Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Exploring the causal relationship between omega-3 and omega-6 fatty acids and kidney cancer: a Mendelian randomization study.

Background: The causal link between kidney cancer and omega-3/6 (ω-3/6) fatty acids is yet to be clearly established. Therefore, the objective of our study was to investigate these potential causal relationships. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to investigate the possible causal association between ω-3/6 fatty acids and kidney cancer. We utilized the random effect inverse variance weighted (IVW) method as our primary analytical approach for the two-sample MR analysis. In addition, sensitivity analyses such as heterogeneity tests, pleiotropy analyses, and leave-one-out analyses were performed to assess the robustness of the MR analysis results. Results: The IVW method showed statistically significant associations between ω-3 and ω-6 fatty acids and increased risk of kidney cancer. The result for ω-3 and ω-6 were [odds ratio (OR) =1.27; 95% confidence interval (CI): 1.04-1.55; P=0.02] and (OR =1.56; 95% CI: 1.17-2.09; P=0.003), respectively. Moreover, in the results of sensitivity analyses, no apparent horizontal gene pleiotropy nor heterogeneity was observed. After performing "the leave-one-out" sensitivity analysis of the data one by one, no single nucleotide polymorphisms (SNPs) sites in each instrumental variable (IV) were found to have greatly affected the disease outcome. Conclusions: Elevated serum ω-3/6 fatty acids levels are causally associated with an increased risk of kidney cancer. Therefore, it is crucial to monitor dietary intake and properly intervene to lower these levels in those at risk of kidney cancer.

Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis.

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model.

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

Giant cell tumor of bone at distal radius suffered more soft tissue recurrence and ultrasonography is effective to detect the soft tissue recurrence.

BACKGROUND: Soft tissue recurrence of giant cell tumor of bone (GCTB) is rare. This study aims to provide its prevalence, recurrent locations, risk factors, effective detection methods and a modified classification for this recurrence. METHODS: Patients with soft tissue recurrence after primary surgery for GCTB were screened from January 2003 to December 2022. General data, recurrence frequency, types according to an original classification (type-I: peripheral ossification; type-II: central ossification; type-III: without ossification), a modified classification with more detailed subtypes (type I-1: ≤ 1/2 peripheral ossification; type I-2: ≥ 1/2 peripheral ossification; type II-1: ≤ 1/2 central ossification; type II-2: ≥ 1/2 central ossification; type III: without ossification), locations, detection methods such as ultrasonography, X-ray, CT or MRI, Musculoskeletal Tumor Society (MSTS) scores were recorded. Multivariate regression analysis was conducted to identify risk factors for recurrence frequency. RESULTS: A total of 558 recurrent cases were identified from 2009 patients with GCTB. Among them, 32 were soft tissue recurrence. The total recurrence rate was 27.78% (558/2009). Soft tissue recurrence rate was 5.73% among 558 recurrent cases, and 1.59% among 2009 GCTB patients, respectively. After excluding one patient lost to follow-up, 10 males and 21 females with the mean age of 28.52 ± 9.93 (16-57) years were included. The definitive diagnosis of all recurrences was confirmed by postoperative pathology. The interval from primary surgery to the first recurrence was 23.23 ± 26.12 (2-27) months. Eight recurrences occurred from primary GCTB located at distal radius, followed by distal femur (6 cases). Recurrence occurred twice in 12 patients and 3 times in 7 patients. Twenty-seven recurrences were firstly detected by ultrasonography, followed by CT or X-ray (10 cases in each). Types at the first recurrence were 5 cases in type-I, 8 in type-II and 18 in type-III. According to the modified classification, 3 patients in type I-1, 2 in type I-2, 1 in type II-1, 7 in type II-2, and 18 in type III. The mean MSTS score was 26.62 ± 4.21 (14-30). Neither Campanacci grade nor recurrence type, modified classification and other characters, were identified as risk factors. CONCLUSIONS: Soft tissue recurrence of GCTB may recur for more than once and distal radius was the most common location of primary GCTB that would suffer a soft tissue recurrence. Ultrasonography was a useful method to detect the recurrence. Since no risk factors were discovered, a careful follow-up with ultrasonography was recommended.

Deep Location Soft-Embedding-Based Network with Regional Scoring for Mammogram Classification.

