Background: Intervertebral disc degeneration (IVDD) is a major pathological contributor to chronic low back pain and functional impairment. In addition to ageing, mechanical loading and metabolic disturbance, its development may also be influenced by broader upstream life-course factors. Age at first birth (AFB) is not a single reproductive endocrine indicator, but rather a composite phenotype that captures reproductive timing, behavioral tendencies, educational trajectory and part of the endocrine context. Whether genetically predicted AFB is consistently associated with IVDD risk, and whether this association can be explained by common body composition traits, has not been systematically evaluated. Methods: Using publicly available GWAS summary statistics, we performed a two-sample Mendelian randomization analysis to systematically screen for associations between 12 candidate phenotypes and IVDD. Univariable analyses were based primarily on the inverse variance weighted method, with weighted median, MR Egger and weighted mode analyses used to assess result stability. After identifying the primary signal, we further used two-step MR to evaluate whether BMI-related pathways might contribute to the association between AFB and IVDD, and conducted multivariable Mendelian randomization (MVMR) as a supplementary analysis to assess whether the estimated direction changed after inclusion of BMI. We then carried out locus-level trait annotation, candidate gene mapping, functional enrichment, broad cluster decomposition, and cis-eQTL colocalization analysis with IVDD for the prioritized phenotype. Results: AFB was the phenotype showing the strongest and most consistent evidence of association with IVDD among the 12 candidate phenotypes. In the inverse variance weighted analysis, genetically predicted later AFB was associated with a lower risk of IVDD (OR = 0.81, 95% CI 0.76 to 0.86, P = 7.10 × 10^-11), and the effect directions from the other methods were consistent with the primary analysis. Further analyses showed that BMI was the body composition trait with the strongest support. AFB was negatively associated with BMI, whereas BMI was positively associated with IVDD. In the supplementary multivariable Mendelian randomization analysis, the estimated direction did not reverse after inclusion of BMI; however, given the limited conditional instrument strength in the multivariable model, this result should be interpreted as supportive evidence only, that BMI may partly contribute to the observed association. External trait annotation of AFB-related loci was mainly enriched for education, risk preference, smoking, sleep disturbance, mood-related traits, and broader neurobehavioral and social developmental themes. Colocalization analysis showed that ESR1 provided the strongest support for a locally shared signal on the IVDD side, whereas RARB provided moderate support. Conclusions: Our findings support the interpretation of AFB as an upstream life-course signal associated with IVDD risk, rather than as a single reproductive endocrine exposure. BMI may represent one of the best-supported explanatory pathways for this association, although the current multivariable results remain supplementary and exploratory. The genetic architecture related to AFB was characterized mainly by neurodevelopmental, behavioral regulatory, and partial endocrine and developmental backgrounds. In colocalization analyses, ESR1 and RARB provided relatively stronger evidence linking cand

Osteoarthritis (OA) is a degenerative joint disease marked by irreversible cartilage destruction, lacking effective disease-modifying therapies. Plant-derived exosome-like nanoparticles (PELNs) have emerged as promising natural nanocarriers. Here, we successfully isolated exosome-like nanoparticles from ginseng (GELNs) and evaluated their therapeutic potential for OA. GELNs were efficiently internalized by chondrocyte-derived SW1353 cells and mitigated IL-1β-induced apoptosis, inflammation, extracellular matrix degradation, and ferroptosis. Integrated transcriptomic and small RNA sequencing revealed significant enrichment of ferroptosis-related pathways and identified ginseng-specific miR-2118 as a key functional cargo within GELNs. Mechanistically, miR-2118 directly targeted the 3′-UTR of the zinc transporter SLC39A7. This targeting downregulated SLC39A7 expression, thereby restoring intracellular zinc homeostasis, improving mitochondrial dysfunction, and ultimately blocking the ferroptosis cascade. These cytoprotective effects were reversed by a miR-2118 inhibitor. In a mouse OA model induced by anterior cruciate ligament transection, intra-articular injection of GELNs markedly attenuated cartilage degradation and subchondral bone destruction. Our findings reveals that GELNs inhibit chondrocyte ferroptosis through the delivery of ginseng-specific miR-2118, which targets the SLC39A7/zinc homeostasis axis, underscoring the unique medicinal value of ginseng. Furthermore, these findings highlight the potential of PELNs as carriers for endogenous miRNAs capable of cross-species communication, providing an expandable nanotherapeutic platform for the treatment of OA.

