Effects of individual metabolic brain network changes co-affected by T2DM and aging on the probabilities of T2DM: protective and risk factors.

Neuroimaging markers for risk and protective factors related to type 2 diabetes mellitus are critical for clinical prevention and intervention. In this work, the individual metabolic brain networks were constructed with Jensen-Shannon divergence for 4 groups (elderly type 2 diabetes mellitus and healthy controls, and middle-aged type 2 diabetes mellitus and healthy controls). Regional network properties were used to identify hub regions. Rich-club, feeder, and local connections were subsequently obtained, intergroup differences in connections and correlations between them and age (or fasting plasma glucose) were analyzed. Multinomial logistic regression was performed to explore effects of network changes on the probability of type 2 diabetes mellitus. The elderly had increased rich-club and feeder connections, and decreased local connection than the middle-aged among type 2 diabetes mellitus; type 2 diabetes mellitus had decreased rich-club and feeder connections than healthy controls. Protective factors including glucose metabolism in triangle part of inferior frontal gyrus, metabolic connectivity between triangle of the inferior frontal gyrus and anterior cingulate cortex, degree centrality of putamen, and risk factors including metabolic connectivities between triangle of the inferior frontal gyrus and Heschl's gyri were identified for the probability of type 2 diabetes mellitus. Metabolic interactions among critical brain regions increased in type 2 diabetes mellitus with aging. Individual metabolic network changes co-affected by type 2 diabetes mellitus and aging were identified as protective and risk factors for the likelihood of type 2 diabetes mellitus, providing guiding evidence for clinical interventions.

White matter fiber integrity and structural brain network topology: implications for balance function in postischemic stroke patients.

Previous studies have suggested that ischemic stroke can result in white matter fiber injury and modifications in the structural brain network. However, the relationship with balance function scores remains insufficiently explored. Therefore, this study aims to explore the alterations in the microstructural properties of brain white matter and the topological characteristics of the structural brain network in postischemic stroke patients and their potential correlations with balance function. We enrolled 21 postischemic stroke patients and 21 age, sex, and education-matched healthy controls (HC). All participants underwent balance function assessment and brain diffusion tensor imaging. Tract-based spatial statistics (TBSS) were used to compare the fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of white matter fibers between the two groups. The white matter structural brain network was constructed based on the automated anatomical labeling atlas, and we conducted a graph theory-based analysis of its topological properties, including global network properties and local node properties. Additionally, the correlation between the significant structural differences and balance function score was analyzed. The TBSS results showed that in comparison to the HC, postischemic stroke patients exhibited extensive damage to their whole-brain white matter fiber tracts (P < 0.05). Graph theory analysis showed that in comparison to the HC, postischemic stroke patients exhibited statistically significant reductions in the values of global efficiency, local efficiency, and clustering coefficient, as well as an increase in characteristic path length (P < 0.05). In addition, the degree centrality and nodal efficiency of some nodes in postischemic stroke patients were significantly reduced (P < 0.05). The white matter fibers of the entire brain in postischemic stroke patients are extensively damaged, and the topological properties of the structural brain network are altered, which are closely related to balance function. This study is helpful in further understanding the neural mechanism of balance function after ischemic stroke from the white matter fiber and structural brain network topological properties.

GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis.

Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the AKT/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the AKT/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.

Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Comparative efficacy of different noninvasive brain stimulation protocols on upper-extremity motor function and activities of daily living after stroke: a systematic review and network meta-analysis.

