Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study.

OBJECTIVES: While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. METHODS: This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. RESULTS: There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors "Postoperative TSH level ≥ 2 mU/L", "Levothyroxine sodium tablet dose<1.4 µg/kg·d", and "Combined with Hashimoto thyroiditis" were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05). CONCLUSION: Optimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Comparative analysis of GoPro and digital cameras in head and neck flap harvesting surgery video documentation: an innovative and efficient method for surgical education.

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

Association of Oral Anticoagulant Therapy with the Prevalence and Severity of Vascular Calcification among Patients with Atrial Fibrillation: A Cohort Study.

Many patients with atrial fibrillation (AF) requiring long-term use of oral anticoagulants (OACs) are at high risk for vascular calcification and anticoagulation therapy with warfarin exacerbate vascular calcification. However, the effect of nonvitamin K agonists on vascular calcification has not been clearly investigated. This study explored the effects of dabigatran etexilate, rivaroxaban, and warfarin on vascular calcification among 1527 patients with AF. Demographics, comorbidities, laboratory test data, medications, and the prevalence and severity of vascular calcification in different vascular beds were compared. After propensity score matching, the incidence of vascular calcification in the rivaroxaban and warfarin group was significantly higher than that in the nonanticoagulant group, while there was no difference between the dabigatran etexilate group and the nonanticoagulant group. Similarly, we found that the rivaroxaban group had more severe calcification in the overall vascular level (P < 0.001), thoracic aorta (P < 0.001), aortic arch (P = 0.001), and left common carotid artery (P = 0.005) than the nonanticoagulant group. In addition, in the left common carotid artery, there was more severe calcification in the rivaroxaban group than that in the dabigatran group (P = 0.005). Our results suggest that rivaroxaban can significantly increase both the incidence and severity of vascular calcification among patients with AF, while dabigatran etexilate has no such effect. Many patients with AF requiring long-term use of OACs are at high risk for vascular calcification. This is the first study to conduct a head-to-head comparison of the effects of dabigatran etexilate and rivaroxaban on vascular calcification. Rivaroxaban, rather than dabigatran etexilate, promotes vascular calcification in patients with AF, providing important implications to aid clinicians in their choice for OAC selection, especially those at high risk for vascular calcification.

Role of Probiotics in Gut Microbiome and Metabolome in Non-Alcoholic Fatty Liver Disease Mouse Model: A Comparative Study.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide. Numerous studies conducted recently have demonstrated a connection between the dysbiosis of the development of NAFLD and gut microbiota. Rebuilding a healthy gut ecology has been proposed as a strategy involving the use of probiotics. The purpose of this work is to investigate and compare the function of probiotics Akkermansia muciniphila (A. muciniphila) and VSL#3 in NAFLD mice. Rodent NAFLD was modeled using a methionine choline-deficient diet (MCD) with/without oral probiotic delivery. Subsequently, qPCR, histological staining, and liver function tests were conducted. Mass spectrometry-based analysis and 16S rDNA gene sequencing were used to investigate the liver metabolome and gut microbiota. We found that while both A. muciniphila and VSL#3 reduced hepatic fat content, A. muciniphila outperformed VSL#3. Furthermore, probiotic treatment restored the ß diversity of the gut flora and A. muciniphila decreased the abundance of pathogenic bacteria such as Ileibacterium valens. These probiotics altered the metabolism in MCD mice, especially the glycerophospholipid metabolism. In conclusion, our findings distinguished the role of A. muciniphila and VSL#3 in NAFLD and indicated that oral-gavage probiotics remodel gut microbiota and improve metabolism, raising the possibility of using probiotics in the cure of NAFLD.

Erratum: [Corrigendum] Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

[This corrects the article DOI: 10.3892/ol.2017.7635.].

The role of the CXCR6/CXCL16 axis in the pathogenesis of fibrotic disease.