OBJECTIVE:To investigate the role of endothelin receptor B (Ednrb/ETB) in tranexamic acid (TXA)-induced post-traumatic osteoarthritis (PTOA) and to elucidate the underlying molecular mechanisms. METHODS:Adult rats were assigned to four groups: control + TXA (T), cartilage scratch + TXA (CT), subchondral fracture + TXA (ST), and combined cartilage-subchondral fracture + TXA (CST). RNA sequencing combined with Venn analysis was used to identify candidate genes, including Ednrb. Molecular docking was performed to evaluate the binding affinity between TXA and ETB. Rats were subsequently regrouped for histological, immunohistochemical, and biochemical analyses of cartilage. ATDC5 chondrocytes were transfected with si-Ednrb-1/2 and co-treated with TXA to assess cell viability and pathway activation. RESULTS:RNA sequencing identified Ednrb as a core upregulated gene in the CT and CST groups. Molecular docking demonstrated strong binding between TXA and ETB (binding energy: -5.1 kcal/mol). In the rat PTOA model, TXA significantly increased OARSI scores in the NCT and NCST groups (P < 0.0001), upregulating the expression of ETB, matrix metalloproteinase 13 (MMP13), RXFP1, endothelin-1 (ET-1), phosphorylated nuclear factor-kappa B, and phosphorylated AKT, as well as the inflammatory mediators interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6. In ATDC5 cells, Ednrb knockdown significantly increased cell viability, reduced apoptosis, and downregulated ETB, MMP13, and pathway-related signaling molecules, thereby attenuating inflammatory responses. TXA treatment significantly reversed these protective effects. CONCLUSION:Ednrb functions as a key mediator in TXA-induced PTOA progression. The binding of TXA to ETB activates the relaxin and ET-1/ETB pathways, thereby promoting cartilage degradation and inflammation. Targeting Ednrb may represent a promising therapeutic strategy for preventing TXA-associated PTOA.

Osteoarthritis (OA) is a long-term chronic, progressive degenerative joint disease characterized via cartilage degradation, subchondral bone remodeling and synovial inflammation, finally leading to joint dysfunction and pain. Aromadendrin, a natural flavonoid has been reported to possess potent antioxidant and anti-inflammatory effect in different pathological conditions. This current study investigates the protective effects of aromadendrin against monoiodoacetate (MIA)-induced OA in rats and explore the underlying mechanism. OA was induced in the rodent via intra-articular administration of MIA (3 mg/50 µL sterile saline), following OA induction, the rats received the oral administration of aromadendrin and diclofenac sodium for 8 weeks. Body weight and joint diameter were estimated at regular intervals. Metabolic parameters such as food intake, water intake, urine output, and fecal output, were monitored throughout the study. End of the study, bone metabolism markers, antioxidant parameters, hepatic, non-hepatic parameters, inflammatory cytokines, inflammatory parameters, apoptosis parameters, and mRNA expression were estimated. Aromadendrin significantly improved the body weight and suppressed the joint diameters at different time intervals (week 2, 4, 6, and 8). Aromadendrin significantly suppressed the level of bone parameters such as COMP, CTX-II, aggrecan, and collagen type II. Aromadendrin altered the food intake, water intake, urine output, fecal output along with oxidative stress (MDA, SOD, CAT, GSH, GPx); inflammatory cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-10, IL-18); inflammatory parameters (COX-2, iNOS, PGE2, NF-κB); apoptosis parameters (Bax. Bcl-2, caspase-3) and MMP level (MMP-1, MMP-2, MMP-3, MMP-9). Aromadendrin significantly altered the mRNA expression of HO-1, Nrf2, Bax, Bcl-2, caspase-3, TLR4, MyD88, and NF-κB. The finding of this study demonstrates the protective effect of aromadendrin against MIA-induced OA in the rats via alteration of TLR4/MyD88/NF-κB, HO-1/Nrf2, and Bcl-2/Caspase-3 pathways.

