Paeoniflorin suppresses ferroptosis after traumatic brain injury by antagonizing P53 acetylation.

BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

Alterations of contralesional hippocampal subfield volumes and relations to cognitive functions in patients with unilateral stroke.

BACKGROUND: The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. METHODS: Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1-weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. RESULTS: Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC-ML-DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. CONCLUSION: Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC-ML-DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.

Altered Brain Functional and Effective Connectivity Induced by Electroacupuncture in Rats Following Anterior Cruciate Ligament Transection.

Background: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.

Evaluating the effect of health insurance reform on health equity and financial protection for elderly in low- and middle-income countries: evidences from China.

BACKGROUND: To achieve Universal Health Coverage (UHC), China have implemented health system reform to expend health coverage and improve health equity. Scholars have explored the implementing effect of this health reform, but gaps remained in health care received by elderly. This study aims to assess the effect of implementing health insurance payment reform on health care received by elderly, as well as to evaluate its effect on cost sharing to identify whether improve financial protection of elderly under this reform. METHODS: We identified hospitalization of 46,714 elderly with cerebral infarction from 2013 to 2023. To examine the determinant role played by DRGs payment reform in healthcare for elderly and their financial protection, this study employs the OLS linear regression model for analysis. In the robustness checks, we validated the baseline results through several methods, including excluding the data from the initial implementation of the reform (2021), reducing the impact of the pandemic, and exploring the group effects of different demographic characteristics. RESULTS: The findings proposed that implementing DRGs payment reduces drug expenses but increases treatment expense of chronic disease for elderly in China. This exacerbates healthcare costs for elderly patients and seems to be contrary to the original purpose of health care reform. Additionally, the implementation of DRGs payment reduced the spending of medical insurance fund, while increased the out-of-pocket of patients, revealing a shift in health care expenses from health insurance fund to out-of-pocket. CONCLUSIONS: This study shares the lessons from China's health reform and provides enlightenment on how to effective implement health reform to improve health equity and achieve UHC in such low- and middle-income countries facing challenges in health financing.

Family migration and well-being of Chinese migrant workers' children.

This article aims to explore the effects of parental migration on the well-being of children and how to adjust social cognitive well-being through the interrelations among family relations and social cognitive well-being indicators using structural equation modelling. Two modified social cognitive well-being models were tested in 1682 Chinese migrant workers' children to examine the pathways among social cognitive well-being and family relation characteristics. The modified models are based on the social cognitive well-being model and the characteristics of Chinese migrant workers' children. The results show that caregiver-child communication frequency, caregiver-child regulation, caregiver-child conflicts, caregiver-child trust and communication, and coactivity positively impact children's social cognitive well-being. In contrast, caregiver-child alienation negatively influences children's social cognitive factors through caregiver-child trust and communication. Additionally, this research revealed that family-related characteristics (caregiver-child regulation, caregiver-child coactivities, caregiver-child communication frequency, caregiver-child alienation, caregiver-child conflicts, and caregiver-child trust and communication) are interconnected with social cognitive well-being indicators (academic satisfaction, outcome expectations, goal progress, lifelong satisfaction, environmental support, positive affect, negative affect, and self-efficacy). This suggests that family migration and relationships with caregiver(s) can significantly affect the well-being of migrant workers' children.

Peripheral nerve transfers for dysfunctions in central nervous system injuries: a systematic review.

BACKGROUND: The review highlights recent advancements and innovative uses of nerve transfer surgery in treating dysfunctions caused by central nervous system (CNS) injuries, with a particular focus on spinal cord injury (SCI), stroke, traumatic brain injury, and cerebral palsy. METHODS: A comprehensive literature search was conducted regarding nerve transfer for restoring sensorimotor functions and bladder control following injuries of spinal cord and brain, across PubMed and Web of Science from January 1920 to May 2023. Two independent reviewers undertook article selection, data extraction, and risk of bias assessment with several appraisal tools, including the Cochrane Risk of Bias Tool, the JBI Critical Appraisal Checklist, and SYRCLE's ROB tool. The study protocol has been registered and reported following PRISMA and AMSTAR guidelines. RESULTS: Nine hundred six articles were retrieved, of which 35 studies were included (20 on SCI and 15 on brain injury), with 371 participants included in the surgery group and 192 in the control group. These articles were mostly low-risk, with methodological concerns in study types, highlighting the complexity and diversity. For SCI, the strength of target muscle increased by 3.13 of Medical Research Council grade, and the residual urine volume reduced by more than 100 ml in 15 of 20 patients. For unilateral brain injury, the Fugl-Myer motor assessment (FMA) improved 15.14-26 score in upper extremity compared to 2.35-26 in the control group. The overall reduction in Modified Ashworth score was 0.76-2 compared to 0-1 in the control group. Range of motion (ROM) increased 18.4-80° in elbow, 20.4-110° in wrist and 18.8-130° in forearm, while ROM changed -4.03°-20° in elbow, -2.08°-10° in wrist, -2.26°-20° in forearm in the control group. The improvement of FMA in lower extremity was 9 score compared to the presurgery. CONCLUSION: Nerve transfer generally improves sensorimotor functions in paralyzed limbs and bladder control following CNS injury. The technique effectively creates a 'bypass' for signals and facilitates functional recovery by leveraging neural plasticity. It suggested a future of surgery, neurorehabilitation and robotic-assistants converge to improve outcomes for CNS.

