Functional near-infrared spectroscopy evidence of cognitive-motor interference in different dual tasks.

Dual tasks (DTs) combining walking with a cognitive task can cause various levels of cognitive-motor interference, depending on which brain resources are recruited in each case. However, the brain activation and functional connectivity underlying cognitive-motor interferences remain to be elucidated. Therefore, this study investigated the neural correlation during different DT conditions in 40 healthy young adults (mean age: 27.53 years, 28 women). The DTs included walking during subtraction or N-Back tasks. Cognitive-motor interference was calculated, and brain activation and functional connectivity were analysed. Portable functional near-infrared spectroscopy was utilized to monitor haemodynamics in the prefrontal cortex (PFC), motor cortex and parietal cortex during each task. Walking interference (decrease in walking speed during DT) was greater than cognitive interference (decrease in cognitive performance during DT), regardless of the type of task. Brain activation in the bilateral PFC and parietal cortex was greater for walking during subtraction than for standing subtraction. Furthermore, brain activation was higher in the bilateral motor and parietal and PFCs for walking during subtraction than for walking alone, but only increased in the PFC for walking during N-Back. Coherence between the bilateral lateral PFC and between the left lateral PFC and left motor cortex was significantly greater for walking during 2-Back than for walking. The PFC, a critical brain region for organizing cognitive and motor functions, played a crucial role in integrating information coming from multiple brain networks required for completing DTs. Therefore, the PFC could be a potential target for the modulation and improvement of cognitive-motor functions during neurorehabilitation.

Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression.

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.

Interpretation of vaginal metagenomic characteristics in different types of vaginitis.

Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain unclear. Here, metagenomic sequencing was applied to analyze the vaginal flora in patients with various forms of vaginitis, including cases with a clue cell proportion ranging from 1% to 20% (Clue1_20), bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC (VVC_BV). Our results identified Prevotella as an important biomarker between BV and Clue1_20. Moreover, a gradual decrease was observed in the relative abundance of shikimic acid metabolism associated with bacteria producing indole as well as a decline in the abundance of Gardnerella vaginalis in patients with BV, Clue1_20, and healthy women. Interestingly, the vaginal flora of patients in the VVC_BV group exhibited structural similarities to that of the VVC group, and its potentially functional characteristics resembled those of the BV and VVC groups. Finally, Lactobacillus crispatus was found in high abundance in healthy samples, greatly contributing to the stability of the vaginal environment. For the further study of L. crispatus, we isolated five strains of L. crispatus from healthy samples and evaluated their capacity to inhibit G. vaginalis biofilms and produce lactic acid in vitro to select the potential probiotic candidate for improving vaginitis in future clinical studies. Overall, we successfully identified bacterial biomarkers of different vaginitis and characterized the dynamic shifts in vaginal flora between patients with BV and healthy females. This research advances our understanding and holds great promise in enhancing clinical approaches for the treatment of vaginitis. IMPORTANCE: Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as Candida albicans and Gardnerella vaginalis. In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant Lactobacillus-producing rich lactic acid in the vagina provides a healthy acidic environment such as Lactobacillus crispatus. The metabolites of Lactobacillus can inhibit the colonization of pathogens. Here, we collected the vaginal samples of patients with bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC to discover the differences and relationships among the different kinds of vaginitis by metagenomic sequencing. Furthermore, because of the importance of L. crispatus in promoting vaginal health, we isolated multiple strains from vaginal samples of healthy females and chose the most promising strain with potential probiotic benefits to provide clinical implications for treatment strategies.

Cortical activation and brain network efficiency during dual tasks: An fNIRS study.

OBJECTIVE: Dual task (DT) is a commonly used paradigm indicative of executive functions. Brain activities during DT walking is usually measured by portable functional near infrared spectroscopy (fNIRS). Previous studies focused on cortical activation in prefrontal cortex and overlooked other brain regions such as sensorimotor cortices. This study is aimed at investigating the modulations of cortical activation and brain network efficiency in multiple brain regions from single to dual tasks with different complexities and their relationships with DT performance. METHODS: Forty-two healthy adults [12 males; mean age: 27.7 (SD=6.5) years] participated in this study. Participants performed behavioral tasks with portable fNIRS simultaneous recording. There were three parts of behavioral tasks: cognitive tasks while standing (serial subtraction of 3's and 7's), walking alone and DT (walk while subtraction, including serial subtraction of 3's and 7's). Cognitive cost, walking cost and cost sum (i.e., sum of cognitive and walking costs) were calculated for DT. Cortical activation, local and global network efficiency were calculated for each task. RESULTS: The cognitive cost was greater and the walking cost was less during DT with subtraction 3's compared with 7's (P's = 0.032 and 0.019, respectively). Cortical activation and network efficiency were differentially modulated among single and dual tasks (P's < 0.05). Prefrontal activation during DT was positively correlated with DT costs, while network efficiency was negatively correlated with DT costs (P's < 0.05). CONCLUSIONS: Our results revealed prefrontal over-activation and reduced network efficiency in individuals with poor DT performance. Our findings suggest that reduced network efficiency could be a possible mechanism contributing to poor DT performance, which is accompanied by compensatory prefrontal over-activation.

