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Abstract Background Bone defects and nonunion following initial treatment remain significant clinical challenges. The Ilizarov method constitutes a fundamental approach for addressing bone defects, and its integration with adjunctive techniques, such as the accordion maneuver, antibiotic spacers, or internal fixation, has become increasingly widespread. Despite this, limited research exists on the clinical outcomes specifically related to the use of the Ilizarov method combined with the accordion technique for treating long bone defects in the lower limbs. Objective This study seeks to systematically review the application of the Ilizarov method in combination with the accordion technique for addressing long bone deficiencies in the lower limbs. Study Design Systematic review; Level of evidence, 4. Methods A systematic review was performed in alignment with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), involving searches of Medline, Embase, Web of Science, and the Cochrane Library, with the search process concluding on August 20, 2024. The study population consisted of patients with bone defects who underwent treatment using the Ilizarov method in conjunction with the accordion technique. The methodological quality of the included studies was evaluated using the MINORS (Methodological Index for Non-Randomized Studies) scoring system. This study recorded and analyzed the participant count for each study that met the inclusion criteria, along with the number of patients who achieved bone healing, the bone and functional outcomes, and complications such as pin infections, pain, and refracture. Results Drawing from eight studies involving 80 patients with bone defects treated through the Ilizarov method combined with the accordion technique, this systematic review evaluated the method’s impact on bone regeneration. Of these patients, 24% presented with femoral defects, while 76% had tibial defects. The mean patient age was 32.8 years, with an average follow-up of 25.2 months. The accordion technique involved daily distraction and compression adjustments ranging from 0.25 to 1 mm, typically in more than two cycles, effectively promoting bone healing. The bone healing rate was high, with the majority of patients rated as having excellent or good functional recovery, according to standards such as ASAMI and Paley. Common complications included superficial pin tract infections (33.75%) and deep pin tract infections (6.25%), both of which were generally manageable with routine treatment. The accordion technique showed promising results in shortening healing time and enhancing the quality of bone healing. Conclusion This systematic review demonstrates that despite variations in parameter settings across studies, the Ilizarov method combined with the accordion technique consistently shows strong efficacy and safety in promoting bone regeneration and functional recovery. While some complications may arise, they are generally well-managed with standard care. This approach represents a reliable option for complex bone reconstruction, with future research needed to optimize parameters and further enhance clinical outcomes.

Abstract Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Abstract The para rubber tree (Hevea brasiliensis) is the world’s sole commercial source of natural rubber, a vital industrial raw material. However, the narrow genetic diversity of this crop poses challenges for rubber breeding. Here, we generate high-quality de novo genome assemblies for three H. brasiliensis cultivars, two H. brasiliensis wild accessions, and three other Hevea species (H. nitida, H. pauciflora, and H. benthamiana). Through analyzing genomes of 94 Hevea accessions, we identify five distinct lineages that do not align with their previous species delineations. We discover multiple accessions with hybrid origins between these lineages, indicating incomplete reproductive isolation between them. Only two out of four wild lineages have been introduced to commercial rubber cultivars. Furthermore, we reveal that the rubber production traits emerged following the development of a large REF/SRPP gene cluster and its functional specialization in rubber-producing laticifers within this genus. These findings would enhance rubber breeding and benefit research communities.

Abstract Background Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health concern as they can cause serious illness and outbreaks. In England, STEC incidence is highest among children and guidance recommends that children under six diagnosed with STEC are excluded from childcare until two consecutive stool cultures are negative. We aimed to describe the barriers and facilitators to implementing exclusion and the impact of exclusion policies on young children and their families. Methods Individual level data was obtained from a wider study focusing on shedding duration among STEC cases aged

ABSTRACT Background Lymph node metastasis (LNM) is a critical factor affecting the outcomes of head and neck squamous cell carcinoma (HNSCC) and the main reason for treatment failure. This study was designed to examine the effects of the key genes involved in the LNM of HNSCC. Methods Tissue samples (HNSCC) were examined by transcriptome sequencing, and the core genes associated with LNM were detected via bioinformatics analysis. The functions of these core genes were then validated using the TCGA biological database and their effects on the propagation, invasion, and metastasis of HNSCC cells were evaluated through cell culture experiments. Moreover, the effect of core gene expression on the LNM capability of HNSCC was confirmed via a footpad xenograft mice model. Results In the findings, a key gene involved in the LNM of HNSCC was identified as SLC7A2. It was correlated with adverse clinical prognosis and expressed with low expression in HNSCC tissues. As shown in cell culture experiments, FaDu and SCC15 cell growth, invasion, and migration were inhibited when SLC7A2 was overexpressed. Further, cell apoptosis was stimulated, and lymphangiogenesis was suppressed through the downregulation of CPB2 expression. Animal studies demonstrated that the growth and LNM of HNSCC cells were inhibited by SLC7A2 overexpression. Conclusion It is concluded that SLC7A2 is involved in HNSCC lymphatic metastasis by controlling CPB2 function. The results are anticipated to offer new directions for the effective treatment of HNSCC.

Identifying molecular markers linked to tobacco bacterial wilt resistance is crucial for developing resistant tobacco varieties, thereby enhancing tobacco production and quality. In this two-year study, we evaluated the tobacco bacterial wilt disease index (TBWDI) in a mapping population of 78 tobacco accessions using SSR/InDel markers across 1377 marker loci. Two association models, GLM_Q and MLM_Q + Kinship, were used for association analysis. By considering multiple environments, selection thresholds, and phenotype values, we identified 19 reliable marker loci (P = 7.07-E05–4.98-E02) that explained 5.37–19.10 % of the phenotypic variation. Among these, we selected 11 accessions with high resistance to tobacco bacterial wilt, each containing at least one excellent locus. The models predicted five hybrid combinations whose offspring aggregated additional excellent loci. Additionally, one locus was identified during quantitative trait loci mapping, with accessions carrying this locus exhibiting significantly different TBWDI values from those without it, confirming its reliability and stability. A candidate gene (LOC107795335) was also identified downstream at 17.58 Kbp of the locus. Our study pinpointed reliable loci associated with bacterial wilt resistance, identified important materials for breeding resistant tobacco varieities, and predicted the best hybrid combinations for low disease indexes. The results of our study offer invaluable theoretical insights for breeding varieties with high and stable resistance.

Abstract Background The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. Results We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. Conclusions Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.

Abstract Introduction The Ilizarov bone transport technique is widely recognised as an effective method for treating large segment bone defects in clinical practice. However, axial deviation is a common complication in the treatment of tibial large segment bone defects, which can have a serious impact on the clinical efficacy of bone transport. Our study aims to construct and validate a nomogram for predicting axial deviation of tibial bone transport. Method This study retrospectively collected data from 363 patients who underwent the tibial Ilizarov technique for bone transport. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for axial deviation, which were later used to construct a nomogram. The nomogram was evaluated using the decision curve analysis (DCA), the calibration curve, and the area under the receiver operating characteristic curve (AUC). Results Of the 363 patients who underwent Ilizarov tibial bone transport, 31.7% (115/363) experienced axial deviation. Multivariate logistic regression analysis showed that gender, height, defect site, and external fixation index were important risk factors for axial deviation. The AUC value of the nomogram model was 0.705. The calibration curve and the decision curve analysis showed a good consistency between the actual axial deviation and the predicted probability. Conclusion The model assigns a quantitative risk score to each variable, which can be used to predict the risk of axial deviation during tibial bone transport.

