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ObjectivesNon-invasive vagus nerve stimulation (nVNS) is an emerging neuromodulation technique in recent years, which plays a role in nervous system diseases, psychiatric diseases, and autoimmune diseases. However, there is currently no comprehensive analysis of all the literature published in this field. Therefore, in this article, a bibliometric analysis will be conducted on all the literature published in the field of nVNS in the past 20 years.MethodsAll articles and reviews published in this field from 2004 to 2023 were extracted from the WOS core database. VOSviewer 1.6.18.0, Scimago Graphica, CiteSpace 6.2.R2, and Excel 2021 were used to analyze the number of publications, participating countries, institutions, authors, references, and research hotspots in this field.ResultsA total of 843 articles were included in the bibliometric analysis of nVNS. Over the past 20 years, the number of publications in this field has gradually increased, reaching a peak in 2023. The United States and China ranked top two in terms of publication volume, and institutions from these two countries also ranked high in terms of publication volume, citation count, and collaboration intensity. Rong Peijing is the author with the most publications, while Bashar W Badran is the most cited author. Articles in the field of nVNS were most frequently published in Frontiers in Neuroscience, while Brain Stimulation had the most citations. Currently, research hotspots in nVNS mainly focus on its application in diseases and related mechanisms.ConclusionWe conducted a comprehensive analysis of the field of nVNS, clarifying the previous research directions, which is helpful to expand its indications and promote clinical application.

Abstract Background Post-stroke cognitive impairment (PSCI) is the focus and difficulty of poststroke rehabilitation intervention with an incidence of up to 61%, which may be related to the deterioration of cerebrovascular function. Computer-aided cognitive training (CACT) can improve cognitive function through scientific training targeting activated brain regions, becoming a popular training method in recent years. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, can regulate the cerebral vascular nerve function, and has an effect on the rehabilitation of cognitive dysfunction after stroke. This study examined the effectiveness of both CACT and tDCS on cognitive and cerebrovascular function after stroke, and explored whether CACT combined with tDCS was more effective. Methods A total of 72 patients with PSCI were randomly divided into the conventional cognitive training (CCT) group (n = 18), tDCS group (n = 18), CACT group (n = 18), and CACT combined with tDCS group (n = 18). Patients in each group received corresponding 20-minute treatment 15 times a week for 3 consecutive weeks. Montreal Cognitive Assessment (MoCA) and the Instrumental Activities of Daily Living Scale (IADL) were used to assess patients’ cognitive function and the activities of daily living ability. Transcranial Doppler ultrasound (TCD) was used to assess cerebrovascular function, including cerebral blood flow velocity (CBFV), pulse index (PI), and breath holding index (BHI). These outcome measures were measured before and after treatment. Results Compared with those at baseline, both the MoCA and IADL scores significantly increased after treatment (P

Abstract Background Chronic neck pain (CNP) is a common public health problem that affects daily living activities and quality of life. There is biomechanical interdependence between the neck and scapula. Studies have shown that shoulder blade function might be related to chronic neck pain. We therefore evaluated the effects of scapular targeted therapy on neck pain and function in patients with CNP. Methods Databases, including MEDLINE (via PubMed), EMBASE (via Ovid), Ovid, Web of Science, and Scopus, were systematically searched for randomized controlled trials published in English investigating treatment of the scapula for CNP before July 16, 2023. Results A total of 313 participants were included from 8 RCTs. Compared with those in the control group, the intervention in the scapular treatment group exhibited greater improvement in pain intensity (standardized mean difference (SMD) = 2.55; 95% CI = 0.97 to 4.13; P = 0.002), with moderate evidence. Subgroup analysis for pain intensity revealed a significant difference between the sexes, with only the female population (SMD = 6.23, 95% CI = 4.80 to 7.65) showing better outcomes than those with both sexes (SMD = 1.07, 95% CI = 0.57 to 1.56) (p

