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The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.
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PURPOSE: Targeted therapies have markedly improved the prognosis of lung cancer patients; nevertheless, challenges persist, including limited beneficiary populations and the emergence of drug resistance. This study investigates the molecular mechanisms of mutant TP53 in lung cancer, aiming to contribute to novel strategies for targeted therapy. METHODS: The TCGA database was employed to delineate the mutational landscape of TP53 in lung cancer patients. Differential gene expression between TP53-mutant and wild-type patients was analyzed, followed by functional enrichment. DSG3 protein expression in lung cancer patients was assessed using IHC, and its impact on prognosis was analyzed in the TCGA database. The influence of TP53 on the downstream gene DSG3 was investigated using qPCR, ChIP-qPCR, and luciferase reporter gene assays. Protein enrichment in the DSG3 promoter region was examined through IP-MS, and the regulatory role of the HIF1-α/TP53 complex on DSG3 was explored using Co-IP, luciferase assays, and ChIP-qPCR. Molecular interactions between TP53 (R273H) and HIF1-α were detected through immunoprecipitation and molecular docking. The effects and mechanisms of DSG3 on lung cancer phenotypes were assessed through WB, transwell, and wound healing assays. RESULTS: TP53 mutations were present in 47.44% of patients, predominantly as missense mutations. DSG3 exhibited high expression in TP53-mutant lung cancer patients, and this elevated expression correlated with a poorer prognosis. TP53 interference led to a reduction in DSG3 mRNA expression, with TP53 mutant P53 enriching at the P2 site of the DSG3 promoter region, a recruitment facilitated by HIF1-α. The DBD region of TP53 (R273H) demonstrated interaction with HIF1-α. DSG3, activated through Ezrin phosphorylation, played a role in promoting invasion and metastasis. CONCLUSIONS: Mutant TP53 facilitates lung cancer cell invasion by modulating desmoglein 3.
Subject(s)
Desmoglein 3 , Lung Neoplasms , Mutation , Neoplasm Invasiveness , Tumor Suppressor Protein p53 , Female , Humans , Male , Middle Aged , Cell Line, Tumor , Desmoglein 3/genetics , Desmoglein 3/metabolism , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Prognosis , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Anterior subcutaneous internal fixation (INFIX) is one of the current representatives of minimally invasive fixation of injuries to the anterior pelvic ring. The nail insertion point of this technique is located at the anterior inferior iliac spinous screw, with an angle of 30° outward and 20° backward. Screw in at an angle, and note that the screw head should be above the deep fascia and maintain a safe distance of 20 to 25 mm from the bone surface. Its improved versions include 3 or 4 nails INFIX with added pubic tubercle screws, unilateral INFIX, short-rod INFIX, and double INFIX. These improvements further enhance stability. The lateral femoral cutaneous nerve (LFCN) is relatively easy to be damaged during anatomy, so special attention should be paid during the operation. Biomechanical stability has advantages over external fixation, and its application is flexible. It is not limited to pubic ramus fracture, symphyseal separation, etc. It also plays an important role in combined anterior and posterior ring fixation. It can be combined with posterior sacroiliac screws, iliac lumbar screws, etc. Fixed etc. Good clinical results have also been reported in children, pregnant women, and people with contraindications for subcutaneous connecting rods. In addition, the current application of robots, reduction frames and other technologies has greatly reduced the difficulty of reduction and improved the quality of closed reduction, making it possible to fix complex pelvic fracture. This technique has high reduction quality and is as effective as traditional steel plates. A common complication is LFCN injury. Careful exposure and adjustment of the position and depth of internal fixation during surgery can effectively avoid this complication.
Subject(s)
Fracture Fixation, Internal , Pelvic Bones , Humans , Fracture Fixation, Internal/methods , Pelvic Bones/injuries , Pelvic Bones/surgery , Fractures, Bone/surgeryABSTRACT
BACKGROUND: Impaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. METHODS: Thirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. RESULTS: Compared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SIGNIFICANCE: The study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. CONCLUSIONS: Distinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.
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Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.