Abstract Background External fixation is widely used in the treatment of traumatic fractures; however, orthopedic surgeons encounter challenges in deciding the optimal time for fixator removal. The axial load-share ratio (LS) of the fixator is a quantitative index to evaluate the stiffness of callus healing. This paper introduces an innovative method for measuring the LS and assesses the method’s feasibility and efficacy. Based on a novel hexapod LS-measurement system, the proposed method is to improve the convenience and precision of measuring LS in vivo, hence facilitating the safe removal of external fixators. Methods A novel hexapod system is introduced, including its composition, theoretical model, and method for LS measurement. We conducted a retrospective study on 82 patients with tibial fractures treated by the Taylor Spatial Frame in our hospital from September 2018 to June 2020, of which 35 took LS measurements with our novel method (Group I), and 47 were with the traditional method (Group II). The external fixator was removed when the measurement outcome (LS 0.05), frame-wearing duration (mean 25.5 weeks vs. 25.8 weeks, P > 0.05), or LS measurement frequency (mean 1.1 times vs. 1.2 times, P > 0.05). The measurement system installation time in Group I was significantly shorter compared to Group II (mean 14.8 min vs. 81.3 min, P 0.05). Conclusion The novel hexapod LS-measurement system and involved method demonstrated enhanced convenience and precision in measuring the LS of the external fixator in vivo. The LS measurement indicates the callus stiffness of fracture healing, and is applicable to evaluate the safety of removing the fixator. Consequently, it is highly recommended for widespread adoption in clinical practice.

Abstract Background Medial patellar ligament reconstruction (MPFL-R) in combination with derotational distal femoral osteotomy (DDFO) for treating recurrent patellar dislocation (RPD) in the presence of increased femoral anteversion is one of the most commonly used surgical techniques in the current clinical practice. However, there are limited studies on the clinical outcomes of MPFL-R in combination with DDFO to treat RPD in the presence of increased femoral anteversion. Purpose To study the role of MPFL-R in combination with DDFO in the treatment of RPD in the presence of increased femoral anteversion. Methods A systematic review was performed according to the PRISMA guidelines by searching the Medline, Embase, Web of Science, and Cochrane Library databases through June 1, 2023. Studies of patients who received MPFL-R in combination with DDFO after presenting with RPD and increased femoral anteversion were included. Methodological quality was assessed using the MINORS (Methodological Index for Nonrandomized Studies) score. Each study’s basic characteristics, including characteristic information, radiological parameters, surgical techniques, patient-reported outcomes, and complications, were recorded and analyzed. Results A total of 6 studies with 231 patients (236 knees) were included. Sample sizes ranged from 12 to 162 patients, and the majority of the patients were female (range, 67-100%). The mean age and follow-up ranges were 18 to 24 years and 16 to 49 months, respectively. The mean femoral anteversion decreased significantly from 34° preoperatively to 12° postoperatively. In studies reporting preoperative and postoperative outcomes, significant improvements were found in the Lysholm score, Kujala score, International Knee Documentation Committee score, and visual analog scale for pain. Postoperative complications were reported in all studies, with an overall reported complication rate of 4.7%, but no redislocations occurred during the follow-up period. Conclusion For RPD with increased femoral anteversion, MPFL-R in combination with DDFO leads to a good clinical outcome and a low redislocation rate. However, there was no consensus among researchers on the indications for MPFL-R combined with DDFO in the treatment of RPD.

【Objective】The study aimed to develop highly polymorphic InDel markers for molecular marker assisted breeding of flowering Chinese cabbage.【Method】The InDel loci were identified by comparing RAD-seq data from four flowering Chinese cabbage accessions with the genome sequence of Chiifu-401-42 as a reference. InDel loci with potential polymorphism were screened out among four accessions by using bioinformatics methods. From these, 80 InDel loci evenly distributed across 10 chromosomes were selected for primer design and genetic diversity of 55 flowering Chinese cabbage accessions were evaluated.【Result】By alignment with reference genome sequence, a total of 84 510 InDel loci were identified in RAD-seq data of four accessions. Among them, 3 609 InDel loci (> 5 bp) were possibly polymorphic among four flowering Chinese cabbage accessions. Of 80 InDel loci selected for PCR amplification validation, 58 (72.5%) InDel markers showed polymorphism in the four sequenced accessions, and 133 alleles were detected in 55 accessions. The polymorphic information content (PIC) of these 58 markers ranged from 0.263 to 0.618, with an average of 0.443. Based on the detection results of InDel markers, the genetic similarity coefficient of 55 accessions ranged from 0.366 to 0.756, with an average of 0.570. The 55 accessions were classified into four groups with a genetic similarity coefficient of 0.564, and no significant difference was found in heat resistance among different groups.【Conclusion】The nDel markers with good polymorphism developed in this study can effectively reveal the genetic distance among different flowering Chinese cabbage germplasm materials, which could provide useful marker information for genetic germplasm analysis and new variety breeding of flowering Chinese cabbage.

Abstract Background Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis’s mechanism. Results Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis. Conclusions Our findings suggest that PKM2 may be a tumor’s promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.

Abstract Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.

Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.

Sarcopenia, a geriatric syndrome characterized by progressive loss of muscle mass and strength, and osteoarthritis, a common degenerative joint disease, are both prevalent in elderly individuals. However, the relationship and molecular mechanisms underlying these two diseases have not been fully elucidated. In this study, we screened microarray data from the Gene Expression Omnibus to identify associations between sarcopenia and osteoarthritis. We employed multiple statistical methods and bioinformatics tools to analyze the shared DEGs (differentially expressed genes). Additionally, we identified 8 hub genes through functional enrichment analysis, protein–protein interaction analysis, transcription factor-gene interaction network analysis, and TF-miRNA coregulatory network analysis. We also discovered potential shared pathways between the two diseases, such as transcriptional misregulation in cancer, the FOXO signalling pathway, and endometrial cancer. Furthermore, based on common DEGs, we found that strophanthidin may be an optimal drug for treating sarcopenia and osteoarthritis, as indicated by the Drug Signatures database. Immune infiltration analysis was also performed on the sarcopenia and osteoarthritis datasets. Finally, receiver operating characteristic (ROC) curves were plotted to verify the reliability of our results. Our findings provide a theoretical foundation for future research on the potential common pathogenesis and molecular mechanisms of sarcopenia and osteoarthritis.

Abstract Human aging is a natural and inevitable biological process that leads to an increased risk of aging-related diseases. Developing anti-aging therapies for aging-related diseases requires a comprehensive understanding of the mechanisms and effects of aging and longevity from a multi-modal and multi-faceted perspective. However, most of the relevant knowledge is scattered in the biomedical literature, the volume of which reached 36 million in PubMed. Here, we presented HALD, a text mining-based human aging and longevity dataset of the biomedical knowledge graph from all published literature related to human aging and longevity in PubMed. HALD integrated multiple state-of-the-art natural language processing (NLP) techniques to improve the accuracy and coverage of the knowledge graph for precision gerontology and geroscience analyses. Up to September 2023, HALD had contained 12,227 entities in 10 types (gene, RNA, protein, carbohydrate, lipid, peptide, pharmaceutical preparations, toxin, mutation, and disease), 115,522 relations, 1,855 aging biomarkers, and 525 longevity biomarkers from 339,918 biomedical articles in PubMed. HALD is available at https://bis.zju.edu.cn/hald .