Early detection and treatment of breast cancer can significantly reduce patient mortality, and mammogram is an effective method for early screening. Computer-aided diagnosis (CAD) of mammography based on deep learning can assist radiologists in making more objective and accurate judgments. However, existing methods often depend on datasets with manual segmentation annotations. In addition, due to the large image sizes and small lesion proportions, many methods that do not use region of interest (ROI) mostly rely on multi-scale and multi-feature fusion models. These shortcomings increase the labor, money, and computational overhead of applying the model. Therefore, a deep location soft-embedding-based network with regional scoring (DLSEN-RS) is proposed. DLSEN-RS is an end-to-end mammography image classification method containing only one feature extractor and relies on positional embedding (PE) and aggregation pooling (AP) modules to locate lesion areas without bounding boxes, transfer learning, or multi-stage training. In particular, the introduced PE and AP modules exhibit versatility across various CNN models and improve the model's tumor localization and diagnostic accuracy for mammography images. Experiments are conducted on published INbreast and CBIS-DDSM datasets, and compared to previous state-of-the-art mammographic image classification methods, DLSEN-RS performed satisfactorily.

Comparison of three concentrations of ropivacaine in posterior quadratus lumborum block: A randomized clinical trial.

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

Preoperative risk prediction models for acute kidney injury after noncardiac surgery: an independent external validation cohort study.

BACKGROUND: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them. METHODS: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases. RESULTS: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis. CONCLUSIONS: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery.

A noninvasive method for predicting clinically significant prostate cancer using magnetic resonance imaging combined with PRKY promoter methylation level: a machine learning study.

BACKGROUND: Traditional process for clinically significant prostate cancer (csPCA) diagnosis relies on invasive biopsy and may bring pain and complications. Radiomic features of magnetic resonance imaging MRI and methylation of the PRKY promoter were found to be associated with prostate cancer. METHODS: Fifty-four Patients who underwent prostate biopsy or photoselective vaporization of the prostate (PVP) from 2022 to 2023 were selected for this study, and their clinical data, blood samples and MRI images were obtained before the operation. Methylation level of two PRKY promoter sites, cg05618150 and cg05163709, were tested through bisulfite sequencing PCR (BSP). The PI-RADS score of each patient was estimated and the region of interest (ROI) was delineated by 2 experienced radiologists. After being extracted by a plug-in of 3D-slicer, radiomic features were selected through LASSCO regression and t-test. Selected radiomic features, methylation levels and clinical data were used for model construction through the random forest (RF) algorithm, and the predictive efficiency was analyzed by the area under the receiver operation characteristic (ROC) curve (AUC). RESULTS: Methylation level of the site, cg05618150, was observed to be associated with prostate cancer, for which the AUC was 0.74. The AUC of T2WI in csPCA prediction was 0.84, which was higher than that of the apparent diffusion coefficient ADC (AUC = 0.81). The model combined with T2WI and clinical data reached an AUC of 0.94. The AUC of the T2WI-clinic-methylation-combined model was 0.97, which was greater than that of the model combined with the PI-RADS score, clinical data and PRKY promoter methylation levels (AUC = 0.86). CONCLUSIONS: The model combining with radiomic features, clinical data and PRKY promoter methylation levels based on machine learning had high predictive efficiency in csPCA diagnosis.

Postoperative haemoglobin and anaemia-associated ischaemic events after major noncardiac surgery: A sex-stratified cohort study.

STUDY OBJECTIVE: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery. DESIGN: A retrospective cohort study with prospective validation. SETTING: A large university hospital health system in China. PATIENTS: Men and women undergoing elective major noncardiac surgery. INTERVENTIONS AND MEASUREMENTS: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation. MAIN RESULTS: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l-1 in men and 120 g l-1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l-1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings. CONCLUSIONS: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.

The evolution and impact of sarcopenia in severe aplastic anaemia survivors following allogeneic haematopoietic cell transplantation.

BACKGROUND: Sarcopenia is a potential risk factor for adverse outcomes in haematopoietic cell transplantation (HSCT) recipients. We aimed to explore longitudinal body changes in muscle and adipose mass and their prognostic value in allogeneic HSCT-treated severe aplastic anaemia (SAA) patients. METHODS: We retrospectively analysed consecutive SAA patients who underwent allogeneic HSCT between January 2017 and March 2022. Measurements of pectoral muscle and corresponding subcutaneous fat mass were obtained via chest computed tomography at baseline and at 1 month, 3 months, 6 months, and 12 months following HSCT. Sarcopenia was defined as pectoral muscle index (PMI) lower than the sex-specific median at baseline. Changes in body composition over time were evaluated by generalized estimating equations. Cox regression models were used to investigate prognostic factors affecting overall survival (OS) and failure-free survival (FFS). A nomogram was constructed from the Cox regression model for OS. RESULTS: We included 298 adult SAA patients (including 129 females and 169 males) with a median age of 31 years [interquartile range (IQR), 24-39 years] at baseline. Sarcopenia was present in 148 (148/298, 50%) patients at baseline, 218 (218/285, 76%) patients post-1 month, 209 (209/262, 80%) patients post-3 month, 169 (169/218, 78%) patients post-6 month, and 129 (129/181, 71%) patients post-12 month. A significant decrease in pectoral muscle mass was observed in SAA patients from the time of transplant to 1 year after HSCT, and the greatest reduction occurred in post 1-3 months (P < 0.001). The sarcopenia group exhibited significantly lower 5-year OS (90.6% vs. 100%, log-rank P = 0.039) and 5-year FFS (89.2% vs. 100%, log-rank P = 0.021) than the nonsarcopenia group at baseline. Sarcopenia at baseline (hazard ratio, HR, 6.344; 95% confidence interval, CI: 1.570-25.538; P = 0.01; and HR, 3.275; 95% CI: 1.159-9.252; P = 0.025, respectively) and the delta value of the PMI at 6 months post-transplantation (ΔPMI6) (HR, 0.531; 95% CI: 0.374-0.756; P < 0.001; and HR, 0.666; 95% CI: 0.505-0.879; P = 0.004, respectively) were demonstrated to be independent prognostic factors for OS and FFS in SAA patients undergoing HSCT, and were used to construct the nomogram. The C-index of the nomogram was 0.75, and the calibration plot showed good agreement between the predictions made by the nomogram and actual observations. CONCLUSIONS: Sarcopenia persists in SAA patients from the time of transplant to the 1-year follow-up after HSCT. Both sarcopenia at baseline and at 6 months following HSCT are associated with poor clinical outcomes, especially in patients with persistent muscle mass loss up to 6 months after transplantation.