The spaceborne turntable is a piece of precision optical equipment utilized for monitoring space information and facilitating laser communication. The measurement accuracy of optical instruments is correlated to some extent with the mechanical properties of the structure. Addressing the design challenge posed by the U-frame in the spaceborne optoelectronic tracking and pointing turntable, this paper proposes a multi-constraint topology optimization method utilizing Abaqus/CAE and TOSCA. This method offers insights for U-frame design and has undergone scientific validation. Initially, the empirical design structure is established, optimization design areas are defined, and the initial model undergoes pre-processing in Abaqus/CAE. Subsequently, conceptual and mathematical models for topology optimization are developed, with the objective of minimizing structural compliance (thereby maximizing stiffness), and including constraints related to volume fraction, first-order natural frequency, and stress. Utilizing TOSCA, the U-frame topology optimization design is finalized, resulting in an optimized conceptual model. A comparative analysis of the optimized design against the empirical design structure demonstrates a significant 27.53% reduction in maximum stress, enhanced static stiffness, an increase of 11.48% in the first natural frequency, and a 4.3% reduction in mass. Moreover, the turntable that utilizes the optimized design structure not only meets reliability requirements in spacecraft structural design but also provides a stable platform for precise optical load alignment. The static and dynamic performance of the optimized U-frame has been enhanced, effectively mitigating the impact of external excitation on optical instrument measurement accuracy and meeting the lightweight design requirements for the U-frame, thus demonstrating the efficacy of the topology optimization method. This research offers valuable insights into U-frame design for spaceborne optoelectronic tracking and pointing turntables and carries significant guiding implications.

Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity. Here, we describe a chimeric costimulatory antigen receptor (CoStAR) comprised of FRα-specific scFv linked to CD28 and CD40 intracellular signaling domains. CoStAR signaling alone does not activate T cells, while the combination of TCR and CoStAR signaling enhances T cell activity resulting in less differentiated T cells, and augmentation of T cell effector functions, including cytokine secretion and cytotoxicity. CoStAR activity resulted in superior T cell proliferation, even in the absence of exogenous IL-2. Using an in vivo transplantable tumor model, CoStAR was shown to improve T cell survival after transfer, enhanced control of tumor growth, and improved host survival. CoStAR could be reliably engineered into TIL from multiple tumor indications and augmented TIL activity against autologous tumor targets both in vitro and in vivo. CoStAR thus represents a general approach to improving TIL therapy with synthetic costimulation.

Abstract Background The accuracy of transvaginal digital examination in determining foetal head position is not high enough. This study aimed to evaluate whether an additional training on our new theory could improve the diagnostic accuracy of the foetal head position. Methods This was a prospective study conducted at a 3a grade hospital. The study included 2 residents in their first year of training in obstetrics without prior experience in transvaginal digital examination. In the observational study, 600 pregnant women without contraindications to vaginal delivery were included. Two residents were simultaneously trained in the theory of traditional vaginal examination, but resident B received an additional theoretical training program. The pregnant women were randomly assigned to have the foetal head position examined by resident A and resident B. The foetal head position was then confirmed by ultrasound, which was performed by the main investigator. After 300 examinations were independently performed by each resident, the accuracy of foetal head position and perinatal outcomes were compared between the two groups. Results During the 3-month period, 300 post training transvaginal digital examinations were performed by each resident in our hospital. The two groups were found to be homogeneous for age at delivery, BMI before delivery, parity, gestational weeks at delivery, the rate of epidural analgesia, foetal head position, presence of caput succedaneum, presence of moulding and foetal head station(p > 0.05). The diagnostic accuracy of head position by digital examination was higher for resident B, who was subjected to an additional theoretical training program, than for resident A (75.00% vs. 60.67%, p 0.05). Conclusion An additional theoretical training program for residents increased the accuracy of vaginal assessment of foetal head position. Trial registration Registered at Chinese Clinical Trial Registry Platform (ChiCTR2200064783), October 17, 2022. https://www.chictr.org.cn/edit.aspx?pid=182857&htm=4