The objectives of the study were to systematically evaluate the rehabilitation effect of noninvasive brain stimulation (NIBS) on upper extremity motor function and activities of daily living in stroke patients and to prioritize various stimulation protocols for reliable evidence-based medical recommendations in patients with upper extremity motor dysfunction after stroke. Web of Science, PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and CBM were searched to collect all randomized controlled trials (RCTs) of NIBS to improve upper extremity motor function in stroke patients. The retrieval time was from the establishment of all databases to May 2023. According to the Cochrane system evaluation manual, the quality of the included studies was evaluated, and the data were extracted. Statistical analysis was carried out by using RevMan 5.3, R 4.3.0, and Stata 17.0 software. Finally, 94 RCTs were included, with a total of 5546 patients. Meta-analysis showed that NIBS improved the Fugl-Meyer assessment (FMA) score (mean difference (MD) = 6.51, 95% CI 6.20 ~ 6.82, P < 0.05), MBI score (MD = 7.69, 95% CI 6.57 ~ 8.81, P < 0.05), ARAT score (MD = 5.06, 95% CI 3.85 ~ 6.27, P < 0.05), and motor evoked potential (MEP) amplitude. The modified Ashworth scale score (MD = - 0.37, 95% CI - 0.60 to - 0.14, P < 0.05), National Institutes of Health Stroke Scale score (MD = - 2.17, 95% CI - 3.32 to - 1.11, P < 0.05), incubation period of MEP (MD = - 0.72, 95% CI - 1.06 to - 0.38, P < 0.05), and central motor conduction time (MD = - 0.90, 95% CI - 1.29 to - 0.50, P < 0.05) were decreased in stroke patients. Network meta-analysis showed that the order of interventions in improving FMA scores from high to low was anodal-transcranial direct current stimulation (tDCS) (surface under the cumulative ranking curve (SUCRA) = 83.7%) > cathodal-tDCS (SUCRA = 80.2%) > high-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (SUCRA = 68.5%) > low-frequency (LF)-rTMS (SUCRA = 66.5%) > continuous theta burst stimulation (cTBS) (SUCRA = 54.2%) > bilateral-tDCS (SUCRA = 45.2%) > intermittent theta burst stimulation (iTBS) (SUCRA = 34.1%) > sham-NIBS (SUCRA = 16.0%) > CR (SUCRA = 1.6%). In terms of improving MBI scores, the order from high to low was anodal-tDCS (SUCRA = 88.7%) > cathodal-tDCS (SUCRA = 85.4%) > HF-rTMS (SUCRA = 63.4%) > bilateral-tDCS (SUCRA = 56.0%) > LF-rTMS (SUCRA = 54.2%) > iTBS (SUCRA = 32.4%) > sham-NIBS (SUCRA = 13.8%) > CR (SUCRA = 6.1%). NIBS can effectively improve upper extremity motor function and activities of daily living after stroke. Among the various NIBS protocols, anodal-tDCS demonstrated the most significant intervention effect, followed by cathodal-tDCS and HF-rTMS.

Transforaminal endoscopic lumbar discectomy using a 45° puncture angle and foraminotomy versus traditional THESYS for L5/S1 lumbar disc herniation: a prospective randomized controlled trial.

PURPOSE: Prospective comparison of the efficacy and safety of transforaminal endoscopic lumbar discectomy (TELD) with a 45° puncture angle versus traditional Thomas Hoogland endoscopy spine systems (THESYS) for the surgical treatment of L5/S1 lumbar disc herniation (LDH). METHODS: Consecutive patients with L5/S1 LDH who underwent TELD were randomized (1:1) assigned to the 45° TELD group and the THESYS group. Clinical outcomes were assessed at pre-operation, 1-day and 3/6-months post-operation till final follow-up. Surgical-related parameters, visual analogue scale (VAS) score, oswestry disability index (ODI), and modified MacNab criteria, and surgical complications were recorded and analysed. RESULTS: All patients were followed up for at least 24 months. Compared to the THESYS group, the 45° TELD group had a shorter operative time (P < 0.001) and intraoperative radiation time (P < 0.001) and a smaller VAS score for back pain (P < 0.001) and leg pain intraoperatively (P < 0.001). The VAS and ODI in the 45° TELD group were significantly better than those in the THESYS group within 3 months postoperatively. However, from 3 months on, both groups showed comparable VAS and ODI. There was no significant difference between the two groups of modified MacNab criteria. There were two cases of residual disc and two cases of recurrence that required reoperation in the THESYS group. CONCLUSION: For L5/S1 LDH, the 45° TELD technique was superior to traditional THESYS in terms of surgery-related parameters and faster improvement of VAS and ODI, with a lower complication rate.