Subject(s)
Autophagy , Glycosides , Pentacyclic Triterpenes , Spermatogonia , Testis , Tripterygium , Triterpenes , Animals , Male , Tripterygium/chemistry , Tripterygium/toxicity , Autophagy/drug effects , Testis/drug effects , Testis/pathology , Glycosides/toxicity , Glycosides/pharmacology , Spermatogonia/drug effects , Mice , Triterpenes/pharmacology , Triterpenes/toxicity , Cell Line , Cell Survival/drug effectsABSTRACT
OBJECTIVE: Hemophilia carriers (HCs), who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene (F8 or F9), may have a wide range of clotting factor levels, from very low, similar to afflicted males, to the upper limit of normal, and may experience mental health issues. The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs. Additionally, we aimed to investigate the mental health status of HCs in China. METHODS: A total of 127 hemophilia mothers, including 93 hemophilia A (HA) mothers and 34 hemophilia B (HB) mothers, were enrolled in this study. Long distance PCR, multiplex PCR, and Sanger sequencing were used to analyze mutations in F8 or F9. Coagulation factor activity was detected by a one-stage clotting assay. The Symptom Checklist 90 (SCL-90, China/Mandarin version) was given to HCs at the same time to assess their mental health. RESULTS: A total of 90.6% of hemophilia mothers were diagnosed genetically as carriers, with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers, respectively. The median clotting factor level in carriers was 0.74 IU/mL (ranging from 0.09 to 1.74 IU/mL) compared with 1.49 IU/mL (ranging from 0.93 to 1.89 IU/mL) in noncarriers, of which 14.3% of HCs had clotting factor levels of 0.40 IU/mL or below. A total of 53.8% (7/13) of HA carriers with low clotting factor levels (less than 0.50 IU/mL) had a history of bleeding, while none of the HB carriers displayed a bleeding phenotype. The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00 (±60.37) and 1.78 (±0.59), respectively. A total of 67.7% of the respondents had psychological symptoms, with obsessive-compulsive disorder being the most prevalent and severe. The pooled estimates of all nine factors were significantly higher than those in the general population (P<0.05). CONCLUSIONS: The detection rate of gene mutations in hemophilia mothers was 90.6%, with a median clotting factor level of 0.74 IU/mL, and 14.3% of HCs had a clotting factor level of 0.40 IU/mL or below. A history of bleeding was present in 41.2% of HCs with low clotting factor levels (less than 0.50 IU/mL). Additionally, given the fragile mental health status of HCs in China, it is critical to develop efficient strategies to improve psychological well-being.
Subject(s)
Hemophilia A , Male , Humans , Hemophilia A/epidemiology , Hemophilia A/genetics , Cross-Sectional Studies , Blood Coagulation Factors , Hemorrhage , Surveys and Questionnaires , Health SurveysABSTRACT
BACKGROUND: Mathematical modeling and computer simulation are important methods for understanding complex neural systems. The whole-brain network model can help people understand the neurophysiological mechanisms of brain cognition and functional diseases of the brain. METHODS: In this study, we constructed a resting-state whole-brain network model (WBNM) by using the Wendling neural mass model as the node and a real structural connectivity matrix as the edge of the network. By analyzing the correlation between the simulated functional connectivity matrix in the resting state and the empirical functional connectivity matrix, an optimal global coupling coefficient was obtained. Then, the waveforms and spectra of simulated EEG signals and four commonly used measures from graph theory and small-world network properties of simulated brain networks under different thresholds were analyzed. RESULTS: The results showed that the correlation coefficient of the functional connectivity matrix of the simulated WBNM and empirical brain networks could reach a maximum value of 0.676 when the global coupling coefficient was set to 20.3. The simulated EEG signals showed rich waveform and frequency-band characteristics. The commonly used graph-theoretical measures and small-world properties of the constructed WBNM were similar to those of empirical brain networks. When the threshold was set to 0.22, the maximum correlation between the simulated WBNM and empirical brain networks was 0.709. CONCLUSIONS: The constructed resting-state WBNM is similar to a real brain network to a certain extent and can be used to study the neurophysiological mechanisms of complex brain networks.
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BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.
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Patients with neurodegenerative diseases exhibit diminished basal forebrain (BF) volume compared to healthy individuals. However, it's uncertain whether this difference is consistent between sexes. It has been reported that BF volume moderately atrophies during aging, but the effect of sex on BF volume changes during the normal aging process remains unclear. In the cross-sectional study, we observed a significant reduction in BF volume in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to Healthy Controls (HCs), especially in the Ch4 subregion. Notably, significant differences in BF volume between MCI and HCs were observed solely in the female group. Additionally, we identified asymmetrical atrophy in the left and right Ch4 subregions in female patients with AD. In the longitudinal analysis, we found that aging seemed to have a minimal impact on BF volume in males. Our study highlights the importance of considering sex as a research variable in brain science.