Abstract Background Community-based exercise is a continuation and complement to inpatient rehabilitation for Parkinson's disease and does not require a professional physical therapist or equipment. The effects, parameters, and forms of each exercise are diverse, and the effect is affected by many factors. A meta-analysis was conducted to determine the effect and the best parameters for improving motor symptoms and to explore the possible factors affecting the effect of community-based exercise. Methods We conducted a comprehensive search of six databases: PEDro, PubMed/Medline, CENTRAL, Scopus, Embase, and WOS. Studies that compared community-based exercise with usual care were included. The intervention mainly included dance, Chinese martial arts, Nordic walking, and home-based exercise. The primary outcome measure was the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) score. The mean difference (95% CI) was used to calculate the treatment outcomes of continuous outcome variables, and the I2 statistic was used to estimate the heterogeneity of the statistical analysis. We conducted subgroup analysis and meta-regression analysis to determine the optimal parameters and the most important influencing factors of the exercise effect. Results Twenty-two studies that enrolled a total of 809 subjects were included in the analysis. Exercise had a positive effect on the UPDRS-III (MD = -5.83; 95% CI, -8.29 to -3.37), Timed Up and Go test (MD = -2.22; 95% CI -3.02 to -1.42), UPDRS ((MD = -7.80; 95% CI -10.98 to -6.42), 6-Minute Walk Test (MD = 68.81; 95% CI, 32.14 to 105.48), and Berg Balance Scale (MD = 4.52; 95% CI, 2.72 to 5.78) scores. However, the heterogeneity of each included study was obvious. Weekly frequency, age, and duration of treatment were all factors that potentially influenced the effect. Conclusions This meta-analysis suggests that community-based exercise may benefit motor function in patients with PD. The most commonly used modalities of exercise were tango and tai chi, and the most common prescription was 60 min twice a week. Future studies should consider the influence of age, duration of treatment, and weekly frequency on the effect of exercise. PROSPERO trial registration number CRD42022327162.

Transcutaneous vagus nerve stimulation, which involves the application of electrical currents to the cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve, may be a potential treatment for improving cognitive dysfunction. taVNS may improve cognitive performance in healthy adults, and fewer studies have been performed on the effects of tcVNS on cognition in healthy subjects. We conducted a randomized, single-blind, crossover-controlled trial to investigate the effects of tcVNS stimulation on cognitive function and neural activity in the brains of healthy adults. This study provides support for further tcVNS studies for the treatment of cognitive impairment. Twenty-one participants were randomly divided into two groups, A and B. Group A received tcVNS first and then sham-tcVNS, while group B received the intervention in the reverse order, receiving sham stimulation first and then true stimulation. All subjects were required to perform cognitive function tests before and after receiving intervention, and functional magnetic resonance imaging (fMRI) was performed concurrently during the intervention. We hypothesized that tcVNS would have an effect on the cognitive performance of the subjects and alter the neural activity of the brain. The present study showed that tcVNS had beneficial effects on cognitive performance, mainly improving memory and language skills and attention. tcVNS intervention produced significant spontaneous neural activity in the calcarine gyrus, fusiform gyrus, lingual gyrus, and parahippocampal gyrus of the brain. Future tcVNS/fMRI trials will need to explore the effects of changes in stimulus parameters on the neural activity response of the brain.

IntroductionCognitive impairment is the main clinical feature after traumatic brain injury (TBI) and is usually characterized by attention deficits, memory loss, and decreased executive function. Vagus nerve stimulation (VNS) has been reported to show potential improvement in the cognition level after traumatic brain injury in clinical and preclinical studies. However, this topic has not yet been systematically reviewed in published literature. In this study, we present a systematic review and meta-analysis of the effects of VNS on cognitive function in animal models of TBI and their underlying mechanisms.MethodsWe performed a literature search on PubMed, PsycINFO, Web of Science, Embase, Scopus, and Cochrane Library from inception to December 2021 to identify studies describing the effects of VNS on animal models of TBI.ResultsOverall, nine studies were identified in animal models (36 mice, 268 rats, and 27 rabbits). An analysis of these studies showed that VNS can improve the performance of TBI animals in behavioral tests (beam walk test: SMD: 4.95; 95% confidence interval [CI]: 3.66, 6.23; p < 0.00001) and locomotor placing tests (SMD: –2.39; 95% CI: –4.07, –0.71; p = 0.005), whereas it reduced brain edema (SMD: –1.58; 95% CI: –2.85, –0.31; p = 0. 01) and decrease TNF-α (SMD: –3.49; 95% CI: –5.78, –1.2; p = 0.003) and IL-1β (SMD: –2.84; 95% CI: –3.96, –1.71; p < 0.00001) expression level in the brain tissue. However, the checklist for SYRCLE showed a moderate risk of bias (quality score between 30% and 60%), mainly because of the lack of sample size calculation, random assignment, and blinded assessment.ConclusionThe present review showed that VNS can effectively promote cognitive impairment and neuropathology in animal models of TBI. We hope that the results of this systematic review can be applied to improve the methodological quality of animal experiments on TBI, which will provide more important and conclusive evidence on the clinical value of VNS. To further confirm these results, there is a need for high-quality TBI animal studies with sufficient sample size and a more comprehensive outcome evaluation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290797, identifier: CRD42021290797.