Abstract Background Tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is the most serious soil-borne disease of tobacco that significantly reduces crop yield. However, the limited availability of resistance in tobacco hinders breeding efforts for this disease. Results In this study, we conducted hydroponic experiments for the root expression profiles of D101 (resistant) and Honghuadajinyuan (susceptible) cultivars in response to BW infection at 0 h, 6 h, 1 d, 3 d, and 7d to explore the defense mechanisms of BW resistance in tobacco. As a result, 20,711 and 16,663 (total: 23,568) differentially expressed genes (DEGs) were identified in the resistant and susceptible cultivars, respectively. In brief, at 6 h, 1 d, 3 d, and 7 d, the resistant cultivar showed upregulation of 1553, 1124, 2583, and 7512 genes, while the susceptible cultivar showed downregulation of 1213, 1295, 813, and 7735 genes. Similarly, across these time points, the resistant cultivar had downregulation of 1034, 749, 1686, and 11,086 genes, whereas the susceptible cultivar had upregulation of 1953, 1790, 2334, and 6380 genes. The resistant cultivar had more up-regulated genes at 3 d and 7 d than the susceptible cultivar, indicating that the resistant cultivar has a more robust defense response against the pathogen. The GO and KEGG enrichment analysis showed that these genes are involved in responses to oxidative stress, plant–pathogen interactions, cell walls, glutathione and phenylalanine metabolism, and plant hormone signal transduction. Among the DEGs, 239 potential candidate genes were detected, including 49 phenylpropane/flavonoids pathway-associated, 45 glutathione metabolic pathway-associated, 47 WRKY, 48 ERFs, eight ARFs, 26 pathogenesis-related genes (PRs), and 14 short-chain dehydrogenase/reductase genes. In addition, two highly expressed novel genes (MSTRG.61386-R1B-17 and MSTRG.61568) encoding nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins were identified in both cultivars at 7 d. Conclusions This study revealed significant enrichment of DEGs in GO and KEGG terms linked to glutathione, flavonoids, and phenylpropane pathways, indicating the potential role of glutathione and flavonoids in early BW resistance in tobacco roots. These findings offer fundamental insight for further exploration of the genetic architecture and molecular mechanisms of BW resistance in tobacco and solanaceous plants at the molecular level.

Electric tractors have many advantages, including high torque, excellent controllability, energy efficiency, a simple structure, and an electric interface for expansion. However, a significant limitation lies in their endurance. This study presents the design of an extended-range power supply system to ensure continuous endurance for an electric tractor. The objective is to provide a continuous power source for our self-developed electric tractor while preserving the benefits of electric propulsion. Extended-range power systems utilize a primary mover, typically an oil-fueled internal combustion engine, to drive the generator for electricity generation, and the generated AC-form electricity is subsequently converted into stable DC bus voltage by a power electronic converter. The hardware and control design of an extended-range power supply system are finalized and validated through experimental trials. The results demonstrate the system’s capability to sustain stable DC bus voltage amidst disruptions such as sudden load shifts and fluctuations in the prime mover’s speed. Even with a 50% sudden load change, the voltage drop is within 12% and can recover to ±3% within 4 s. The extended-range can be used alone without a battery to power the electric tractor, or it can used in parallel with other extended ranges or batteries for power sharing thanks to the droop control ability.

Abstract Understanding the genetic basis of rubber tree (Hevea brasiliensis) domestication is crucial for further improving natural rubber production to meet its increasing demand worldwide. Here we provide a high-quality H. brasiliensis genome assembly (1.58 Gb, contig N50 of 11.21 megabases), present a map of genome variations by resequencing 335 accessions and reveal domestication-related molecular signals and a major domestication trait, the higher number of laticifer rings. We further show that HbPSK5, encoding the small-peptide hormone phytosulfokine (PSK), is a key domestication gene and closely correlated with the major domestication trait. The transcriptional activation of HbPSK5 by myelocytomatosis (MYC) members links PSK signaling to jasmonates in regulating the laticifer differentiation in rubber tree. Heterologous overexpression of HbPSK5 in Russian dandelion (Taraxacum kok-saghyz) can increase rubber content by promoting laticifer formation. Our results provide an insight into target genes for improving rubber tree and accelerating the domestication of other rubber-producing plants.

Abstract Background The purpose of this study was to report the outcomes of single-level bone transport with a unilateral external fixator for treatment of proximal, intermediate and distal tibial bone defects caused by fracture-related infection (FRI) and compare their complications. Methods The clinical records and consecutive X-ray photographs of patients with tibial bone defects treated by single-level bone transport using a unilateral external fixator (Orthofix Limb Reconstruction System) were analyzed retrospectively, from January 2012 to December 2018. Patients were divided into the proximal group (P, n = 19), intermediate group (I, n = 25), and distal group (D, n = 18) according to the location of the tibial bone defect. The Association for the Study and Application of the Method of Ilizarov (ASAMI) standard was applied to assess the bone and functional outcomes and postoperative complications evaluated by the Paley classification. Results A total of 62 participants were included in this study, with a median age of 36 ± 7.14 years. Sixty patients with tibial bone defects caused by FRI were successfully treated by single-level bone transport using a unilateral external fixator, with a mean bone union time (BUT) of 7.3 ± 1.71 months. According to the ASAMI criteria, there were statistical differences in bone and function results between the three groups (P vs. I vs. D, P

【Objective】Natural rubber is an important industrial raw materials and strategic materials, and played a very important role in national economic development. As a resource constraint industry, it was mainly produced by Brazilian rubber tree (Hevea brasiliensis) and it has the highest yield and the best quality among the mankind known rubber-producing plants. Harvesting latex is the main economic purpose of Brazilian rubber tree, latex yield is a quantitative trait controlled by minorgene, with many influencing factors, and its phenotypic value is affected by heredity and environmental effect. To determine the relationship among the yield and agronomic traits of the wild germplasm resources of Hevea brasiliensis, this study provides a scientific basis for the evaluation and screening of rubber tree germplasm resources and the selection and breeding of new varieties.【Method】The yield, growth and other related agronomic traits of 13 wild germplasm resources of Hevea brasiliensis planted in the experimental field of Chinese Academy of Tropical Agricultural Sciences (CATAS) were studied and analyzed by grey relational analysis.【Result】The results showed that the association order of the eight main agronomic traits related to the dry rubber yield per plant were stem girth, dry rubber content, average number of laticifer cells, average number of laticifer columns, bark thickness, mean stem girth increment, lateral vein latex grade and gum value ratio, and the weights of each trait were 0.1380, 0.1338, 0.1322, 0.1264, 0.1205, 0.1182, 0.1178, 0.1143. In summary, stem girth, dry rubber content, quantity of laticifers bark thickness and other traits are closely related to and have a great impact on dry rubber yield per plant.【Conclusion】Among the main agronomic traits, the stem girth, dry rubber content and quantity of laticifer should be paid more attention on the evaluation of rubber tree germplasm resources, at the same time the potential impact of other traits on yield also need to be laid some stress on.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is highly aggressive with a significant tropism of lymph nodes, which restricts treatment options and negatively impacts patient outcomes. Although progress has been made in understanding the molecular mechanisms underlying lymphatic metastasis (LM), these mechanisms remain elusive. ANXA6 is a scaffold protein that participates in tumor pathogenesis and autophagy regulation; however, how ANXA6 affects autophagy and LM in HNSCC cells remains unknown. Methods RNA sequencing was performed on HNSCC clinical specimens with or without metastasis as well as on The Cancer Genome Atlas dataset to investigate ANXA6 expression and survival. Both in vitro and in vivo studies were performed to investigate the role of ANXA6 in the regulation of LM in HNSCC. The molecular mechanism by which ANXA6 interacts with TRPV2 was examined at the molecular level. Results ANXA6 expression was significantly upregulated in HNSCC patients with LM and higher expression was associated with poor prognosis. ANXA6 overexpression promoted the proliferation and mobility of FaDu and SCC15 cells in vitro; however, ANXA6 knockdown retarded LM in HNSCC in vivo. ANXA6 induced autophagy by inhibiting the AKT/mTOR signaling pathway in HNSCC, thereby regulating the metastatic capability of the disease. Furthermore, ANXA6 expression positively correlated with TRPV2 expression both in vitro and in vivo. Lastly, TRPV2 inhibition reversed ANXA6-induced autophagy and LM. Conclusions These results indicate that the ANXA6/TRPV2 axis facilitates LM in HNSCC by stimulating autophagy. This study provides a theoretical basis for investigating the ANXA6/TRPV2 axis as a potential target for the treatment of HNSCC, as well as a biomarker for predicting LM.