Electroencephalography oscillations can predict the cortical response following theta burst stimulation.

BACKGROUND: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. METHOD: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. RESULT: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. CONCLUSION: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

Red pandas with different diets and environments exhibit different gut microbial functional composition and capacity.

The red panda (Ailurus fulgens) is a distinctive mammal known for its reliance on a diet primarily consisting of bamboo. The gut microbiota and overall health of animals are strongly influenced by diets and environments. Therefore, conducting research to explore the taxonomical and functional variances within the gut microbiota of red pandas exposed to various dietary and environmental conditions could shed light on the dynamic complexities of their microbial communities. In this study, normal fecal samples were obtained from red pandas residing in captive and semi-free environments under different dietary regimes and used for metabolomic, 16S rRNA, and metagenomic sequencing analysis, with the pandas classified into four distinct cohorts according to diet and environment. In addition, metagenomic sequencing was conducted on mucus fecal samples to elucidate potential etiological agents of disease. Results revealed an increased risk of gastrointestinal diseases in red pandas consuming bamboo shoots due to the heightened presence of pathogenic bacteria, although an increased presence of microbiota-derived tryptophan metabolites appeared to facilitate intestinal balance. The red pandas fed bamboo leaves also exhibited a decrease in gut microbial diversity, which may be attributed to the antibacterial flavonoids and lower protein levels in leaves. Notably, red pandas residing in semi-free environments demonstrated an enriched gut microbial diversity. Moreover, the occurrence of mucus secretion may be due to an increased presence of species associated with diarrhea and a reduced level of microbiota-derived tryptophan metabolites. In summary, our findings substantiate the influential role of diet and environment in modulating the gut microbiota of red pandas, offering potential implications for improved captive breeding practices.

DNA methylation and transcriptome analysis reveal epigenomic differences among three macaque species.

Macaques (genus Macaca) are the most widely distributed non-human primates, and their evolutionary history, gene expression profiles, and genetic differences have been extensively studied. However, the DNA methylomes of macaque species are not available in public databases, which hampers understanding of epigenetic differences among macaque species. Epigenetic modifications can potentially affect development, physiology, behavior, and evolution. Here, we investigated the methylation patterns of the Tibetan macaque (M. thibetana; TM), Chinese rhesus macaque (M. mulatta lasiota; CR), and crab-eating macaque (M. fascicularis; CE) through whole-genome bisulfite sequencing from peripheral blood. We compared genome-wide methylation site information for the three species. We identified 12,128 (CR vs. CE), 59,165 (CR vs. TM), and 39,751 (CE vs. TM) differentially methylated regions (DMRs) in the three macaques. Furthermore, we obtained the differentially expressed genes (DEGs) among the three macaque species. The differences between CR and CE were smaller at both the methylome and transcriptome levels than compared with TM (CR vs. TM and CE vs. TM). We also found a change in the density of single nucleotide mutations in DMRs relative to their flanking regions, indicating a potential mechanism through which genomic alterations may modulate methylation landscapes, thereby influencing the transcriptome. Functional enrichment analyses showed the DMR-related genes were enriched in developmental processes and neurological functions, such as the growth hormone-related pathway, insulin secretion pathway, thyroid hormone synthesis pathway, morphine addiction, and GABAergic synapses. These differences may be associated with variations in physiology and habitat among the macaques. Our study provides one of the first genome-wide comparisons of genetic, gene expression, and epigenetic variations across different macaques. Our results should facilitate further research on comparative genomic and genetic differences in macaque species.

Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

Oral frailty: A concept analysis.

