Inhibition of ESCRT-independent extracellular vesicles biogenesis suppresses enterovirus 71 replication and pathogenesis in mice.

Enterovirus 71 (EV71) causes hand-foot-and-mouth disease (HFMD), neurological complications, and even fatalities in infants. Clinically, the increase of extracellular vesicles (EVs) in EV71 patients' serum was highly associated with the severity of HFMD. EV71 boosts EVs biogenesis in an endosomal sorting complex required for transport (ESCRT)-dependent manner to facilitate viral replication. Yet, the impact of EVs-derived from ESCRT-independent pathway on EV71 replication and pathogenesis is highly concerned. Here, we assessed the effects of EV71-induced EVs from ESCRT-independent pathway on viral replication and pathogenesis by GW4869, a neutral sphingomyelinase inhibitor. Detailly, in EV71-infected mice, blockade of the biogenesis of tissue-derived EVs in the presence of GW4869 restored body weight loss, attenuated clinical scores, and improved survival rates. Furthermore, GW4869 dampens EVs biogenesis to reduce viral load and pathogenesis in multiple tissues of EV71-infected mice. Consistently, GW4869 treatment in a human intestinal epithelial HT29 cells decreased the biogenesis of EVs, in which the progeny EV71 particle was cloaked, leading to the reduction of viral infection and replication. Collectively, GW4869 inhibits EV71-induced EVs in an ESCRT-independent pathway and ultimately suppresses EV71 replication and pathogenesis. Our study provides a novel strategy for the development of therapeutic agents in the treatment for EV71-associated HFMD.

Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.

Background: Amyloid-ß (Aß) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aß plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aß plaques. Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aß42/40 ratio. Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aß42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results: Results from ADNI (mean age 72.6, Aß+ rate 49.5%) and BAI (mean age 66.2, Aß+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aß42/40 (0.73 and 0.81) predictors. CONCLUSIONS: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aß plaques and structural MRI.

[Molecular mechanism of residual lumbago and leg pain after transforaminal endoscopic treatment of lumbar disc herniation].

OBJECTIVE: To observe the residual of lumbago and leg pain with contained type （CT） and non-contained type （NCT） lumbar disc herniation （LDH） after transforaminal endoscopic treatment, and to explore the role of hypoxia-inducible factor-1α（HIF-1α） and transient receptor potential vanillate 1（TRPV1） pathway. METHODS: A total of 68 single-segment LDH patients were selected from July 2021 to October 2022, including 44 males and 24 females；aged 26 to 67 years old with an average of（43.63±11.94） years old；course of disease was 4 to 36 （18.91±10.34） months；body mass index was （24.45±4.00） kg·m-2；there were 7 cases of L3,4 segments, 32 cases of L4,5 segments, and 29 cases of L5S1 segments. All of them were performed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained group（CT group） and non-contained group （NCT group） with 34 cases respectively according to the integrity of outer layer of fibrous annulus observed during operation. A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were selected as control group, including 12 males and 5 females；aged 21 to 65 years old with an average of （39.41±12.80） years old；body mass index was （24.86±4.11） kg·m-2. The relative mRNA expression quantity of HIF-1α, TRPV1 in nucleus pulposus were measured by quantitative real-time PCR. The contents of neurokinin 1 receptor （NK1R）, nerve growth factor （NGF）, vascular endothelial growth factor （VEGF） in nucleus pulposus and the serum substance P （SP） and calcitonin gene-related peptide （CGRP） were detected by enzyme linked immunosorbent assay （ELISA）. The threshold of lumbar tenderness was detected by a pressure pain meter. The degree of lumbago and lumbar function were evaluated by visual analog scale （VAS） and Oswestry disability index （ODI） separately. The residual rate of postoperative lumbago and leg pain was assessed. RESULTS: The mRNA relative expression quantity of HIF-1α and TRPV1, and the contents of NK1R, NGF and VEGF in nucleus pulposus, and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT group（P<0.05）, and those in the CT group were higher than the control group（P<0.05）. At day 7 after surgery, the serum SP and CGRP levels, lumbago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery （P<0.05）, and those in the NCT group were higher than the CT group（P<0.05）, and the threshold of lumbar tenderness in the NCT group was lower than the CT group（P<0.05）. The differences of lumbago and leg pain VAS scores, lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT group（P<0.05）. The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT group（P<0.05）. CONCLUSION: HIF-1α and TRPV1 pathway promoted the excessive production of NGF, VEGF, NK1R in nucleus pulposus and serum neuropeptides SP and CGRP, which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.

