Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation.

Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

Expression and function identification of senescence-associated genes under continuous drought treatment in grapevine (Vitis vinifera L.) leaves.

Natural leaf senescence is critical for plant fitness. Drought-induced premature leaf senescence affects grape yield and quality. However, reports on the regulatory mechanisms underlying premature leaf senescence under drought stress are limited. In this study, two-year-old potted 'Muscat Hamburg' grape plants were subjected to continuous natural drought treatment until mature leaves exhibited senescence symptoms. Physiological and biochemical indices related to drought stress and senescence were monitored. Transcriptome and transgenic Arabidopsis were used to perform expression analyses and functional identification of drought-induced senescence-associated genes. Twelve days of continuous drought stress was sufficient to cause various physiological disruptions and visible senescence symptoms in mature 'Muscat Hamburg' leaves. These disruptions included malondialdehyde and H2O2 accumulation, and decreased catalase activity and chlorophyll (Chl) levels. Transcriptome analysis revealed that most genes involved in photosynthesis and Chl synthesis were downregulated after 12 d of drought treatment. Three key Chl catabolic genes (SGR, NYC1, and PAO) were significantly upregulated. Overexpression of VvSGR in wild Arabidopsis further confirmed that SGR directly promoted early yellowing of cotyledons and leaves. In addition, drought treatment decreased expression of gibberellic acid signaling repressors (GAI and GAI1) and cytokinin signal components (AHK4, AHK2, RR22, RR9-1, RR9-2, RR6, and RR4) but significantly increased the expression of abscisic acid, jasmonic acid, and salicylic acid signaling components and responsive transcription factors (bZIP40/ABF2, WRKY54/75/70, ANAC019, and MYC2). Moreover, some NAC members (NAC0002, NAC019, and NAC048) may also be drought-induced senescence-associated genes. These results provide extensive information on candidate genes involved in drought-induced senescence in grape leaves. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01465-2.

Recent Development of Biodegradable Occlusion Devices for Intra-Atrial Shunts.

Atrial septal defect (ASD) is the third most common type of structural congenital heart defect. Patent foramen ovale (PFO) is an anatomical anomaly in up to 25% of the general population. With the innovation of occlusion devices and improvement of transcatheter techniques, percutaneous closure has become a first-line therapeutic alternative for treatment of ASD and PFO. During the past few decades, the development of biodegradable occlusion devices has become a promising direction for transcatheter closure of ASD/PFO due to their biodegradability and improved biocompatibility. The purpose of this review is to comprehensively summarize biodegradable ASD/PFO occlusion devices, regarding device design, materials, biodegradability, and evaluation of animal or clinical experiments (if available). The current challenges and the research direction for the development of biodegradable occluders for congenital heart defects are also discussed.

Abscisic Acid Induces DNA Methylation Alteration in Genes Related to Berry Ripening and Stress Response in Grape (Vitis vinifera L).

Abscisic acid (ABA) is a major regulator of nonclimacteric fruit ripening, with its processes involving epigenetic mechanisms. It remains unclear whether DNA methylation is associated with ABA-regulated ripening. In this study, we investigated the patterns of DNA methylation and gene expression following ABA treatment in grape berries by using whole-genome bisulfite sequencing and RNA-sequencing. ABA application changed global DNA methylation in grapes. The hyper-/hypo-differently methylated regions were enriched in defense-related metabolism, degreening processes, or ripening-related metabolic pathways. Many differentially expressed genes showed an alteration in DNA methylation after ABA treatment. Specifically, ten downregulated genes with hypermethylation in promoters were involved in the ripening process, ABA homeostasis/signaling, and stress response. Nine upregulated genes exhibiting hypo-methylation in promoters were related to the ripening process and stress response. These findings demonstrated ABA-induced DNA alteration of ripening related and stress-responsive genes during grape ripening, which provides new insights of the epigenetic regulation of ABA on fruit ripening.

Clinical characteristics and outcomes associated with culture-negative status in limb osteomyelitis patients.

Aims: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.

Retracted: Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Rongfeng Zhang, Jianwei Liu, Shengpeng Yu, Dong Sun, Xiaohua Wang, Jingshu Fu, Jie Shen, Zhao Xie. Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair. Med Sci Monit, 2019; 25: 5572-5579. DOI: 10.12659/MSM.916838.

Whether weekend warriors (WWs) achieve equivalent benefits in lipid accumulation products (LAP) reduction as other leisure-time physical activity patterns? -Results from a population-based analysis of NHANES 2007-2018.

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.

Activated allograft combined with induced menbrane technique for the reconstruction of infected segmental bone defects.

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4-17) cm in length. After a mean follow-up of 71.84 (61-82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5-28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone.

The induced membrane technique for the management of infected segmental bone defects.