AIM: To clarify the concept of oral frailty to provide a clear and standardized conceptual basis for further research in older people. DESIGN: Rodgers and Knafl's evolutionary concept analysis approach. METHODS: The narrative analysis detailedly extracted and synthesized the attributes of oral frailty, as well as its antecedents, consequences and related terms under the guidance of Rodgers' evolutionary method. DATA SOURCES: Multiple databases including Pubmed, CINAHL and Cochrane were searched using selected search terms 'oral frail*', 'oral health' and 'aged' respectively. Articles written between 2013 and 2023 were included, and grey literature was excluded. RESULTS: A total of 32 articles were included for further analysis and synthesis. The attributes of oral frailty were hypofunction, predisposing in nature, non-specific and multidimensional. Antecedents of prefrailty were classified into four categories, namely, sociodemographic characteristics, comorbidity, physical function and psychosocial factors. Consequences of oral frailty include three themes: increased risk of adverse outcomes, poor nutritional status and possibility of social withdrawal. Related terms that had shared attributes with oral frailty were oral health, functional dentition, oral hypofunction and deterioration of oral function. CONCLUSIONS: Oral frailty is an age-related phenomenon reflected in decreased oral function. The findings of this concept analysis are conducive to understanding and clarifying the oral frailty, which can help clinicians or other healthcare providers to consider how to distinguish oral frailty in older adults and further promote the development of this field. IMPACT: Oral frailty is increasingly recognized as an age-related phenomenon reflected in decreased oral function. As it is newly proposed, no consensus has been reached regarding the theoretical and operational concept of it. Through clarifying the concept, this paper will guide future healthcare research on oral frailty regarding the influencing factors, mechanisms and interventions, thus raising the awareness with regard to oral health among older adults. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: In the context of older adults, oral frailty is a concept that requires further research to guide future theoretical development, and the influencing factors, mechanisms and interventions need to be further studied. Raise awareness with regard to oral health among older people and more attention will be paid to the early identification and intervention of oral frailty, so as to further improve the quality of life of older adults.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.

Neurophysiological characterization of stroke recovery: A longitudinal TMS and EEG study.

AIMS: Understanding the neural mechanisms underlying stroke recovery is critical to determine effective interventions for stroke rehabilitation. This study aims to systematically explore how recovery mechanisms post-stroke differ between individuals with different levels of functional integrity of the ipsilesional corticomotor pathway and motor function. METHODS: Eighty-one stroke survivors and 15 age-matched healthy adults participated in this study. We used transcranial magnetic stimulation (TMS), electroencephalography (EEG), and concurrent TMS-EEG to investigate longitudinal neurophysiological changes post-stroke, and their relationship with behavioral changes. Subgroup analysis was performed based on the presence of paretic motor evoked potentials and motor function. RESULTS: Functional connectivity was increased dramatically in low-functioning individuals without elicitable motor evoked potentials (MEPs), which showed a positive effect on motor recovery. Functional connectivity was increased gradually in higher-functioning individuals without elicitable MEP during stroke recovery and influence from the contralesional hemisphere played a key role in motor recovery. In individuals with elicitable MEPs, negative correlations between interhemispheric functional connectivity and motor function suggest that the influence from the contralesional hemisphere may be detrimental to motor recovery. CONCLUSION: Our results demonstrate prominent clinical implications for individualized stroke rehabilitation based on both functional integrity of the ipsilesional corticomotor pathway and motor function.

Research Progress on the Mechanism of Anti-Tumor Immune Response Induced by TTFields.

Tumor treating fields (TTFields), a biophysical therapy technology that uses alternating electric fields to inhibit tumor proliferation, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of newly diagnosed or recurrent glioblastomas (GBM) and malignant pleural mesotheliomas (MPM). Clinical trials have confirmed that TTFields are effective in slowing the tumor growth and prolonging patient survival. In recent years, many researchers have found that TTFields can induce anti-tumor immune responses, and their main mechanisms include upregulating the infiltration ratio and function of immune cells, inducing the immunogenic cell death of tumor cells, modulating immune-related signaling pathways, and upregulating the expression of immune checkpoints. Treatment regimens combining TTFields with tumor immunotherapy are emerging as a promising therapeutic approach in clinical practice. Given the increasing number of recently published studies on this topic, we provide an updated review of the mechanisms and clinical implications of TTFields in inducing anti-tumor immune responses. This review not only has important reference value for an in-depth study of the anticancer mechanism of TTFields but also provides insights into the future clinical application of TTFields.