BackgroundCoronavirus disease 2019 (COVID-19) significantly impacts physical, psychological, and social functioning and reduces quality of life, which may persist for at least 6 months. Given the fact that COVID-19 is a highly infectious disease and therefore healthcare facilities may be sources of contagion, new methods avoiding face-to-face contact between healthcare workers and patients are urgently needed. Telerehabilitation is the provision of rehabilitation services to patients at a distance via information and communication technologies. However, high-quality evidence of the efficacy of telerehabilitation for COVID-19 is still lacking. This meta-analysis aimed to investigate the efficacy of telerehabilitation for patients with and survivors of COVID-19.MethodsWe searched the Cochrane Library, EMBASE, Medline (via PubMed), PEDro, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from January 1st, 2020 to April 30th, 2022 for randomized controlled trials published in English, which aimed to evaluate the efficacy of telerehabilitation vs. face-to-face rehabilitation, usual care, or no treatment for COVID-19. Methodological quality and overall evidence quality of the included studies were assessed. The statistical reliability of the data was quantified using the trial sequential analysis.ResultsSeven randomized controlled trials with eight comparisons were included and all of them were used for meta-analysis. The meta-analyses of absolute values showed the superiority of telerehabilitation over no treatment or usual care for dyspnea (Borg scale: mean difference = −1.88, −2.37 to −1.39; Multidimensional dyspnea-12: mean difference = −3.70, −5.93 to −1.48), limb muscle strength (mean difference = 3.29; 2.12 to 4.47), ambulation capacity (standardized mean difference = 0.88; 0.62 to 1.14), and depression (mean difference = −5.68; −8.62 to −2.74). Significant improvement in these variables persisted in the meta-analyses of change scores. No significant difference was found in anxiety and quality of life. No severe adverse events were reported in any of the included studies.ConclusionsModerate- to very low-quality evidence demonstrates that telerehabilitation may be an effective and safe solution for patients with and survivors of COVID-19 in dyspnea, lower limb muscle strength, ambulation capacity, and depression. Further well-designed studies are required to evaluate the long-term effects, cost-effectiveness, and satisfaction in larger samples.

Despite the remarkable success of chimeric antigen receptor-modified T (CAR-T) cell therapy for blood malignancies, the clinical efficacy of this novel therapy in solid tumor treatment is largely limited by the immunosuppressive tumor microenvironment (TME). For instance, immune checkpoints (e.g., programmed cell death protein 1 [PD-1]/programmed death ligand 1 [PD-L1]) in TME play an important role in inhibiting T cell proliferation and functions. Transforming growth factor β (TGF)-β secreted by cancer cells in TME induces regulatory T cells (Tregs) and inhibits cytotoxic T cells. To overcome the inhibitory effect of immune checkpoints, we have previously engineered CAR-T cells to secrete anti-PD-1 to block the PD-1/PD-L1 pathway activity, a step demonstrating superior antitumor efficacy compared with conventional CAR-T cells. In this study, we engineered CAR-T cells that secrete bispecific trap protein co-targeting PD-1 and TGF-β, with the aim of further improving antitumor immunity. Compared with conventional CAR-T cells and anti-PD-1-secreting CAR-T cells, data from in vitro and in vivo experiments showed that CAR-T cells with trap protein secretion further attenuated inhibitory T cell signaling, enhanced T cell persistence and expansion, and improved effector function and resistance to exhaustion. In the xenograft mouse model, CAR-T cells with trap protein secretion exhibited significantly enhanced antitumor immunity and efficacy. With these observations, we demonstrate the potential of trap protein self-secreting CAR-T cells as a potent therapy for solid tumors.