【Objective】By detecting the natural variation of Auxin Up-regulated F-box protein2 (AUF2) gene and exploring the elite alleles associated with agronomic traits in order to provide theoretical references for molecular marker assisted breeding of flowering Chinese cabbage.【Method】PCR amplification and sequencing was used to detect the natural variations in AUF2 gene among 156 flowering Chinese cabbage accessions. By using the mixed linear model (MLM) of Tassel 5.0 software, the correlation between the variation sites of AUF2 gene and six agronomic traits of flowering Chinese cabbage was analyzed, including plant height, single plant weight, maximum leaf length, maximum leaf width, maximum petiole length and chlorophyll content (SPAD), and the polymorphic sites significantly associated with agronomic traits would be identified. Then, elite alleles and excellent haplotypes were determined.【Result】Through sequencing analysis, a total of 34 mutation sites were detected in the 2 996 bp amplification region of AUF2 gene, including 36 haplotypes. The AUF2 gene showed high nucleotide diversity (π = 0.00503) and haplotype diversity (Hd = 0.780). Among them, 2 InDels and 26 SNPs were in the 1 498 bp upstream non-conding region, and 1 InDel and 5 SNPs were in the 960 bp coding region. No mutation sites were detected in the 538 bp downstream non-conding region. Neutral test analysis showed that Tajima's D value, Fu and Li's D* value, and Fu and Li's F* value of the AUF2 gene were positive, and deviated significantly from neutral evolutionary model. One plausible reason was that flowering Chinese cabbage population was subject to balancing selection. The association analysis showed that 4 SNPs were significantly associated with at least one of the four agronomic traits, including single plant weight, maximum leaf length, maximum leaf width and maximum petiole length. The phenotypic variation of a given trait explained by each associated SNP ranged from 5.04% to 6.52%. The haplotype Hap2, which contained elite alletes of the four SNPs mentioned above, could significantly raise the single plant weight, and remarkably increase the length of the maximum petiole.【Conclusion】There are abundant variations in the AUF2 gene, which has a significant impact on the agronomic traits of flowering Chinese cabbage. These elite alleles and excellent haplotypes of AUF2 gene will benefit the genetic improvement of flowering Chinese cabbage.

Abstract Background With the rise of high-calorie diets and the aging of populations, the incidence of diabetes was increased dramatically in the world and the number of people with diabetes was predicted to rise to 600 million by 2045. Numerous studies have confirmed that several organ systems, including the skeletal system, are seriously affected by diabetes. In that study, the bone regeneration and the biomechanics of the newly regenerated bone were investigated in diabetic rats, which may provide a supplement for previous studies. Methods A total of 40 SD rats were randomly divided into the type 2 diabetes mellitus (T2DM) group (n = 20) and the control group (n = 20). Beyond that high fat diet and streptozotocin (STZ) were jointly used in the T2DM group, there were no differences between the two groups in terms of treatment conditions. Distraction osteogenesis was used in all animals for the next experimental observation. The evaluation criterion of the regenerated bone was based on radioscopy (once a week), micro-computed tomography (CT), general morphology, biomechanics (including ultimate load, modulus of elasticity, energy to failure, and stiffness), histomorphometry (including von Kossa, Masson trichrome, Goldner trichrome, and safranin O staining), and immunohistochemistry. Results All rats in the T2DM group with fasting glucose levels (FGL, > 16.7 mmol/L) were allowed to complete the following experiments. The results showed that rats with T2DM have a higher body weight (549.01 g ± 31.34 g) than rats in the control group (488.60 g ± 33.60 g) at the end of observation. Additionally, compared to the control group, slower bone regeneration in the distracted segments was observed in the T2DM group according to radiography, micro-CT, general morphology, and histomorphometry. Furthermore, a biomechanical test showed that there was a worse ultimate load (31.01 ± 3.39%), modulus of elasticity (34.44 ± 5.06%), energy to failure (27.42 ± 5.87%), and stiffness (34.55 ± 7.66%) than the control group (45.85 ± 7.61%, 54.38 ± 9.33%, 59.41 ± 10.96%, and 54.07 ± 9.30%, respectively). Furthermore, the decreased expressions of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were presented in T2DM group by immunohistochemistry. Conclusion The present study demonstrated that diabetes mellitus impairs bone regeneration and biomechanics in newly regenerated bone, a phenomenon that might be related to oxidative stress and poor angiogenesis brought on by the disease.

Abstract Background Several randomized clinical trials showed that aspirin could decrease the incidence of preeclampsia (PE) in women at high risk, but data from sources other than traditional clinical trials that investigating the preventive effect of aspirin 75 mg on PE is still lacking, especially in mainland China. We aimed to use Chinese real-world data to estimate the preventive effect of low-dose aspirin (LDA) on PE. Methods Clinical data of pregnant women who were at high risk of PE and had their first prenatal visit at the affiliated Taicang People’s Hospital of Soochow University during November 31, 2018 and May 10, 2021 was retrospectively analyzed. Among the 266 included pregnant women, 115 individuals treated with aspirin 75 mg per day and the other 151 without such treatment were considered as the LDA group and the control group, respectively. Results In the LDA group, 64 (55.65%) of 115 pregnant women took aspirin before 16 weeks of gestation. Besides, 12 (10.43%) and 34 (22.52%) women developed PE in the LDA group and control group, respectively; the aspirin prophylaxis was associated with a lower risk of PE (odds ratio = 0.40, 95% confidence interval = 0.20–0.82, P = 0.0098). In addition, LDA is slightly more effective when initiated before 16 weeks of gestation or in those without chronic hypertension, when compared with their counterparts. Conclusion Prophylaxis with 75 mg per day of aspirin in high-risk women resulted in a significantly lower incidence of PE than that in the control group.

Abstract Background The purpose of this study was to investigate the risk factors of transport gap bending deformity (TGBD) in the treatment of critical-size bone defect (CSBD) after the removal of the external fixator. Methods From January 2008 to December 2019, 178 patients with bone defects of the lower extremity caused by infection were treated by bone transport using a unilateral external fixator in our medical institution. TGBD was defined as the bone callus in the distraction area with a deviation to the force line of the femur (> 10°) or tibia (> 12°) after removal of the external fixator. The Association for the Study and Application of the Method of Ilizarov (ASAMI) standard was applied to assess the bone and functional outcomes. After the data were significant by the T-test or Pearson’s Chi-square test was analyzed, odds ratios were calculated using logistic regression tests to describe factors associated with the diagnosis of TGBD. Results A total of 178 patients were enrolled in the study, with a mean follow-up time of 28.6 ± 3.82 months. The positive result of the bacteria isolated test was observed in 144 cases (80.9%). The rate of excellent and good in the bone outcomes (excellent/good/fair/poor/failure, 41/108/15/14/0) was 83.7%, and 92.3% in the functional results (excellent/good/fair/poor/failure, 50/98/16/14/0) according to the ASAMI criteria. TGBD after removal of external fixator occurred in twenty-two patients (12.3%), including 6 tibias, and 16 femurs. Age > 45 years, BMI > 25 kg/m2, femoral defect, diabetes, osteoporosis, glucocorticoid intake, duration of infection > 24 months, EFT > 9 months, EFI > 1.8 month/cm were associated significantly with a higher incidence of TGBD in the binary logistic regression analysis (P 25 kg/m2 (69.0%), diabetes (59.5%), glucocorticoid intake (54.7%). In the multivariate logistic regression analyses, the following factors were associated independently with TGBD, including age > 45 years, BMI > 25 kg/m2, femoral defect, diabetes, and osteoporosis. Conclusions Bone transport using a unilateral external fixator was a safe and practical method in the treatment of CSBD caused by infection. The top five risk factors of TGBD included femoral defect, BMI > 25 kg/m2, duration of bone infection > 24 months, age > 45 years, and diabetes. Age > 45 years, BMI > 25 kg/m2, femoral defect, osteoporosis, and diabetes were the independent risk factors. The higher incidence of TGBD may be associated with more risk factors.

