Machine learning models to predict osteonecrosis in patients with femoral neck fractures undergoing internal fixation.

OBJECTIVE: This study aimed to use machine learning (ML) to establish risk factor and prediction models of osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures (FNFs) after internal fixation. METHODS: We retrospectively collected clinical data of patients with FNFs who were followed up for at least 2 years. Only intracapsular FNFs were included. In total, 437 patients and 24 variables were enrolled. The entire dataset was divided into training (89.5 %) and test (10.5 %) datasets. Six models-logistic regression, naive Bayes, decision tree, random forest, multilayer perceptron, and AdaBoost-were established and validated for predicting postoperative ONFH. We compared the area under the receiver operating characteristic curve (AUC), accuracy, recall, and F1 score of different models. In addition, a confusion matrix, density curve, and learning curve were used to evaluate the model performance. RESULTS: The logistic regression model performed best at predicting ONFH in patients with FNFs undergoing internal fixation surgery, with an AUC, accuracy, recall, F1 score, and prediction value of 0.84, 0.89, 1.00, 0.94, and 89.1 %, respectively. The learning and density curves demonstrated a good prediction fitting degree and distinct separation. When establishing the ML models, the reduction quality, internal fixation removal, American Society of Anesthesiologists classification, injury mechanism, and displacement distance of the medial cortex were the top five risk factors positively correlated with the occurrence of ONFH. CONCLUSIONS: The logistic regression model had excellent performance in predicting ONFH in patients with FNFs after internal fixation and could provide valuable guidance in clinical decision-making. When choosing treatment options for patients with FNFs, doctors should identify the risk factors and consider using the presented models to help anticipate outcomes and select individualised treatment.

DNA Methylation Profiling of Salivary Gland Tumors Supports and Expands Conventional Classification.

Tumors of the major and minor salivary glands histologically encompass a diverse and partly overlapping spectrum of frequent diagnostically challenging neoplasms. Despite recent advances in molecular testing and the identification of tumor-specific mutations or gene fusions, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that achieved a mean balanced accuracy of 0.991. Of note, we showed that cribriform adenocarcinoma is epigenetically distinct from classical polymorphous adenocarcinoma, which could support risk stratification of these tumors. Myoepithelioma and pleomorphic adenoma form a uniform epigenetic class, supporting the theory of a single entity with a broad but continuous morphologic spectrum. Furthermore, we identified a histomorphologically heterogeneous but epigenetically distinct class that could represent a novel tumor entity. In conclusion, our study provides a comprehensive resource of the DNA methylation landscape of salivary gland tumors. Our data provide novel insight into disputed entities and show the potential of DNA methylation to identify new tumor classes. Furthermore, in future, our machine learning classifier could support the histopathologic diagnosis of salivary gland tumors.

Structural identification, rheological properties and immunological receptor of a complex galacturonoglucan from fruits of Schisandra chinensis (Turcz.) Baill.

A complex heteropolysaccharide SCP-2 named schisanan B (Mw = 1.005 × 105 g/mol) was obtained from water extracts of Schisandra chinensis fruits, and its planar structure was finally deduced as a galacturonoglucan by a combination of monosaccharide compositions, methylation analysis, partial acid hydrolysis, enzymatic hydrolysis and 1D/2D-nuclear magnetic resonance spectroscopy. The conformation of SCP-2 exhibited a globular shape with branching in ammonium formate aqueous solutions. The rheological properties of SCP-2 were investigated on concentrations, temperature, pH and salts. The in vitro immunomodulatory activity assay demonstrated that SCP-2 significantly enhanced the production of nitric oxide (NO) and stimulated the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in macrophages. Through a combination of high-resolution live-cell imaging, surface plasmon resonance, and molecular docking techniques, SCP-2 exhibited a strong binding affinity with the Toll-like receptor 4 (TLR4). Moreover, western blot analysis revealed that SCP-2 effectively induced downstream signaling proteins associated with TLR4 activation, thereby promoting macrophage activation. The evidence strongly indicates that TLR4 functions as a membrane protein target in the activation of macrophages and immune regulation induced by SCP-2.