Identification and validation of a novel nine-gene prognostic signature of stem cell characteristic in hepatocellular carcinoma.

Currently, cancer stem cells (CSCs) are regarded as the most promising target for cancer therapy due to their close association with tumor resistance, invasion, and recurrence. Thus, identifying CSCs-related genes and constructing a prognostic risk model associated with CSCs may be crucial for hepatocellular carcinoma (HCC) therapy. Xena Browser was used to download gene expression profiles and clinical data, while MSigDB was used to obtain genes associated with CSCs. Firstly, the non-negative matrix factorization (NMF) algorithm was used to cluster the HCC samples based on CSCs-related genes. To evaluate the predictive performance of the risk model, the receiver operating characteristic curves (ROC) and Kaplan-Meier analysis were used. The R package "rms" was used to construct the final nomogram based on risk scores and clinical characteristics. Based on 449 CSCs-related genes, a total of 588 HCC samples from TCGA-LIHC and ICGC-LIRI_JP were classified into four molecular subtypes with marked differences in survival and mRNA stemness index (mRNAsi) between subtypes. Univariate Cox regression, multivariate Cox regression, and LASSO regression analyses were performed on a total of 1417 differentially expressed genes (DEGs) between subtypes, and a nine-gene prognostic model was constructed with TTK, ST6GALNAC4, SPP1, SGCB, MEP1A, HTRA1, CD79A, C6, and ATP2A3. In both the training and testing sets and the external validation cohort, the risk model performed well in predicting HCC patients' survival. A nomogram was constructed and had high predictive efficacy in short-term survival. In comparison with the other two prognostic models, our nine-gene signature model performed best. We constructed a nine-gene signature model to predict the survival of HCC patients, which has good predictive efficacy and stability. The model may contribute to guiding the prognostic assessment of HCC patients in clinical practice.

Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

A New Type of Si-Based MOSFET for Radiation Reinforcement.

This paper thoroughly analyses the role of drift in the sensitive region in the single-event effect (SEE), with the aim of enhancing the single-particle radiation resistance of N-type metal-oxide semiconductor field-effect transistors (MOSFETs). It proposes a design for a Si-based device structure that extends the lightly doped source-drain region of the N-channel metal-oxide semiconductor (NMOS), thereby moderating the electric field of the sensitive region. This design leads to a 15.69% decrease in the charge collected at the leaky end of the device under the standard irradiation conditions. On this basis, a device structure is further proposed to form a composite metal-oxide semiconductor (MOS) by connecting a pn junction at the lightly doped source-drain end. By adding two charge paths, the leakage collection charge is further reduced by 13.85% under standard irradiation conditions. Moreover, the deterioration of the drive current in the purely growing lightly doped source-drain region can be further improved. Simulations of single-event effects under different irradiation conditions show that the device has good resistance to single-event irradiation, and the composite MOS structure smoothly converges to a 14.65% reduction in drain collection charge between 0.2 pC/µm and 1 pC/µm Linear Energy Transfer (LET) values. The incidence position at the source-to-channel interface collects the highest charge reduction rate of 28.23%. The collecting charge reduction rate is maximum, at 17.12%, when the incidence is at a 45-degree angle towards the source.

Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors.

The fusion genes NRG1 and NRG2 , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1 -positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2 . Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Precise single column resection and reconstruction with femoral head plus total hip replacement for primary malignant peri-acetabulum tumors.