Swelling-induced morpholine functionalized adamantane-containing poly(aryl ether ketone) (MAPEK) membranes were prepared for vanadium flow batteries. MAPEK membranes were prepared from chloromethylated polymer and morpholine and further swelling-induced with hot phosphoric acid to obtain membranes with enhanced ionic conductivity. The swelling, selectivity, and ionic conductivity of MAPEK membranes were regulated by varying the swelling temperature. Selective swelling-induced microphase separation in MAPEK membranes, forming wider ion transport pathways and resulting in low area resistance. The unique rigid adamantane-containing backbone limited the swelling of membranes. Consequently, MAPEK membranes showed excellent selectivity and conductivity (vanadium ion permeability coefficient of MAPEK membranes was lower than 3.82 × 0−7 cm2min−1) (Nafion212 membrane, 42.5 × 0−7 cm2min−1), and MAPEK-150 membrane exhibited low area resistance (0.17 Ωcm2). The vanadium flow batteries (VFB) with MAPEK-150 membrane exhibited high energy efficiency (91.1% at 80 mAcm−2, 81.4% at 200 mAcm−2). Furthermore, MAPEK membranes showed good stability in VFB and oxidative electrolytes. The swelling-induced method utilized in this work is a versatile and facile method to enhance the conductivity of ion-exchange membranes.

BackgroundTendon adhesions after hand tendon repair are one of the most difficult complications of hand surgery and can cause severe disability. This study aimed to assess the risk factors associated with tendon adhesions after hand tendon repair to provide a theoretical foundation for the early prevention of tendon adhesions in patients with tendon injuries. Moreover, this study intends to increase doctors' awareness of the issue and serves as a reference for developing new prevention and treatment strategies.MethodsWe retrospectively analyzed 1,031 hand trauma cases that underwent repair after finger tendon injury in our department between June 2009 and June 2019. Tendon adhesions, tendon injury zones, and other relevant information were collected, summarized, and analyzed. The significance of data was determined using a t-test or Pearson's chi-square test, and odds ratios (OR) were calculated using logistic regression tests to describe factors associated with post-tendon repair adhesions.ResultsA total of 1,031 patients were enrolled in this study. There were 817 males and 214 females with an average age of 34.98 (2–82) years. The injured side included 530 left and 501 right hands. Postoperative finger tendon adhesions occurred in 118 cases (11.45%), including 98 males and 20 females, 57 left and 61 right hands. The risk factors for the total sample in the descending order were degloving injury, no functional exercise, zone II flexor tendon injury, time from injury to surgery >12 h, combined vascular injury, and multiple tendon injuries. The flexor tendon sample shared the same risk factors as the total sample. Risk factors for the extensor tendon sample were degloving injury, no functional exercise.ConclusionsClinicians should pay close attention to patients with tendon trauma in hand having the following risk factors: degloving injury, zone II flexor tendon injury, lack of functional exercise, time from injury to surgery >12 h, combined vascular injury, and multiple tendon injuries. Due to the high risk of post-repair adhesions in patients with the conditions mentioned above, individualized treatment measures should be designed for the risk factors, and postoperative functional exercise of the hand is required.

Abstract Background Lymphatic metastasis was an independent prognostic risk factor for hypopharyngeal carcinoma and was the main cause of treatment failure. The purpose of this study was to screen the differential genes and investigate the mechanism of lymphatic metastasis in hypopharyngeal carcinoma. Methods Transcriptome sequencing was performed on primary tumors of patients, and differential genes were screened by bioinformatics analysis. The expression of differential genes was verified by qRT-PCR, western-blotting and immunohistochemical, and prognostic value was analyzed by Kaplan–Meier and log-rank test and Cox’s test. Next, FADU and SCC15 cell lines were used to demonstrate the function of differential genes both in vitro by EdU, Flow cytometry, Wound Healing and Transwell assays and in vivo by a foot-pad xenograft mice model. Proteomic sequencing was performed to screen relevant targets. In addition, in vitro and in vivo experiments were conducted to verify the mechanism of lymphatic metastasis. Results Results of transcriptome sequencing showed that RAF1 was a significantly differential gene in lymphatic metastasis and was an independent prognostic risk factor. In vitro experiments suggested that decreased expression of RAF1 could inhibit proliferation, migration and invasion of tumor cells and promote apoptosis. In vivo experiments indicated that RAF1 could promote tumor growth and lymphatic metastasis. Proteomic sequencing and subsequent experiments suggested that LAGE1 could promote development of tumor and lymphatic metastasis, and was regulated by RAF1. Conclusions It suggests that RAF1 can promote lymphatic metastasis of hypopharyngeal carcinoma by regulating LAGE1, and provide a basis for the exploring of novel therapeutic target and ultimately provide new guidance for the establishment of intelligent diagnosis and precise treatment of hypopharyngeal carcinoma.

【Objective】Powdery mildew of rubber tree is the most serious leaf disease of rubber tree in China so far. The PMA-qPCR detection system for powdery mildew of rubber tree was constructed by combining propidium monoazide (PMA) with real-time fluorescence quantitative PCR (qPCR), which provided technical support for the timely and efficient detection of viable conidia of powdery mildew in rubber tree.【Method】Primers were designed according to the conserved region of ribosomal internal transcribed spacer (ITS) sequence of Erysiphe quercicola and its specificity was verified. The standard curve was drawn with the recombinant plasmid pMD-19T-Eq. A PMA-qPCR detection system for powdery mildew of rubber tree was established to evaluate its repeatability and sensitivity. The system was used to detect the viable count of powdery mildew after propiconazole treatment.【Result】The designed primers had good specificity. A good linear relationship between cycle threshold (Ct) and template concentration was found in the constructed qPCR standard curve for Erysiphe quercicola, the correlation coefficient was 0.9981, and the amplification efficiency was 107.97%. PMA-qPCR had little effect on the amplification of live spore suspension, and the detection sensitivity was 4.77×102 copies/μL. After treatment with propiconazole for 15 min, the proportion of live bacteria decreased from 66.13% to 23.18%.【Conclusion】The PMA-qPCR system could rapidly and quantitatively detect the number of live bacteria of powdery mildew in rubber tree, which had the advantages of sensitivity, accuracy and efficiency, and provided theoretical basis and technical means for the prediction and control of the disease.