Because of their wide detection range and rich functions, autonomous underwater vehicles (AUVs) are widely used for observing the marine environment, for exploring natural resources, for security and defense purposes, and in many other fields of interest. Compared with a single AUV, a multi-AUV formation can better perform various tasks and adapt to complex underwater environments. With changes in the mission or environment, a change in the UAV formation may also be required. In the last decade, much progress has been made in the transformation of multi-AUV formations. In this paper, we aim to analyze the core concepts of multi-AUV formation transformation; summarize the effects of the AUV model, underwater environment, and communication between AUVs within formations on formation transformation; and elaborate on basic theories and implementation approaches for multi-AUV formation transformation. Moreover, this overview includes a bibliometric analysis of the related literature from multiple perspectives. Finally, some challenging issues and future research directions for multi-AUV formation transformation are highlighted.

Abstract Background Clinically, bromadiolone poisoning is characterized by severe bleeding complications in various organs and tissues. Bromadiolone-induced toxic encephalopathy is extremely rare. Here, we report a special case of bromadiolone-induced reversible toxic encephalopathy in a patient who had symmetrical lesions in the deep white matter. Case presentation A 23-year-old woman mainly presented with dizziness, fatigue, alalia and unsteady gait after the ingestion of bromadiolone. The laboratory examinations showed normal coagulation levels. Brain magnetic resonance imaging (MRI) showed apparent diffusion restriction in the bilateral deep white matter. The clinical manifestations and MRI alterations were reversible within one month of treatment with vitamin K. The neuropsychological assessment showed no neurodegenerative changes at the 2-year follow-up. Conclusion With the increased use of bromadiolone as a rodenticide, more cases of ingestion have been reported annually over the past several years. Bromadiolone-induced toxic encephalopathy has no special clinical manifestations and is potentially reversible with timely treatment. Because of the reversible restricted diffusion on diffusion-weighted images (DWI) and low apparent diffusion coefficient (ADC) values, transient intramyelinic cytotoxic oedema is thought to be the cause rather than persistent ischaemia. The underlying pathophysiological mechanism is still unknown and may be coagulant-independent. This clinical case extends the current knowledge about neurotoxicity in cases of bromadiolone poisoning and indicates that MRI is useful for the early detection of bromadiolone-induced toxic encephalopathy.

Cognitive impairment, defined as a decline in memory and executive function, is one of the most severe complications of traumatic brain injury (TBI). Patients with TBI are often unable to return to work due to cognitive impairment and their overall quality of life is reduced. TBI can bring a serious economic burden to patient's families and to society. Reported findings on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving cognitive impairment following TBI are inconsistent. The purpose of the proposed study is to investigate whether rTMS can improve memory and executive function in patients with TBI. Herein, we propose a prospective randomized placebo-controlled (rTMS, sham rTMS, cognitive training), parallel-group, single-center trial. 36 participants with a TBI occurring at least 6 months prior will be recruited from an inpatient rehabilitation center. Participants will be randomly assigned to the real rTMS, sham rTMS, or cognitive training groups with a ratio of 1:1:1. A 20-session transcranial magnetic stimulation protocol will be applied to the left and right dorsolateral prefrontal cortices (DLPFC) at frequencies of 10 Hz and 1 Hz, respectively. Neuropsychological assessments will be performed at four time points: baseline, after the 10th rTMS session, after the 20th rTMS session, and 30 days post-intervention. The primary outcome is change in executive function assessed using the Shape Trail Test (STT). The secondary outcome measures are measures from neuropsychological tests: the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test (BVMT), the Digit Span Test (DST). We report on positive preliminary results in terms of improving memory and executive function as well as beneficial changes in brain connectivity among TBI patients undergoing rTMS and hypothesize that we will obtain similar results in the proposed study.