ObjectiveThis study aimed to identify genes and signaling pathways associated with acute cartilage injury using RNA sequencing (RNA-seq).MethodsKnee joint cartilage samples were collected from normal mice and 2 models of acute cartilage injury (non-invasive and groove models) within an 8-hour time limit. RNA-seq revealed differential gene expression between the injury models and controls, with subsequent validation using real-time quantitative polymerase chain reaction (RT-qPCR) for 9 representative genes.ResultsCompared to controls, the non-invasive model showed 36 differentially expressed genes (DEGs) (13 up-regulated, 23 down-regulated), with Gm14648 and Gm35438 showing the most significant upregulation and downregulation, respectively. The groove model exhibited 255 DEGs (13 up-regulated, 23 down-regulated), with Gm14648 and Gm35438 showing the (222 up-regulated, 33 down-regulated). Six overlapping genes were identified between the non-invasive and groove models, including up-regulated genes (Igfn1, Muc6, Hmox1) and down-regulated genes (Pthlh, Cyp1a1, Gm13490), validated by RT-qPCR. Gene ontology (GO) analysis highlighted involvement in environmental information processing and cartilage organ system function, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis implicated the JAK-STAT signaling pathway. RT-qPCR and immunohistochemistry confirmed downregulation of Fhl1 in the non-invasive model, supported by Western blotting of p-JAK2/t-JAK2 levels.ConclusionsThis study identifies DEGs (13 up-regulated, 23 down-regulated), with Gm14648 and Gm35438 showing the in acute cartilage injury, suggesting potential therapeutic targets. The role of Fhl1 in cartilage protection via the JAK-STAT pathway warrants further investigation in acute cartilage injury research.

BACKGROUND:This study aimed to evaluate the risk of fracture with weight-bearing after medial femoral condyle (MFC) harvest with varying harvest size and location using finite element analysis (FEA). METHODS:FEA evaluated the potential impact of MFC harvest on donor femur strength. Donor flaps were modeled as cubes of corticocancellous defects within the descending genicular angiosome (DGA). Stress and safety factors were recorded during simulated single-leg stance as a function of harvest size and location within the DGA. An S-N curve was used to determine the number of cycles to failure due to stress. RESULTS:Among the 15 simulated harvest size and location combinations for each femur, the smallest (1x1x1 cm) corticocancellous flap centered 1 cm proximal to the medial epicondyle demonstrated the most favorable stress (34.95±9.81 MPa), safety factor (3.42±0.85), and fatigue (>106 cycles) profiles during single-leg stance, but saw notably increased stress and lower safety factors at larger sizes. Flaps centered at the medial epicondyle and shifted 0.5 cm proximally exhibited consistent stress and safety factor values. The largest (2x2x2 cm) and most proximally based flap (2 cm proximal) resulted in a precipitous increase in stress (92.23±21.19 MPa) and fatigue profile (102-103 cycles). CONCLUSIONS:Our results suggest that small corticocancellous flaps centered no more than 0.5 cm proximal to the medial epicondyle are the most favorable for harvest, resulting in physiologically tolerable stress values on the donor femur during single-leg stance. Caution and potential weight-bearing restrictions should be considered when harvesting larger and more proximally based flaps. LEVEL OF EVIDENCE:Biomechanical study.