Aims: The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Methods: Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis. Results: Among the 203 enrolled patients, infection recurred in 27 patients (13.3%) after bone grafting. The union rate was 75.9% (154 patients) after second-stage surgery without additional procedures, and final union was achieved in 173 patients (85.2%) after second-stage surgery with or without additional procedures. The mean healing time was 9.3 months (3 to 37). Multivariate logistic regression analysis of 203 patients showed that the number (≥ two) of debridements (first stage) was an independent risk factor for infection recurrence and nonunion. Larger defect sizes were associated with higher odds of nonunion. After excluding 27 patients with infection recurrence, multivariate analysis of the remaining 176 patients suggested that intramedullary nail plus plate internal fixation, smoking, and an allograft-to-autograft ratio exceeding 1:3 adversely affected healing time. Conclusion: The IMT is an effective method to achieve infection eradication and union in the management of infected segmental bone defects. Our study identified several risk factors associated with unfavourable outcomes. Some of these factors are modifiable, and the risk of adverse outcomes can be reduced by adopting targeted interventions or strategies. Surgeons can fully inform patients with non-modifiable risk factors preoperatively, and may even use other methods for bone defect reconstruction.

Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis.

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.

Limb Fractures Treated With the Novel Plate Osteosynthesis Application Technique: Second to Minimally Invasive Plates osteosynthesis.

BACKGROUND: The main aim of this article was to propose a new concept of minimally invasive surgery for treating limb fractures, named as second to minimally invasive plates osteosynthesis (STMIPO). METHODS: We have described the STMIPO technique in a step-wise and standardized manner based on our findings from a study involving six patients treated at our institution. All patients with fracture achieved satisfactory outcomes. RESULTS: Ours clinical trials have shown that the STMIPO technique can be successfully applied in various limb fractures, including fibula fractures, tibial fractures, femur fractures, humerus fractures, ulna fractures, and radius fractures. All fracture patients achieved satisfactory outcomes. CONCLUSION: As a new minimally invasive technology, the STMIPO technique can serve as an alternative solution for fractures that are difficult to reduce with minimally invasive plates osteosynthesis (MIPO).

Ensemble Prototype Network For Weakly Supervised Temporal Action Localization.

Weakly supervised temporal action localization (TAL) aims to localize the action instances in untrimmed videos using only video-level action labels. Without snippet-level labels, this task should be hard to distinguish all snippets with accurate action/background categories. The main difficulties are the large variations brought by the unconstraint background snippets and multiple subactions in action snippets. The existing prototype model focuses on describing snippets by covering them with clusters (defined as prototypes). In this work, we argue that the clustered prototype covering snippets with simple variations still suffers from the misclassification of the snippets with large variations. We propose an ensemble prototype network (EPNet), which ensembles prototypes learned with consensus-aware clustering. The network stacks a consensus prototype learning (CPL) module and an ensemble snippet weight learning (ESWL) module as one stage and extends one stage to multiple stages in an ensemble learning way. The CPL module learns the consensus matrix by estimating the similarity of clustering labels between two successive clustering generations. The consensus matrix optimizes the clustering to learn consensus prototypes, which can predict the snippets with consensus labels. The ESWL module estimates the weights of the misclassified snippets using the snippet-level loss. The weights update the posterior probabilities of the snippets in the clustering to learn prototypes in the next stage. We use multiple stages to learn multiple prototypes, which can cover the snippets with large variations for accurate snippet classification. Extensive experiments show that our method achieves the state-of-the-art weakly supervised TAL methods on two benchmark datasets, that is, THUMOS'14, ActivityNet v1.2, and ActivityNet v1.3 datasets.

Eclipse web service application programming interface.

Objective.Low-coupling seamless integration of multiple systems is the core foundation of smart radiotherapy. Following Service-Oriented Architecture style, a set of named operations (Eclipse Web Service API, EWSAPI) was developed for realizing network call of Eclipse.Approach.Under the guidance of Vertical Slice Architecture, EWSAPI was implemented in the C# language and based on ASP .Net Core 6.0. Each operation consists of three components: Request, Endpoint and Response. Depending on the function, the exchanged data for each operation, as input or output parameters, is the empty or a predefined JSON data. These operations were realized and enriched gradually, layer by layer, with reference to the clinical business classification. The business logic of each operation was developed and maintained independently. In situations where Eclipse Scripting API(ESAPI) was required, constraints of ESAPI were followed.Main results.Selected features of Eclipse TPS were encapsulated as standard web services, which can be invocated by other software through network. Several processes for data quality control and planning were encapsulated into interfaces, thereby extending the functionality of Eclipse. Currently, EWSAPI already covers testing of service interface, quality control of radiotherapy data, automation tasks for plan designing and DICOM RT files' transmission. All the interfaces support asynchronous invocation. A separate Eclipse context will be created for each invocation, and is released in the end.Significance.EWSAPI which is a set of standard web services for calling Eclipse features through network is flexible and extensible. It is an efficient way to integration of Eclipse and other systems and will be gradually enriched with the deepening of clinical applications.