Transcutaneous electrical nerve stimulation (TENS) is a non-invasive therapeutic intervention that is typically used for many years to treat chronic pain in patients who are refractory to pain medications. However, evidence of the efficacy of TENS treatment for neuropathic pain is lacking in humans. To further understand the efficacy of TENS under various intervention conditions and illuminate the current circumstance and future research directions, we systematically reviewed animal studies investigating the efficacy of TENS in relieving pain in neuropathic pain rodent models. We searched the Cochrane Library, EMBASE, MEDLINE (via PubMed), and Web of Science and identified 11 studies. Two meta-analyses were performed. The first meta-analysis showed that a single TENS treatment was capable of temporarily ameliorating neuropathic pain when compared to control groups with a significant effect (standardized mean difference: 1.54; 95% CI: 0.65, 2.42; p = 0.0007; I2 = 58%). Significant temporary alleviation in neuropathic pain intensity was also observed in the meta-analysis of repetitive TENS (standardized mean difference: 0.85; 95% CI: 0.31, 1.40; p = 0.002; I2 = 75%). Subgroup analysis showed no effect of the timing of the application of TENS (test for subgroup difference, p = 0.47). Leave-one-out sensitivity analyses suggested that no single study had an outsized effect on the pooled estimates, which may partly prove the robustness of these findings. Other stratified analyses were prevented by the insufficient number of included studies. Overall, current data suggest that TENS might be a promising therapy to ameliorate neuropathic pain. However, the high risk of bias in the included studies suggests that cautions must be considered when interpreting these findings and it is not reasonable to directly generalize the results obtained from animal studies to clinical practice. Future studies should pay more attention to improving the quality of study design and reporting, thereby facilitating the understanding of mechanisms underlying TENS treatment, reducing more potentially unsuccessful clinical trials, and optimizing the efficacy of TENS for people with neuropathic pain.

Infarct size is associated with stroke severity in clinical studies, so reducing it has become an important target and research hotspot in the treatment of ischemic stroke. Some preclinical studies have shown transcranial direct current stimulation (tDCS) reduced infarct size and improved neurological deficit, but others have not found beneficial effects. Besides, the optimal pattern of tDCS for ischemic stroke remains largely unknown. To shed light on the current circumstance and future research directions, the systematic review evaluated the effect of different tDCS paradigms in reducing infarct size and improving neurological deficit in rodent models of ischemic stroke and assessed the methodological quality of current literature. We searched the MEDLINE (via PubMed), EMBASE, Web of Science, and Scopus from their inception to August 18, 2021, to identify studies evaluating the effects of tDCS in rodent models of ischemic stroke. Eight studies were included, of which seven studies were included in the meta-analysis. The results showed cathodal tDCS, rather than anodal tDCS, reduced infarct size mainly measured by tetrazolium chloride and magnetic resonance imaging (standardized mean difference: −1.13; 95% CI: −1.72, −0.53; p = 0.0002) and improved neurological deficit assessed by a modified neurological severity score (standardized mean difference: −2.10; 95% CI: −3.78, −0.42; p = 0.01) in an early stage of focal ischemic stroke in rodent models. Subgroup analyses showed effects of cathodal tDCS on infarct size were not varied by ischemia duration (ischemia for 1, 1.5, and 2 h or permanent ischemia) and anesthesia (involving isoflurane and ketamine). The overall quality of studies included was low, thus the results must be interpreted cautiously. Published studies suggest that cathodal tDCS may be a promising avenue to explore for augmenting rehabilitation from focal ischemic stroke. Considering the methodological limitations, it is unreliable to blindly extrapolate the animal data to the clinical practice. Future research is needed to investigate the mechanism of tDCS in a randomized and blinded fashion in clinically relevant stroke models, such as elderly animals, female animals, and animals with comorbidities, to find an optimal treatment protocol.