Posttraumatic osteoarthritis (PTOA) is directly associated with early acute articular cartilage injury. Inhibition of cartilage destruction immediately following joint damage can effectively slow or prevent PTOA progression. Therefore, we sought to determine intervention targets and therapeutic strategies in the acute stage of cartilage injury. The benefits of chronic intermittent hypobaric hypoxia (CIHH) extend to various body tissues, but its impact on acute cartilage injury remains unclear. We selected PTOA initiation as the therapeutic window and administered CIHH treatment immediately following cartilage injury initiation to investigate its protective effect on cartilage and molecular mechanism changing with time-varying. The non-invasive PTOA mouse model was established by applying a single rapid specific impact force to the right knee’s tibial plateau, initiating load-induced PTOA development, closely resembling the pathological changes in human diseases. Following loading, we inhibited cartilage destruction by treating mice immediately in a hypobaric chamber with a hypobaric hypoxia mimic at 5000 m altitude. Cohorts of mice subjected to distinct experimental conditions were monitored for 3, 7, 14 or 28 days. Safranin O-Fast Green staining, Immunohistochemistry, immunofluorescence, ELISA, and western blotting were performed to evaluate the therapeutic effects of CIHH on cartilage in vivo. The nuclear translocation of NF-κB p65 and Nrf2 were detected by immunofluorescence. The results showed that inhibiting cartilage destruction using CIHH immediately following acute articular cartilage injury initiation delayed the progression of PTOA, decreased the Mankin score and suppressed the expression of proinflammatory factors, including iNOS, NO, TNF-α, and IL-1β. Meanwhile, immediate CIHH treatment reduced levels of the catabolic enzymes ADAMTS5 and MMP13 in the cartilage matrix, reversed degradation of Collagen II and COMP, and inhibited oxidative stress by decreasing ROS levels. Moreover, CIHH suppressed NF-κB signaling by activating the Nrf2 in vivo studies. Our study demonstrated that immediate CIHH treatment following cartilage injury initiation can attenuate load-induced cartilage damage by activating Nrf2/HO-1 and inhibiting the NF-κB p65 signalling pathways to counteract oxidative stress and inflammatory reactions, enhance the metabolic balance of the cartilage matrix and delay cartilage degeneration. This treatment may represent a potential therapeutic strategy for limiting PTOA progression.

Background:Post-traumatic osteoarthritis (PTOA) constitutes a distinct subtype of osteoarthritis (OA). Despite extensive research, no effective pharmacological intervention has been established to prevent or halt the progression of PTOA. Current therapeutic approaches are primarily limited to symptomatic management and pain relief. SkQ1, a novel mitochondria-targeted antioxidant, has emerged as a promising therapeutic agent due to its dual capacity to scavenge excessive intracellular reactive oxygen species (ROS) and modulate inflammatory responses. Objective:This study aimed to investigate the therapeutic potential of SkQ1 in the early stages of PTOA and elucidate its underlying molecular mechanisms. Methods:Chondrocytes were cultured under varying concentrations of SkQ1 to evaluate its cytotoxicity. Additionally, an in vitro oxidative stress model was established to assess the antioxidant effects of SkQ1 across different concentration levels, from which the optimal concentration for PTOA treatment was determined. The rat PTOA model was established through medial meniscal tear (MMT) surgery, followed by intra-articular administration of SkQ1 postoperatively. The gait characteristics of rats in each group were assessed biweekly following surgery. Outcome measures were evaluated at 2 and 6 weeks postoperatively, including pathological evaluation of knee cartilage, ROS levels, markers of oxidative damage, such as malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OHdG), mitochondrial membrane potential, mitochondrial DNA copy number, and apoptosis-related cytokines. Results:In vitro, lower concentrations of SkQ1 (500 nM) exhibited superior antioxidant efficacy while minimizing cytotoxicity. The results indicated that SkQ1 administration significantly enhanced knee joint functionality and mitigated articular cartilage degeneration in both the acute and subacute phases of PTOA by inhibiting oxidative stress pathways. In a rat model of PTOA, SkQ1 not only alleviated gait abnormalities, but also substantially reduced levels of oxidative stress biomarkers, including ROS, MDA, and 8-OHdG. Furthermore, SkQ1 effectively preserved mitochondrial membrane potential and increased mitochondrial DNA copy number. Mechanistically, SkQ1 inhibited the release of cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) and downregulated key components of the mitochondria-mediated apoptotic pathway, such as Bax, Bak, cleaved caspase-3, and cleaved caspase-9. Conclusion:The findings suggested that SkQ1 exerts its therapeutic effects via multiple mechanisms, including the reduction of ROS accumulation, mitigation of oxidative damage, preservation of mitochondrial function, and inhibition of apoptotic pathways. These diverse actions position SkQ1 as a promising disease-modifying agent for PTOA treatment, potentially offering benefits that extend beyond those provided by current symptomfocused therapies.