Magnesium polypeptide combined with microbially induced calcite precipitation for remediation of lead contamination in phosphate mining wasteland soil.

Soil Pb contamination is inevitable, as a result of phosphate mining. It is essential to explore more effective Pb remediation approaches in phosphate mining wasteland soil to ensure their viability for a gradual return of soil quality for cultivation. In this study, a Pb-resistant urease-producing bacterium, Serratia marcescens W1Z1, was screened for remediation using microbially induced carbonate precipitation (MICP). Magnesium polypeptide (MP) was prepared from soybean meal residue, and the combined remediation of Pb contamination with MP and MICP in phosphate mining wasteland soil was studied. Remediation of Pb using a combination of MP with MICP strain W1Z1 (WM treatment) was the most effective, with the least exchangeable Pb at 30.37% and the most carbonate-bound Pb at 40.82%, compared to the other treatments, with a pH increase of 8.38. According to the community analysis, MP moderated the damage to microbial abundance and diversity caused by MICP. Total nitrogen (TN) was positively correlated with Firmicutes, pH, and carbonate-bound Pb. Serratia inoculated with strain W1Z1 were positively correlated with bacteria belonging to the Firmicutes phylum and negatively correlated with bacteria belonging to Proteobacteria. The available phosphate (AP) in the phosphate mining wasteland soil could encapsulate the precipitated Pb by ion exchange with carbonate, making it more stable. Combined MP-MICP remediation of Pb contamination in phosphate mining wasteland soil was effective and improved the soil microenvironment.

The prophylactic application of low-dose rabbit antithymocyte globulin in matched siblings HSCT with high-risk factors for graft-versus-host disease.

Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.

Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.

Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.

GFPT2: A novel biomarker in mesothelioma for diagnosis and prognosis and its molecular mechanism in malignant progression.

BACKGROUND: Mesothelioma (MESO) is an insidious malignancy with a complex diagnosis and a poor prognosis. Our study unveils Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2) as a valuable diagnostic and prognostic marker for MESO, exploring its role in MESO pathogenesis. METHODS: We utilised tissue samples and clinicopathologic data to evaluate the diagnostic and prognostic significance of GFPT2 as a biomarker for MESO. The role of GFPT2 in the malignant progression of MESO was investigated through in vitro and in vivo experiments. The activation of NF-κB-p65 through O-GlcNAcylation at Ser75 was elucidated using experiments like HPLC-QTRAP-MS/MS and mass spectrometry analysis. RESULTS: The study demonstrates that GFPT2 exhibits a sensitivity of 92.60% in diagnosing MESO. Overexpression of it has been linked to an unfavourable prognosis. Through rigorous verification, we have confirmed that elevated GFPT2 levels drive malignant proliferation, invasiveness, and metastasis in MESO. At the molecular level, GFPT2 augments p65 O-GlcNAcylation, orchestrating its nuclear translocation and activating the NF-κB signalling pathway. CONCLUSIONS: Our insights suggest GFPT2's potential as a distinctive biomarker for MESO diagnosis and prognosis, and as an innovative therapeutic target, offering a new horizon for identification and treatment strategies in MESO management.

Mesenchymal stromal cells restrain the Th17 cell response via L-amino-acid oxidase within lymph nodes.

Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within the lymph nodes of mice afflicted with autoimmune diseases, but this phenomenon was not observed in healthy mice. The specific distribution is driven by the heightened expression of the CCL21-CCR7 axis in mice with autoimmune diseases, facilitating the targeted homing of MSC to the lymph nodes. Within the lymph nodes, MSC exhibit a remarkable capacity to modulate Th17 cell function, exerting a pronounced anti-inflammatory effect. Transplanted MSC stimulates the secretion of L-amino-acid oxidase (LAAO), a response triggered by elevated levels of tumor necrosis factor-α (TNF-α) in mice with autoimmune diseases through the NF-κB pathway. The presence of LAAO is indispensable for the efficacy of MSC, as it significantly contributes to the inhibition of Th17 cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves as a potent suppressor of Th17 cells by activating the aryl hydrocarbon receptor (AHR) pathway. These findings advance our understanding of the global immunomodulatory effects exerted by MSC, providing valuable information for optimizing therapeutic outcomes.