Immunoassay for detailed analysis of immune−cancer intercellular interactions can achieve more promising diagnosis and treatment strategies for cancers including nasopharyngeal cancer (NPC). In this study, we report a microfluidic live−cell immunoassay integrated with a microtopographic environment to meet the rising demand for monitoring intercellular interactions in different tumor microenvironments. The developed assay allows: (1) coculture of immune cells and cancer cells on tunable (flat or micrograting) substrates, (2) simultaneous detection of different cytokines in a wide working range of 5–5000 pg/mL, and (3) investigation of migration behaviors of mono- and co-cultured cells on flat/grating platforms for revealing the topography-induced intercellular and cytokine responses. Cytokine monitoring was achieved on-chip by implementing a sensitive and selective microbead-based sandwich assay with an antibody on microbeads, target cytokines, and the matching fluorescent-conjugated detection antibody in an array of active peristaltic mixer-assisted cytokine detection microchambers. Moreover, this immunoassay requires a low sample volume down to 0.5 μL and short assay time (30 min) for on-chip cytokine quantifications. We validated the biocompatibility of the co-culture strategy between immune cells and NPC cells and compared the different immunological states of undifferentiated THP-1 monocytic cells or PMA-differentiated THP-1 macrophages co-culturing with NP460 and NPC43 on topographical and planar substrates, respectively. Hence, the integrated microfluidic platform provides an efficient, broad-range and precise on-chip cytokine detection approach, eliminates the manual sampling procedures and allows on-chip continuous cytokine monitoring without perturbing intercellular microenvironments on different topographical ECM substrates, which has the potential of providing clinical significance in early immune diagnosis, personalized immunotherapy, and precision medicine.

Staphylococcus aureus (S. aureus) is the most common pathogen causing infections from skin to systemic infections. The success of S. aureus infections can partially be attributed to its antibiotic resistance and to its ability to form biofilm. An increasing prevalence of methicillin-resistant S. aureus (MRSA) becomes a global public health problem in recent decades. Here, the effects of tea catechin extracts on the growth and biofilm formation of three MRSA strains were investigated. The results revealed that tea catechin extracts potently suppressed MRSA growth, and the minimal inhibitory concentration of tea catechin extracts against these MRSA strains was 0.1 g/L. Then, tea catechin extracts inhibited biofilm formation of these strains in a dose-dependent manner measured with a colorimetric method, and the inhibitory effect was also demonstrated by scanning electron microscopy assay. Moreover, adhesin genes biofilm-associated protein (bap), bone sialoprotein-binding protein (bbp), collagen-binding protein (cna), clumping factors A (clfA), fibronectin binding protein A and B (fnbA and fnbB), and intercellular adhesion gene BC (icaBC) were scanned, and the results shown that fnbA and icaBC were present in these three strains. Furthermore, tea catechin extracts depressed fnbA and icaBC expression in the strains. Therefore, inhibition of biofilm formation by tea catechin extracts probably was associated with downregulation of fnbA and icaBC expression in these strains.

ObjectiveTo estimate the prevalence of disability and anxiety in Covid-19 survivors at discharge from hospital and analyze relative risk by exposures.DesignMulti-center retrospective cohort study.SettingTwenty-eight hospitals located in eight provinces of China.MethodsA total of 432 survivors with laboratory-confirmed SARS CoV-2 infection participated in this study. At discharge, we assessed instrumental activities of daily living (IADL) with Lawton's IADL scale, dependence in activities of daily living (ADL) with the Barthel Index, and anxiety with Zung's self-reported anxiety scale. Exposures included comorbidity, smoking, setting (Hubei vs. others), disease severity, symptoms, and length of hospital stay. Other risk factors considered were age, gender, and ethnicity (Han vs. Tibetan).ResultsPrevalence of at least one IADL problem was 36.81% (95% CI: 32.39-41.46). ADL dependence was present in 16.44% (95% CI: 13.23-20.23) and 28.70% (95% CI: 24.63-33.15) were screened positive for clinical anxiety. Adjusted risk ratio (RR) of IADL limitations (RR 2.48, 95% CI: 1.80-3.40), ADL dependence (RR 2.07, 95% CI 1.15-3.76), and probable clinical anxiety (RR 2.53, 95% CI 1.69-3.79) were consistently elevated in survivors with severe Covid-19. Age was an additional independent risk factor for IADL limitations and ADL dependence; and setting (Hubei) for IADL limitations and anxiety. Tibetan ethnicity was a protective factor for anxiety but a risk factor for IADL limitations.ConclusionA significant proportion of Covid-19 survivors had disability and anxiety at discharge from hospital. Health systems need to be prepared for an additional burden resulting from rehabilitation needs of Covid-19 survivors.