Intestinal microbiota promoted NiONPs-induced liver fibrosis via effecting serum metabolism.

Nickel oxide nanoparticles (NiONPs) are toxic heavy metal compounds that induce liver fibrosis and metabolic disorders. Current research shows that the intestinal microbiota regulates liver metabolism through the gut-liver axis. However, it is unclear whether NiONPs affect the intestinal microbiota and the relationship between microbiota and liver metabolic disorders. Therefore, in this study, we established liver fibrosis model by administering 0.015, 0.06 and 0.24 mg/mL NiONPs through tracheal instillation twice a week for 9 weeks in rats, then we collected serum and fecal sample for whole metabolomics and metagenomic sequencing. As the result of sequencing, we screened out seven metabolites (beta-D-glucuronide, methylmalonic acid, linoleic acid, phosphotidylcholine, lysophosphatidylinositol, docosapentaenoic acid and progesterone) that related to functional alterations (p < 0.05), and obtained a decrease of probiotics abundances (p < 0.05) as well as a variation of the microbiota enzyme activity (p < 0.05), indicating that NiONPs inhibited the proliferation of probiotics. As the result of correlation analysis, we found a positive correlation between differential metabolites and probiotics, such as lysophosphatidylinositol was positively correlated with Desulfuribacillus, Jeotgallibacillus and Rummeliibacillus (p < 0.05). We also found that differential metabolites had correlations with differential proteins and enzymes of intestinal microbiota, such as glucarate dehydratase, dihydroorotate dehydrogenase and acetyl-CoA carboxylase (p < 0.05). Finally, we screened six metabolic pathways with both differential intestinal microbiota enzymes and metabolites were involved, such as pentose and glucuronate interconversions, and linoleic acid metabolism. In vitro experiments showed that NiONPs increased the transcriptional expression of Col1A1 in LX-2 cells, while reducing the mRNA expression of serine/threonine activators, acetyl coenzyme carboxylase, and lysophosphatidylinositol synthase, and short chain fatty acid sodium butyrate can alleviate these variation trends. The results proved that the intestinal microbiota enzyme systems were associated with serum metabolites, suggesting that the disturbance of intestinal microbiota and reduction of probiotics promoted the occurrence and development of NiONPs-induced liver fibrosis by affecting metabolic pathways.

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).

The moderating role of information processing speed in the relationship between brain remodeling and episodic memory in amnestic mild cognitive impairment.

INTRODUCTION: The role of information processing speed (IPS) on relationships between episodic memory (EM) and central remodeling features in amnestic mild cognitive impairment (aMCI) was investigated. METHODS: Neuropsychological evaluations and multimodal magnetic resonance imaging were performed on 48 patients diagnosed with aMCI and 50 healthy controls (HC). Moderation models explored the moderating effect of IPS on associations between EM and imaging features at single-region, connectivity, and network levels. RESULTS: IPS significantly enhanced the positive correlations between recall and cortical thickness of left inferior temporal gyrus. IPS also notably amplified negative correlations between recognition and functional connectivity (FC) of left inferior parietal lobe and right occipital, as well as between recall/recognition and nodal clustering coefficient of left anterior cingulate cortex. DISCUSSION: IPS functioned as a moderator of associations between recall and neuroimaging metrics at the "single region-connectivity-network" level, providing new insights for cognitive rehabilitation in aMCI patients. HIGHLIGHTS: aMCI patients exhibited brain functional and structural remodeling alterations. IPS moderated relations between episodic memory and brain remodeling metrics. Therapy targeted at IPS can be considered for improving episodic memory in aMCI.

A cross-sectional study: correlation of forehead morphology and dentoskeletal malocclusion in Chinese people.

