Delivery-mediated exosomal therapeutics in ischemia-reperfusion injury: advances, mechanisms, and future directions.

Ischemia-reperfusion injury (IRI) poses significant challenges across various organ systems, including the heart, brain, and kidneys. Exosomes have shown great potentials and applications in mitigating IRI-induced cell and tissue damage through modulating inflammatory responses, enhancing angiogenesis, and promoting tissue repair. Despite these advances, a more systematic understanding of exosomes from different sources and their biotransport is critical for optimizing therapeutic efficacy and accelerating the clinical adoption of exosomes for IRI therapies. Therefore, this review article overviews the administration routes of exosomes from different sources, such as mesenchymal stem cells and other somatic cells, in the context of IRI treatment. Furthermore, this article covers how the delivered exosomes modulate molecular pathways of recipient cells, aiding in the prevention of cell death and the promotions of regeneration in IRI models. In the end, this article discusses the ongoing research efforts and propose future research directions of exosome-based therapies.

Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

Transcutaneous electrical acupoint stimulation for prevention of postoperative urinary retention: A systematic review.

Introduction: Transcutaneous electrical acupoint stimulation (TEAS) has been proposed for postoperative urinary retention (POUR). This meta-analysis evaluated the effect of TEAS in preventing POUR. Methods: Databases were searched until February 6, 2023. Randomized controlled trials (RCTs) about TEAS for preventing POUR were included. The primary concern was the incidence of POUR, with post-void residual urine volume as a secondary outcome. Results: Fourteen studies with 2865 participants were identified. TEAS reduced the incidence of POUR (RR = 0.44, 95%CI = 0.33 to 0.58, P < 0.00001) and decreased the post-void residual urine volume (MD = -75.41 mL, 95%CI = -118.76 to -32.06, P = 0.0007). The preventive effect on POUR was found in patients receiving anorectal, gynecologic, orthopedic and biliary surgery, but not urinary surgery. Dilatational- and continuous-wave TEAS had a great outcome in preventing POUR. Intraoperative TEAS, preoperative and intraoperative TEAS, and postoperative TEAS were beneficial, and TEAS was more beneficial when compared with sham TEAS and blank control. It is nevertheless difficult to rule out publication bias. Conclusions: TEAS could prevent POUR. Due to insufficient evidence, multicenter, large-sample and high-quality RCTs should be conducted. (Registration:INPLASY202320095).

Phlorizin, a novel caloric restriction mimetic, stimulates hypoxia and protects cardiomyocytes through activating autophagy via modulating the Hif-1α/Bnip3 axis in sepsis-induced myocardial dysfunction.

BACKGROUND: Sepsis is a systemic inflammatory syndrome that can lead to multiple organ dysfunction and life-threatening complications. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to be present in half of patients with septic shock, increasing their mortality rate to 70-90%. The pathogenesis of SIMD is complex, and no specific clinical treatment has yet been developed. Caloric restriction mimetics (CRM), compounds that simulate the biochemical and functional properties of CR, can improve cardiovascular injury by activating autophagy. This study investigated the effect of a new type of CRM which can induce hypoxia, the SGLT nonspecific inhibitor phlorizin on SIMD. MATERIALS AND METHODS: In vivo, phlorizin was administered at 1 mg/kg/day intragastrically for 28 days. In vitro, AC16 was treated with 120 µM phlorizin for 48 h. Echocardiography was used to assess cardiac function. Myocardial injury markers were detected in serum and cell supernatant. Western blotting was employed to detect changed proteins associated with apoptosis and autophagy. Immunofluorescence, immunohistochemistry, co-immunoprecipitation, molecular docking, and other methods were also used to illustrate cellular changes. RESULTS: In vivo, phlorizin significantly improved the survival rate and cardiac function after sepsis injury, reduced markers of myocardial injury, inhibited myocardial apoptosis and oxidative stress, and promoted autophagy. In vitro, phlorizin alleviated the apoptosis of AC16, as well as inhibited oxidative stress and apoptotic enzyme activity. Phlorizin acts on autophagy at multiple sites through low energy (activation of AMPK) and hypoxia (release of Beclin-1 by Hif-1α/Bnip3 axis), promoting the formation and degradation of autophagosomes. CONCLUSION: We indicated for the first time that phlorizin could inhibit glucose uptake via GLUT-1 and conforms to the metabolic characteristics of CRM, it can induce the hypoxic transcriptional paradigm. In addition, it inhibits apoptosis and improves SIMD by promoting autophagy generation and unobstructing autophagy flux. Moreover, it affects autophagy by releasing Beclin-1 through the Hif-1α/Bnip3 axis.