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Human brain structure shows heterogeneous patterns of change across adults aging and is associated with cognition. However, the relationship between cortical structural changes during aging and gene transcription signatures remains unclear. Here, using structural magnetic resonance imaging data of two separate cohorts of healthy participants from the Cambridge Centre for Aging and Neuroscience (n = 454, 18-87 years) and Dallas Lifespan Brain Study (n = 304, 20-89 years) and a transcriptome dataset, we investigated the link between cortical morphometric similarity network and brain-wide gene transcription. In two cohorts, we found reproducible morphometric similarity network change patterns of decreased morphological similarity with age in cognitive related areas (mainly located in superior frontal and temporal cortices), and increased morphological similarity in sensorimotor related areas (postcentral and lateral occipital cortices). Changes in morphometric similarity network showed significant spatial correlation with the expression of age-related genes that enriched to synaptic-related biological processes, synaptic abnormalities likely accounting for cognitive decline. Transcription changes in astrocytes, microglia, and neuronal cells interpreted most of the age-related morphometric similarity network changes, which suggest potential intervention and therapeutic targets for cognitive decline. Taken together, by linking gene transcription signatures to cortical morphometric similarity network, our findings might provide molecular and cellular substrates for cortical structural changes related to cognitive decline across adults aging.
Subject(s)
Aging , Brain , Adult , Humans , Brain/physiology , Aging/physiology , Cognition/physiology , Temporal Lobe , Magnetic Resonance Imaging/methodsABSTRACT
Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.
Subject(s)
Bipolar Disorder , Humans , Child , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/psychology , Brain/diagnostic imaging , Emotions/physiology , Frontal Lobe , Prefrontal Cortex , Brain Mapping , Magnetic Resonance ImagingABSTRACT
Brain function changes affect cognitive functions in older adults, yet the relationship between cognition and the dynamic changes of brain networks during naturalistic stimulation is not clear. Here, we recruited the young, middle-aged and older groups from the Cambridge Center for Aging and Neuroscience to investigate the relationship between dynamic metrics of brain networks and cognition using functional magnetic resonance imaging data during movie-watching. We found six reliable co-activation pattern (CAP) states of brain networks grouped into three pairs with opposite activation patterns in three age groups. Compared with young and middle-aged adults, older adults dwelled shorter time in CAP state 4 with deactivated default mode network (DMN) and activated salience, frontoparietal and dorsal-attention networks (DAN), and longer time in state 6 with deactivated DMN and activated DAN and visual network, suggesting altered dynamic interaction between DMN and other brain networks might contribute to cognitive decline in older adults. Meanwhile, older adults showed easier transfer from state 6 to state 3 (activated DMN and deactivated sensorimotor network), suggesting that the fragile antagonism between DMN and other cognitive networks might contribute to cognitive decline in older adults. Our findings provided novel insights into aberrant brain network dynamics associated with cognitive decline.
Subject(s)
Brain , Magnetic Resonance Imaging , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/physiology , Cognition/physiology , Brain Mapping , Nerve Net/diagnostic imaging , Nerve Net/physiologyABSTRACT
Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.