Accuracy of detecting burst of the lateral wall in intertrochanteric hip fractures with plain radiographs: Is postoperative CT necessary?

Background: Postoperative burst of the lateral femoral wall is thought to be the main predictor of reoperation for intertrochanteric fractures, which is routinely evaluated using plain radiographs. We retrospectively compared computed tomography (CT) scans and radiographs regarding the ability to detect burst of the lateral wall. We also investigated whether intramedullary nails may cause iatrogenic burst of the lateral wall. Methods: From January 2010 to December 2021, patients aged 65 years and older who undergone intertrochanteric fractures treated with the proximal femoral nail antirotation 2 (PFNA-Ⅱ) were included. The incidence of burst of the lateral wall was evaluated with two different imaging modalities by two observers. Two rounds of evaluation were performed: (1) with plain radiographs alone; and (2) with CT scans combined with radiographs. Interobserver and intraobserver agreement (κ value) for evaluation of the lateral wall burst was assessed. Results: A total of 1507 patients were included (362 males and 1145 females). Compared with radiographs alone (12.0 %, 181/1507 patients), a higher rate of lateral wall burst was found by CT scans combined with radiographs (72.9 %, 1098/1507 patients) for observer 1 at first reading (P < 0.001). Similar results were seen in other evaluations. Interobserver and intraobserver agreement was substantial for radiographs alone (κ, 0.659-0.727) and almost perfect for CT scans combined with radiographs (κ, 0.847-0.926). Conclusions: Computed tomography combined with radiographs is superior to radiographs alone for detecting burst of the lateral wall after intertrochanteric fracture fixation. Additionally, PFNA-Ⅱ could cause iatrogenic burst of the lateral wall for intertrochanteric fractures in the elderly.

Multivariate analysis of alveolar bone dehiscence and fenestration in anterior teeth after orthodontic treatment: A retrospective study.

OBJECTIVE: To compare the prevalence of fenestration and dehiscence between pre- and post-orthodontic treatment and to explore the factors related to fenestration and dehiscence in the anterior teeth after treatment. METHODS: This study included 1000 cone-beam computed tomography (CBCT) scans of 500 patients before (T1) and after (T2) orthodontic treatment. These images were imported into Dolphin 11.9 software to detect alveolar fenestration and dehiscence in the anterior teeth area. The chi-square test and Fisher's exact test were performed to compare the prevalence of alveolar bone defects between time points T1 and T2. A total of 499 patients were selected for logistic regression analysis to examine the correlation among age, sex, crowding, sagittal facial type, extraction, miniscrew use and fenestration or dehiscence post-treatment. RESULTS: Except for the maxillary lingual fenestration and labial fenestration of mandibular canines, a significant change in the prevalence of fenestration and dehiscence was noted between time points T1 and T2 (P < .025). Multinomial logistic regression showed that age, miniscrew use and extraction highly influenced the prevalence of anterior lingual dehiscence (P < .05). Dehiscence of the mandibular labial side (skeletal Class III vs. I, OR = 2.368, P = .000) and fenestration of the mandibular lingual side (skeletal Class II vs. I, OR = 2.344, P = .044) were strongly correlated with the sagittal facial type. Dehiscence of the maxillary labial side (moderate vs. mild, OR = 1.468, P = .017) was significantly associated with crowding. CONCLUSIONS: Older age, maxillary moderate crowding, skeletal Class III, extraction and miniscrew potentially significantly affect the prevalence of anterior teeth dehiscence. Adult females, skeletal Class III patients on the mandibular labial side and skeletal Class II patients on the mandibular lingual side should be monitored for anterior teeth fenestration.

Recovery of valuable metals from spent lithium-ion batteries via zinc powder reduction roasting and cysteine leaching.