Temporal and spatial differences in the vaginal microbiome of Chinese healthy women.

Background: Up the reproductive tract, there are large differences in the composition of vaginal microbes. Throughout the menstrual cycle, the structure of the vaginal microbiome shifts. Few studies have examined both in combination. Our study was designed to explore trends in the microbiome of different parts of the vagina in healthy women over the menstrual cycle. Methods: We performed metagenomic sequencing to characterize the microbiome differences between the cervical orifice and mid-vagina throughout the menstrual cycle. Results: Our results showed the vaginal microbiome of healthy women in the cervical orifice and the mid-vagina was similar during the periovulatory and luteal phases, with Lactobacillus being the dominant bacteria. In the follicular phase, Acinetobacter was detected in the cervical orifice. From the follicular phase to the luteal phase, the community state types (all five community status types were defined as CSTs) in samples No. 10 and No. 11 changed from CST III to CST I. In addition, the composition of the vaginal microbiome in healthy women from different regions of China was significantly different. We also detected viruses including Human alphaherpesvirus 1 (HSV-1) during periovulatory phase. Conclusion: This study is valuable for understanding whether the microbial composition of the vagina is consistent in different parts of the menstrual cycle.

Crosstalk of nervous and immune systems in pancreatic cancer.

Pancreatic cancer is a highly malignant tumor known for its extremely low survival rate. The combination of genetic disorders within pancreatic cells and the tumor microenvironment contributes to the emergence and progression of this devastating disease. Extensive research has shed light on the nature of the microenvironmental cells surrounding the pancreatic cancer, including peripheral nerves and immune cells. Peripheral nerves release neuropeptides that directly target pancreatic cancer cells in a paracrine manner, while immune cells play a crucial role in eliminating cancer cells that have not evaded the immune response. Recent studies have revealed the intricate interplay between the nervous and immune systems in homeostatic condition as well as in cancer development. In this review, we aim to summarize the function of nerves in pancreatic cancer, emphasizing the significance to investigate the neural-immune crosstalk during the advancement of this malignant cancer.

Metagenomic analysis reveals distinct changes in the gut microbiome of obese Chinese children.

BACKGROUND: The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China. RESULTS: We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children. CONCLUSIONS: Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children.

Causal Association of Cytokines and Growth Factors with Stroke and Its Subtypes: a Mendelian Randomization Study.

Cytokines and growth factors contribute to nerve growth and angiogenesis and are associated with the development of vascular disease. This Mendelian randomization (MR) study was designed to examine the causal relationship between factors associated with stem cell paracrine mechanisms and with stroke and its subtypes. We used pooled statistics on cytokine levels from three studies (INTERIAL, Olink Proseek CVD array, and KORA) encompassing 7795 participants in Europe. Data for stroke and its subtypes were pooled from these European populations (40,585 cases and 406,111 controls) in a multiprogenitor genome-wide association study (GWAS). MR was performed using established analytical methods, including inverse variance weighting (IVW), weighted median (WM), and MR-Egger. Genetically determined high IGF-1 levels were found to associate negatively with risk of stroke, ischemic stroke (large-artery atherosclerosis), and ischemic stroke (cardiogenic embolism). Meanwhile, high IL-13 levels had a positive causal relationship with ischemic stroke (large-artery atherosclerosis). An additional 27 cytokines were found to have a causal association with stroke or its subtypes. However, these results should be interpreted with caution given that the power efficacy was <80%. This MR study supports the concept of a causal relationship of 29 cytokines with stroke or its subtypes. Our genetic analysis provides new insights into stroke prevention and treatment by demonstrating an association of stem cell paracrine-related cytokines with stroke risk.

The effectiveness of intermittent theta burst stimulation for upper limb motor recovery after stroke: a systematic review and meta-analysis of randomized controlled trials.

