyruvate kinase M2 isoform (PKM2) silencing on the radiosensitivity of lung adenocarcinoma cell line (A549 cells) and the radiation synergy of xenografts, and to explore their mechanisms. Methods Plasmid pshRNA?PKM2 for interference with PKM2 expression was transfected into A549 cells, and empty vector?transfected cells and untransfected cells were set as con?trols. The silencing efficiency of pshRNA?PKM2 and the expression level of microtubule?associated protein 1 light chain 3(LC3) were measured by Western blot assay. The radiosensitizing effects in A549 cells and xen?ografts after PKM2 silencing were determined by colony?forming assay and xenografts growth curves. Autoph?agy formation in A549 cells and xenografts was analyzed by transmission electron microscopy, and the ex?pression level of PKM2 in xenografts was measured by immunohistochemistry. Comparison between groups was made by Student′s t?test, and the body weights of nude mice and xenograft volumes were subjected to a?nalysis of variance for continuous variables. Results Stable A549 cell lines transfected with pshRNA?PKM2 were successfully produced. Transfection with pshRNA?PKM2 significantly down?regulated PKM2 expression in A549 cells and xenografts (P= 0?? 001;P= 0?? 000). The sensitizer enhancement ratios for A549 cells and xenografts were 1?? 47 and 2?? 00, respectively. Interference with PKM2 expression enhanced radiation?in duced autophagy formation and significantly increased the ratio of LC 3 ? II / I ( P= 0.000 1 ) . Conclusions Silencing of PKM2 expression may enhance the radiosensitivity of A549 cells and xenografts by regulation of autophagy, which holds promise for becoming an effective radiosensitizing target for non?small cell lung canc?er, but still needs to be confirmed by further studies.

Estimating taxonomic content constitutes a key problem in metagenomic sequencing data analysis. However, extracting such content from high-throughput data of next-generation sequencing is very time-consuming with the currently available software. Here, we present CloudLCA, a parallel LCA algorithm that significantly improves the efficiency of determining taxonomic composition in metagenomic data analysis. Results show that CloudLCA (1) has a running time nearly linear with the increase of dataset magnitude, (2) displays linear speedup as the number of processors grows, especially for large datasets, and (3) reaches a speed of nearly 215 million reads each minute on a cluster with ten thin nodes. In comparison with MEGAN, a well-known metagenome analyzer, the speed of CloudLCA is up to 5 more times faster, and its peak memory usage is approximately 18.5% that of MEGAN, running on a fat node. CloudLCA can be run on one multiprocessor node or a cluster. It is expected to be part of MEGAN to accelerate analyzing reads, with the same output generated as MEGAN, which can be import into MEGAN in a direct way to finish the following analysis. Moreover, CloudLCA is a universal solution for finding the lowest common ancestor, and it can be applied in other fields requiring an LCA algorithm.
Algorithms ; Databases, Genetic ; Metagenomics ; Search Engine ; User-Computer Interface