With the annual increase in lithium-ion batteries (LIBs) disposal, valuable resources are being generated with worrying waste, so it is strategically important to recover the critical metals from them. Individual high temperature or leaching processes do not apparently achieve very satisfactory results. In the present work, the reduction with zinc powder was able to convert the lithium in LiNixCoyMnzO2 (NCM) to soluble LiOH, while the reduction and ammonia complexation environment generated by the decomposition of cysteine (Cys) achieved an efficient leaching of transition metals without additional additives. The leaching efficiency of Li can reach more than 92 %, while that of Ni/Co/Mn reaches more than 97 % through the regulation of the parameters of each process. In particular, an in-situ redox mechanism is proposed to explain the efficient leaching of transition metals, which further enriches the theory of spent LIBs recycling and provides a promising idea for various hydrometallurgical extraction systems.

Featured interactome of homocysteine-inducible endoplasmic reticulum protein uncovers novel binding partners in response to ER stress.

Homocysteine-inducible endoplasmic reticulum protein (HERP) is an endoplasmic reticulum (ER)-resident protein and important for the adaptation of cellular protein homeostasis by ER-associated degradation (ERAD) system. HERP interactors are critical for cellular viability and the reaction to ER stress. To explore the exact mechanisms by which HERP performed the biological functions, we conducted an interaction analysis of HERP protein in HeLa cells by co-immunoprecipitation (Co-IP) and liquid chromatography-mass spectrometer (LC-MS)/MS coupled with label-free quantification (LFQ). Among the interactome results, 123 proteins significantly interacted with HERP, which leads to numerous biological processes including protein import into nucleus, ubiquitin-dependent ERAD pathway, negative regulation of apoptotic process, and protein transport from ER, along with multiple pathways including several diseases, protein processing in ER, fatty acid metabolism, and steroid biosynthesis. Furthermore, we selected several prey proteins from the interactome data and confirmed that HERP interacted with ancient ubiquitous protein 1 (AUP1), Fas-associated factor family member 2 (FAF2), tripartite motif containing 47 (TRIM47), acyl-CoA synthetase long-chain family member 3 (ACSL3), sequestosome 1 (SQSTM1), and poly(rC) binding protein 2 (PCBP2) by Co-IP and confocal microscopy experiments, respectively. Moreover, the expression and location of several interacted proteins were obviously altered in response to ER stress induced by Thapsigargin stimulation and Enterovirus 71 infection. In conclusion, our findings revealed that the vital proteins interacted with HERP to mediate signaling transduction, thus providing novel clues for the mechanisms of HERP associated with ERAD and metabolism in response to ER stress under physiological and pathological conditions.

The porcine piRNA transcriptome response to Senecavirus a infection.

Introduction: Senecavirus A (SVA) belongs to the genus Senecavirus in the family Picornaviridae. PIWI-interacting RNAs (piRNAs) are a class of small Ribonucleic Acids (RNAs) that have been found in mammalian cells in recent years. However, the expression profile of piRNAs in the host during SVA infection and their roles are poorly understood. Methods: Here, we found the significant differential expression of 173 piRNAs in SVA-infected porcine kidney (PK-15) cells using RNA-seq and 10 significant differentially expressed (DE) piRNAs were further verified by qRT-PCR. Results: GO annotation analysis showed that metabolism, proliferation, and differentiation were significantly activated after SVA infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that significant DE piRNAs were mainly enriched in AMPK pathway, Rap1 pathway, circadian rhythm and VEGF pathway. It was suggested that piRNAs may regulated antiviral immunity, intracellular homeostasis, and tumor activities during SVA infection. In addition, we found that the expression levels of the major piRNA-generating genes BMAL1 and CRY1 were significantly downregulated after SVA infection. Discussion: This suggests that SVA may affect circadian rhythm and promote apoptosis by inhibiting the major piRNA-generating genes BMAL1 and CRY1. The piRNA transcriptome in PK-15 cells has never been reported before, and this study will further the understanding of the piRNA regulatory mechanisms underlying SVA infections.

Natural Oncolysis of Enterovirus 71 in Antitumor Therapy of Colorectal Cancer.