Background: Intermittent theta burst stimulation (iTBS) is a promising noninvasive therapy to restore the excitability of the cortex, and subsequently improve the function of the upper extremities. Several studies have demonstrated the effectiveness of iTBS in restoring upper limb function and modulating cortical excitability. We aimed to evaluate the effects of iTBS on upper limb motor recovery after stroke. Objective: The purpose of this article is to evaluate the influence of intermittent theta-burst stimulation on upper limb motor recovery and improve the quality of life. Method: A literature search was conducted using PubMed, EMBASE, MEDLINE, The Cochrane Library, Web of Science, and CBM, including only English studies, to identify studies that investigated the effects of iTBS on upper limb recovery, compared with sham iTBS used in control groups. Effect size was reported as standardized mean difference (SMD) or weighted mean difference (WMD). Results: Ten studies were included in the meta-analysis. The results of the meta-analysis indicated that when compared to the control group, the iTBS group had a significant difference in the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT) (WMD: 3.20, 95% CI: 1.42 to 4.97; WMD: 3.72, 95% CI: 2.13 to 5.30, respectively). In addition, there was also a significant improvement in the modified Ashworth scale (MAS) compared to the sham group (WMD: -0.56; 95% CI: -0.85 to -0.28). More evidence is still needed to confirm the effect of Barthel Index (BI) scores after interventions. However, no significant effect was found for the assessment of Motor Evoked Potential (MEP) amplitude and MEP latency (SMD: 0.35; 95% CI: -0.21 to 0.90; SMD: 0.35, 95% CI: -0.18 to 0.87; SMD: 0.03, 95% CI: -0.49 to 0.55; respectively). Conclusion: Our results showed that iTBS significantly improved motor impairment, functional activities, and reduced muscle tone of upper limbs, thereby increasing the ability to perform Activities of Daily Living (ADL) in stroke patients, while there were no significant differences in MEPs. In conclusion, iTBS is a promising non-invasive brain stimulation as an adjunct to therapy and enhances the therapeutic effect of conventional physical therapy. In the future, more randomized controlled trials with large sample sizes, high quality, and follow-up are necessary to explore the neurophysiological effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392739.

Biomarkers associated with functional improvement after stroke rehabilitation: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study aims to identify blood and cerebrospinal fluid biomarkers that are correlated to the functional improvement of stroke patients after rehabilitation therapy, and provide ideas for the treatment and evaluation of stroke patients. Methods: The PubMed, Web of Science, and Embase databases were searched for articles published in the English language, from inception to December 8, 2022. Results: A total of 9,810 independent records generated 50 high-quality randomized controlled trials on 119 biomarkers. Among these records, 37 articles were included for the meta-analysis (with a total of 2,567 stroke patients), and 101 peripheral blood and cerebrospinal fluid biomarkers were included for the qualitative analysis. The quantitative analysis results revealed a moderate quality evidence that stroke rehabilitation significantly increased the level of brain-derived neurotrophic factor (BDNF) in serum. Furthermore, the low-quality evidence revealed that stroke rehabilitation significantly increased the concentration of serum noradrenaline (NE), peripheral blood superoxide dismutase (SOD), peripheral blood albumin (ALB), peripheral blood hemoglobin (HB), and peripheral blood catalase (CAT), but significantly decreased the concentration of serum endothelin (ET) and glutamate. In addition, the changes in concentration of these biomarkers were associated with significant improvements in post-stroke function. The serum BNDF suggests that this can be used as a biomarker for non-invasive brain stimulation (NIBS) therapy, and to predict the improvement of stroke patients. Conclusion: The concentration of serum BNDF, NE, ET and glutamate, and peripheral blood SOD, ALB, HB and CAT may suggest the function improvement of stroke patients.

Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors.

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Integrating network pharmacology and experimental verification to explore the mechanisms of salidroside against myocardial fibrosis.

Myocardial fibrosis (MF) is the manifestation of a variety of cardiovascular diseases. Salidroside (SAL) has been proved to have a certain effect on anti-fibrosis in various organs. However, the mechanism of SAL in the treatment of MF remains unclear. Network pharmacology showed that there were 1228 SAL-related target genes and 2793 MF-related target genes. The intersection of these genes resulted in 271 drug-disease interactions, and 15 core active targets were filtered from protein-protein interaction mapping. The top 20 Gene ontology biological processes analysis showed that the involved processes were close to the pathogenesis of MF. Among the top 20 enriched KEGG pathways, Wnt/ß-catenin and TGF-ß1/Smad3 signaling pathways were identified. In vivo, MI rats exhibited thinning of the myocardial region and the formation of fibrous scars, the expression of smad3 and ß-catenin were increased. After SAL treatment, there was a significant reduction in collagen area and a decrease in the ratio of collagen type I to type III. The expression of smad3 and ß-catenin was suppressed and positively correlated with the dosage of SAL. SAL may contribute to the progression of MF through the TGF-ß1/Smad3 and Wnt/ß-catenin signaling pathways.