BACKGROUND: The lateral profile is an important indicator of facial attractiveness. This study explored the general characteristics of the forehead profile and protrusion, and their relationship with related factors in structure and development. METHODS: Four hundred fourteen Chinese participants in the Yangtze River Delta region were involved. Including 206 males (17.15 ± 7.68 years old) and 208 females (18.35 ± 8.06 years old); 94 children (8.54 ± 2.21 years old, ranging from 4 to 12 years old), 166 adolescents (14.83 ± 1.50 years old, ranging from 13 to 17 years old), and 154 adults (25.52 ± 4.89, 18 years or older). The frontal section of the forehead was used to explore its shape. The straight distance between the vertical line of the FH plane through the nasal root point and its parallel line, which is tangential to the forehead, indicates the forehead prominence. Frontal sinus width was measured using the method described by Mahmood. RESULTS: The general shape of the forehead was straight and slightly bulged near the eyebrow arch in males but rounder in females. The average forehead protrusion in males was higher than that in females in adults. Significant differences in forehead protrusion between the dentoskeletal classifications and growth phases were notable. Frontal protrusion significantly correlated with frontal sinus depth, especially in males, adults, Class I, and those whose convex points were located in the lower section of the forehead. CONCLUSIONS: Age, race, and sex affect the forehead protrusion and frontal sinus width. Forehead protrusion may be an indicator of dentoskeletal deformities in the early stage. And dentoskeletal deformities may impair the correlation between the frontal sinuses and forehead protrusion during development. TRIAL REGISTRATION: This retrospective, cross-sectional study was reviewed and approved by the Research Ethical Committee (T2020008), and registered at ClinicalTrial.gov with an identified number (ChiCTR2100041913).

Morphological alterations of contralesional hemisphere relate to functional outcomes after stroke.

The present study aimed to investigate poststroke morphological alterations contralesionally and correlations with functional outcomes. Structural magnetic resonance images were obtained from 27 poststroke patients (24 males, 50.21 ± 10.97 years) and 20 healthy controls (13 males, 46.63 ± 12.18 years). Voxel-based and surface-based morphometry analysis were conducted to detect alterations of contralesional grey matter volume (GMV), cortical thickness (CT), gyrification index (GI), sulcus depth (SD), and fractal dimension (FD) in poststroke patients. Partial correlation analysis was used to explore the relationship between regions with significant structural differences and scores of clinical assessments, including Modified Barthel Index (MBI), Berg Balance Scale (BBS), Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Correction for multiplicity was conducted within each parameter and for all tests. GMV significantly decreased in the contralesional motor-related, occipital and temporal cortex, limbic system, and cerebellum lobe (P < 0.01, family-wise error [FWE] correction). Lower CT was found in the contralesional precentral and lingual gyrus (P < 0.01, FWE correction), while lower GI found in the contralesional superior temporal gyrus and insula (P < 0.01, FWE correction). There were significant correlations between GMV of contralesional lingual gyrus and MBI (P = 0.031, r = 0.441), and BBS (P = 0.047, r = 0.409) scores, and GMV of contralesional hippocampus and FMA-UE scores (P = 0.048, r = 0.408). In conclusion, stroke patients exhibited wide grey matter loss and cortical morphological changes in the contralesional hemisphere, which correlated with sensorimotor functions and the ability of daily living.

Effects of electroacupuncture on imaging and behavior in rats with ischemic stroke through miR-212-5p.

BACKGROUND: Ischemic stroke is a serious disease leading to significant disability in humans worldwide. Increasing evidence suggests that some microRNAs (miRNAs) participate in the pathophysiology of ischemic stroke. A key role for MiR-212 has been found in neuronal function and synaptic plasticity. Ischemic stroke can be effectively treated with electroacupuncture (EA); however, there is a lack of understanding of the relevant mechanisms. In this study, we employed behavioral test and resting-state functional magnetic resonance imaging (rs-fMRI) to detect behavioral and brain function alterations in rats suffering from ischemic stroke. The efficacy of EA therapy and miR-212-5p's role in this process were also evaluated. METHODS AND RESULTS: Forty rats were randomly divided into the following groups: Sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EA, MCAO/R + EA + antagomir-negative control and MCAO/R + EA + antagomir-212-5p groups. Behavioral changes were assessed by Catwalk gait analysis prior to and after modeling. Rs-fMRI was performed at one week after EA treatment, amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated to reveal neural activity. Furthermore, neuronal apoptosis in the ischemic penumbra was analyzed using a TUNEL assay. Treatment with EA significantly improved the performance of rats in the behavioral test. The motor and cognition-related brain regions showed decreased ALFF and ReHo following focal cerebral ischemia-reperfusion, and EA treatment could reactivate these brain regions. Moreover, EA treatment significantly decreased MCAO/R-induced cell death. However, the transfection of antagomir-212-5p attenuated the therapeutic effect of EA. CONCLUSIONS: In conclusion, the results suggested that EA improved the behavioral and imaging outcomes of ischemic stroke through miR-212-5p.