Colorectal cancer (CRC) is an intestinal malignant tumor with high morbidity and mortality worldwide. Inoperability or resistanance to radiation and chemotherapy occur in the conventional treatments against CRC. Oncolytic viruses (OVs) are one kind of virus that selectively infects and lyses cancer cells, which is considered to be a new anticancer therapy with biological and immune-based approaches. Enterovirus 71 (EV71), belonging to the enterovirus genus in the family Picornaviridae, is a single positive-stranded RNA virus. EV71 is transmitted in a fetal-oral route and infects gastrointestinal tract in infants. Here, EV71 is exploited to be a novel oncolytic virus in colorectal cancer. It is revealed that EV71 infection can selectively cause colorectal cancer cells cytotoxicity but not primary intestinal epithelial cells. Consistently, EV71 injection significantly inhibits tumor growth in nude mice xenografted colorectal cancer cells. In detail, EV71 infects colorectal cancer cells to repress the expression of Ki67 and B-cell leukemia 2 (Bcl-2) leading to the inhibition of cell proliferation, while activating the cleavage of poly-adenosine diphosphatase-ribose polymerase and Caspase-3 protein resulting in the promotion of cell apoptosis. The findings demonstrate the oncolytic feature of EV71 in CRC treatment and may provide a potential clue for clinical anticancer therapy.

A Surface-Based Federated Chow Test Model for Integrating APOE Status, Tau Deposition Measure, and Hippocampal Surface Morphometry.

BACKGROUND: Alzheimer's disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofibrillary tangles are the primary driver of downstream neurodegeneration and subsequent cognitive impairment in AD, resulting in structural deformations such as hippocampal atrophy that can be observed in magnetic resonance imaging (MRI) scans. OBJECTIVE: To build a surface-based model to 1) detect differences between APOE subgroups in patterns of tau deposition and hippocampal atrophy, and 2) use the extracted surface-based features to predict cognitive decline. METHODS: Using data obtained from different institutions, we develop a surface-based federated Chow test model to study the synergistic effects of APOE, a previously reported significant risk factor of AD, and tau on hippocampal surface morphometry. RESULTS: We illustrate that the APOE-specific morphometry features correlate with AD progression and better predict future AD conversion than other MRI biomarkers. For example, a strong association between atrophy and abnormal tau was identified in hippocampal subregion cornu ammonis 1 (CA1 subfield) and subiculum in e4 homozygote cohort. CONCLUSION: Our model allows for identifying MRI biomarkers for AD and cognitive decline prediction and may uncover a corner of the neural mechanism of the influence of APOE and tau deposition on hippocampal morphology.

Design of well-matched end-structure of anatomical proximal femoral locking plate based on computer-assisted imaging combined with 3D printing technology: a quality improvement study.

BACKGROUND: The extramedullary locking plate system was the common internal fixation method for hip fractures. However, common plates were poorly matched to femur, which was because they were designed based on anatomical parameters of the Western populations. Therefore, the aim was to design an end-structure of the anatomical proximal femoral locking plate that closely matched the anatomy of the Chinese population. MATERIALS AND METHODS: From January 2010 to December 2021, consecutive patients aged 18 years and older who underwent a full-length computed tomography scan of the femur were included. The end-structure (male and female model) of the anatomical proximal femoral locking plate was designed based on anatomical parameters of femurs that were measured in three-dimensional space using computer-assisted virtual technology. The match degree between the end-structure and femur were evaluated. Inter-observer and intra-observer agreement for the evaluation of match degree was assessed. The matching evaluation based on a three-dimensional printing model was regarded as the gold standard to assess the reliability. RESULTS: A total of 1672 patients were included, with 701 men and 971 women. Significant differences were seen between male and female for all parameters of the proximal femur (all P <0.001). All match degree of end-structure was over 90%. Inter-observer and intra-observer agreement was almost perfect (all kappa value, >0.81). The sensitivity, specificity, and percentage of correct interpretation of matching evaluation in the computer-assisted virtual model was all greater than 95%. From femur reconstruction to completion of internal fixation matching, the process takes about 3 min. Moreover, reconstruction, measurement, and matching were all completed in one system. CONCLUSIONS: The results showed that based on the larger sample of femoral anatomical parameters, a highly matching end-structure of anatomical proximal femoral locking plate for Chinese population could be designed with use of computer-assisted imaging technology.

Long-term morphometric changes in the anterior alveolar bone in adolescents and adults after space closure: A retrospective study.