Theaflavins mitigate diabetic symptoms in GK rats by modulating the INSR/PI3K-Akt/GSK-3 pathway and intestinal microbiota.

Dietary management and interventions are crucial in the clinical management of diabetes. Numerous active dietary components in black tea have demonstrated positive effects on blood glucose levels and metabolic functions. However, limited research has explored the potential of theaflavins (TF), polyphenols in black tea, for diabetes management. In this study, high-purity TF was administered to Goto-Kakizaki (GK) diabetic model rats for four weeks to investigate its impact on diabetic pathology and analyze the underlying mechanisms through liver transcriptomics, hepatocyte metabolomics, and gut microbiome analysis. The findings indicated that continuous administration of TF (100 mg/kg) significantly suppressed blood glucose levels, reduced insulin resistance, and decreased the expression of oxidative stress indicators and inflammatory factors in GK rats. Further analysis revealed that TF might alleviate insulin resistance by improving hepatic glycogen conversion and reducing hepatic lipid deposition through modulation of key pathways, such as peroxisome proliferator-activated receptors and PI3K/AKT/GSK-3 pathways within the liver, thereby ameliorating diabetic symptoms. Additionally, TF intake facilitated the restoration of the intestinal microbial community structure by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. It also reduced endotoxin lipopolysaccharide production, thereby lowering the chances of insulin resistance development and enhancing its efficacy in regulating blood glucose levels. These findings offer a novel perspective on the potential of black tea and its active constituents to prevent and treat diabetes and other metabolic disorders, providing valuable references for identifying and applying active dietary components from tea.

Overexpression of sesame O-acetylserine(thiol)lyase induces male sterility by delaying tapetum programmed cell death.

Male sterile lines are key resources for hybrid seed production and for ensuring high varietal purity. However, the genes and mechanisms underlying sesame male sterility remain largely unknown. Hence, this study identified an O-acetylserine(thiol)lyase gene SiOASTL1 and functionally characterized its roles in inducing defective anther development. Spatiotemporal expression analysis revealed that SiOASTL1 is significantly (2.7 fold) up-regulated in sterile sesame anthers at the microspore stage compared with fertile ones. Sequence and phylogenetic analyses showed that SiOASTL1 is homologous to Arabidopsis OAS-TL plastid isoforms. We thus overexpressed SiOASTL1 in Arabidopsis to unravel its regulatory roles. Cytological observation revealed that SiOASTL1 overexpression transformed transgenic plants into male sterile lines arising at the microspore development stage. SiOASTL1 overexpression decreased cysteine biosynthesis and down-regulated the expression of the sporopollenin synthesis-related genes, including AtTKPR1, AtTKPR2, AtPKSA, and AtPKSB in transgenic Arabidopsis. Consequently, the tapetum programmed cell death (PCD) was delayed, resulting in the formation of defective pollen grains with irregular walls and empty cytoplasm. Our findings prove that the induction of SiOASTL1 expression disrupts pollen development and contributes to sesame male sterility. Moreover, these results suggest that genetic manipulation of SiOASTL1 expression may facilitate the development of new hybrid varieties in sesame and other crops.

Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (Milan IVB) and Its Subgroups: A Multi-Institutional Analysis of Risk of Neoplasm and Malignancy.

OBJECTIVES: Fine needle aspiration (FNA) plays a crucial role in their initial assessment of salivary gland neoplasms. In the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the category of Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) categorizes lesions with ambiguous features. This study aims to investigate the risk of neoplasm (RON) and risk of malignancy (ROM) within different subgroups of SUMP lesions using data from three large academic institutions. METHODS: We analyzed salivary gland (FNA) cases from three academic institutions post-MSRSGC implementation. Salivary gland FNA cases categorized as Milan IVB (SUMP) with subsequent surgical pathology follow-up were analyzed. Cases were divided into basaloid, oncocytic, and clear cell SUMP subtypes, with RON and ROM assessed and compared. RESULTS: Out of 1377 MSRSGC cases, 231 were SUMP (16.8%), with 101 subjected to surgical pathology follow-up. The overall ROM for SUMP was 20.8%, with variations of 10% to 29.5% observed amongst institutions, but no significant difference was observed among three institutions (p = 0.15). Basaloid and oncocytic SUMP displayed 17.1% and 20.5% ROM, respectively, without significant disparity. However, all clear cell SUMP cases were malignant on surgical resection. CONCLUSIONS: This study highlights the variability in ROM for SUMP lesions and the significantly higher ROM in SUMP cases with clear cell features. These findings emphasize the importance of accurately subcategorizing SUMP lesions, particularly those with clear cell features, for appropriate clinical management.

