Non-invasive assessment of response to transcatheter arterial chemoembolization for hepatocellular carcinoma with the deep neural networks-based radiomics nomogram.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a mainstay treatment for intermediate and advanced hepatocellular carcinoma (HCC), with the potential to enhance patient survival. Preoperative prediction of postoperative response to TACE in patients with HCC is crucial. PURPOSE: To develop a deep neural network (DNN)-based nomogram for the non-invasive and precise prediction of TACE response in patients with HCC. MATERIAL AND METHODS: We retrospectively collected clinical and imaging data from 110 patients with HCC who underwent TACE surgery. Radiomics features were extracted from specific imaging methods. We employed conventional machine-learning algorithms and a DNN-based model to construct predictive probabilities (RScore). Logistic regression helped identify independent clinical risk factors, which were integrated with RScore to create a nomogram. We evaluated diagnostic performance using various metrics. RESULTS: Among the radiomics models, the DNN_LASSO-based one demonstrated the highest predictive accuracy (area under the curve [AUC] = 0.847, sensitivity = 0.892, specificity = 0.791). Peritumoral enhancement and alkaline phosphatase were identified as independent risk factors. Combining RScore with these clinical factors, a DNN-based nomogram exhibited superior predictive performance (AUC = 0.871, sensitivity = 0.844, specificity = 0.873). CONCLUSION: In this study, we successfully developed a deep learning-based nomogram that can noninvasively and accurately predict TACE response in patients with HCC, offering significant potential for improving the clinical management of HCC.

Radiological assessment of immunotherapy effects and immune checkpoint-related pneumonitis for lung cancer.

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

Quasi-Zero Stiffness Vibration Sensing and Energy Harvesting Integration Based on Buckled Piezoelectric Euler Beam.

This paper presents a novel quasi-zero stiffness vibration sensing and energy harvesting integration system for absolute displacement measurements based on a buckled piezoelectric Euler beam (BPEB) with quasi-zero stiffness (QZS) characteristics. On one hand, BPEB provides negative stiffness to the system, thus creating a vibration-free point within the system and transforming the absolute displacement measurement problem into a relative motion sensing problem. On the other hand, during the measurement process, the BPEB collects the vibration energy from the system, which can provide electrical energy for low-power relative motion sensing devices and remarkably suppress the frequency range of the jump phenomenon, thereby further expanding the frequency domain measurement range of the sensing system. The research results have shown that this system can measure the absolute motion signal of the tested object in low-frequency vibration with small excitation. By adjusting parameters such as the force-electric coupling coefficient and damping ratio, the measurement accuracy of the sensing system can be improved. Furthermore, the system can convert the mechanical energy of vibrations into electrical energy to power the surrounding low-power sensors or provide partial power. This could potentially achieve self-powering integrated quasi-zero stiffness vibration sensing, offering another approach and possibility for the automation development in wireless sensing systems and the Internet of Things field.

Effect of Chaihu plus Longgu Muli decoction plus five-element music therapy in the treatment of cancer-related depression.

BACKGROUND: Ninety percent of tumour patients have negative emotions during or after anti-tumour treatment, resulting in depression. Western medicine antidepressants have many adverse reactions. Patients often discontinue antidepressants due to intolerance. AIM: This study aims to observe the clinical effect of Chaihu plus Longgu Muli decoction with five-element music therapy in treating cancer-related mild and moderate depression. METHODS: A total of 120 patients with depression in the Oncology Department of Tangshan Hospital of Traditional Chinese Medicine, Hebei Province, from July 2017 to March 2019, were selected and randomly divided into the control and study groups (60 cases each) by the random number table method. The study group was treated with Chaihu plus Longgu Muli decoction with five-element music therapy for depression. The control group was treated with escitalopram tablets. After three courses of treatment, the degree of depression, clinical efficacy, quality of life, serum norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels were observed. RESULTS: After treatment, the HAMD-24 (Hamilton Depression 24) scale scores of the study group (13.93 ± 6.32) were lower than the control group (19.04 ± 7.46), and the difference was statistically significant (x2 = 4.048, p = 0.008). The total effective rate of the study group (93.33%) was higher than the control group (73.33%), and the difference was statistically significant (x2 = 7.260, p = 0.000). After treatment, according to the QLQ-C30 (quality of life questionnaire) scale, the functional score of the study group was higher than the control group (p < 0.05), and the symptom score of the study group was lower than the control group (p < 0.05). After treatment, the serum NE and 5-HT levels in the study group were higher than the control group, and the difference was statistically significant (p < 0.05) (NE: 221.81 ± 31.14 vs 198.91 ± 29.97, t = 4.078, p = 0.000; 5-HT: 141.41 ± 20.35 vs 125.32 ± 14.58, t = 5.781, p = 0.000). CONCLUSION: Chaihu plus Longgu Muli decoction with five-element music therapy can effectively alleviate patients' cancer-related depression and improve their quality of life, which is worthy of promotion.