Mind In Vitro Platforms: Versatile, Scalable, Robust, and Open Solutions to Interfacing with Living Neurons.

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro-electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long-term recording. Overall, this technology, termed "mind in vitro" to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10× cost reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

Atrophy of hippocampal subfields relates to memory decline during the pathological progression of Alzheimer's disease.

Background: It has been well documented that atrophy of hippocampus and hippocampal subfields is closely linked to cognitive decline in normal aging and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, evidence is still sparce regarding the atrophy of hippocampus and hippocampal subfields in normal aging adults who later developed MCI or AD. Objective: To examine whether atrophy of hippocampus and hippocampal subfields has occurred in normal aging before a diagnosis of MCI or AD. Methods: We analyzed structural magnetic resonance imaging (MRI) data of cognitively normal (CN, n = 144), MCI (n = 90), and AD (n = 145) participants obtained from the Alzheimer's Disease Neuroimaging Initiative. The CN participants were categorized into early dementia converters (CN-C) and non-converters (CN-NC) based on their scores of clinical dementia rating after an average of 36.2 months (range: 6-105 months). We extracted the whole hippocampus and hippocampal subfields for each participant using FreeSurfer, and analyzed the differences in volumes of hippocampus and hippocampal subfields between groups. We then examined the associations between volume of hippocampal subfields and delayed recall scores in each group separately. Results: Hippocampus and most of the hippocampal subfields demonstrated significant atrophy during the progression of AD. The CN-C and CN-NC groups differed in the left hippocampus-amygdala transition area (HATA). Furthermore, the volume of presubiculum was significantly correlated with delayed recall scores in the CN-NC and AD groups, but not in the CN-C and MCI groups. Conclusion: Hippocampal subfield atrophy (i.e., left HATA) had occurred in cognitively normal elderly individuals before clinical symptoms were recognized. Significant associations of presubiculum with delayed recall scores in the CN-NC and AD groups highlight the essential role of the hippocampal subfields in both early dementia detection and AD progression.

Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age.

Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.

Early-life gut microbiota in food allergic children and its impact on the development of allergic disease.

BACKGROUND: The prevalence of food allergies (FA) has been steadily increasing over 2 to 3 decades, showing diverse symptoms and rising severity. These long-term outcomes affect children's growth and development, possibly linking to inflammatory bowel disease. However, the cause remains unclear. Previous studies reveal that early infancy significantly impacts FA development through gut microbiota. Yet, a consistent view on dysbiosis characteristics and its connection to future allergies is lacking. We explored how early-life gut microbiota composition relates to long-term clinical signs in children with FA through longitudinal research. METHODS: We employed high-throughput 16S rDNA gene sequencing to assess gut microbiota composition in early-life FA children in southern Zhejiang. Follow-up of clinical manifestations over 2 years allowed us to analyze the impact of early-life gut microbiota dysbiosis on later outcomes. RESULTS: While the diversity of gut microbiota in FA children remained stable, there were shifts in microbiota abundance. Abundant Akkermansia, Parabacteroides, Blautia, and Escherichia-Shigella increased, while Bifidobacterium and Clostridium decreased. After 2 years, two of ten FA children still showed symptoms. These two cases exhibited increased Escherichia-Shigella and reduced Bifidobacterium during early childhood. The other eight cases experienced symptom remission. CONCLUSIONS: Our study suggests that FA and its prognosis might not correlate with early-life gut microbiota diversity. Further experiments are needed due to the small sample size, to confirm these findings.

Characteristics and risk factors for colorectal polyps among children in an urban area of Wenzhou, China: a retrospective case control study.