Abstract Purpose The study’s objective was to assess the effect of the screw insertion depth into fractured vertebrae in treating thoracolumbar fractures. Materials and methods This was a retrospective analysis of 92 patients with thoracolumbar fractures from December 2018 to February 2020. Patients had AO type A2, A3 thoracolumbar fractures. The patients were divided into two groups according to the screw insertion depth. The vertebral wedge angle (VWA), Cobb angle (CA), anterior vertebral body height (AVBH), middle vertebral body height (MVBH), visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were compared preoperatively and at one week and 12 months postoperatively. The correlation between Vertebral height loss and potential risk factors, such as sex, age, BMD and BMI was evaluated. Results Compared with the preoperative data, the postoperative clinical and radiographic findings were significantly different in both groups, But no significant difference between the two groups at 1 week. At 1 year postoperatively, there was a significant difference in the CA (p < 0.0001), VWA (p = 0.047), AVBH (p < 0.0001), MVBH (p < 0.0001), VAS score (p < 0.0001), and ODI (p < 0.0001) between the two groups, Except for age, bone density and other influencing factors the long screw group had better treatment results than the short screw group. Conclusion A longer screw provides greater grip on the fractured vertebral body and stronger support to the vertebral plate. The optimal screw placement depth exceeds 60% of the vertebral body length on the lateral view.

Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). At present, there are no ideal drugs that can effectively prevent and treat PTOA.The current strateg for treating PTOA is to control symptoms and reduce pain. SkQ1 is novel mitochondria-targeted antioxidant which can eliminate excessive intracellular ROS and exhibit anti-inflammatory effects. In this study, we evaluate the therapeutic effect of SkQ1 on PTOA and the mechanisms involved. Our results showed that SkQ1 significantly alleviated articular cartilage degeneration of PTOA in acute and chronic phase of PTOA rat model through inhibiting the oxidative stress. SkQ1 not only decreased the production of reactive oxygen species (ROS), MDA and 8-OHdg, but also suppressed the decrease of mitonchondrial membrane potential in PTOA rat model. We further found that SkQ1 protected mitochondrial function by inhibiting the release of cytochrome C and the expression of mitochondrial-related apoptotic pathway factors such as Bax, Bak, cleaved-caspase-3 and cleaved-caspase-9, increasing the copy number of mitochondrial DNA. In conclusion, SkQ1 may maintain mitochondrial function and inhibit the progression of PTOA by reducing ROS levels, inhibiting oxidative damage and apoptosis. SkQ1 may be used as a potential treatment for PTOA in the future.

Aim:A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens.Methods:Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis.Results:The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA.Conclusion:Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging.

Abstract Objective The intra-articular injection of tranexamic acid (TXA) has been shown to be effective at reducing perioperative bleeding. However, the damage to human articular cartilage caused by TXA could contribute to posttraumatic osteoarthritis (PTOA) after acute cartilage injury. In the present study, we aimed to investigate the genes and molecular programmes controlling PTOA pathogenesis associated with TXA using RNA sequencing (RNA-seq). Methods We performed RNA-seq and computational analyses of cartilage tissues obtained from various groups of rats. The differentially expressed genes between the control group and each experimental group were collated to identify those genes that were regulated by TXA. We investigated the role of TXA in cartilage tissue degeneration using RT‒qPCR analysis and histological assays. Results We identified 3113 genes (1834 upregulated and 1279 downregulated) that were differentially expressed between the cartilage-subchondral bone damage group and the control group. Furthermore, 57 genes were differentially expressed (45 upregulated and 12 downregulated) between the cartilage damage group and the control group. EDNRB was identified in both sets of differentially expressed genes and was thus considered a gene specifically regulated by TXA. Upregulation of EDNRB mRNA in the TXA injection model was confirmed by RT‒qPCR. Notably, immunohistochemistry analysis revealed that EDNRB is involved in PTOA pathogenesis. Conclusion These study results suggest that the ETB receptor plays a pivotal role in cartilage degeneration after acute injury induced by topical administration of TXA and may be a new target for the development of therapies for this condition.