OBJECTIVES: To analyse the morphometric changes in the anterior alveolar bone of both the maxilla and mandible after space closure and retention for 18-36 mo in adults and adolescents. MATERIALS AND METHODS: Forty-two subjects with 4 first premolars extracted followed by retracting anterior teeth were included and divided into two age groups: adult group (4 males, 17 females, mean age: 23.67 ± 5.29 y, treatment duration: 27.95 mo, retention duration: 26.96 mo, ANB: 4.8 ± 2.1, U1-L1: 117.2 ± 9.2, U1-PP: 120.2 ± 7.2, L1-MP: 99.2 ± 5.3) and adolescent group (6 males, 15 females, mean age: 11.52 ± 1.21 y, treatment duration: 26.18 mo, retention duration: 25.79 mo, ANB: 5.2 ± 2.1, U1-L1: 116.0 ± 8.6, U1-PP: 119.8 ± 4.9, L1-MP: 99.7 ± 4.9). Alveolar bone height and thickness of anterior teeth in both groups were measured using cone beam computed tomography (CBCT) imaging performed at the pretreatment (T1), posttreatment (T2) and retention phases (T3). One-way repeated-measure ANOVAs were performed to evaluate the alveolar bone changes. Voxel-based superimpositions were performed to measure the amount of tooth movement. RESULTS: After orthodontic treatment, the lingual bone height and thickness of both arches and the labial bone height of the mandible decreased significantly in both age groups (P < .05). Most of the labial bone height and thickness of the maxilla in both groups remained unchanged (P > .05). After retention, the lingual bone height and thickness increased significantly in both age groups (P < .05). The amounts of increased height ranged from 1.08 to 1.64 mm in adults and from 0.78 to 1.21 mm in adolescents, and the amounts of increased thickness ranged from 0.23 mm to 0.62 mm in adults and from 0.16 mm to 0.36 mm in adolescents. Obvious movements of the anterior teeth during retention were not found (P > .05). CONCLUSIONS: Although lingual alveolar bone loss occurred in adolescents and adults during orthodontic treatment, continuous remodelling occurred in the later retention phase, which provides a reference for clinical treatment planning of bimaxillary dentoalveolar protrusion.

Comprehensive positional and morphological assessments of the temporomandibular joint in adolescents with skeletal Class III malocclusion: a retrospective CBCT study.

BACKGROUND: Condyle-fossa relationships in adolescents with skeletal Class III malocclusion remain unclear. Therefore, this study used cone-beam computed tomography (CBCT) to evaluate the position and morphology of the temporomandibular joint (TMJ) in adolescents with skeletal Class III malocclusion. METHODS: In this cross-sectional retrospective study, CBCT images from 90 adolescents with skeletal Class III malocclusion and 30 controls were analysed. Adolescents with skeletal Class III malocclusion were divided into different groups based on (1) sex (male and female), (2) sides (right and left), (3) age (early, middle, and late adolescence), and (4) vertical skeletal patterns (hyperdivergent, normodivergent, and hypodivergent). Morphology of the condyle and fossa as well as condylar position, was compared among groups. Data were collected and submitted for statistical analysis. This study adheres to STROBE guidelines. RESULTS: Regarding the intergroup comparisons, there were significant differences in TMJ position and morphology between the skeletal Class III malocclusion with different vertical skeletal patterns and control groups (P < 0.05). Within groups, condyle-fossa relationships differed significantly according to sex, age, and vertical skeletal patterns (P < 0.05); however, the mean values were not statistically different between left and right sides in adolescents with skeletal Class III malocclusion. CONCLUSIONS: Our findings can be used clinically and radiographically to evaluate the condyle and glenoid fossa features in adolescents with skeletal Class III malocclusion, providing a basis for better TMD diagnosis and orthodontic treatment.

Surgically Relevant Morphological Parameters of the L5-S1 Interlaminar Window: A Statistical Analysis Based on 3D Reconstruction of CT Data.