Comparison of the prognosis of four different surgical strategies for proximal gastric cancer: a network meta-analysis.

BACKGROUND: There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC). METHODS: We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval. RESULTS: There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy. CONCLUSION: Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced.

Exploration of the molecular characteristics of the tumor-immune interaction and the development of an individualized immune prognostic signature for neuroblastoma.

Neuroblastoma (NBL) exists in a complex tumor-immune microenvironment. Immune cell infiltration and tumor-immune molecules play a critical role in tumor development and significantly impact the prognosis of patients. However, the molecular characteristics describing the NBL-immune interaction and their prognostic potential have yet to be investigated systematically. We first employed multiple machine learning algorithms, such as Gene Sets Enrichment Analysis and cell type identification by estimating relative subsets of RNA transcripts, to identify immunophenotypes and immunological characteristics in NBL patient data from public databases and then investigated the prognostic potential and regulatory networks of identified immune-related genes involved in the NBL-immune interaction. The immunity signature combining nine immunity genes was confirmed as more effective for individual risk stratification and survival outcome prediction in NBL patients than common clinical characteristics (area under the curve [AUC] = 0.819, C-index = 0.718, p < .001). A mechanistic exploration revealed the regulatory network of molecules involved in the NBL-immune interaction. These immune molecules were also discovered to possess a significant correlation with plasma cell infiltration, MYCN status, and the level of chemokines and macrophage-related molecules (p < .001). A nomogram was constructed based on the immune signature and clinical characteristics, which showed high potential for prognosis prediction (AUC = 0.856, C-index = 0.755, p < .001). We systematically elucidated the complex regulatory mechanisms and characteristics of the molecules involved in the NBL-immune interaction and their prognostic potential, which may have important implications for further understanding the molecular mechanism of the NBL-immune interaction and identifying high-risk NBL patients to guide clinical treatment.

CRiSP: accurate structure prediction of disulfide-rich peptides with cystine-specific sequence alignment and machine learning.

MOTIVATION: High-throughput sequencing discovers many naturally occurring disulfide-rich peptides or cystine-rich peptides (CRPs) with diversified bioactivities. However, their structure information, which is very important to peptide drug discovery, is still very limited. RESULTS: We have developed a CRP-specific structure prediction method called Cystine-Rich peptide Structure Prediction (CRiSP), based on a customized template database with cystine-specific sequence alignment and three machine-learning predictors. The modeling accuracy is significantly better than several popular general-purpose structure modeling methods, and our CRiSP can provide useful model quality estimations. AVAILABILITY AND IMPLEMENTATION: The CRiSP server is freely available on the website at http://wulab.com.cn/CRISP. CONTACT: wuyd@pkusz.edu.cn or jiangfan@pku.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Migration ability and Toll-like receptor expression of human mesenchymal stem cells improves significantly after three-dimensional culture.