The study aimed to explore the pathogenesis of secondary frozen shoulder and its influence on synovium tissue and angiogenesis by constructing a rat secondary frozen shoulder model along with transforming growth factor. 40 healthy male rats aged 8 weeks were divided into Sham group (n=10, no modeling treatment), Control group (n=10, modeling treatment), Low group (n=10, modeling treatment, and 10 mL/d transforming growth factor), and High group (n=10, modeling treatment, and 20 mL/d transforming growth factor). Hematoxylin and Eosin (HE) method was used for histological detection, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining method were adopted to detect the expression of Matrix metalloproteinase-14 (MMP-14), mitogen-activated protein kinase (p38MAPK), and Vascular endothelial growth factor (VEGF). Compared with Sham group, the range of abduction and external rotation of rat glenohumeral joint in Control group, Low group, and High group was significantly reduced, and High group had the smallest range. Compared with the Sham group, the synovium in the Control group, the Low group, and the High group had obvious hyperplasia, and the blood vessels were significantly increased. Immunohistochemical staining and RT-PCR results showed that compared with Sham group, MMP-14, p38 MAPK, and VEGF in Control group, Low group, and High group all increased significantly, among which High group increased most. The secondary frozen shoulder is mainly manifested as synovial hyperplasia and increased blood vessels, which are related to the induction of MMP-14, p38 MAPK, and VEGF by transforming growth factor, which reveals the pathogenesis of secondary frozen shoulder to a certain extent, and lays a foundation for subsequent clinical treatment of secondary frozen shoulder.

目的 比较CT三维重建引导下双平面克氏针撬拨辅助复位与有限切开复位治疗难复性股骨颈骨折的临床疗效.方法 回顾性分析2019 年1 月～2021 年6 月我院创伤急救中心采用CT三维重建引导下双平面克氏针撬拨辅助复位与有限切开复位治疗难复位性股骨颈骨折 44 例(Garden Ⅲ型 19 例和Ⅳ型 25 例),采用双平面克氏针撬拨辅助复位 25 例(撬拨复位组),切开复位 19 例(切开复位组),比较 2 组患者手术时间、术中出血量、术后复位质量、术后并发症情况.结果 撬拨复位组手术时间(102.6±13.4)min,明显短于切开复位组(128.9±13.0)min(t =-6.546,P =0.000);术中出血量(66.7±11.5)ml,明显少于切开复位组(103.6±12.4)ml(t =-10.185,P =0.000).撬拨复位组复位质量Ⅰ级20 例,Ⅱ级5 例,切开复位组Ⅰ级 16 例,Ⅱ级 3 例,2 组复位质量差异无统计学意义(Z =-0.355,P =0.723).44 例平均随访 2.1 年(1.5～2.5 年),骨折均愈合,撬拨复位组无术后并发症发生,切开复位组1 例术后切口感染,1 例随访1 年后发生股骨头坏死.结论 与切开复位相比,CT三维重建引导下双平面克氏针撬拨辅助复位治疗难复性股骨颈骨折,复位快捷,手术创伤小,是切开复位前值得尝试的方法.