Comparison of different immobilisation durations following open surgery for acute achilles tendon rupture: a prospective cohort study.

BACKGROUND: In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. METHODS: This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. RESULTS: The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P < 0.001). The VAS scores decreased over time, reaching 0 in all groups by 10 weeks. The mean scores in groups A and B were higher than those in the other groups at 2 and 4 weeks (P < 0.001), whereas the opposite was true at 8 weeks (P < 0.001). ATRS and the AOFAS Ankle-Hindfoot scale score increased across all groups over time, showing significant between-group differences from weeks 6 to 16 (P < 0.001) and weeks 6 to 12 (P < 0.001). The mean scores were better in groups A and B than in groups C and D. Thirty-eight complications (3.5%) were observed, including 20 re-ruptures and 18 superficial infections. All complications were resolved at the last follow-up, with no significant between-group differences. CONCLUSIONS: Immobilisation for 2 weeks after open surgery for ATR repair may be the optimal strategy for early rehabilitation with relatively minimal pain and other complications. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04663542).

Metformin relieves bone cancer pain by reducing TGFßRI-TRPV1 signaling in rats.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFß1 in the metastatic bone tissue, and raised the expression of TGFßRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFßRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFß1, TGFßRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFß1-TGFßRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Presentation and management of marantic endocarditis: A case series.

Marantic endocarditis is defined as a sterile endocarditis that is rarely encountered in clinical practice. This case series illustrates five cases of marantic endocarditis. All cases were diagnosed on trans thoracic echocardiography and verified on transesophageal echocardiography. The first three cases occur in the setting of antiphospholipid syndrome; the last two occur in the setting of advanced malignancy. Two cases were treated successfully with anticoagulation, while two others required valvular surgery. One case resulted in mortality. The treatment course of these five patients mirrors certain patterns described in the literature.

The effectiveness of extended reality on relieving pain after total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Patients with total knee arthroplasty (TKA) often suffer from severe postoperative pain, which seriously hinders postoperative rehabilitation. Extended reality (XR), including virtual reality, augmented reality, and mixed reality, has been increasingly used to relieve pain after TKA. The purpose of this study was to evaluate the effectiveness of XR on relieving pain after TKA. METHODS: The electronic databases including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov were searched for studies from inception to July 20, 2023. The outcomes were pain score, anxiety score, and physiological parameters related to pain. Meta-analysis was performed using the Review Manager 5.4 software. RESULTS: Overall, 11 randomized control trials (RCTs) with 887 patients were included. The pooled results showed XR had lower pain scores (SMD = - 0.31, 95% CI [- 0.46 to - 0.16], P < 0.0001) and anxiety scores (MD = - 3.95, 95% CI [- 7.76 to - 0.13], P = 0.04) than conventional methods. The subgroup analysis revealed XR had lower pain scores within 2 weeks postoperatively (SMD = - 0.49, 95% CI [- 0.76 to - 0.22], P = 0.0004) and XR had lower pain scores when applying XR combined with conventional methods (SMD = - 0.43, 95% CI [- 0.65 to - 0.20], P = 0.0002). CONCLUSION: This systematic review and meta-analysis found applying XR could significantly reduce postoperative pain and anxiety after TKA. When XR was combined with conventional methods, postoperative pain can be effectively relieved, especially within 2 weeks after the operation. XR is an effective non-pharmacological analgesia scheme.

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-ß1 in colitis treatment.

BACKGROUND: Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. METHODS: First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-ß1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. RESULTS: The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-ß1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-ß1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. CONCLUSIONS: MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-ß1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC. AIM: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC. METHODS: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines. RESULTS: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC (P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher (P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC (P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased (P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) (P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS. CONCLUSION: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis.