Association of PFN1 Gene Polymorphisms with Bone Mineral Density, Bone Turnover Markers, and Osteoporotic Fractures in Chinese Population.

Recent studies have discovered an association between the PFN1 gene and Paget's disease. However, it is currently unknown whether the PFN1 gene is related to osteoporosis. This study was performed to investigate the association of Single-Nucleotide Polymorphisms (SNPs) in the PFN1 gene with Bone Mineral Density (BMD) as well as bone turnover markers and osteoporotic fractures in Chinese subjects. A total of 2836 unrelated Chinese subjects comprising 1247 healthy subjects and 1589 osteoporotic fractures patients (Fracture group) were enrolled in this study. Seven tagSNPs (rs117337116, rs238243, rs6559, rs238242, rs78224458, rs4790714, and rs13204) of the PFN1 gene were genotyped. The BMD of the lumbar spine 1-4 (L1-4), femoral neck, and total hip as well as bone turnover markers, such as ß-C-Terminal telopeptide of type 1 collagen (ß-CTX) and Procollagen type 1 N-terminal Propeptide (P1NP), were measured. The association between 7 tagSNPs and BMD and bone turnover markers was analyzed in 1247 healthy subjects only. After age matching, we selected 1589 osteoporotic fracture patients (Fracture group) and 756 nonfracture controls (Control group, selected from 1247 healthy subjects) for a case-control study, respectively. For the case-control study, we used logistic regression to investigate the relationship between 7 tagSNPs and osteoporotic fractures risk. In the All group, the PFN1 haplotype GAT was associated with the ß-CTX (P = 0.007). In the Female group, the PFN1 haplotype GAT was associated with the ß-CTX (P = 0.005). In the Male group, the rs13204, the rs78224458, and the PFN1 haplotype GAC were associated with the BMD of the L1-4 (all P = 0.012); the rs13204, the rs78224458, and the PFN1 haplotype GAC were associated with the BMD of the femoral neck (all P = 0.012); the rs13204 and rs78224458 were associated with the BMD of the total hip (both P = 0.015); and the PFN1 haplotype GAT was associated with the ß-CTX (P = 0.013). In the subsequent case-control study, the rs13204 and rs78224458 in the male group were associated with the risk of L1-4 fracture (P = 0.016 and 0.010, respectively) and total hip fracture (P = 0.013 and 0.016, respectively). Our study reveals that PFN1 gene polymorphisms are associated with BMD in Chinese males and ß-CTX in Chinese people and confirmed the relationship between PFN1 gene polymorphisms and Chinese male osteoporotic fractures in a case-control study.

Effects of cortico-cortical paired associative stimulation based on multisensory integration to brain network connectivity in stroke patients: study protocol for a randomized doubled blind clinical trial.

INTRODUCTION: Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. METHOD: This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the 'Fugl-Meyer Assessment of the Upper Extremity ', secondary outcomes were 'The line bisection test', 'Modified Taylor Complex Figure', 'NIHSS' and neuroimaging assessments. All adverse events will be recorded. DISCUSSION: Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

Endoscopic mucosal resection of gastrointestinal polyps with a novel low-temperature plasma radio frequency generator: a non-inferiority multi-center randomized control study.