BACKGROUND: The interlaminar window is the most important anatomical corridor during the posterior approach for lumbar and lumbosacral pathologies. Three-dimensional (3D) reconstruction of the L5-S1 interlaminar window including accurate measurements may be beneficial for the surgeon. The aim of this study was to measure relevant surgical parameters of the L5-S1 interlaminar window based on 3D reconstruction of lumbar computed tomography (CT). METHODS: Fifty thin-layer CT data were retrospectively collected, segmented, and reconstructed. Relevant surgical parameters included the width, left height, right height, interpedicular distance (IPD), area, and suitable approach area of the L5-S1 interlaminar window. Morphological measurements were performed independently by two experienced experts. Patients with disk herniation at L5-S1 were regarded as group A (n = 28) and those without L5-S1 disk herniation were regarded as group B (n = 22). RESULTS: The average left height, right height, width, and area of the L5-S1 interlaminar window were 9.14 ± 2.45 mm, 9.55 ± 2.46 mm, 23.55 ± 4.91 mm, and 144.57 ± 57.05 mm2, respectively. The average IPD at the superior, middle, and inferior pedicle levels was 29.29 ± 3.39, 27.96 ± 3.38, and 37.46 ± 4.23 mm, respectively, with significant differences among these three parameters (p < 0.05). The average suitable approach areas of the L5-S1 interlaminar window were the following: left axilla-24.52 ± 15.91 mm2; left shoulder-27.14 ± 15.48 mm2; right axilla-29.95 ± 17.17 mm2; and right shoulder-31.12 ± 16.40 mm2 (p > 0.05). There were no significant differences between groups A and B in these parameters (p > 0.05), except the inferior IPD (36.69 ± 3.73 vs. 39.23 ± 3.01 mm, p = 0.017 < 0.05). CONCLUSION: The morphological measurement of the L5-S1 interlaminar window based on 3D reconstruction provided accurate and reliable reference data for posterior microsurgical and endoscopic approaches as well as percutaneous infiltrations.

Morroniside induces cardiomyocyte cell cycle activity and promotes cardiac repair after myocardial infarction in adult rats.

Introduction: Acute myocardial infarction (AMI) is characterized by the loss of cardiomyocytes, which impairs cardiac function and eventually leads to heart failure. The induction of cardiomyocyte cell cycle activity provides a new treatment strategy for the repair of heart damage. Our previous study demonstrated that morroniside exerts cardioprotective effects. This study investigated the effects and underlying mechanisms of action of morroniside on cardiomyocyte cell cycle activity and cardiac repair following AMI. Methods: Neonatal rat cardiomyocytes (NRCMs) were isolated and exposed to oxygen-glucose deprivation (OGD) in vitro. A rat model of AMI was established by ligation of the left anterior descending coronary artery (LAD) in vivo. Immunofluorescence staining was performed to detect newly generated cardiomyocytes. Western blotting was performed to assess the expression of cell cycle-related proteins. Electrocardiography (ECG) was used to examine pathological Q waves. Masson's trichrome and wheat germ agglutinin (WGA) staining assessed myocardial fibrosis and hypertrophy. Results: The results showed that morroniside induced cardiomyocyte cell cycle activity and increased the levels of cell cycle proteins, including cyclin D1, CDK4, cyclin A2, and cyclin B1, both in vitro and in vivo. Moreover, morroniside reduced myocardial fibrosis and remodeling. Discussion: In conclusion, our study demonstrated that morroniside stimulates cardiomyocyte cell cycle activity and cardiac repair in adult rats, and that these effects may be related to the upregulation of cell cycle proteins.

Expert consensus on the bone repair strategy for osteoporotic fractures in China.

Osteoporotic fractures, also known as fragility fractures, are prevalent in the elderly and bring tremendous social burdens. Poor bone quality, weak repair capacity, instability, and high failure rate of internal fixation are main characteristics of osteoporotic fractures. Osteoporotic bone defects are common and need to be repaired by appropriate materials. Proximal humerus, distal radius, tibia plateau, calcaneus, and spine are common osteoporotic fractures with bone defect. Here, the consensus from the Osteoporosis Group of Chinese Orthopaedic Association concentrates on the epidemiology, characters, and management strategies of common osteoporotic fractures with bone defect to standardize clinical practice in bone repair of osteoporotic fractures.

Evaluation of condyle-fossa relationships in skeletal Class I malocclusion with variable degrees of deep overbite and open bite.