Among many plant polysaccharides, arabinogalactan had the best growth-promoting effect on Akkermansia muciniphila (Akk) model strain (DSM 22959). In order to further explore the influence of arabinogalactan on Akk metabolites, arabinogalactan was used as part of the carbon source to ferment Akk in vitro for the first time, and determined the supplementary amount of arabinogalactan to facilitate the Akk fermentation broth. In the subsequent analysis of the samples, high-resolution non-targeted metabolomics technology was used to detect and analyze the differential metabolites in the Akk fermentation broth samples. The results showed that there were 85 different metabolites (VIP>1, P

Abstract Background This study aimed to evaluate the clinical and functional outcomes of patients with femoral and tibial critical-sized bone defect (CSBD) treated by trifocal bone transport using the Ilizarov method. Methods From March 2011 and January 2017, clinical and radiographic data of patients with CSBD (> 6 cm) caused by infection were documented and analyzed. Patients were divided into the femur group (n = 18) and tibia groups (n = 21) according to the location of bone transport. The bone and functional outcomes were evaluated according to the Association for the Study and Application of the Method of the Ilizarov (ASAMI) criterion, and postoperative complications were evaluated by Paley classification. Results A total of 39 patients were managed by the trifocal bone transport for the femur (n = 18) or tibia (n = 21) bone defects with a mean follow-up time of 26.1 months (range 17–34 months). Eighteen femurs and 21 tibias with a mean distraction regenerate length (DRL) of 8.3 cm (range 6–13 cm) and 7.5 cm (range 6–11 cm) respectively. Infection was eradicated in all patients, and the total bone union was received in all cases (100%). Statistical difference of bone grade (excellent/good/fair/poor, 3/11/3/1 vs 2/13/4/2, P

Abstract Background Tardy ulnar nerve palsy is a common late complication of traumatic cubitus valgus. At present, the treatment of tardy ulnar nerve palsy associated with traumatic cubitus valgus is still controversial, whether these two problems can be corrected safely and effectively in one operation is still unclear. To investigate the supracondylar shortening wedge rotary osteotomy combined with in situ tension release of the ulnar nerve in the treatment of tardy ulnar nerve palsy associated with traumatic cubitus valgus. Methods Between 2012 and 2019, 16 patients who had traumatic cubitus valgus deformities with tardy ulnar nerve palsy were treated with simultaneous supracondylar shortening wedge rotary osteotomy and ulnar nerve in situ tension release. we compared a series of indicators of preoperative and postoperative follow-up for at least 24 months, (1) elbow range of motion; (2) the radiographic correction of the preoperative and postoperative humerus-elbow-wrist angles; (3) the static two-point discrimination and grip strength; and (4) the preoperative and postoperative DASH scores of upper limb function. The minimum follow-up was 24 months postoperative (mean, 33 months; range, 24 ~ 44 months). Results The mean ROM was improved from 107 ° preoperatively to 122 ° postoperatively (P = 0.001). The mean preoperative elbow wrist angle was 24.6 °, and the mean postoperative humerus-elbow wrist angle was 12.1 ° (P

Abstract Background External fixation, which can preserve the biomechanical microenvironment of fracture healing, plays an important role in managing the high-energy fractures with poor surrounding soft tissues. The purpose of this study was to determine the differences of clinical outcomes, if any, between hexapod external fixator and monolateral external fixator in the definitive treatment of high-energy tibial diaphyseal fractures. Methods A total of 53 patients with high-energy tibial diaphyseal fractures and definitively treated by the hexapod external fixator (HEF) or monolateral external fixator (MEF) were retrospectively collected and analyzed, from March 2015 to June 2019. There were 31 patients in the HEF treatment, and the other 22 patients were managed by the MEF. The demographic data, surgical duration, external fixation time, final radiological results, complications, and clinical outcomes were documented and analyzed. Difficulties that occurred during the treatment were classified according to Paley. The clinical outcomes were evaluated by the Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at the last clinical visit. Results The mean surgical duration in the HEF group (62.4 ± 8.3 min) was shorter than that in the MEF group (91.4 ± 6.9 min) (P 0.05). Conclusion There is no statistically significant difference in finally clinical outcomes between hexapod external fixator and monolateral external fixator in the definitive treatment of high-energy tibial diaphyseal fractures. The hexapod external fixation treatment is a superior effective method, including advantages of stable fixation, less surgical duration, postoperatively satisfactory fracture reduction, and fewer complications.

Abstract Background Humeral nonunion with significant bone loss or shortening is uncommon and poses a complex clinical problem. We present a case of humeral nonunion with a large segmental bone defect treated with the distraction osteogenesis technique and remedy the radial nerve palsy produced during distraction osteogenesis by forearm tendon transfers. The reconstruction of upper limb function was achieved with satisfactory results. This case provides a referenceable alternative method for repairing large segmental bone defects due to complex nonunion of the upper extremity, as well as a remedy in the unfortunate event of radial nerve palsy, providing a reference and lessons learned for the treatment of similar cases and the management of possible complications. Case presentation A 31-year-old male patient experienced 9 years of hypertrophic nonunion due to an unreliable internal fixation. The radiographs showed the absence of bone bridging between the two fragments, loosening of the screws, and extensive osteolysis around the internal screws. The patient was treated with distraction osteogenesis. At the end of the distraction period, the patient unfortunately developed right radial nerve paresis, which was salvaged by forearm tendon transplantation, and finally reconstructed hand function and achieved bone union of the humerus. Conclusion Distraction osteogenesis, although not a panacea for all humeral nonunions with significant segmental bone loss, does offer a viable salvage procedure in this unusual and often complex clinical problem. When irreversible radial nerve palsy occurs during distraction, forearm tendon transfers can have a good clinical effect.

Abstract Backgroud When the reduction of long bone shaft fracture fragments is performed by a hexapod external fixator, the collision and interference between bony ends often results in an incomplete reduction and a time-consuming procedure. The purpose of this study was to present and determine the clinical effectiveness of staged correction trajectory with hexapod external fixator in the reduction of a long bone shaft fracture. Methods A total of 57 patients with tibial shaft fractures treated by hexapod external fixator were retrospectively analyzed from June 2016 to February 2020. Thirty-one cases (Group I) underwent a conventional one-step reduction trajectory from June 2016 to July 2018. Starting in September 2018, the other twenty-six patients (Group II) underwent staged correction trajectory (three key points reduction trajectory of “distraction-derotation-reduction”). The demographic data, residual deformities before and after correction, number of repeated X-rays after the first postoperative X-ray, duration of deformity correction process, and external fixation time were analyzed. Johner-Wruhs criteria were used to evaluate the final clinical outcomes. Results All the 57 patients achieved satisfactory fracture reduction and bone union. There were no significant differences between the two groups in demographic data, residual deformities before and after correction, external fixation time, and final clinical outcomes (p > 0.05). The average number of repeated X-rays after the first postoperative X-ray and mean duration of deformity correction process in Group II (1.3 times, 2.9 days) were all less than those in Group I (2.3 times, 5.1 days) (p

Abstract Background The Taylor Spatial Frame (TSF) has been widely used for tibial fracture. However, traditional radiographic measurement method is complicated and the reduction accuracy is affected by various factors. The purpose of this study was to propose a new marker- three dimensional (3D) measurement method and determine the differences of reduction outcomes, if any, between marker-3D measurement method and traditional radiographic measurement in the TSF treatment. Methods Forty-one patients with tibial fracture treated by TSF in our institution were retrospectively analyzed from January 2016 to June 2019, including 21 patients in the marker-3D measurement group (experimental group) and 20 patients in the traditional radiographic measurement group (control group). In the experimental group, 3D reconstruction with 6 markers installed on the TSF was performed to determine the electronic prescription. In the control group, the anteroposterior (AP) and lateral radiographs were performed for the traditional parameter measurements. The effectiveness was evaluated by the residual displacement deformity (RDD) and residual angle deformity (RAD) in the coronal and sagittal plane, according to the AP and lateral X-rays after reduction. Results All patients achieved functional reduction. The residual RDD in AP view was 0.5 (0, 1.72) mm in experimental group and 1.74 (0.43, 3.67) mm in control group. The residual RAD in AP view was 0 (0, 1.25) ° in experimental group and 1.25 (0.62, 1.95) °in control group. As for the lateral view, the RDD was 0 (0, 1.22) mm in experimental group and 2.02 (0, 3.74) mm in control group, the RAD was 0 (0, 0) ° in experimental group and 1.42 (0, 1.93) ° in control group. Significant differences in all above comparisons were observed between the two groups (AP view RDD: P = 0.024, RAD: P = 0.020; Lateral view RDD: P = 0.016, RAD: P = 0.004). Conclusions The present study introduced a marker-3D measurement method to complement the current TSF treatment. This method avoids the manual measurement error and improves the accuracy of fracture reduction, providing potential advantages of bone healing and function rehabilitation.