BACKGROUND: To evaluate the efficacy and safety of novel plasma radio frequency generator and its single-use polypectomy snares for endoscopic mucosal resection (EMR) of gastrointestinal (GI) polyps. METHODS: A total of 217 patients with 413 GI polyps were recruited from four centers in China. Patients were assigned to experimental or control groups using a central randomization method. The experimental group used the novel plasma radio frequency generator and its matched single-use polypectomy snares (Neowing, Shanghai), while the control group used the high-frequency electrosurgical unit (Erbe, Germany) and disposable electrosurgical snares (Olympus, Japan). The primary endpoint was the en bloc resection rate, and the non-inferiority margin was set at 10%. Secondary endpoint included operation time, coagulation success rate, intraoperative and postoperative bleeding rate, and perforation rate. RESULTS: The en bloc resection rate was 97.20% (104/107) in the experimental group and 95.45% (105/110) in the control group (P = 0.496). The operation time was 29.14 ± 20.21 min in the experimental group and 30.26 ± 18.74 min in the control group (P = 0.671). The average removal time of a single polyp in the experimental group was 7.52 ± 4.45 min, which was slightly shorter than that in the control group 8.90 ± 6.67 min, with no statistical difference (P = 0.076). The intraoperative bleeding rates of the experimental group and control group were 8.41% (9/107) and 10.00% (11/110), respectively (P = 0.686). No intraoperative perforation occurred in either group. The postoperative bleeding rates of the experimental group and the control group were 1.87% (2/107) and 4.55% (5/110), respectively (P = 0.465). No postoperative perforation occurred in the experimental group (0/107), while one case of delayed perforation occurred in the control group (1/110, 0.91%). There was no statistical difference between the two groups. CONCLUSIONS: Endoscopic mucosal resection of GI polyps with the novel plasma radio frequency generator is safe and effective, and non-inferior to the conventional high-frequency electrosurgical system.

Focal ischemic stroke modifies microglia-derived exosomal miRNAs: potential role of mir-212-5p in neuronal protection and functional recovery.

BACKGROUND: Ischemic stroke is a severe type of stroke with high disability and mortality rates. In recent years, microglial exosome-derived miRNAs have been shown to be promising candidates for the treatment of ischemic brain injury and exert neuroprotective effects. Mechanisms underlying miRNA dysregulation in ischemic stroke are still being explored. Here, we aimed to verify whether miRNAs derived from exosomes exert effects on functional recovery. METHODS: MiR-212-5p agomir was employed to upregulate miR-212-5p expression in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Western blot analysis, qRT-PCR and immunofluorescence staining and other methods were applied to explore the underlying mechanisms of action of miR-212-5p. RESULTS: The results of our study found that intervention with miR-212-5p agomir effectively decreased infarct volume and restored motor function in MCAO/R rats. Mechanistically, miR-212-5p agomir significantly reduced the expression of PlexinA2 (PLXNA2). Additionally, the results obtained in vitro were similar to those achieved in vivo. CONCLUSION: In conclusion, the present study indicated that PLXNA2 may be a target gene of miR-212-5p, and miR-212-5p has great potential as a target for the treatment and diagnosis of ischemic stroke.

Osteochondral Autograft From the Hamate for Treating Partial Defect of the Proximal Interphalangeal Joint.

PURPOSE: The management of a proximal interphalangeal (PIP) joint fracture dislocation becomes more challenging when the joint surface is damaged because of severe comminution or inadequate treatment in the acute phase. The purpose of this study was to evaluate the clinical outcomes of an osteochondral autograft for the reconstruction of the joint surface in patients with a partial PIP joint defect. METHODS: Twelve patients underwent osteochondral autograft surgery from May 2007 to July 2018. The average age at the time of surgery was 38 years (range, 21-67 years), and there were 10 men and 2 women. Plain radiographs and computed tomography scans showed a partial middle phalangeal base defect in all the cases. The surgeries were performed 2 weeks to 20 months after the fracture or a previous surgery. Partial hamate grafts were harvested to reconstruct volar lip (n = 7), middle portion (n = 2), and dorsal lip (n = 3) defects of the middle phalangeal base. Bone healing, postoperative range of motion, instability, and pain were evaluated. The average follow-up duration was 27.8 months (range, 12-53 months). RESULTS: Radiographic graft union was observed in all the patients 6-8 weeks after the surgery. The deformity was corrected in 11 patients. The active range of motion of the involved PIP joint was improved from 28.3° (range, 0°-60°) to 75.0° (range, 25°-95°). Complications were observed during follow-up, including degenerative arthritis (n = 2), instability (n = 3), and stiffness (n = 5). CONCLUSIONS: Various types of partial joint defects of the middle phalangeal base following a PIP fracture dislocation can be reconstructed using an osteochondral autograft from the hamate. The functional recovery is generally acceptable, with a well-restored joint architecture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Immature permanent incisors with complicated crown fractures treated with partial pulpotomy using white mineral trioxide aggregate and IRoot BP plus-a retrospective long-term study.