BACKGROUND: Scarce evidence exists on pediatric colorectal polyp risk factors. This study explored the clinical manifestations, morphological and pathological characteristics of, and risk factors for pediatric colorectal polyps. METHODS: This retrospective case-control study included children who received colonoscopy, divided into a colorectal polyp group and a normal control group based on colonoscopy results. The risk factors for colorectal polyps in children were analyzed through logistic regression analysis. RESULTS: The mean age of children with polyps was 6.77 ± 3.44 years. Polyps were detected predominantly in males (72.9%); hematochezia was the primary clinical manifestation (80.25%). Most polyps were juvenile (88.9%) and solitary (87.7%); 50.6% were located in the rectosigmoid area. Univariate analysis showed that gender (P = 0.037), age (P < 0.001), family aggregation (P < 0.001), specific immunoglobulin E (sIgE) (P < 0.001), platelet count (P = 0.001), aspartate aminotransferase (AST) (P = 0.016), meat intake (P = 0.010), and vegetable intake (P < 0.001) were significantly associated with colorectal polyps. Age ≤ 6 years (3-6 years: OR: 26.601, 95% CI: 3.761-160.910; < 3 years: OR: 22.678, 95% CI: 1.873-274.535), positive family aggregation (OR: 3.540, 95% CI: 1.177-10.643), positive sIgE (OR:2.263, 95% CI: 1.076-4.761), and higher meat intake (OR:1.046, 95% CI: 1.029-1.063) were risk factors for pediatric colorectal polyps in logistic regression analysis. Higher vegetable intake (OR: 0.993, 95% CI: 0.986-1.000) was a protective factor against pediatric colorectal polyps. The area under the curve (AUC) of meat intake in the receiver operating characteristic (ROC) curve analysis for predicting colorectal polyps was 0.607; the best cut-off value was 92.14 g/d (P = 0.010, 95% CI: 0.527-0.687). The meat and vegetable intake combination AUC in predicting pediatric colorectal polyps was 0.781 (P < 0.001, 95% CI: 0.718-0.845). CONCLUSIONS: Juvenile, solitary, and located in the rectosigmoid region polyps are most common in children. Hematochezia is the main clinical manifestation. Most polyps were, but multiple and proximally located polyps were also detected. Age ≤ 6 years, especially 3-6 years, positive family aggregation, positive sIgE, and higher meat intake are risk factors for pediatric colorectal polyps. A higher vegetable intake is a protective factor.

Acupuncture for gait disturbance of patients with subacute and chronic stroke: a systematic review and meta-analysis protocol.

INTRODUCTION: Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters. METHODS AND ANALYSIS: A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ2 test and I2 statistic will be used for assessing heterogeneity between studies. ETHICS AND DISSEMINATION: No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings. PROSPERO REGISTRATION NUMBER: CRD42022384348.

Absence of associations with prefrontal cortex and cerebellum may link to early language and social deficits in preschool children with ASD.

Introduction: Autism spectrum disorder (ASD) is a complex developmental disorder, characterized by language and social deficits that begin to appear in the first years of life. Research in preschool children with ASD has consistently reported increased global brain volume and abnormal cortical patterns, and the brain structure abnormalities have also been found to be clinically and behaviorally relevant. However, little is known regarding the associations between brain structure abnormalities and early language and social deficits in preschool children with ASD. Methods: In this study, we collected magnetic resonance imaging (MRI) data from a cohort of Chinese preschool children with and without ASD (24 ASD/20 non-ASD) aged 12-52 months, explored group differences in brain gray matter (GM) volume, and examined associations between regional GM volume and early language and social abilities in these two groups, separately. Results: We observed significantly greater global GM volume in children with ASD as compared to those without ASD, but there were no regional GM volume differences between these two groups. For children without ASD, GM volume in bilateral prefrontal cortex and cerebellum was significantly correlated with language scores; GM volume in bilateral prefrontal cortex was significantly correlated with social scores. No significant correlations were found in children with ASD. Discussion: Our data demonstrate correlations of regional GM volume with early language and social abilities in preschool children without ASD, and the absence of these associations appear to underlie language and social deficits in children with ASD. These findings provide novel evidence for the neuroanatomical basis associated with language and social abilities in preschool children with and without ASD, which promotes a better understanding of early deficits in language and social functions in ASD.

Coupling Between Hippocampal Parenchymal Fraction and Cortical Grey Matter Atrophy at Different Stages of Cognitive Decline.

BACKGROUND: Hippocampal atrophy is a significant brain marker of pathology in Alzheimer's disease (AD). The hippocampal parenchymal fraction (HPF) was recently developed to better assess the hippocampal volumetric integrity, and it has been shown to be a sensitive measure of hippocampal atrophy in AD. OBJECTIVE: To investigate the clinical relevance of hippocampal volumetric integrity as measured by the HPF and the coupling between the HPF and brain atrophy during AD progression. METHODS: We included data from 143 cognitively normal (CN), 101 mild cognitive impairment (MCI), and 125 AD participants. We examined group differences in the HPF, associations between HPF and cognitive ability, and coupling between the HPF and cortical grey matter volume in the CN, MCI, and AD groups. RESULTS: We observed progressive decreases in HPF from CN to MCI and from MCI to AD, and increases in the asymmetry of HPF, with the lowest asymmetry index (AI) in the CN group and the highest AI in the AD group. There was a significant association between HPF and cognitive ability across participants. The coupling between HPF and cortical regions was observed in bilateral hippocampus, parahippocampal gyrus, temporal, frontal, and occipital regions, thalamus, and amygdala in CN, MCI, and AD groups, with a greater involvement of temporal, occipital, frontal, and subcortical regions in MCI and AD patients, especially in AD patients. CONCLUSION: This study provides novel evidence for the neuroanatomical basis of cognitive decline and brain atrophy during AD progression, which may have important clinical implications for the prognosis of AD.