While the conventional two-dimensional (2D) culture protocol is well accepted for the culture of mesenchymal stem cells (MSCs), this method fails to recapitulate the in vivo native three-dimensional (3D) cellular microenvironment, and may result in phenotypic changes, and homing and migration capacity impairments. MSC preparation in 3D culture systems has been considered an attractive preparatory and delivery method recently. We seeded human umbilical cord-derived MSCs (hUCMSCs) in a 3D culture system with porcine acellular dermal matrix (PADM), and investigated the phenotypic changes, the expression changes of some important receptors, including Toll-like receptors (TLRs) and C-X-C chemokine receptor type 4 (CXCR4) when hUCMSCs were transferred from 2D to 3D systems, as well as the alterations in in vivo homing and migration potential. It was found that the percentage of CD105-positive cells decreased significantly, whereas that of CD34- and CD271-positive cells increased significantly in 3D culture, compared to that in 2D culture. The mRNA and protein expression levels of TLR2, TLR3, TLR4, TLR6, and CXCR4 in hUCMSCs were increased significantly upon culturing with PADM for 3 days, compared to the levels in 2D culture. The numbers of migratory 3D hUCMSCs in the heart, liver, spleen, and bone marrow were significantly greater than the numbers of 2D hUCMSCs, and the worst migration occurred in 3D + AMD3100 (CXCR4 antagonist) hUCMSCs. These results suggested that 3D culture of hUCMSCs with PADM could alter the phenotypic characteristics of hUCMSCs, increase their TLR and CXCR4 expression levels, and promote their migratory and homing capacity in which CXCR4 plays an important role.

Safety and efficacy of intraoperative iodine-125 seed implantation brachytherapy for rectal cancer patients: A retrospective clinical research.

BACKGROUND: This pilot study was performed to evaluate the risk of anastomotic leakage (AL) and pelvic autonomic nerve dysfunction, and the effects of (125) I brachytherapy after intraoperative permanent implantation of iodine-125 seeds within the patients with rectal carcinoma. METHODS: In a cohort consisting of 80 rectal cancer patients who received potentially curative resection of rectal carcinoma with implantation of (125) I brachytherapy or radical resection of rectal carcinoma underwent total mesorectal excision. The incidences of AL, fecal incontinence, urinary dysfunction, and sexual dysfunction were calculated for comparison, and risk factors for these complications were analyzed by logistic regression. Rates of tumor recurrence and overall survival were evaluated. RESULTS: Six out of 17 (35.29%) patients in the (125) I implant group and 1 out of 34 (2.94%) patients in the non-implant group were complicated with AL (P = 0.006). The incidences of urinary dysfunction (P = 0.005) and fecal incontinence (P = 0.023) were significantly different between the two groups. Multivariate analyses revealed that (125) I brachytherapy was an independent risk factor for AL (odds ratio, 18.702; 95%CI, 1.802-194.062; P = 0.014) and urinary dysfunction (odds ratio, 4.340; 95%CI, 1.158-16.264; P = 0.029), respectively. At postoperative 2-year, the recurrence rates were 5.56% in the (125) I implant group and 9.09% in the non-implant group (P = 0.029). CONCLUSIONS: Intraoperative implantation of (125) I brachytherapy significantly increases the risk of AL, fecal incontinence, urinary dysfunction, and improves local control and do not improve overall survival after total mesorectal excision.

Interaction of pepsin-[C16mim]Br system: interfacial dilational rheology and conformational studies.

The interfacial rheological property is closely related to the stabilities of foams and emulsions, yet there have been limited studies on the interaction between proteins with ionic liquid-type imidazolium surfactants at the decane-water interface as well as in the bulk. Herein, we investigated the interfacial and bulk properties of pepsin (PEP) and an ionic liquid (IL), 1-hexadecyl-3-methylimidazolium bromide, [C(16)mim]Br. The interfacial pressure and dilational rheology studies were performed to describe the formation of [C(16)mim]Br-pepsin complexes. The influence of the oscillating frequency and the bulk concentration of [C(16)mim]Br on the dilational properties were explored. The conformational changes were studied by monitoring the fluorescence and far UV-CD spectra. The results reveal that the globular structure of pepsin is one of the decisive factors controlling the nature of the interfacial film. The monotonous increase in the dilational elastic modulus of pepsin-[C(16)mim]Br solutions with the surface age indicates that no loops and tails had formed. Interestingly, with an increase in the concentration of [C(16)mim]Br, the εd-c curve first passes through a plateau value due to steric hindrance and the electrostatic barrier of already absorbed tenacious pepsin-[C(16)mim]Br complexes. With the further addition of [C(16)mim]Br, the remarkable decrease in dilational elastic modulus indicates that the compact structure is destroyed gradually. The results of the fluorescence spectra and far UV-CD spectra confirm that [C(16)mim]Br did not produce perceptible changes in pepsin at the concentrations studied in the dilational experiment. Possible schematic programs of the pepsin-[C(16)mim]Br interaction model at the interface and in bulk phase are proposed.