Mitochondrial RNA modification-based signature to predict prognosis of lower grade glioma: a multi-omics exploration and verification study.

Mitochondrial RNA modification (MRM) plays a crucial role in regulating the expression of key mitochondrial genes and promoting tumor metastasis. Despite its significance, comprehensive studies on MRM in lower grade gliomas (LGGs) remain unknown. Single-cell RNA-seq data (GSE89567) was used to evaluate the distribution functional status, and correlation of MRM-related genes in different cell types of LGG microenvironment. We developed an MRM scoring system by selecting potential MRM-related genes using LASSO regression analysis and the Random Survival Forest algorithm, based on multiple bulk RNA-seq datasets from TCGA, CGGA, GSE16011, and E-MTAB-3892. Analysis was performed on prognostic and immunological features, signaling pathways, metabolism, somatic mutations and copy number variations (CNVs), treatment responses, and forecasting of potential small-molecule agents. A total of 35 MRM-related genes were selected from the literature. Differential expression analysis of 1120 normal brain tissues and 529 LGGs revealed that 22 and 10 genes were upregulated and downregulated, respectively. Most genes were associated with prognosis of LGG. METLL8, METLL2A, TRMT112, and METTL2B were extensively expressed in all cell types and different cell cycle of each cell type. Almost all cell types had clusters related to mitochondrial RNA processing, ribosome biogenesis, or oxidative phosphorylation. Cell-cell communication and Pearson correlation analyses indicated that MRM may promoting the development of microenvironment beneficial to malignant progression via modulating NCMA signaling pathway and ICP expression. A total of 11 and 9 MRM-related genes were observed by LASSO and the RSF algorithm, respectively, and finally 6 MRM-related genes were used to establish MRM scoring system (TRMT2B, TRMT11, METTL6, METTL8, TRMT6, and TRUB2). The six MRM-related genes were then validated by qPCR in glioma and normal tissues. MRM score can predict the malignant clinical characteristics, abundance of immune infiltration, gene variation, clinical outcome, the enrichment of signaling pathways and metabolism. In vitro experiments demonstrated that silencing METTL8 significantly curbs glioma cell proliferation and enhances apoptosis. Patients with a high MRM score showed a better response to immunotherapies and small-molecule agents such as arachidonyl trifluoromethyl ketone, MS.275, AH.6809, tacrolimus, and TTNPB. These novel insights into the biological impacts of MRM within the glioma microenvironment underscore its potential as a target for developing precise therapies, including immunotherapeutic approaches.

Single-cell RNA sequencing analysis provides novel insights into the role of apoptosis-related genes in muscle aging.

OBJECTIVE: This study employed a comprehensive single-cell analysis approach to explore the role of cell apoptosis-related genes in muscle aging. METHODS: The single-cell RNA sequencing data from the GSE143704 dataset were used to identify distinct cell clusters and assess gene expression patterns related to apoptosis activation. The "limma" package was used to identify hub genes, after which we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify relevant pathways. Additionally, Gene Set Enrichment Analysis(GSEA) and Gene Set Variation Analysis (GSVA) were used to uncover relevant biological pathways. The Receiver Operating Characteristic Curve (ROC) was used to evaluate the diagnostic value of the hub genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to analyze the immune cell infiltration levels. RESULTS: Single-cell sequencing data from muscle aging patients allowed the identification of various cell types, including epithelial cells, adipocytes, and tissue-resident macrophages. By conducting a differential expression analysis that intersected active and nonactive apoptosis, as well as comparing elderly and young samples, a total of 22 hub genes were identified (p < 0.05). The 22 hub genes have discriminative ability as potential biomarkers for diagnosing muscle aging. The enrichment analysis indicated that these genes were closely associated with diverse pathways, including "response to UV-B" and "extracellular matrix organization" (p < 0.05). Furthermore, GSEA and GSVA indicated that multiple pathways emerged-for example, the "complement and coagulation cascades", "proteasome", "insulin signaling pathway", and "MAPK signaling pathway". Additionally, the analysis of immune cell infiltration revealed positive correlations between most of the hub genes and immune cells. CONCLUSION: Our study identified 22 apoptosis-related genes involved in muscle aging and indicated their potential diagnostic value. These findings offer a novel perspective on the pathogenesis of muscle aging and present potential targets for therapeutic interventions.