OBJECTIVE: To compare the temporomandibular joint (TMJ) position and shape between skeletal Class I subjects with different degrees of deep overbite or open bite and unaffected peers. METHODS: Cone beam computed tomography (CBCT) images of 90 participants, equally divided into deep bite, open bite, and control groups (DBG, OBG, and CG, respectively), were analyzed. The DBG and OBG were further subdivided into three subgroups based on the severity. Linear and angular measurements were used to determine the positional and morphological characteristics of the TMJ. RESULTS: DBG showed significantly larger superior joint space, anterior inclination of the condyle, and articular eminence inclination than CG and OBG. The severity of deep bite and open bite significantly influenced the TMJ position and morphology. CONCLUSION: In severe deep overbite and open bite cases, there were considerable alterations in TMJ components, most likely as a result of functional demands.

Accuracy and reliability analysis of a machine learning based segmentation tool for intertrochanteric femoral fracture CT.

Introduction: Three-dimensional (3D) reconstruction of fracture fragments on hip Computed tomography (CT) may benefit the injury detail evaluation and preoperative planning of the intertrochanteric femoral fracture (IFF). Manually segmentation of bony structures was tedious and time-consuming. The purpose of this study was to propose an artificial intelligence (AI) segmentation tool to achieve semantic segmentation and precise reconstruction of fracture fragments of IFF on hip CTs. Materials and Methods: A total of 50 labeled CT cases were manually segmented with Slicer 4.11.0. The ratio of training, validation and testing of the 50 labeled dataset was 33:10:7. A simplified V-Net architecture was adopted to build the AI tool named as IFFCT for automatic segmentation of fracture fragments. The Dice score, precision and sensitivity were computed to assess the segmentation performance of IFFCT. The 2D masks of 80 unlabeled CTs segmented by AI tool and human was further assessed to validate the segmentation accuracy. The femoral head diameter (FHD) was measured on 3D models to validate the reliability of 3D reconstruction. Results: The average Dice score of IFFCT in the local test dataset for "proximal femur", "fragment" and "distal femur" were 91.62%, 80.42% and 87.05%, respectively. IFFCT showed similar segmentation performance in cross-dataset, and was comparable to that of human expert in human-computer competition with significantly reduced segmentation time (p < 0.01). Significant differences were observed between 2D masks generated from semantic segmentation and conventional threshold-based segmentation (p < 0.01). The average FHD in the automatic segmentation group was 47.5 ± 4.1 mm (41.29∼56.59 mm), and the average FHD in the manual segmentation group was 45.9 ± 6.1 mm (40.34∼64.93 mm). The mean absolute error of FHDs in the two groups were 3.38 mm and 3.52 mm, respectively. No significant differences of FHD measurements were observed between the two groups (p > 0.05). All ICCs were greater than 0.8. Conclusion: The proposed AI segmentation tool could effectively segment the bony structures from IFF CTs with comparable performance of human experts. The 2D masks and 3D models generated from automatic segmentation were effective and reliable, which could benefit the injury detail evaluation and preoperative planning of IFFs.

Age-related variations in position and morphology of the temporomandibular joint in individuals with anterior openbite and crossbite: a multi-cross-sectional comparative study.

BACKGROUND: This study aimed to compare the age-related positional and morphological characteristics of the temporomandibular joint (TMJ) between individuals with anterior openbite or crossbite and controls. METHODS: This multi-cross-sectional comparative study analysed cone-beam computed tomography images of 750 participants, equally divided into the openbite, crossbite, and control groups (OBG, CBG, and CG, respectively). Each group was further divided into five subgroups (8-11 years, 12-15 years, 16-19 years, 20-24 years, and 25-30 years). Measurements of the TMJ included the position of the condyles in their respective fossae and morphology of the condyles and fossae. Data were submitted to statistical analysis. The study adhered to the STROBE Statement checklist for reporting of cross-sectional studies. RESULTS: Condyles were positioned more posteriorly with increasing age in all groups, and the condylar position was more posterior in the OBG than in the CBG. The articular eminence inclination increased with age in all the groups. There were significant differences in the articular eminence inclination among the three major groups at the age of > 15 years, and the condylar path was flatter in the CBG than in the OBG. CONCLUSIONS: Age-related morphological and positional characteristics of the TMJ differed considerably among OBG, CBG and CG. Contrary to CBG, OBG was found to have relatively posterior condylar position and steeper condylar path.