CXC chemokine receptor 6 (CXCR6), a seven-transmembrane domain G-protein-coupled receptor, plays a pivotal regulatory role in inflammation and tissue damage through its interaction with CXC chemokine ligand 16 (CXCL16). This axis is implicated in the pathogenesis of various fibrotic diseases and correlates with clinical parameters that indicate disease severity, activity, and prognosis in organ fibrosis, including afflictions of the liver, kidney, lung, cardiovascular system, skin, and intestines. Soluble CXCL16 (sCXCL16) serves as a chemokine, facilitating the migration and recruitment of CXCR6-expressing cells, while membrane-bound CXCL16 (mCXCL16) functions as a transmembrane protein with adhesion properties, facilitating intercellular interactions by binding to CXCR6. The CXCR6/CXCL16 axis is established to regulate the cycle of damage and repair during chronic inflammation, either through modulating immune cell-mediated intercellular communication or by independently influencing fibroblast homing, proliferation, and activation, with each pathway potentially culminating in the onset and progression of fibrotic diseases. However, clinically exploiting the targeting of the CXCR6/CXCL16 axis requires further elucidation of the intricate chemokine interactions within fibrosis pathogenesis. This review explores the biology of CXCR6/CXCL16, its multifaceted effects contributing to fibrosis in various organs, and the prospective clinical implications of these insights.

Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

Application of PRI-E-a combined learning method in oral and maxillofacial oncology education.

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. METHODS: With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. RESULTS: This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19. CONCLUSION: This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.

Dual biomarkers-activatable hollow MnO2-Based theranostic nanoplatform for efficient breast cancer-specific multisite fluorescence imaging and synergistic therapy.

BACKGROUND: Theranostic nanoplatforms with integrated diagnostic imaging and multiple therapeutic functions play a vital role in precise diagnosis and efficient treatment for breast cancer, but unfortunately, these nanoplatforms are usually stuck in single-site imaging and single mode of treatment, causing unsatisfactory diagnostic and therapeutic efficiency. Herein, a dual biomarkers-activatable facile hollow mesoporous MnO2 (H-MnO2)-based theranostic nanoplatform, DNAzyme@H-MnO2-MUC1 aptamer (DHMM), was constructed for the simultaneous multi-site diagnosis and multiple treatment of breast cancer. RESULTS: The DHMM acted as an integrated diagnostic and therapeutic nanoplatform that realizes multi-site fluorescence imaging-guided high-efficient photothermal/chemodynamic/gene synergistic therapy (PTT/CDT/GT) for breast cancer. The H-MnO2 exhibits high loading capacity for Cy5-MUC1 aptamer (3.05 pmoL µg-1) and FAM-DNAzyme (3.37 pmoL µg-1), and excellent quenching for the probes. In the presence of MUC1 on the cell membrane and GSH in the cytoplasm, Cy5-MUC1 aptamer and FAM-DNAzyme was activated triggering dual-channel fluorescence imaging at different sites. Moreover, the self-supplied Mn2+ was further supplied as DNAzyme cofactors to catalytic cleavage intracellular EGR-1 mRNA for high-efficient GT and stimulated the Fenton-like reaction for CDT. The H-MnO2 also showcases a favorable photothermal performance with a photothermal conversion efficiency of 44.16%, which ultimately contributes to multi-site fluorescence imaging-guided synergistic treatment with an apoptosis rate of 71.82%. SIGNIFICANCE: This dual biomarker-activatable multiple therapeutic nanoplatform was realized multi-site fluorescence imaging-guided PTT/CDT/GT combination therapy for breast cancer with higher specificity and efficiency, which provides a promising theranostic nanoplatform for the precision and efficiency of breast cancer treatment.

C-type lectin 4 of Toxocara canis activates NF-ĸB and MAPK pathways by modulating NOD1/2 and RIP2 in murine macrophages in vitro.

Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.

Using U-Net convolutional neural network to model pixel-based electrostatic potential distributions in GaN power MIS-HEMTs.

This study demonstrates a novel use of the U-Net convolutional neural network (CNN) for modeling pixel-based electrostatic potential distributions in GaN metal-insulator-semiconductor high-electron mobility transistors (MIS-HEMTs) with various gate and source field plate designs and drain voltages. The pixel-based images of the potential distribution are successfully modeled from the developed U-Net CNN with an error of less than 1% error relative to a TCAD simulated reference of a 500-V electrostatic potential distribution in the AlGaN/GaN interface. Furthermore, the modeling time of potential distributions by U-Net takes about 80 ms. Therefore, the U-Net CNN is a promising approach to efficiently model the pixel-based distributions characteristics in GaN power devices.

Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Dependence of evolution of Cyanobacteria superiority on temperature and nutrient use efficiency in a meso-eutrophic plateau lake.

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.

Deep Self-Reconstruction Fusion Similarity Hashing for the Diagnosis of Alzheimer's Disease on Multi-Modal Data.

The pathogenesis of Alzheimer's disease (AD) is extremely intricate, which makes AD patients almost incurable. Recent studies have demonstrated that analyzing multi-modal data can offer a comprehensive perspective on the different stages of AD progression, which is beneficial for early diagnosis of AD. In this paper, we propose a deep self-reconstruction fusion similarity hashing (DS-FSH) method to effectively capture the AD-related biomarkers from the multi-modal data and leverage them to diagnose AD. Given that most existing methods ignore the topological structure of the data, a deep self-reconstruction model based on random walk graph regularization is designed to reconstruct the multi-modal data, thereby learning the nonlinear relationship between samples. Additionally, a fused similarity hash based on anchor graph is proposed to generate discriminative binary hash codes for multi-modal reconstructed data. This allows sample fused similarity to be effectively modeled by a fusion similarity matrix based on anchor graph while modal correlation can be approximated by Hamming distance. Especially, extracted features from the multi-modal data are classified using deep sparse autoencoders classifier. Finally, experiments conduct on the AD Neuroimaging Initiative database show that DS-FSH outperforms comparable methods of AD classification. To conclude, DS-FSH identifies multi-modal features closely associated with AD, which are expected to contribute significantly to understanding of the pathogenesis of AD.

Differential alternative splicing landscape identifies potentially functional RNA binding proteins in early embryonic development in mammals.

Alternative splicing (AS) as one of the important post-transcriptional regulatory mechanisms has been poorly studied during embryogenesis. In this study, we comprehensively collected and analyzed the transcriptome data of early embryos from human and mouse. We found that AS plays an important role in this process and predicted candidate RNA binding protein (RBP) regulators that are associated with reproductive development. The predicted RBPs such as EIF4A3, MAK16, SRSF2, and UTP23 were found to be associated with reproductive disorders. By Smart-seq2 sequencing analysis, we identified 5445 aberrant alternative splicing events in Eif4a3-knockdown embryos. These events were preferentially associated with RNA processing. In conclusion, our work on the landscape and potential function of alternative splicing events will boost further investigation of detailed mechanisms and key factors regulating mammalian early embryo development and promote the inspiration of pharmaceutical approaches for disorders in this crucial biology process.

SEU2-Net: multi-scale U2-Net with SE attention mechanism for liver occupying lesion CT image segmentation.

Liver occupying lesions can profoundly impact an individual's health and well-being. To assist physicians in the diagnosis and treatment of abnormal areas in the liver, we propose a novel network named SEU2-Net by introducing the channel attention mechanism into U2-Net for accurate and automatic liver occupying lesion segmentation. We design the Residual U-block with Squeeze-and-Excitation (SE-RSU), which is to add the Squeeze-and-Excitation (SE) attention mechanism at the residual connections of the Residual U-blocks (RSU, the component unit of U2-Net). SEU2-Net not only retains the advantages of U2-Net in capturing contextual information at multiple scales, but can also adaptively recalibrate channel feature responses to emphasize useful feature information according to the channel attention mechanism. In addition, we present a new abdominal CT dataset for liver occupying lesion segmentation from Peking University First Hospital's clinical data (PUFH dataset). We evaluate the proposed method and compare it with eight deep learning networks on the PUFH and the Liver Tumor Segmentation Challenge (LiTS) datasets. The experimental results show that SEU2-Net has state-of-the-art performance and good robustness in liver occupying lesions segmentation.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Identification of a novel Scn3b mutation in a Chinese Brugada syndrome pedigree: implications for Nav1.5 electrophysiological properties and intracellular distribution of Nav1.5 and Navß3.

Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55 mv and peaked at -25 mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25 mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.