Effect of capsule treatment on visual acuity and quality after phacoemulsification lens implantation in myopic patients with cataract.

BACKGROUND: Cataracts pose a significant clinical burden due to their complex pathogenesis. In recent years, an increase in cataracts coexisting with myopia has heightened the incidence of retinopathy and posterior vitreous detachment. Additionally, symptoms of ocular axis elongation, lens nucleus hardening, and vitreous liquefaction have become more prevalent. While conventional extracapsular cataract extraction is commonly employed, it often yields suboptimal visual outcomes. Subsequent advancements in cataract phacoemulsification and lens implantation surgeries have gained widespread acceptance for their ability to improve refraction and significantly improve uncorrected visual acuity. AIM: To investigate the effect of capsular treatment after phacoemulsification lens implantation in myopic patients with cataract. METHODS: We selected 110 patients (with 134 eyes) with myopia and cataracts treated. These patients were categorized into two groups: an observation group (57 patients with 70 eyes) and a control group (53 patients with 64 eyes). The control group underwent cataract phacoemulsification and lens implantation, while the observation group received a refined capsular treatment based on the control group's procedure. We assessed the differences in visual acuity and quality between the two groups before and after surgery. RESULTS: At six months post-operation, the observation group exhibited significantly improved far vision, intermediate vision, near vision, lower objective scattering index, higher Modulation transfer function cut-off frequency, and overall vision metrics at different contrast levels (100%, 20% and 9%) compared to the control group (P < 0.05). The total score of the National Eye Institute Visual Function Questionnaire in the observation group at 6 months after operation was significantly higher than that in the control group (P < 0.05). No significant difference in the incidence of adverse reactions was observed between the observation group and control group (P > 0.05). CONCLUSION: Capsular treatment demonstrates efficacy in improving visual acuity and quality after phacoemulsification lens implantation in myopic patients with cataracts, warranting its clinical application.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Applying 3D-printed prostheses to reconstruct critical-sized bone defects of tibial diaphysis (> 10 cm) caused by osteomyelitis and aseptic non-union.

BACKGROUND: Clinical repair of critical-sized bone defects (CBDs) in the tibial diaphysis presents numerous challenges, including inadequate soft tissue coverage, limited blood supply, high load-bearing demands, and potential deformities. This study aimed to investigate the clinical feasibility and efficacy of employing 3D-printed prostheses for repairing CBDs exceeding 10 cm in the tibial diaphysis. METHODS: This retrospective study included 14 patients (11 males and 3 females) with an average age of 46.0 years. The etiologies of CBDs comprised chronic osteomyelitis (10 cases) and aseptic non-union (4 cases), with an average defect length of 16.9 cm. All patients underwent a two-stage surgical approach: (1) debridement, osteotomy, and cement spacer implantation; and (2) insertion of 3D-printed prostheses. The interval between the two stages ranged from 8 to 12 weeks, during which the 3D-printed prostheses and induced membranes were meticulously prepared. Subsequent to surgery, patients engaged in weight-bearing and functional exercises under specialized supervision. Follow-up assessments, including gross observation, imaging examinations, and administration of the Lower Extremity Functional Scale (LEFS), were conducted at 3, 6, and 12 months postoperatively, followed by annual evaluations thereafter. RESULTS: The mean postoperative follow-up duration was 28.4 months, with an average waiting period between prosthesis implantation and weight-bearing of 10.4 days. At the latest follow-up, all patients demonstrated autonomous ambulation without assistance, and their LEFS scores exhibited a significant improvement compared to preoperative values (30.7 vs. 53.1, P < 0.001). Imaging assessments revealed progressive bone regeneration at the defect site, with new bone formation extending along the prosthesis. Complications included interlocking screw breakage in two patients, interlocking screw loosening in one patient, and nail breakage in another. CONCLUSIONS: Utilization of 3D-printed prostheses facilitates prompt restoration of CBDs in the tibial diaphysis, enabling early initiation of weight-bearing activities and recovery of ambulatory function. This efficacious surgical approach holds promise for practical application.