Clinical efficacy of the shallow puncture and more-twirling acupuncture method in migraine treatment and its effects on serum 5-HT and ß-EP levels.

BACKGROUND: The incidence rate for migraine is 12% worldwide, and recurrence is common, which seriously affects the physical and mental health of patients. OBJECTIVE: To observe the clinical effect of Shallow Puncture and More Twirling method of acupuncture in treating migraine and its impact on serum 5-HT and ß-EP. METHODS: A total of 76 patients with migraine were randomized into a control group and acupuncture group with 38 cases in each. In the control group, patients were orally administered flunarizine hydrochloride before sleep, 2 capsules once daily for 4 weeks. In the acupuncture group, Shallow Puncture and More Twirling method was adopted for the acupoints of Sizhukong (SJ 23), Toulinqi (GB 15) Shuaigu (GB 8), Xuanlu (GB 5), Fengchi (GB 20), Waiguan (SJ 5), Zulinqi (GB 41). Patients were given acupuncture 3 times per week for 4 weeks. Then, the total VAS (Visual Analogue Scale) scores, composite score of migraine, serum level of 5-HT and ß-EP, and the clinical efficacy differences were observed before and after treatment and the side-effects were recorded among the two groups. RESULTS: The total VAS scores and composite score of migraine were significantly reduced among both groups after the treatment (P< 0.05), and the serum level of 5-HT and ß-EP was significantly improved (P< 0.05). Compared with control group, the acupuncture group reported lower results in VAS score and migraine composite score (P< 0.05), and higher results in serum 5-HT and ß-EP level (P< 0.05). The acupuncture group with shallow puncture and more twirling method showed a total effective rate of 86.5%, which is higher than the control group (78.4%). The difference is statistically significant (P< 0.05). CONCLUSION: Shallow Puncture and More Twirling method was superior to flunarizine hydrochloride in the treatment of clinical symptoms of migraine. Acupuncture also increases the serum level of 5-HT and ß-EP in migraine.

3,4-benzopyrene aggravates myocardial ischemia-reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation.

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia-reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation-reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53-BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53-BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.

Transcutaneous electrical acupoint stimulation for the prevention of postoperative delirium in elderly surgical patients: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to evaluate the preventive effect of transcutaneous electrical acupoint stimulation on postoperative delirium in elderly surgical patients. Methods: PubMed, CENTRAL, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials regarding the effect of transcutaneous electrical acupoint stimulation on preventing postoperative delirium in elderly patients undergoing any type of surgery. The primary outcome was the incidence of postoperative delirium. The secondary outcome was the duration of postoperative delirium. All analyses were conducted using RevMan 5.3 and Stata 13.0 software. Results: Twelve trials with 991 participants were included, and most of them were at high/unclear risk of bias. Meta-analysis showed transcutaneous electrical acupoint stimulation could reduce the incidence of postoperative delirium (RR = 0.40, 95%CI = 0.29 to 0.55, p < 0.00001) and shorten the duration of postoperative delirium (MD = -0.97 days, 95%CI = -1.72 to -0.22, p = 0.01). Subgroup analyses demonstrated that transcutaneous electrical acupoint stimulation reduced the incidence of postoperative delirium in elderly patients undergoing orthopedic surgery and thoracic surgery, but not digestive surgery; transcutaneous electrical acupoint stimulation with dilatational wave and with continuous wave were both beneficial; and transcutaneous electrical acupoint stimulation was favored when compared to blank and sham control. Conclusion: Transcutaneous electrical acupoint stimulation could reduce the incidence of postoperative delirium and shorten the duration of postoperative delirium in elderly surgical patients. The findings should be interpreted with caution due to weak evidence. High-quality, large sample, and multi-center trials are needed to further confirm the preliminary findings.Systematic review registration: https://inplasy.com/inplasy-2022-7-0096/, identifier: INPLASY202270096.