Purpose:Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and red blood cell distribution width (RDW) are novel biomarkers to indicate the inflammatory/immune response, and demonstrated to be effective in diagnosis, severity evaluation, and prognosis in a variety of chronic or acute conditions. This study aims to examine whether NLR, PLR and EDW are independently associated with mortality in necrotizing fasciitis (NF).Methods:This study retrospectively enrolled patients diagnosed with NF and based on vitality status during hospitalization or within 30 days after discharge, survival and non-survival groups were defined. For distinctly comparing NLR, PLR, RDW and others, we enrolled the matched healthy controls of the same age and sex as the survivors of NF in a 1:1 ratio, which constituted the healthy control group. Comparisons were made between three groups. Variables tested with a P value < 0.10 were further entered into the multivariate logistic regression model to identify their independent association with mortality.Results:A total of 281 subjects were included, including 127 healthy controls, 127 survivors, and 27 nonsurvivors with NF, respectively, indicating a mortality rate of 17.5%. ROC analysis showed that the optimal cutoff value for NLR, PLR and RDW was 11.1, 196.0 and 15.5%, respectively, and was tested as significant only for the first two (P < 0.001, = 0.004). Multivariate logistic analysis showed that NLR ≥ 11.1 (OR, 2.51) and PLR ≥ 196.0 (OR, 2.09) were independently associated with an increased risk of mortality in NF patients, together with age ((OR, 1.28, for each 10-year increment), comorbid diabetes mellitus (OR, 2.69) and liver disease (OR, 1.86), and elevated creatinine level (OR, 1.21 for each 10 umol/L elevation).Conclusion:Elevated NLR and PLR are significant and independent predictors of mortality and can be considered for use when evaluating patients at risk of mortality.

目的 探讨 Yes相关蛋白 1(YAP1)、程序性死亡-配体 1(PD-L1)及错配修复(MMR)蛋白在消化道神经内分泌癌组织中的表达及临床意义.方法 应用组织芯片及免疫组化法,检测 122 例消化道神经内分泌癌组织中 YAP1、PD-L1 及 MMR蛋白的表达情况,并结合消化道神经内分泌癌不同临床病理参数和患者预后进行比较分析.结果 YAP1 核、YAP1 质、PD-L1 及 MMR蛋白缺失的阳性率分别为 27.1%、35.3%、22.1%、2.5%.YAP1 在神经内分泌癌组织中的表达显著高于正常组织或神经内分泌瘤(均P＜0.05),YAP1 核表达与脉管浸润、淋巴结转移及 TNM分期呈显著正相关(均P＜0.05).PD-L1 表达与临床病理特征无明显相关性(均P＞0.05).相关性分析显示 YAP1 核表达与PD-L1 表达呈负相关(P＜0.05).生存分析未发现 YAP1 及PD-L1 的预后意义.结论 YAP1 核表达可能与消化道神经内分泌癌的发生发展有关;消化道神经内分泌癌表达 PD-L1 及错配修复缺陷(dMMR);针对 YAP1 的靶向治疗及抗PD-1/PD-L1 治疗可能成为消化道神经内分泌癌的潜在新疗法.

Objective This study aimed to examine the effect of the endplate reduction (EPR) technique combined with bone grafting for treating thoracolumbar burst fractures using posterior short-segmental fixation. Methods Patients with thoracolumbar fractures admitted between January 2018 and October 2021 were retrospectively analyzed, and those meeting the criteria were assigned to the EPR group and the intermediate screws (IS) group. The vertebral wedge angle (VWA), Cobb angle (CA), anterior vertebral body height (AVBH), middle vertebral body height (MVBH), upper endplate line (UEPL), upper intervertebral angle (UIVA), and upper intervertebral disc height (UIDH) indices were examined and compared preoperatively, first day postoperatively, as well as at 12 months postoperatively. Results The result indicated that the EPR group achieved better MVBH reduction (p<0.001), UEPL reduction (p<0.001), vertebral body fracture healing (p=0.006), as well as implant breakage (p=0.04) than the IS group; VWA (p<0.001), CA (p=0.005), AVBH (p<0.001), MVBH (p<0.001), UEPL (p<0.001), and UIDH (p<0.001) were lost after reduction less than those in the IS group. There was no significant difference in operative time (p=0.315) and intraoperative bleeding (p=0.274) between the 2 groups. Conclusion The EPR group achieved better results in repositioning and maintaining MVBH and endplate morphology, with less correction loss after the reduction of the VWA, CA, AVBH, and endplate morphology. The EPR group exhibited a better healing pattern after vertebral fracture and disc degeneration was better relieved.