To evaluate whether single acetabular column can be reserved and the effect of reconstruction with femoral head plus total hip replacement (THR) for primary malignant peri-acetabulum tumors. From 2007 to 2015, nineteen patients with primary malignant peri-acetabulum tumors were enrolled. All cases underwent single column resection with clear surgical margins. Ten of the 19 tumor's resections were assisted by computer navigation. Femoral heads were applied to reconstruct anterior or posterior column defects; THR was used for joint reconstruction. The surgical safety, oncologic outcome and prosthesis survivorship and function were evaluated by regular follow-up. The average follow-up period was 65.9 months. Surgical margins contained wide resection in 12 cases and marginal resection in 7 cases. One patient with Ewing's sarcoma died 14 months postoperative due to lung metastasis. One case with chondrosarcoma had recurrence. One prosthesis was removed due to infection. The average MusculoSkeletal Tumor Society (MSTS) function score was 83.7%. Due to the relative small number of cases, there was no significant difference in the recurrence rate and prosthesis failure rate between the navigation group and non-navigation group. Single column resection and reconstruction with femoral head autograft plus THR is an effective, safe method with less complication rate and better functional outcome for patients with peri-acetabular tumors.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

An early warning model to predict acute kidney injury in sepsis patients with prior hypertension.

Background: In the context of sepsis patients, hypertension has a significant impact on the likelihood of developing sepsis-associated acute kidney injury (S-AKI), leading to a considerable burden. Moreover, sepsis is responsible for over 50 % of cases of acute kidney injuries (AKI) and is linked to an increased likelihood of death during hospitalization. The objective of this research is to develop a dependable and strong nomogram framework, utilizing the variables accessible within the first 24 h of admission, for the anticipation of S-AKI in sepsis patients who have hypertension. Methods: In this study that looked back, a total of 462 patients with sepsis and high blood pressure were identified from Nanfang Hospital. These patients were then split into a training set (consisting of 347 patients) and a validation set (consisting of 115 patients). A multivariate logistic regression analysis and a univariate logistic regression analysis were performed to identify the factors that independently predict S-AKI. Based on these independent predictors, the model was constructed. To evaluate the efficacy of the designed nomogram, several analyses were conducted, including calibration curves, receiver operating characteristics curves, and decision curve analysis. Results: The findings of this research indicated that diabetes, prothrombin time activity (PTA), thrombin time (TT), cystatin C, creatinine (Cr), and procalcitonin (PCT) were autonomous prognosticators for S-AKI in sepsis individuals with hypertension. The nomogram model, built using these predictors, demonstrated satisfactory discrimination in both the training (AUC = 0.823) and validation (AUC = 0.929) groups. The S-AKI nomogram demonstrated superior predictive ability in assessing S-AKI within the hypertension grade I (AUC = 0.901) set, surpassing the hypertension grade II (AUC = 0.816) and III (AUC = 0.810) sets. The nomogram exhibited satisfactory calibration and clinical utility based on the calibration curve and decision curve analysis. Conclusion: In patients with sepsis and high blood pressure, the nomogram that was created offers a dependable and strong evaluation for predicting S-AKI. This evaluation provides valuable insights to enhance individualized treatment, ultimately resulting in improved clinical outcomes.

An innovative staged prosthetic lengthening reconstruction strategy for osteosarcoma-related leg discrepancy.

Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6-15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1-14.2) before the lengthening to 0.3 cm (- 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%-53.3%) before the lengthening to 96.3% (86.7%-100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.

The correlation between clinical outcomes and genomic analysis with high risk factors for the progression of osteosarcoma.

Osteosarcoma (OS) is a rare but aggressive malignancy. Despite previous reports, molecular characterization of this disease is not well understood, and little is known regarding OS in Chinese patients. Herein, we analyzed the genomic signatures of 73 Chinese OS cases. TP53, NCOR1, LRP1B, ATRX, RB1, and TFE3 were the most frequently mutated gene in our OS cohort. In addition, the genomic analysis of Western OS patients was performed. Notably, there were remarkable disparities in mutational landscape, base substitution pattern, and tumor mutational burden between the Chinese and Western OS cohorts. Specific molecular mechanisms, including DNA damage repair (DDR) gene mutations, copy number variation (CNV) presence, aneuploidy, and intratumoral heterogeneity, were associated with disease progression. Additionally, 30.1% of OS patients carried clinically actionable alterations, which were mainly enriched in PI3K, MAPK, DDR, and RTK signaling pathways. A specific molecular subtype incorporating DDR alterations and CNVs was significantly correlated with distant metastasis-free survival and event-free survival, and this correlation was observed in all subgroups with different characteristics. These findings comprehensively elucidated the genomic profile and revealed novel prognostic factors in OS, which would contribute to understanding this disease and promoting precision medicine of this population.