Predicting axillary lymph node metastasis in breast cancer patients: A radiomics-based multicenter approach with interpretability analysis.

PURPOSE: To develop a MRI-based radiomics model, integrating the intratumoral and peritumoral imaging information to predict axillary lymph node metastasis (ALNM) in patients with breast cancer and to elucidate the model's decision-making process via interpretable algorithms. METHODS: This study included 376 patients from three institutions who underwent contrast-enhanced breast MRI between 2021 and 2023. We used multiple machine learning algorithms to combine peritumoral, intratumoral, and radiological characteristics with the building of radiological, radiomics, and combined models. The model's performance was compared based on the area under the curve (AUC) obtained from the receiver operating characteristic analysis and interpretable machine learning techniques to analyze the operating mechanism of the model. RESULTS: The radiomics model, incorporating features from both intratumoral tissue and the 3 mm peritumoral region and utilizing the backpropagation neural network (BPNN) algorithm, demonstrated superior diagnostic efficacy, achieving an AUC of 0.820. The AUC of the combination of the RAD score, clinical T stage, and spiculated margin was as high as 0.855. Furthermore, we conducted SHapley Additive exPlanations (SHAP) analysis to evaluate the contributions of RAD score, clinical T stage, and spiculated margin in ALNM status prediction. CONCLUSIONS: The interpretable radiomics model we propose can better predict the ALNM status of breast cancer and help inform clinical treatment decisions.

SIRT3 alleviates high glucose-induced chondrocyte injury through the promotion of autophagy and suppression of apoptosis in osteoarthritis progression.

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin 3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.

Sustainable strategy for online physical education teaching using ResNet34 and big data.

Since the global COVID-19 outbreak in the spring of 2020, online instruction has replaced traditional classroom instruction as the main method of educating students. Teaching physical education online can be challenging, as it may be difficult to teach students certain movements, accurate student mobility, and appropriate exercise assignments. This paper proposed an online teaching support system with sustainable development features that utilize several large data sets. The system is based on the deep learning image recognition algorithm ResNet34, which can analyze and correct student actions in real-time for gymnastics, dance, basketball, and other sports. By combining the attention mechanism module with the original ResNet34, the detection precision of the system can be enhanced. The sustainability of the system is evident from the fact that the data set can be expanded in response to the emergence of new sports categories and can be kept current in real-time. According to experiments, the target identification accuracy of the proposed system, which combines ResNet34 and the attention mechanism, is higher than that of several other methods currently in use. The proposed techniques outperform the original ResNet34 in terms of accuracy, precision, and recall by 4.1%, 2.8%, and 3.6%, respectively. The suggested approach significantly improves student action correction in virtual sports instruction.

Pan-cancer analysis of the prognostic and immunological role of SNX29: a potential target for survival and immunotherapy.