Active Factor Graph Network for Group Activity Recognition.

Group activity recognition aims to identify a consistent group activity from different actions performed by respective individuals. Most existing methods focus on learning the interaction between each two individuals (i.e., second-order interaction). In this work, we argue that the second-order interactive relation is insufficient to address this task. We propose a third-order active factor graph network, which models the third-order interaction in each pair of three active individuals. At first, to alleviate the noisy individual actions, we select active individuals by measuring each individual's influence. The individuals with the top-k largest influence weights are selected as active individuals. Then, for each three-individuals pair, we build a new factor node and contact the factor node with these individual nodes. In other words, we extend the base second-order interactive graph to a new third-order interactive graph, which is defined as factor graph. Next, we design a two-branch factor graph network, in which one branch is to consider all individuals (denoted as full factor graph) and the other one takes the active individuals into consideration (denoted as active factor graph). We leverage both the active and full factor graphs comprehensively for group activity recognition. Besides, to enforce group consistency, a consistency-aware reasoning module is designed with two penalty terms, which describe the inconsistency between individual actions and group activity respectively. Extensive experiments demonstrate that our method achieves state-of-the-art performance on four benchmark datasets, i.e., Volleyball, Collective Activity, Collective Activity Extended, and SoccerNet-v3 datasets. Visualization results further validate the interpretability of our method.

Discovery of multipotent progenitor cells from human induced membrane: Equivalent to periosteum-derived stem cells in bone regeneration.

Background: The periosteum stem cells (PSCs) plays a critical role in bone regeneration and defect reconstruction. Insertion of polymethyl methacrylate (PMMA) bone cement can form an induced membrane(IM) and showed promising strategy for bone defect reconstruction, the underlying mechanism remains unclear. Our study sought to determine whether IM-derived cells(IMDCs) versus PSCs have similar characteristics in bone regeneration. Methods: IM and periosteum were harvested from ten bone defect patients treated with PMMA, the IMDCs and PSCs were isolated respectively. Morphological, functional and molecular evaluation was performed and matched for comparison. Results: Both progenitor-like IMDCs and PSCs were successfully isolated. In vitro, we found IMDCs were similar to PSCs in morphology, colony forming capacity and expression of surface marker(CD90+, CD73+, CD105+, CD34-/CD45-). Meanwhile, these IMSCs displayed multipotency with chondrogenic, adipogenic and osteogenic differentiation, but differed in some IMSCs(3/10) population showing relatively poor osteogenic differentiation. The molecular profiles suggests that cell cycle and DNA replication signaling pathways were associated with these varying osteogenic potential. In vivo, we established a cell-based tissue-engineered bone by seeding IMDSs/PSCs to demineralized bone matrix (DBM) scaffold and demonstrated both IMDSs and PSCs enhanced bone regeneration in SCID mice bone defect model compared with DBM alone. Conclusion: Our data demonstrated IM containing multipotent progenitor cells similar to that periosteum promoting bone regeneration, and indicated the existence of multiple subsets in osteogenic differentiation. Overall, the study provided a cellular and molecular insights in understanding the successful or failed outcome of bone defect healing.The translational potential of this article: This study confirmed IMDCs and PSCs share similar regeneration capacity and inform a translation potential of that cellular therapy applying IMDCs in bone defect repair.

Incidence and risk factors of recurrence in limb osteomyelitis patients after antibiotic-loaded cement spacer for definitive bone defect treatment.

Aims: This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis. Methods: We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients' demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed. Results: In total, 314 patients with a mean age of 52.1 years (SD 12.1) were enrolled. After a mean of 50 months' (24 to 96) follow-up, 53 (16.9%) patients had infection recurrence including 32 tibiae, ten femora, ten calcanea, and one humerus. Of all patients with recurrence, 30 (9.6%) occurred within one year and 39 (12.4%) within two years. Among them, 41 patients needed reoperation, five received antibiotics treatment only, and seven ultimately required amputations. Following multivariable analysis, we found that patients infected with Gram-negative bacilli were more likely to have a recurrence (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.20 to 6.94; p = 0.046) compared to Staphylococcus aureus; segmental bone defects (OR 5.25, 95% CI 1.80 to 15.26; p = 0.002) and smoking (OR 3.00, 95% CI 1.39 to 6.50; p = 0.005) were also independent risk factors for recurrence after treatment. Conclusion: Permanent ALCS might be an alternative strategy for definitive bone defect management in selected osteomyelitis cases. However, the overall high recurrence found suggests that it should be cautiously treated. Additionally, segmental defects, Gram-negative infections, and smoking were associated with an increased risk of infection recurrence.

The safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine among patients undergoing elective surgery for closed fractures: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial.

BACKGROUND: Vaccines are urgently required to control Staphylococcus aureus hospital and community infections and reduce the use of antibiotics. Here, we report the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in patients undergoing elective surgery for closed fractures. METHODS: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial was carried out in 10 clinical research centers in China. Patients undergoing elective surgery for closed fractures, aged 18-70 years, were randomly allocated at a ratio of 1:1 to receive the rFSAV or placebo at a regimen of two doses on day 0 and another dose on day 7. All participants and investigators remained blinded during the study period. The safety endpoint was the incidence of adverse events within 180 days. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as opsonophagocytic antibodies. RESULTS: A total of 348 eligible participants were randomized to the rFSAV (n = 174) and placebo (n = 174) groups. No grade 3 local adverse events occurred. There was no significant difference in the incidence of overall systemic adverse events between the experimental (40.24 %) and control groups (33.72 %) within 180 days after the first immunization. The antigen-specific binding antibodies started to increase at days 7 and reached their peaks at 10-14 days after the first immunization. The rapid and potent opsonophagocytic antibodies were also substantially above the background levels. CONCLUSIONS: rFSAV is safe and well-tolerated in patients undergoing elective surgery for closed fractures. It elicited rapid and robust specific humoral immune responses using the perioperative immunization procedure. These results provide evidence for further clinical trials to confirm the vaccine efficacy. China's Drug Clinical Trials Registration and Information Publicity Platform registration number: CTR20181788. WHO International Clinical Trial Registry Platform identifier: ChiCTR2200066259.

Modified endoscopic submucosal tunnel dissection for large esophageal submucosal gland duct adenoma: A case report.

BACKGROUND: With the recent improvement of endoscopic techniques, endoscopic ultrasound-guided fine needle aspiration and endoscopic submucosal tunnel dissection (ESTD) have been widely used for accurate diagnosis and dissection acceleration of esophageal tumors. CASE SUMMARY: We used a modified submucosal tunnel technique during endoscopic en bloc resection in a 58-year-old man with large esophageal submucosal gland duct adenoma (ESGDA). During modified ESTD, the oral end of the involved mucosa was cut transversely, followed by a submucosal tunnel created from the proximal to the distal end, and the anal end of the involved mucosa blocked by the tumor was incised. As a result of retaining submucosal injection solutions using the submucosal tunnel technique, it was possible to reduce the amount of injection required and increase the efficiency and safety of dissection. CONCLUSION: Modified ESTD is an effective treatment strategy for large ESGDAs. Single-tunnel ESTD appears to be a time-saving procedure compared with conventional endoscopic submucosal dissection.

[Death-Related Factors in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease Treated by Sequential Mechanical Ventilation].

Objective To analyze the death-related factors of elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) treated by sequential mechanical ventilation,so as to provide evidence for clinical practice. Methods The clinical data of 1204 elderly patients (≥60 years old) with AECOPD treated by sequential mechanical ventilation from June 2015 to June 2021 were retrospectively analyzed.The probability and influencing factors of death were analyzed. Results Among the 1204 elderly patients with AECOPD treated by sequential mechanical ventilation,167 (13.87%) died.Multivariate analysis showed that plasma procalcitonin ≥0.5 µg/L (OR=2.762, 95%CI=1.920-3.972, P<0.001),daily invasive ventilation time ≥12 h (OR=2.202, 95%CI=1.487-3.262,P<0.001),multi-drug resistant bacterial infection (OR=1.790,95%CI=1.237-2.591,P=0.002),oxygenation index<39.90 kPa (OR=2.447,95%CI=1.625-3.685,P<0.001),glycosylated hemoglobin >6% (OR=2.288,95%CI=1.509-3.470,P<0.001),and acute physiology and chronic health evaluation Ⅱ score ≥25 points (OR=2.126,95%CI=1.432-3.156,P<0.001) were independent risk factors for death in patients with AECOPD treated by sequential mechanical ventilation.Oral care>twice/d (OR=0.676,95%CI=0.457-1.000,P=0.048) and sputum excretion>twice/d (OR=0.492, 95%CI=0.311-0.776, P=0.002) were independent protective factors for death in elderly patients with AECOPD treated by sequential mechanical ventilation. Conclusions The outcomes of sequential mechanical ventilation in the treatment of elderly patients with AECOPD are affected by a variety of factors.To reduce the mortality,we put forward the following measures:attaching great importance to severe patients,restoring oxygenation function,shortening unnecessary invasive ventilation time,controlling blood glucose,preventing multidrug resistant bacterial infection,oral care twice a day,and sputum excretion twice a day.