Unsociability and social adjustment of Chinese preschool migrant children: The moderating role of resilience.

Objectives: The present study examined the moderating effect of children's resilience on the relations between unsociability and social adjustment (i.e., prosocial behaviors, peer exclusion, interpersonal skills, internalizing problems) in Chinese preschool migrant children. Methods: Participants were N = 148 children (82 boys, M age = 62.32 months, SD = 6.76) attending two public kindergartens in Shanghai, People's Republic of China. Mothers provided ratings of children's unsociability and resilience; teachers assessed children's social adjustment outcomes, and children reported their receptive vocabulary. Results: Unsociability was positively associated with peer exclusion and internalizing problems, and negatively associated with prosocial behaviors and interpersonal skills among Chinese preschool migrant children. Moreover, children's resilience significantly moderated the relationship between unsociability and social adjustment. Specifically, among children with lower levels of resilience, unsociability was significantly and positively associated with peer exclusion and internalizing problems, while among children with higher levels of resilience, unsociability was not associated with social adjustment difficulties. Conclusion: The current findings inform us of the importance of improving children's resilience to buffer the negative adjustment among Chinese migrant unsociable young children. The findings also highlight the importance of considering the meaning and implication of unsociability for preschool migrant children in Chinese culture.

Cost-Effectiveness Analysis of Dapagliflozin Plus Standard Treatment for Patients With Type 2 Diabetes and High Risk of Cardiovascular Disease in China.

Purpose: To evaluate the long-term cost-effectiveness of dapagliflozin, in addition to standard treatment, for the treatment of adult patients with type 2 diabetes (T2DM) at high cardiovascular risk from the Chinese healthcare system perspective. Methods: A decision-analytic Markov model with one-year cycles was developed to evaluate the health and economic outcomes in patients with T2DM and high risk of cardiovascular disease (CVD) treated with standard treatment and dapagliflozin plus standard treatment for 30 years. Clinical data, cost, and utility data were extracted from databases or published literature. Quality-adjusted life-years (QALYs), costs (€/¥ 2021) as well as incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty in the results. Results: Compared with standard treatment, dapagliflozin plus standard treatment was predicted to result in an additional 0.25 QALYs (12.26 QALYs vs. 12.01 QALYs) at an incremental cost of €4,435.81 (¥33,875.83) per patient. The ICER for dapagliflozin plus standard treatment vs. standard treatment was €17,742.07 (¥135,494.41) per QALY gained, which was considered cost-effective in China compared to three times the GDP per capita in 2021 (€31,809.77/¥242,928). The deterministic and probabilistic sensitivity analyses showed the base-case results to be robust. Conclusions: The study suggests that, from the perspective of the Chinese health system, dapagliflozin plus standard treatment is a cost-effective option for patients with T2DM at high cardiovascular risk. These findings may help clinicians make the best treatment decisions for patients with T2DM at high cardiovascular risk.

Shexiang Baoxin Pill attenuates myocardial ischemia/reperfusion injury by activating autophagy via modulating the ceRNA-Map3k8 pathway.

BACKGROUND: The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice. MATERIALS AND METHODS: In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 µg/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results. RESULTS: SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pyroptosis, inhibited oxidative stress, reduced IL-1ß and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p. CONCLUSION: We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.

Empowering engineered muscle in biohybrid pump by extending connexin 43 duration with reduced graphene oxides.

Engineered skeletal muscle act as therapeutics invaluable to treat injured or diseased muscle and a "living" material essential to assemble biological machinery. For normal development, skeletal myoblasts should express connexin 43, one of the gap junction proteins that promote myoblast fusion and myogenesis, during the early differentiation stage. However, myoblasts cultured in vitro often down-regulate connexin 43 before differentiation, limiting myogenesis and muscle contraction. This study demonstrates that tethering myoblasts with reduced graphene oxide (rGO) slows connexin 43 regression during early differentiation and increases myogenic mRNA synthesis. The whole RNA sequencing also confirms that the rGO on cells increases regulator genes for myogenesis, including troponin, while decreasing negative regulator genes. The resulting myotubes generated a three-fold larger contraction force than the rGO-free myotubes. Accordingly, a valveless biohybrid pump assembled with the rGO-tethered muscle increased the fluid velocity and flow rate considerably. The results of this study would provide an important foundation for developing physiologically relevant muscle and powering up biomachines that will be used for various bioscience studies and unexplored applications.