BACKGROUND: There is growing evidence that the SNX family is critical for clinical prognosis, immune infiltration and drug sensitivity in many types of tumors. The relationships between the SNX29 gene and clinical prognosis as well as pan-cancer cell infiltration and drug sensitivity have not been fully elucidated. METHODS: In the current study, we explored the correlation between SNX29 expression and 33 types of malignancies via TCGA and GTEx. The relationship between SNX29 expression and prognostic outcome in the pan-caner cohort was also analyzed. Immune infiltration, microsatellite instability, tumor mutational burden and potential therapeutic targets of SNX29 were investigated by analyzing public databases. RESULTS: The expression of SNX29 was found to be significantly upregulated in most tumor tissues compared to normal tissues. SNX29 expression was associated with prognosis and clinical stage. In the immune infiltration analysis, a significant relationship was found between SNX29 expression and the level of immune infiltration. In addition, we found associations between the SNX29 gene and tumor mutation burden, microsatellite instability, immunoinhibition-related genes and autophagy-related genes. Finally, the expression of SNX29 was significantly associated with the sensitivity of various tumor cell lines to 8 antitumor drugs. These results suggest that SNX29 expression is important in determining the progression, immune infiltration and drug sensitivity of various cancers. CONCLUSION: This study provides novel insights into the potential pan-cancer targets of SNX29.

The early infection characterization of septic arthritis by Staphylococcus aureus after anterior cruciate ligament reconstruction in a novel rat model.

BACKGROUND: The present study aimed to explore the time of maximum bacterial load and main colonization knee site in bacterial infection process based on a novel rat model of septic arthritis (SA) after anterior cruciate ligament reconstruction (ACLR). METHODS: Ninety-five Wistar rats with unilateral ACLR, random enrolled into control surgery (CS) group; joint inject (JI) group; presoaking (PS) group, were injected with 30 µl sterile saline or 30 µl × 107 colony forming units/ml Staphylococcus aureus via the knee joint or graft with presoaked Staphylococcus aureus during ACLR, respectively. At 1, 4, 7, 11, and 14 days postoperatively, samples were harvested to evaluate progress of knee joint infection by postoperative body weight, body temperature, knee temperature, knee width, scales of tissue damage, serum inflammatory markers, microbiological counting, microcomputed tomography (Micro-CT), digital radiography, magnetic resonance imaging (MRI) examination, and scanning electron microscopy (SEM). RESULTS: No systemic infection was observed in all rats. Comparing with serum inflammatory markers, tissue scores of inflammatory reactions, bacterial counts in the CS group, these data were significantly elevated in the JI group and PS group. The bone mass around the bone tunnel was lower and the soft tissue of knee showed more obvious swelling on MRI in the infection groups than that in the CS group at 7 and 14 days postoperatively. Staphylococcus aureus clusters on the surface of screw and graft were observed in the infection group. The whole colony forming units of Staphylococcus aureus maintained a continuous upward trend peaking 7 and 11 days followed by a balanced curve in the infection groups. Bone and soft tissue were found to have more bacterial counts than graft and screws. CONCLUSION: This animal model effectively mimics the acute knee infection after ACLR. We found that the bacterial colonization exhibited the peak of acute infection between 7 and 11 days postoperatively, with the major bacteria loads found in the bone, soft tissue.

Propensity score-matched analysis of enhanced recovery after surgery in total hip arthroplasty for displaced femoral neck fractures.

OBJECTIVE: The concept of enhanced recovery after surgery (ERAS) has been proposed in recent years, which indeed bring about evident convenience for the patients. This prospective cohort study was aimed to investigate the impact of ERAS on the clinical outcome of patients who undergoing total hip arthroplasty due to displaced femoral neck fractures. METHODS: Patients in two periods were included in our research, before ERAS (n = 194) and after ERAS (n = 65). The clinical outcome, such as patient statistics, details of perioperative management, length of stay (LOS), pain, Harris hip score, in-hospital complications, and interim postoperative survival were collected. This retrospective observational study addressed confounding bias using propensity score matching (PSM) analysis. RESULTS: With PSM, 55 pairs of well-matched patients were generated for comparison (conventional vs. ERAS). LOS decreased to 13.0 ± 3.2 days for the ERAS group, compared to 15.7 ± 3.5 days in the conventional group. VAS pain scores decreased significantly in both groups, and the decrease in the ERAS group was more significant than that in the conventional group at 3, 7, and 14 days postoperatively. The Harris scores of both groups significantly improved, but were better for the ERAS group than the conventional group at 7 and 14 days and 1 month postoperatively. However, no significant difference was observed at 6 months postoperatively. Additionally, the incidence of complications during hospitalization was lower in the ERAS group than that in the conventional group. No significant difference was observed in the medium-term survival between the two groups. CONCLUSIONS: ERAS apparently benefit patients in early rehabilitation by reducing complications and shortening hospital stays but not for the long-term hip function or survival.