BACKGROUND/AIMS: Calcium silicate cements have been widely used for pulpotomies in immature permanent teeth with complicated crown fractures due to their superior properties. However, few studies have evaluated the long-term outcomes of white mineral trioxide aggregate (WMTA) and iRoot BP Plus for partial pulpotomies. The aim of this study was to investigate the long-term clinical and radiographic outcomes of WMTA and iRoot BP Plus for partial pulpotomies in immature permanent incisors with complicated crown fractures. MATERIALS AND METHODS: Children who had partial pulpotomies of immature permanent incisors with complicated crown fractures using WMTA or iRoot BP Plus as capping agents were enrolled. Eighty immature permanent incisors in 68 children (aged 8-13 years) were included. They were divided into two groups (WMTA and iRoot BP Plus) according to the capping agents. Clinical and radiographic information was collected during a 5-year follow-up period. Study data were analyzed using Chi-square tests or Fisher exact tests. RESULTS: The clinical and radiographic success rates in the WMTA (n = 36) and iRoot BP Plus groups (n = 44) were 94.4% versus 97.7% and 88.9% versus 97.7%, respectively (both p < .05). The average observation period was 74.5 ± 13.2 months and 61.9 ± 1.6 months in the WMTA and iRoot BP Plus groups, respectively (p < .01). Five cases presented with periapical radiolucencies. The WMTA group had four cases of pulp canal calcification (11.1%), while the iRoot BP Plus group had two cases (4.6%). There was crown discolouration in all cases in the WMTA group, but none in the iRoot BP Plus group. CONCLUSION: Both WMTA and iRoot BP Plus had favorable outcomes in promoting physiological development and maintaining the basic functions of immature permanent incisors with complicated crown fractures. As a partial pulpotomy material, iRoot BP Plus may be more suitable for the esthetic zone than WMTA.

Molecular feature of neutrophils in immune microenvironment of muscle atrophy.

Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments.

Genetically modified mesenchymal stem cells promote spinal fusion through polarized macrophages.

Spinal fusion is an effective treatment for low back pain and typically applied with prosthetic fixation devices. Spinal fusion can be improved by transplantation of mesenchymal stem cells (MSCs) into the paraspinal muscle. However, in contrast to the direct contribution of MSCs to spinal fusion, the indirect effects of MSCs on spinal infusion have not been studied and were thus addressed here. The correlation between the outcome of spinal fusion and the local macrophage number, polarization and the levels of placental growth factor (PlGF) in patients was analyzed. MSCs were genetically modified to overexpress PlGF, and its effects on macrophage proliferation and polarization were analyzed in vitro in a transwell co-culture system, as well as in vivo in a mouse model for spinal fusion, for which the cells were bilaterally injected into paravertebral muscles of the mouse lumbar spine. The effects on spinal fusion were assessed by microcomputed tomography and a custom four-point bending apparatus for structural bending stiffness. Local macrophages were analyzed by flow cytometry. We found that posterior spinal fusion could be improved by PlGF-expressing MSCs, compared to the control MSCs, evident by significant improvement of bone bridging of the targeted vertebrae. Mechanistically, PlGF-expressing MSCs appeared to attract macrophages and induce their M2 polarization, which in turn promotes the bone formation. Together, our data suggest that PlGF-expressing MSCs may improve spinal fusion through macrophage recruitment and polarization.