Machine learning and deep learning to identifying subarachnoid haemorrhage macrophage-associated biomarkers by bulk and single-cell sequencing.

We investigated subarachnoid haemorrhage (SAH) macrophage subpopulations and identified relevant key genes for improving diagnostic and therapeutic strategies. SAH rat models were established, and brain tissue samples underwent single-cell transcriptome sequencing and bulk RNA-seq. Using single-cell data, distinct macrophage subpopulations, including a unique SAH subset, were identified. The hdWGCNA method revealed 160 key macrophage-related genes. Univariate analysis and lasso regression selected 10 genes for constructing a diagnostic model. Machine learning algorithms facilitated model development. Cellular infiltration was assessed using the MCPcounter algorithm, and a heatmap integrated cell abundance and gene expression. A 3 × 3 convolutional neural network created an additional diagnostic model, while molecular docking identified potential drugs. The diagnostic model based on the 10 selected genes achieved excellent performance, with an AUC of 1 in both training and validation datasets. The heatmap, combining cell abundance and gene expression, provided insights into SAH cellular composition. The convolutional neural network model exhibited a sensitivity and specificity of 1 in both datasets. Additionally, CD14, GPNMB, SPP1 and PRDX5 were specifically expressed in SAH-associated macrophages, highlighting its potential as a therapeutic target. Network pharmacology analysis identified some targeting drugs for SAH treatment. Our study characterised SAH macrophage subpopulations and identified key associated genes. We developed a robust diagnostic model and recognised CD14, GPNMB, SPP1 and PRDX5 as potential therapeutic targets. Further experiments and clinical investigations are needed to validate these findings and explore the clinical implications of targets in SAH treatment.

Erratum: [Corrigendum] Aloperine activates the Nrf2­ARE pathway when ameliorating early brain injury in a subarachnoid hemorrhage model.

[This corrects the article DOI: 10.3892/etm.2018.5896.].

Sports promote brain evolution: a resting-state fMRI study of volleyball athlete.

Background: Long-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear. Method: We conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups. Results: No significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group. Conclusion: This study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registration: Registration number: ChiCTR2400079602. Date of Registration: January 8, 2024.

Ultrahigh Heat/Fire-Resistant, Mechanically Robust, and Closed-Loop Chemical Recyclable Polycarbonate Enabled by Facile Bond Dissociation Energy Modulation.

Plastics serve as an essential foundation in contemporary society. Nevertheless, meeting the rigorous performance demands in advanced applications and addressing their end-of-life disposal are two critical challenges that persist. Here, an innovative and facile method is introduced for the design and scalable production of polycarbonate, a key engineering plastic, simultaneously achieving high performance and closed-loop chemical recyclability. The bisphenol framework of polycarbonate is strategically adjusted from the low-bond-dissociation-energy bisphenol A to high-bond-dissociation-energy 4,4'-dihydroxydiphenyl, in combination with the incorporation of polysiloxane segments. As expected, the enhanced bond dissociation energy endows the polycarbonate with an extremely high glow-wire flammability index surpassing 1025 °C, a 0.8 mm UL-94 V-0 rating, a high LOI value of 39.2%, and more than 50% reduction of heat and smoke release. Furthermore, the π-π stacking interactions within biphenyl structures resulted in a significant enhancement of mechanical strength by as more as 37.7%, and also played a positive role in achieving a lower dielectric constant. Significantly, the copolymer exhibited outstanding closed-loop chemical recyclability, allowing for facile depolymerization into bisphenol monomers and the repolymerized copolymer retains its high heat and fire resistance. This work provides a novel insight in the design of high-performance and closed-loop chemical recyclable polymeric materials.

Development of Recombinant High-Density Lipoprotein Platform with Innate Adipose Tissue-Targeting Abilities for Regional Fat Reduction.

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.

Overcoming one-sidedness in cadre personnel management: Developing a competency framework for China's central state-owned enterprise executives.

China's central state-owned enterprises (SOEs) are politically and economically significant, and executives play a crucial role in determining their performance. In a competitive business environment, the selection and competencies of central SOE executives are crucial. This study aims to identify the competencies required to operate central SOEs and develops a competency framework for their executives. Through qualitative studies (face-to-face interviews and Delphi method) and two quantitative studies, we identify four dimensions-self-development, interpersonal, positional and organizational development-comprising 12 factors and 45 competencies, and use these to construct a competency framework. The competencies identified include some previously identified, but also unique competencies that are specific to the Chinese context. The proposed framework is valuable for understanding and improving managerial practices in central SOEs, and will help in the selection and development of executives. It also provides insights for central SOEs, and for individuals considering career and competency development.