Risk factors for lateral pelvic lymph node metastasis in patients with lower rectal cancer: a systematic review and meta-analysis.

Background and objective: Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods. Methods: We searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis. Results: A total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age <60 years, pretherapeutic CEA level >5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) <50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8 mm before nCRT, short axis (SA) of LPLN ≥5 mm after nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P <0.05). Conclusion: This study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life.

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma.

BACKGROUND: The defense response is a type of self-protective response of the body that protects it from damage by pathogenic factors. Although these reactions make important contributions to the occurrence and development of tumors, the role they play in osteosarcoma (OS), particularly in the immune microenvironment, remains unpredictable. METHODS: This study included the clinical information and transcriptomic data of 84 osteosarcoma samples and the microarray data of 12 mesenchymal stem cell samples and 84 osteosarcoma samples. We obtained 129 differentially expressed genes related to the defense response (DRGs) by taking the intersection of differentially expressed genes with genes involved in the defense response pathway, and prognostic genes were screened using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression and multivariate Cox regression were then used to establish a DRG prognostic signature (DGPS) via the stepwise method. DGPS performance was examined using independent prognostic analysis, survival curves, and receiver operating characteristic (ROC) curves. In addition, the molecular and immune mechanisms of adverse prognosis in high-risk populations identified by DGPS were elucidated. The results were well verified by experiments. RESULT: BNIP3, PTGIS, and ZYX were identified as the most important DRGs for OS progression (hazard ratios of 2.044, 1.485, and 0.189, respectively). DGPS demonstrated outstanding performance in the prediction of OS prognosis (area under the curve (AUC) values of 0.842 and 0.787 in the training and test sets, respectively, adj-p < 0.05 in the survival curve). DGPS also performed better than a recent clinical prognostic approach with an AUC value of only 0.674 [metastasis], which was certified in the subsequent experimental results. These three genes regulate several key biological processes, including immune receptor activity and T cell activation, and they also reduce the infiltration of some immune cells, such as B cells, CD8+ T cells, and macrophages. Encouragingly, we found that DGPS was associated with sensitivity to chemotherapeutic drugs including JNK Inhibitor VIII, TGX221, MP470, and SB52334. Finally, we verified the effect of BNIP3 on apoptosis, proliferation, and migration of osteosarcoma cells through experiments. CONCLUSIONS: This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

Gambogenic acid induces cell death in human osteosarcoma through altering iron metabolism, disturbing the redox balance, and activating the P53 signaling pathway.

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents with extremely poor prognosis. Gambogenic acid (GNA), one of the major bioactive ingredients isolated from Gamboge, has been shown to possess a multipotent antitumor effect, its activity on OS remains unclear yet. In this study, we found that GNA could trigger multiple cell death modalities, including ferroptosis and apoptosis in human OS cells, reduce the cell viability, inhibit the proliferation and invasiveness. Furthermore, GNA provoked oxidative stress leading to GSH depletion-inducing ROS generation and lipid peroxidation, altered iron metabolism represented by the induction of labile iron, mitochondrial membrane potential decreased, mitochondrial morphological changed, decreased the cell viability. In addition, ferroptosis inhibitors (Fer-1) and apoptosis inhibitors (NAC) can partially reversed GNA' s effects on OS cells. Further investigation showed that GNA augmented the expression of P53, bax, caspase 3 and caspase 9 and decreased the expression of Bcl-2, SLC7A11 and glutathione peroxidase-4 (GPX4). In vivo, GNA was showed to delay tumor growth significantly in axenograft osteosarcoma mouse model. In conclusion, this study reveals that GNA simultaneously triggers ferroptosis and apoptosis in human OS cells by inducing oxidative stress via the P53/SLC7A11/GPX4 axis.