后踝骨折是临床常见的骨折,也是临床治疗的重难点,本研究首次采用新型特殊构型接骨板固定后踝骨折,完成骨折块的加压及固定,与传统内固定方式相比,具有操作较为简单方便,踝关节后方软组织的损伤较小,避免骨折块的破坏等优势,值得进一步研究和推广.

Objective To determine the effect of endplate reduction on the final healing morphology and degenerative changes in intervertebral discs. Methods Forty-eight patients with single-level thoracolumbar fractures with endplate injury were included. All patients underwent posterior reduction and pedicle screw fixation, and postoperative imaging was used to determine whether endplate reduction was successful. The healing morphology of the endplate was divided into three types: increased endplate curvature, irregular healing and traumatic Schmorl node. MRI was performed at baseline and at the last follow-up evaluation to observe changes in disc degeneration (disc height and nucleus pulposus signal) and Modic changes. Results The reduction rate in the central area was significantly lower than that in the peripheral area (P = 0.017). In patients with successful reduction, 90.9% (20/22) of the endplates healed with increased curvature. In patients with an unsuccessful endplate reduction, 63.4% (26/41) of the endplates healed irregularly, and 34.1% (14/41) of the endplates formed traumatic Schmorl nodes. Endplate reduction was closely related to the final healing morphology of the endplate (P < 0.001), which had a significant protective effect on the degeneration of the intervertebral disc. At the last follow-up evaluation, there was no statistically significant correlation between different endplate healing morphologies and new Modic changes. Conclusions The reduction rate in the central area is significantly lower than that in the peripheral area. Although all of the intervertebral discs corresponding to fractured endplates had degenerated to different degrees, successful endplate fracture reduction can obviously delay the degeneration of intervertebral discs.

Background Tibial plateau fractures (TPFs) are a challenging type of fracture in orthopedic traumatology. We previously designed a plate (Patent Number: CN201520195596.5) for posterolateral TPF combined with posterior lateral collapse.. In this study, finite element analysis was used to compare the biomechanical characteristics of two internal fixation methods for posterolateral TPF. We investigated the support effect of the new steel plate on lateral TPFs combined with posterior TPFs. Methods Two models of complex TPF were established. Model A was fixed with the new type of plate, and model B was fixed without the plate. Three axial loads of 500, 1,000, and 1,500 N were applied using FEA on the two fracture models (A and B) to analyze the data. Results In model A, the maximum displacement at 500, 1,000, and 1,500 N was 0.085797, 0.17043, and 0.25465 mm, respectively; the maximum stress of the bone block was 11.285, 20.648, and 29.227 MPa, respectively; and the maximum strain of the bone block was 0.0012474, 0.007435, and 0.0035769 mm, respectively. The maximum displacement of the internal fixation was 0.096932, 0.18682, and 0.27655 mm, respectively; the maximum stress was 69.54, 112.1, and 155.71 MPa, respectively; and the maximum strain was 0.00066228, 0.0010676, and 0.0014829 mm, respectively. In model B, the maximum displacement of fractures at 500, 1,000, and 1,500 N was 0.15675, 0.29868, and 0.44017 mm, respectively; the maximum stress of the bone block was 6.5519, 12.575, and 18.842 MPa, respectively; and the maximum strain of the bone block was 0.0032554, 0.0074357, and 0.012146 mm, respectively. The maximum displacement of the screw was 0.14177, 0.27109, and 0.39849 mm, respectively; the maximum stress was 48.916, 92.251, and 135.27 MPa, respectively; and the maximum strain was 0.00046608, 0.00087893, and 0.0012887 mm, respectively. Conclusions The fixation method using this type of plates and screws can replace other methods using two plates to fix complex TPF.