Abstract Background Lymph node metastasis is the main cause of poor prognosis of head and neck squamous carcinoma (HNSCC) patients. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression, and as a novel m6A reader protein, IGF2BP2 has been implicated in tumor progression and metastasis. However, not much is currently known about the functional roles of IGF2BP2 in HNSCC, and whether IGF2BP2 regulates lymphatic metastasis through m6A modification in HNSCC remains to be determined. Methods The expression and overall survival (OS) probability of m6A-related regulators in HNSCC were analyzed with The Cancer Genome Atlas (TCGA) dataset and GEPIA website tool, respectively. The expression levels of IGF2BP2 were measured in HNSCC tissues and normal adjacent tissues. To study the effects of IGF2BP2 on HNSCC cell metastasis in vitro and in vivo, gain- and loss- of function methods were employed. RIP, MeRIP, luciferase reporter and mRNA stability assays were performed to explore the epigenetic mechanism of IGF2BP2 in HNSCC. Results We investigated 20 m6A-related regulators in HNSCC and discovered that only the overexpression of IGF2BP2 was associated with a poor OS probability and an independent prognostic factor for HNSCC patients. Additionally, we demonstrated that IGF2BP2 was overexpressed in HNSCC tissues, and significantly correlated to lymphatic metastasis and poor prognosis. Functional studies have shown that IGF2BP2 promotes both HNSCC cell migration as well as invasion via the epithelial-mesenchymal transition (EMT) process in vitro, and IGF2BP2 knockdown significantly inhibited lymphatic metastasis and lymphangiogenesis in vivo. Mechanistic investigations revealed that Slug, a key EMT-related transcriptional factor, is the direct target of IGF2BP2, and essential for IGF2BP2-regulated EMT and metastasis in HNSCC. Furthermore, we demonstrated that IGF2BP2 recognizes and binds the m6A site in the coding sequence (CDS) region of Slug and promotes its mRNA stability. Conclusions Collectively, our study uncovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.

Abstract Background The purpose of this study was to compare the effectiveness of multiple cannulated screws combined with medial buttress plate or not for the treatment of unstable femoral neck fracture in nonelderly patients. Methods Sixty-nine nonelderly patients with Garden type III-IV femoral neck fracture were retrospectively analyzed. The patients were divided into MCS (multiple cannulated screws) group and CMBP (combined with medial buttress plate) group according to the surgical method. Patient’s demographic data, Harris Hip Score, EQ-5D index and complications at a minimum of 2 years follow-up were analyzed. Results There were 47 patients in the MCS group (35 male and 12 females) with a mean age of 40.28 ± 12.64 years, whereas 22 patients in the CMBP group (17 male and 5 females) with a mean age of 43.86 ± 12.55 years. In the MCS group, there were 1 (2.1%) avascular necrosis, 5 (10.6%) postoperative nonunion, 5 (10.6%) implant failure, and 2 (4.3%) femoral neck shortening. While 1 (4.5%) implant failure, 2 (9.1%) postoperative nonunion and 2 (9.1%) impingement in the CMBP group. For patients with Pauwels type II and III femoral neck fracture, the CMBP group had higher HHS scores at 3 months after surgery than the MCS group (P 0.05). The same results were found in the EQ-5D index. Conclusions In our cohort, we observed better outcomes in the CMBP group at 3 and 6 months, with later results similar between groups. However, there were fewer complications in the CMBP group, without obviously blood-supply disruption, especially in Pauwels type II and III. Further, anatomic reduction and stable fixation may contribute to satisfactory outcomes in the treatment of nonelderly displaced femoral neck fractures.

ObjectiveDiet structure has changed greatly over the last few decades, and high-calorie diets have become an integral part of people’s daily diet, as well as the important cause of obesity in society. Several organ systems, including the skeletal system, are seriously affected by high-fat-diets (HFD) in the world. There is, however, still a lack of knowledge about the effects of HFD on bone regeneration and the possible mechanisms involved. In this study, the difference in bone regeneration between rats under HFD and low-fat-diets (LFD) was evaluated by monitoring the process of bone regeneration in distraction osteogenesis (DO) model animals, as well as the possible mechanisms.MethodsA total of 40 Sprague Dawley (SD) rats (5 weeks old) were randomly divided into HFD group (n=20) and LFD group (n=20). Except for feeding methods, there were no differences between the two groups in terms of treatment conditions. All animals received the DO surgery eight weeks after starting to feed. After a delay of 5 days (latency phase), the active lengthening phase was performed for 10 days (0.25 mm/12 h), and the consolidation phase followed for 42 days. An observational study of bone included radioscopy (once a week), micro-computed tomography (CT), general morphology, biomechanics, histomorphometry, and immunohistochemistry.ResultThe results showed that HFD group had a higher body weight than LFD group after 8, 14, and 16 weeks of feeding. Furthermore, at the final observation, there were statistically significant differences between LFD group and HFD group in terms of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Additionally, observations on bone regeneration showed a slower regeneration and a lower biomechanical strength in HFD group than LFD group, based on radiography, micro-CT, general morphology, biomechanics, histomorphometry, and immunohistochemistry.ConclusionIn this study, HFD resulted in elevated blood lipids, increased adipose differentiation at the bone marrow level, and delayed bone regeneration. The pieces of evidence are beneficial to better understand the association between diet and bone regeneration and to adjust the diet optimally for fracture patients.

IntroductionThyroid function has a large impact on humans’ metabolism and is affected by iodine levels, but there is a scarcity of studies that elucidate the association between thyroid function and other elements.MethodsWe performed a cross-sectional study on 1,067 adults to evaluate the associations of the common essential metals with thyroid function in adults living in an iodine-adequate area of China. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and blood metals (zinc, iron, copper, magnesium, manganese, and calcium) were measured. Further, the thyroid hormone sensitivity indexes, FT3:FT4 ratio, and thyrotropin T4 resistance index (TT4RI) were calculated. Linear regression, quantile g-computation, and Bayesian kernel machine regression methods were used to explore the association of metals with thyroid function.ResultsWe found that the TSH levels correlated with copper (negative) and zinc (positive). Iron and copper were positively associated with FT3 and FT4 levels, respectively. Iron (positive) and copper (negative) were correlated with the FT3:FT4 ratio. Furthermore, we found that manganese was inversely correlated with TT4RI, while zinc was positively correlated.DiscussionOur findings suggest that manganese, iron, copper, and zinc levels were strongly correlated with thyroid function, and patients with thyroid disorders are recommended to measure those metals levels.