Objective To explore the effect of motor relearning programme (MRP) on motor function recovery of patients with hemiplegia after acute stroke. Methods A total of 64 hemiplegic patients with acute stroke (duration ≤ 14 d) were randomly divided into 2 groups: control group (N = 32) and observation group (N = 32). Control group received routine drug therapy and conventional rehabilitation training, and observation group was treated by routine therapy and MRP training. Fugl-Meyer Assessment Scale - Balance (FMA - Balance), Modified Rivermead Mobility Index (MRMI) and modified Barthel Index (mBI) were used to assess the motor function of patients in both groups before and after treatment. Results All patients successfully completed the rehabilitation training without severe adverse events. A few patients felt fatigue occasionally after training and recovered after rest. Compared to before treatment, the FMA-Balance score (P = 0.000), MRMI score (P = 0.000) and mBI score (P = 0.000) after treatment in both groups were significantly increased. Compared to control group, the FMA-Balance score (P = 0.031), MRMI score (P = 0.013) and mBI score (P = 0.049) after treatment in observation group were significantly increased. Conclusions MRP training in the early stage of stroke is beneficial to the recovery of motor function of patients. DOI: 10.3969/j.issn.1672-6731.2017.03.007

Survivors of stroke commonly experience a different range of dysfunction, and recovery can be slow and incomplete, which lead to a serious and long-term impact on patients themselves and their families. Although the treatment of stroke patients relies mainly on rehabilitation intervention, but the rehabilitation needs of discharged patients are not fully met due to lots of restrictions, such as the lack of professional rehabilitation services, the difficulty and inconvenience in transportation from home to hospital, therefore their prognosis of rehabilitation are affected. At present a number of new rehabilitation technologies, including telerehabilitation (TR), virtual reality (VR), robotics, electronic textiles (E-textiles), etc., are coming into being and may solve these problems. This article tries to discuss the research progress of these new rehabilitation technologies, and provide a new perspective for the rehabilitation intervention of stroke patients. DOI: 10.3969/j.issn.1672-6731.2017.03.003

Myelination of axons is important for central nervous system function, but oligodendrocytes, which constitute CNS myelin, are vulnerable to excitotoxic injury and death. Although mature oligodendrocytes express functional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) and kainate-type glutamate receptors, the relative roles of these subtypes in excitotoxicity are not well understood. Using recently developed selective antagonists for subtypes of ionotropic non-NMDA receptors, we addressed this issue. By examining the pharmacological, biochemical, and morphologic features of kainite-induced excitotoxic death, we also determined whether it occurs by apoptosis, necrosis, or both. We conclude that when mature oligodendrocytes die after exposure to kainate: (1) AMPA receptors are the most important mediators, (2) kainate receptors play a smaller role, and (3) death occurs predominantly by necrosis, not apoptosis.

Stroke is the third leading cause of long-term disability. Effective stroke rehabilitation should be provided to patients with a moderate or severe stroke so as to achieve functional recovery. Also, stroke rehabilitation is moving towards more intense therapy models that incorporate technologies such as robotics and computer games. Evidence-based guidelines are useful for promoting the best possible clinical practices. This guideline summarises the modes of stroke rehabilitation in China—three-stage rehabilitation network, rehabilitation of stroke dysfunction, training for activities of daily living, stroke complications and rehabilitation care. The aim of this guideline was to provide a synopsis of best clinical practices in the stroke rehabilitation of adult patients in China.

Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity. Here, we describe a chimeric costimulatory antigen receptor (CoStAR) comprised of FRα-specific scFv linked to CD28 and CD40 intracellular signaling domains. CoStAR signaling alone does not activate T cells, while the combination of TCR and CoStAR signaling enhances T cell activity resulting in less differentiated T cells, and augmentation of T cell effector functions, including cytokine secretion and cytotoxicity. CoStAR activity resulted in superior T cell proliferation, even in the absence of exogenous IL-2. Using an in vivo transplantable tumor model, CoStAR was shown to improve T cell survival after transfer, enhanced control of tumor growth, and improved host survival. CoStAR could be reliably engineered into TIL from multiple tumor indications and augmented TIL activity against autologous tumor targets both in vitro and in vivo. CoStAR thus represents a general approach to improving TIL therapy with synthetic costimulation. [ABSTRACT FROM AUTHOR]