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Anhedonia is a core feature of major depressive disorder (MDD) and the limbic system has been indicated to be associated with anhedonia in MDD due to its crucial role within the reward circuit. However, the relationship between different regions of the limbic system and MDD, particularly anhedonic symptoms, remains unclear. Therefore, the purpose of this study was to investigate volume changes of various parts of the subcortical limbic (ScLimbic) system in MDD with and without anhedonia. A total of 120 individuals, including 30 MDD patients with anhedonia, 43 MDD patients without anhedonia, and 47 healthy controls (HCs) were enrolled in this study. All subjects underwent structural magnetic resonance imaging scans. After that, ScLimbic system segmentation was performed using the FreeSurfer pipeline ScLimbic. Analysis of covariance (ANCOVA) was performed to identify brain regions with significant volume differences among three groups, and then, post hoc tests were calculated for inter-group comparisons. Finally, correlations between volumes of different parts of the ScLimbic and clinical characteristics in MDD patients were further analyzed. The ANCOVA revealed significant volume differences of the ScLimbic system among three groups in the bilateral fornix (Fx), and the right basal forebrain (BF). As compared with HCs, both groups of MDD patients showed decreased volume in the right Fx, meanwhile, MDD patients with anhedonia further exhibited volume reductions in the left Fx and right BF. However, no significant difference was found between MDD patients with and without anhedonia. No significant association was observed between subregion volumes of the ScLimbic system and clinical features in MDD. The present findings demonstrated that MDD patients with and without anhedonia exhibited segregated brain structural alterations in the ScLimbic system and volume loss of the ScLimbic system might be fairly extensive in MDD patients with anhedonia.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/pathology , Anhedonia , Brain/pathology , Magnetic Resonance ImagingABSTRACT
INTRODUCTION: The segmental bone defects post open distal femur fracture presents a reconstructive challenge, which often requires extreme solutions. The present study reviewed a new treatment strategy which used a cylindrical titanium mesh cage as an adjunct to the Masquelet technique. METHODS: We retrospectively reviewed a consecutive series of 23 patients treated for segmental bone defects post open distal femur fracture using a titanium mesh cage combined with the Masquelet technique under a 2-staged protocol in our institution from 2017 to 2021. The study group consisted of 13 men and 10 women with an average age of 44.1 years. The surgical debridement was performed with antibiotic polymethylmethacrylate (PMMA) cement spacer implanted into the bone defect combined with cement-wrapped plate stabilization, or antibiotic beads with vacuum sealing drainage (VSD) to cover the wound. The second stage of the Masquelet technique for bone defect repair began at least 4-6 weeks after the first stage, once all signs of possible infection were eliminated. After the cement spacer was removed, the definitive reconstruction was completed with exchange to a cylindrical titanium mesh cage filled with cancellous autograft within the induced membrane. The bone defect with cage was stabilized with a distal femoral Less Invasive Stabilization System (LISS). The radiological and clinical records of the enrolled patients were retrospectively analyzed. RESULTS: The mean follow-up was 38.6 months. The average number of operations before the second stage was 1.3. The mean interval between the two stages was 12.7 weeks. The average length of the defect measured 8.3 cm (ranging from 6.1 to 12.4 cm). All the defects filled with autograft within the cage achieved bony union, with a mean healing time of 8.4 months. At the latest follow-up, the mean knee extension measured 6.2° (ranging from 0° to 20°), and the mean flexion measured 101.8° (ranging from 60° to 120°). Complications included two instances of superficial stitch abscess, which eventually healed. CONCLUSIONS: The use of a titanium cage implanted into an induced membrane in a 2-staged Masquelet protocol could achieve satisfactory clinical outcomes in cases of segmental defects following open distal femur fractures.
Subject(s)
Femoral Fractures, Distal , Femoral Fractures , Male , Humans , Female , Adult , Titanium , Retrospective Studies , Femoral Fractures/diagnostic imaging , Femoral Fractures/surgery , Anti-Bacterial Agents/therapeutic use , Bone Transplantation/methods , Treatment OutcomeABSTRACT
Atypical functional connectivity (FC) patterns have been identified in autism spectrum disorders (ASD), especially within salience network (SN) and between SN and default mode network (DMN) and central executive network (CEN). But whether the dynamic configuration of intra-SN and inter-SN (SN with DMN and CEN) FC in ASD is also heterogeneous remains unknown. Based on the resting-state functional magnetic resonance imaging data from 105 ASD and 102 typically-developing controls (TC), we calculated the time-varying FC of intra-SN and inter-SN (SN with DMN and CEN). Then, the joint recurrence features for the time-varying FC were calculated to assess how the SN dynamically recruits different configurations of network segregation and integration in ASD, that is, synergies, from the dynamical systems perspective. We analyzed the differences in synergetic patterns between ASD subtypes obtained by k-means clustering algorithm based on the synergy of SN and TC, and investigated the relationships between synergy of SN and severity of clinical symptoms of ASD for ASD subtypes. Two ASD subtypes were revealed, where the synergy of SN in ASD subtype 1 has lower stability and periodicity compared to the TC, and ASD subtype 2 exhibits the opposite alteration. Synergy of SN for ASD subtype 1 and 2 was found to predict the severity of communication impairments and restricted and repetitive behaviors in ASD, respectively. These results suggest the existence of subtypes with distinct patterns of the synergy of SN in ASD, and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD.