Abstract Background It is challenging to determine the orthogonality of radiographs in daily clinical practice. The purpose of this study was to show the usefulness of an additional foot ring which might determine the orthogonality of postoperative radiographs for the parameter measurement of hexapod external fixator. Methods We retrospectively analyzed 81 consecutive trauma patients with tibial shaft fractures treated by the hexapod external fixator at our institution from September 2014 to July 2019. Starting in March 2016, the postoperative radiographs for parameter measurement were obtained under the control of an additional foot ring. The final data consisted of 47 patients in traditional radiographs (Group I) and 34 patients under the control of foot ring during the radiographic process (Group II). The demographic data, original postoperative deformities, residual deformities after final correction, number of repeated radiographs after the first postoperative radiographs, time to the satisfactory reduction achieved, and external fixation time in all patients were documented and analyzed. The Johner–Wruhs criteria were used for the final clinical outcomes evaluation at the last clinical visit. Results Satisfactory reduction and bone union were achieved in all patients. There were no statistical significances between the two groups in the demographic data, original postoperative deformities, residual deformities after final correction, external fixation time, and the final clinical outcomes (P > 0.05). The mean number of repeated radiographs after the first radiographs (1.4 times) and mean time to the satisfactory reduction achieved (3.3 days) in patients with an additional foot ring used were all less than those without foot ring (2.4 times, 5.3 days) (P

Abstract Background The bone transport using the unilateral external fixator, one of the Ilizarov techniques, is widely practiced in lower limb reconstructive surgery. Pin tract infection (PTI), one of most common complication, has become the important postoperative problems which plague clinicians gradually. Methods A group of 130 patients who received bone transport surgery for tibia or femur defects using the unilateral external fixation (Orthofix limb reconstruction system, Verona, Italy) and met the inclusion criteria were selected for the study from 2015 to 2019. Regular pin tract care was performed twice a day, and the conditions of the pin tract were evaluated by the same observer using clinical appearance criteria. The Saw’s classification of PTI was used to assess the condition around screws. After the data were significant by the T-test or Pearson’s Chi-square test analyzed, odds ratios were calculated using logistic regression tests to describe factors associated with the diagnosis of PTI. Results Ninety-one males and thirty-nine females with a mean age of 43 years (range 28–58 years) were included in this cohort. 7816 observations were documented from 12 to 36 months, and 58 cases (44.6%) of PTI (thirty-nine cases in grade 1, 17 cases in grade 2, and 2 cases in grade 3). The top five risk factors were agricultural work (OR 1.86, CI 0.94–2.39), non-urban living (OR 1.75, CI 1.24–3.26), male (OR 1.71, CI 1.02–2.31), smoking (OR 1.53, CI 0.76–1.89), and diabetes (OR 1.26, CI 1.12–2.64). No long-term sequelae were observed at the latest clinical visit. Conclusion Occupation, gender, living environment (non-urban), smoking, and diabetes were the top five significant risk factors for PTI in the period of bone transport using unilateral external fixation. Awareness of predictable risk factors of PTI is beneficial to avoid or early detect the severe complications which can affect the effectiveness.

Flowering Chinese cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee, 2n=20, AA) is a vegetable species in southern parts of China that faces high temperatures in the summer and winter seasons. While heat stress adversely impacts plant productivity and survival, the underlying molecular and biochemical causes are poorly understood. This study investigated the gene expression profiles of heat-sensitive (HS) ‘3T-6’ and heat-tolerant (HT) ‘Youlu-501’ varieties of flowering Chinese cabbage in response to heat stress using RNA sequencing. Among the 37,958 genes expressed in leaves, 20,680 were differentially expressed genes (DEGs) at 1, 6, and 12 h, with 1,078 simultaneously expressed at all time points in both varieties. Hierarchical clustering analysis identified three clusters comprising 1,958, 556, and 591 down-regulated, up-regulated, and up- and/or down-regulated DEGs (3205 DEGs; 8.44%), which were significantly enriched in MAPK signaling, plant–pathogen interactions, plant hormone signal transduction, and brassinosteroid biosynthesis pathways and involved in stimulus, stress, growth, reproductive, and defense responses. Transcription factors, including MYB (12), NAC (13), WRKY (11), ERF (31), HSF (17), bHLH (16), and regulatory proteins such as PAL, CYP450, and photosystem II, played an essential role as effectors of homeostasis, kinases/phosphatases, and photosynthesis. Among 3205 DEGs, many previously reported genes underlying heat stress were also identified, e.g., BraWRKY25, BraHSP70, BraHSPB27, BraCYP71A23, BraPYL9, and BraA05g032350.3C. The genome-wide comparison of HS and HT provides a solid foundation for understanding the molecular mechanisms of heat tolerance in flowering Chinese cabbage.

ObjectiveThe purpose of the study is to evaluate the effects of anticardiolipin (aCL) and/or anti-β2-glycoprotein-I (aβ2GPI) antibodies, namely antiphospholipid antibodies (aPL), on in vitro fertilization (IVF) outcomes.Materials and methodsThe study group comprised infertile women with aPL undergoing IVF-ET cycles. Controls were infertile women with tubal etiology without aPL. The impact of aPL on reproductive outcomes, such as oocyte quality, embryo quality, and implantation capacity, was compared between the study group and controls. Additionally, peripheral blood T cell subsets, such as T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells and cytokines, were analyzed by the flow cytometry. Differences between the study group and controls were analyzed.ResultsA total of 132 infertile women, including 44 women with aPL, and 88 controls were sequentially recruited for this study. Women with aPL had lower numbers of total and perfect/available embryos and lower rates of MII oocytes, blastocyst formation, perfect and available embryos, implantation, clinical pregnancy, and take-home baby. Additionally, imbalanced Th1/Th2 and Th17/Treg ratios, significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A, and a significantly lower serum IL-4 were noticed in women with aPL compared to controls.ConclusionWomen with aPL such as aCL and/or aβ2GPI antibodies were associated with adverse IVF outcomes. Early screening for aPL and appropriate consultation for couples undergoing IVF should be considered. In addition, underlying immunopathology and inflammatory immune mechanisms associated with aPL should be further explored.

Due to the emergence and wide spread of methicillin-resistant Staphylococcus aureus, the treatment of this kind of infection becomes more and more difficult. To solve the problem of drug resistance, it is urgent to develop new antibiotics to avoid the most serious situation of no drug available. Three new Ru complexes [Ru (dmob)2PMA] (PF6)2 (Ru-1) [Ru (bpy)2PMA] (PF6)2 (Ru-2) and [Ru (dmb)2PMA] (PF6)2 (Ru-3) (dmob = 4,4′-dimethoxy-2,2′-bipyridine, bpy = 2,2′-bipyridine, dmb = 4,4′-dimethyl-2,2′-bipyridine and PMA = N-(4-(1H-imidazo [4,5-f] [1,10] phenanthrolin-2-yl) -4-methyl-N-(p-tolyl) aniline) were synthesized and characterized by 1H NMR, 13C NMR and HRMS. The detailed molecular structure of Ru-3 was determined by single crystal X-ray diffraction. Their antibacterial activities against Staphylococcus aureus (Staphylococcus aureus) were obvious and Ru-3 showed the best antibacterial effect with the minimum inhibitory concentration value of 4 μg ml−1. Therefore, further study on its biological activity showed that Ru-3 can effectively inhibit the formation of biofilm and destroy cell membrane. In vitro hemolysis test showed that Ru-3 has almost negligible cytotoxicity to mammalian red blood cells. In the toxicity test of wax moth insect model, Ru-3 exhibited low toxicity in vivo. These results, combined with histopathological studies, strongly suggest that Ru-3 was almost non-toxic. In addition, the synergistic effect of Ru-3 with common antibiotics such as ampicillin, chloramphenicol, tetracycline, kanamycin and gentamicin on Staphylococcus aureus was detected by chessboard method. Finally, in vivo results revealed that Ru-3 could obviously promote the wound healing of Staphylococcus aureus infected mice.