Coupling coordination of urbanization with ecological environment and influencing factors in Loess Plateau of China.

The ecological damage caused by the accelerated urbanization process has continued to endanger the sustainable development of the Loess Plateau region, and the conflict between economic development and environmental protection has become increasingly critical. It is meaningful to explore the coupling coordination degree (CCD) between urbanization (UZ) and the ecological environment (EE) in the Loess Plateau and the mechanism of its influence to eliminate the locking of the rapid urbanization development paths in ecologically fragile regions, using panel data of 39 cities in the Loess Plateau region from 2010 to 2020. The empirical results have found that the level of UZ shows a fluctuating upward trend while the level of EE fluctuates and decreases. The synthesis CCD is at a barely coordinated level with an apparent upward trend, and the spatial characteristics are represented by "central depression," with low levels in the neighboring cities and high levels in the provincial capital cities. Regarding the driving factors, residents' living, industrial structure, and openness have a favorable impact on CCD, while enhancing the government's regulatory capacity has a negative blocking effect. These findings provide novel insights into the Loess Plateau's regional sustainable development.

How does diagnosis-related group payment impact the health care received by rural residents? Lessons learned from China.

OBJECTIVES: There is growing evidence that differences exist between rural and urban residents in terms of health, access to care and the quality of health care received, especially in low- and middle-income countries (LMICs). To improve health equity and the performance of health systems, a diagnosis-related group (DRG) payment system has been introduced in many LMICs to reduce financial risk and improve the quality of health care. The aim of this study was to examine the impact of DRG payments on the health care received by rural residents in China, and to help policymakers identify and design implementation strategies for DRG payment systems for rural residents in LMICs. STUDY DESIGN: Health impact assessment. METHODS: This study compared the impact of DRG payments on the healthcare received by rural residents in China between the pre- and post-reform periods by applying a difference-in-difference (DID) methodology. The study population included individuals with three common conditions; namely, cerebral infarction, transient ischaemic attack (TIA), and vertebrobasilar insufficiency (VBI). Data on patient medical insurance type were assessed, and those who did not have rural insurance were excluded. RESULTS: This study included 13,088 patients. In total, 33.63% were from Guangdong (n = 4401), 38.21% were from Shandong (n = 5002), and 28.16% were from Guangxi (n = 3685). The DID results showed that the implementation of DRGs was positively associated with hospitalization expense (ß4 = 0.265, P = 0.000), treatment expense (ß4 = 0.343, P = 0.002), drug expense (ß4 = 0.607, P = 0.000), the spending of medical insurance funds (ß4 = 0.711, P = 0.000) and out-of-pocket costs (ß4 = 0.164, P = 0.000). CONCLUSIONS: The findings of this study suggest that the implementation of DRG payments increases health care costs and the financial burden on health systems and rural patients in LMICs. This is contrary to the original intention of implementing the DRG payment system.

Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

Motor imagery-based brain-computer interface rehabilitation programs enhance upper extremity performance and cortical activation in stroke patients.

BACKGROUND: The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain-computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia. DESIGN: A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial. METHODS: Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures. RESULTS: A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P < 0.05), the mean zReHo of the right cuneus (r = 0.399, P < 0.05). CONCLUSION: In conclusion, BCI therapy is effective and safe for arm rehabilitation after severe poststroke hemiparesis. The correlation of the zALFF of the contralateral precentral gyrus and the zReHo of the ipsilateral cuneus with motor improvements suggested that these values can be used as prognostic measures for BCI-based stroke rehabilitation. We found that motor function was related to visual and spatial processing, suggesting potential avenues for refining treatment strategies for stroke patients. TRIAL REGISTRATION: The trial is registered in the Chinese Clinical Trial Registry (number ChiCTR2000034848, registered July 21, 2020).

VezA/vezatin facilitates proper assembly of the dynactin complex in vivo.

Cytoplasmic dynein-mediated intracellular transport needs the multi-component dynactin complex for cargo binding and motor activation. However, cellular factors involved in dynactin assembly remain unexplored. Here we found in Aspergillus nidulans that the vezatin homolog VezA is important for dynactin assembly. VezA affects the microtubule plus-end accumulation of dynein before cargo binding and cargo adapter-mediated dynein activation, two processes that both need dynactin. The dynactin complex contains multiple components including an Arp1 (actin-related protein 1) mini-filament associated with a pointed-end sub-complex. VezA physically interacts with dynactin either directly or indirectly via the Arp1 mini-filament and its pointed-end sub-complex. Loss of VezA causes a defect in dynactin integrity, most likely by affecting the connection between the Arp1 mini-filament and its pointed-end sub-complex. Using various dynactin mutants, we further revealed that assembly of the dynactin complex must be highly coordinated. Together, these results shed important new light on dynactin assembly in vivo.