Subject(s)
Autism Spectrum Disorder , Child , Humans , Magnetic Resonance Imaging/methods , Neural Pathways , Cluster Analysis , Algorithms , Brain/diagnostic imaging , Brain Mapping/methodsABSTRACT
An efficient synthesis of α-(1,3,5-triazinylthio)-ketones from 1,3-dicarbonyl compounds with 1,3,5-triazine-2-thiols has been developed. The reaction proceeds through the C-C bond cleavage and C-S bond reconstruction of 1,3-dicarbonyl compounds, and ß-keto esters, ß-keto amides, and 1,3-diones were tolerated. In addition, the annulation of 1,3,5-triazine-2-thiols with chalcones has been achieved for the synthesis of thiazolo[3,2-a][1,3,5]triazines. The method occurred in moderate to good yields and tolerated chalcone with a broad functional group.
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Neuro-navigation is a key technology to ensure the clinical efficacy of TMS. However, the neuro-navigation system based on positioning sensor is currently unable to be promoted and applied in clinical practice due to its time-consuming and high-cost. In the present study, we designed I-Helmet system to promote an individualized and clinically friendly neuro-navigation approach to TMS clinical application. I-Helmet system is based on C++ with a graphical user interface that allows users to design a 3D-printed helmet model for coil navigation. Besides, a dedicated coil positioning accuracy detection method was promoted based on three-dimensional (3D) printing and 3D laser scanning for evaluation. T1 images were collected from 24 subjects, and based on each image, phantom were created to simulate skin and hair. Six 3D-printed helmets with the head positioning hole enlarged by 0-5% tolerance in 1% increments were designed to evaluate the influences of skin, hair, and helmet-tolerance on the positioning accuracy and contact force of I-Helmet. Finally, I-Helmet system was evaluated by comparing its positioning accuracy with three skin hardnesses, three hair styles, three operators, and with or without landmarks. The accuracy of the proposed coil positioning accuracy detection method was about 0.30 mm in position and 0.22° in orientation. Skin and hair had significant influences on positioning accuracy (p < 0.0001), whereas different skin hardnesses, hair styles, and operators did not (p > 0.05). The tolerance of the helmet presented significant influences on positioning accuracy (p < 0.0001) and contact force (p < 0.0001). The positioning accuracy significantly increased (p < 0.0001) with landmark guided I-Helmet. 3D-printed helmet-type Neuro-navigation approach (I-Helmet) with 3% tolerance and landmarks met the positioning requirements for TMS in clinical practice with less than 5 N mean contact force, 3-5 mm positioning accuracy, 65.7 s mean operation time, and 50-yuan material cost. All the results suggest that the cost of I-Helmet system may be much less than the that of training clinical doctors to position the coil of TMS operation during short period of time.
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OBJECTIVE: This study was to evaluate plasma galectin-3 levels from early pregnancy to delivery and explore the effects of galectin-3 on the function of trophoblast cells under high glucose exposure. METHODS: The plasma galectin-3 levels were quantified by enzyme-linked immunosorbent assay (ELISA) in the China National Birth Cohort (CNBC) at Peking University First Hospital, and the underlying signaling pathway was identified by protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), quantitative PCR (qPCR), western blotting, small interfering RNA (siRNA) transfections, and flow cytometry. RESULTS: Significantly higher galectin-3 levels were found in patients with gestational diabetes mellitus (GDM group; n = 77) during the first and second trimesters than that in healthy pregnant women (HP group; n = 113) (P < 0.05). No significant differences in plasma galectin-3 levels were detected between GDM and HP groups in maternal third-trimester blood and cord blood. PPI analysis suggested potential interactions between galectin-3 and foxc1. The findings of GSEA showed that galectin-3 was involved in the cytochrome P450-related and complement-related pathways, and foxc1 was associated with type I diabetes mellitus. Additionally, high glucose (25 mM) significantly increased the expression levels of galectin-3 and foxc1 and induced apoptosis in HTR-8/SVneo cells. Further in vitro experiments showed that galectin-3/foxc1 pathway could protect HTR-8/SVneo cells against high glucose - induced apoptosis. CONCLUSION: Future studies were required to validate whether plasma galectin-3 might become a potential biomarker for hyperglycemia during pregnancy. Elevated galectin-3 levels might be a vital protective mechanism among those exposed to hyperglycemia during pregnancy.
Subject(s)
Galectin 3 , Hyperglycemia , Female , Humans , Pregnancy , Apoptosis , Galectin 3/genetics , Glucose , TrophoblastsABSTRACT
BACKGROUND: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear. METHODS: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents. RESULTS: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents. CONCLUSIONS: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents.