The role of LOXL2 in tumor progression, immune response and cellular senescence: a comprehensive analysis.

LOXL2, an enzyme belonging to the LOX family, facilitates the cross-linking of extracellular matrix (ECM) elements. However, the roles of the LOXL2 gene in mechanisms of oncogenesis and tumor development have not been clearly defined. In this pan-cancer study, we examined the notable disparity in LOXL2 expression at the mRNA and protein levels among various cancer types and elucidated its interconnected roles in tumor progression, mutational profile, immune response, and cellular senescence. Apart from investigating the hyperexpression of LOXL2 being related to poorer prognosis in different types of tumors, this study also unveiled noteworthy connections between LOXL2 and genetic mutations, infiltration of tumor immune cells, and genes in immune checkpoint pathways. Further analysis revealed the participation of LOXL2 in multiple pathways related to cancer extracellular matrix remodeling and cellular senescence. Moreover, our investigation uncovered that the knockdown and inhibition of LOXL2 significantly attenuated the proliferation and migration of PC-9 and HCC-LM3 cells. The knock-down and inhibition of LOXL2 enhanced cellular senescence in lung and liver cancer cells, as confirmed by SA-ß-Gal staining and quantitative RT-PCR analyses. This comprehensive analysis offers valuable insights on the functions of LOXL2 in different types of cancer and its role in regulating the senescence of cancer cells.

Measurement properties of health-related quality of life measures for people living with metastatic disease of the spine: a systematic review.

PURPOSE: Patients with spinal metastases (SM) suffer from a significant quality of life (QoL) deterioration. The measurement of QoL has garnered significant attention. In this study, the authors aimed to investigate the frequency of QoL measurement, systematically appraise the measurement properties of identified instruments, and facilitate the effective selection of an appropriate QoL instrument for patients with SM. METHODS: This systematic review adhered to the newly revised Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. The methodological quality of the studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Measurement property results were assessed using the adapted criteria. Each measurement property was allocated a separate rating (excellent, good, fair, or poor). 'Best evidence synthesis' was performed using COSMIN outcomes and the quality of findings. RESULT: Two hundred and nine publications were included, and 18 instruments were identified. ECOG, EuroQol-5D, SF-36, SOSGOQ, and EORTC-QLQ-C30 were the top five instruments used for patients with SM in published literature. The measurement properties evaluated included internal consistency (four instruments), reliability (three instruments), validity (five instruments), validity (nine measures), floor and ceiling effects (four instruments), responsiveness (four instruments), and interpretability (three measures). Based on the limited evidence, the Brief Pain Inventory (BPI) had the best methodological quality. CONCLUSIONS: Owing to the limitations of BPI in assessment domains, we cannot fully support the use of BPI. For the lack of high-quality research, it is challenging to nominate a single appropriate measure. Additional studies are needed to explore the evidence before a confirmatory decision is made.

Surgical Treatments and Long-Term Outcomes for Pediatric Patients With Lumbar Spinal Tumors.

STUDY DESIGN: Retrospective case‒control study. OBJECTIVES: This study aimed to report the effects of surgical intervention on spinal stability recovery and to assess the long-term outcomes of children and adolescents with lumbar tumors. METHODS: From January 2016 to June 2021, 42 pediatric patients with lumbar tumors were selected and separated into different groups based on the surgical method used (total en bloc resection (TER) group, n = 21; piecemeal resection (PR) group, n = 21; titanium mesh (TM) group n = 23; artificial vertebrae (AV) group n = 19). The clinicopathological characteristics, treatments and related outcomes were described in detail and compared between groups, with P value ≤.05 indicating statistically significant differences. RESULTS: The average follow-up duration was 24.89 months, and the mean age was 14.89 ± 2.41 years. There were no significant differences in the mean operation time, average blood loss, complication rate, or length of hospital stay between the groups. The ODI, VAS and JOA scores at the final follow-up (FF) were elevated after surgery in all groups. The FF local angular drift (LOD) and lumbar angular drift (LUD) were greater in the TM group than in the AV group (P = .03, P = .001). CONCLUSIONS: After surgery, pediatric patients with lumbar tumors can obtain satisfactory spinal stability, effective relief of pain symptoms and substantial improvements in neurological function. There was no significant difference in the invasiveness, safety or timeliness between the 2 surgical methods, so TER is recommended due to its low postoperative recurrence rate and good local control. Spinal fusion in the AV group resulted in better spinal stability.

PRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2.

Methionine is an essential branch of diverse nutrient inputs that dictate mTORC1 activation. In the absence of methionine, SAMTOR binds to GATOR1 and inhibits mTORC1 signaling. However, how mTORC1 is activated upon methionine stimulation remains largely elusive. Here, we report that PRMT1 senses methionine/SAM by utilizing SAM as a cofactor for an enzymatic activity-based regulation of mTORC1 signaling. Under methionine-sufficient conditions, elevated cytosolic SAM releases SAMTOR from GATOR1, which confers the association of PRMT1 with GATOR1. Subsequently, SAM-loaded PRMT1 methylates NPRL2, the catalytic subunit of GATOR1, thereby suppressing its GAP activity and leading to mTORC1 activation. Notably, genetic or pharmacological inhibition of PRMT1 impedes hepatic methionine sensing by mTORC1 and improves insulin sensitivity in aged mice, establishing the role of PRMT1-mediated methionine sensing at physiological levels. Thus, PRMT1 coordinates with SAMTOR to form the methionine-sensing apparatus of mTORC1 signaling.

Prognostic factors of sarcomas occurring in bone and joint: A SEER based study.

To clarify the epidemiology, treatment, and prognosis of sarcomas occurring in the bones and joints. The surveillance, epidemiology, and end results (SEER) 18 registries, comprising sarcoma diagnoses made between 2008 and 2014, were queried for sarcomas arising in bones or joints. Kaplan-Meier analysis, multivariate logistic regression analysis, Cox proportional hazards model, and nomograms were used to identify prognostic factors. 2794 patients aged from 1 to 99 (55.8% male) with microscopically confirmed diagnosed as sarcomas (including osteosarcoma, chondrosarcoma, Ewing sarcoma, and soft tissue sarcomas) which primary site limited to bone and joint were identified. Eight independent factors, including age, race, sex, tumor site, histology, pathology grade, tumor size, and total number of malignant tumors (TNOMT), were associated with tumor metastasis. Nine independent prognostic factors, including age (>=60 year, hazard ratio [HR] = 4.145, 95% confidence interval [CI], P < .001), sex (female, HR = 0.814, 95%CI, P = .007), tumor site (spine, HR = 2.527, 95%CI, P < .001), histology, pathology grade (undifferentiated, HR = 5.816, 95%CI, P < .001), tumor size (>=20 cm, HR = 3.043, 95%CI, P < .001), tumor extent (distant, HR = 4.145, 95%CI, P < .001), surgery (no performed, HR = 2.436, 95%CI, P < .001), and TNOMT (1, HR = 0.679, 95%CI, P < .001, were identified and incorporated to construct a nomogram for 2- and 5-year overall survival (OS). The calibration curve for the probability of survival showed good agreement between prediction by the nomogram and actual observation. The C-index of the nomogram for survival prediction was 0.814. Patients who received chemotherapy had a significantly decreased risk of death only for Ewing sarcoma, poorly differentiated tumors, undifferentiated tumors, and distant tumor invasion (P < .05). However, radiotherapy did not show significant differences in OS. This study presents population-based estimates of prognosis for patients with bone sarcomas and demonstrates the impact of age, race, sex, tumor site, histology, pathology grade, tumor size, tumor extent, surgery, radiotherapy, chemotherapy, and the TNOMT on OS. Moreover, the nomogram resulted in a more accurate prognostic prediction. However, in our study, radiotherapy showed no survival benefit, perhaps because detailed data on treatment factors were unavailable and which may have influenced the results.

Mechanical Behavior of Anchor Bolts for Shallow Super-Large-Span Tunnels in Weak Rock Mass.

Based on the Xiabeishan No.2 tunnel project of the Hang-Shao-Tai high-speed railway in China, the mechanical behavior of the anchor bolts for shallow super-large-span (SSLS) tunnels in weak rock mass is comprehensively investigated through laboratory tests, numerical simulation, and field tests. Firstly, an eight-month field test is conducted in the Xiabeishan No.2 tunnel, and it is discovered that the blasting vibration created by the construction of the middle pilot tunnel caused serious damage to the temporary support, seriously affecting the development of the bolt axial force and causing great construction risks. Then, the refined finite difference model of the SSLS tunnels is formulated, and a series of field and laboratory tests are conducted to acquire the calculation parameters. By comparing the monitored and simulated bolt axial force, the reliability of the numerical model is verified. Subsequently, the influence of the rock condition, construction scheme and bolt length on the mechanical behavior of anchor bolts is discussed. It is revealed that the rock grade significantly affects the bearing characteristics of anchor bolts. The construction scheme can greatly affect the magnitude and development mode of the bolt axial force, but the final distribution characteristics of the bolt axial force do not change regardless of the construction sequence. The axial force of the anchor bolts grows rapidly with the bolt length when the bolt length is within 18 m; meanwhile, when the bolt length exceeds 18 m, increasing the bolt length has a limited effect on the improvement in the bolt support performance. Finally, some optimization measures are proposed according to the monitoring data and simulation results.

Thyroid function and associated mood changes after COVID-19 vaccines in patients with Hashimoto thyroiditis.

Context: Severe acute respiratory syndrome-coronavirus 2 (COVID-19) vaccines may incur changes in thyroid functions followed by mood changes, and patients with Hashimoto thyroiditis (HT) were suggested to bear a higher risk. Objectives: We primarily aim to find whether COVID-19 vaccination could induce potential subsequent thyroid function and mood changes. The secondary aim was to find inflammatory biomarkers associated with risk. Methods: The retrospective, multi-center study recruited patients with HT receiving COVID-19-inactivated vaccines. C-reactive proteins (CRPs), thyroid-stimulating hormones (TSHs), and mood changes were studied before and after vaccination during a follow-up of a 6-month period. Independent association was investigated between incidence of mood state, thyroid functions, and inflammatory markers. Propensity score-matched comparisons between the vaccine and control groups were carried out to investigate the difference. Results: Final analysis included 2,765 patients with HT in the vaccine group and 1,288 patients in the control group. In the matched analysis, TSH increase and mood change incidence were both significantly higher in the vaccine group (11.9% versus 6.1% for TSH increase and 12.7% versus 8.4% for mood change incidence). An increase in CRP was associated with mood change (p< 0.01 by the Kaplan-Meier method) and severity (r = 0.75) after vaccination. Baseline CRP, TSH, and antibodies of thyroid peroxidase (anti-TPO) were found to predict incidence of mood changes. Conclusion: COVID-19 vaccination seemed to induce increased levels and incidence of TSH surge followed by mood changes in patients with HT. Higher levels of pre-vaccine serum TSH, CRP, and anti-TPO values were associated with higher incidence in the early post-vaccine phase.

Ring domains are essential for GATOR2-dependent mTORC1 activation.

The GATOR2-GATOR1 signaling axis is essential for amino-acid-dependent mTORC1 activation. However, the molecular function of the GATOR2 complex remains unknown. Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, via interacting with Ring domains of WDR59 and WDR24, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity, disruption of which leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24 and confers its availability to UBE2D3 and subsequent ubiquitination of NPRL2, contributing to GATOR2-mediated GATOR1 inactivation. As such, WDR24 ablation or Ring deletion prevents mTORC1 activation, leading to severe growth defects and embryonic lethality at E10.5 in mice. Hence, our findings demonstrate that Ring domains are essential for GATOR2 to transmit amino acid availability to mTORC1 and further reveal the essentiality of nutrient sensing during embryonic development.

Surgical efficacy and survival prediction of patients with unspecified malignant bone tumors.

BACKGROUND: The surgical efficacy and prognostic outcomes of patients with unspecific malignant bone tumors (UMBTs) remain unclear. The study is to address: 1) What are the clinicopathological features and prognostic determinants for patients with UMBTs? 2) Can a nomogram be developed for clinicians to predict the short and long-term outcomes for individuals with UMBTs? 3) Does surgery improve outcomes for UMBT patients who received radiotherapy or chemotherapy after balancing the confounding bias? METHODS: 400 UMBT patients were filtrated from the Surveillance, Epidemiology, and End Results database to assess the clinicopathological features, treatments, and factors affecting prognosis. The optimal cutoff values of continuous variables were identified by the x-tile software. Kaplan-Meier method and multivariate Cox proportional hazard modeling were performed to evaluate the independent prognostic factors. Nomogram was further developed by using R software with rms package. The surgical efficacy was further assessed for patients receiving radiotherapy or chemotherapy after performing propensity score matching. RESULTS: The enrolled cohort included 195 (48.8%) female and 205 (51.2%) male patients. The 2- and 5-year cancer-specific survival (CSS) and overall survival (OS) rate were 58.2 ± 3.0%, 46.8 ± 3.2%, and 46.5 ± 2.6%, 34.4 ± 2.5%, respectively. Nomogram was finally developed for CSS and OS according to the identified independent factors: age, tumor extent, primary tumor surgery, tumor size, and pathology grade. For UMBT patients who received radiotherapy or chemotherapy, surgical intervention was associated with better CSS (pr = 0.003, pc = 0.002) and OS (pr = 0.035, pc = 0.002), respectively. CONCLUSIONS: Nomogram was developed for individual UMBT patient to predict short and long-term CSS and OS rate, and more external patient cohorts are warranted for validation. Surgery improves outcomes for UMBT patients who received either radiotherapy or chemotherapy.

Identification of ATG7 as a Regulator of Proferroptosis and Oxidative Stress in Osteosarcoma.

Background: Ferroptosis has gained significant attention from oncologists as a vital outcome of oxidative stress. The aim of this study was to develop a prognostic signature that was based on the ferroptosis-related genes (FRGs) for osteosarcoma patients and explore their specific role in osteosarcoma. Methods: The training cohort dataset was extracted from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Different techniques like the univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, multivariate Cox regression analyses, and the Kaplan-Meier (KM) survival analyses were utilized to develop a prognostic signature. Then, the intrinsic relationship between the developed gene signature and the infiltration levels of the immune cells was further investigated. An external validation dataset from the Gene Expression Omnibus (GEO) database was employed to assess the predictive ability of the developed gene signature. Subsequently, the specific function of potential FRG in affecting the oxidative stress reaction and ferroptosis of osteosarcoma cells was identified. Results: A prognostic signature based on 5 FRGs (CBS, MUC1, ATG7, SOCS1, and PEBP1) was developed, and the patients were classified into the low- and high-risk groups (categories). High-risk patients displayed poor overall survival outcomes. The risk level was seen to be an independent risk factor for determining the prognosis of osteosarcoma patients (p < 0.001, hazard ratio: 7.457, 95% CI: 3.302-16.837). Additionally, the risk level was associated with immune function, which might affect the survival status of osteosarcoma patients. Moreover, the findings of the study indicated that the expression of ATG7 was related to the regulation of oxidative stress in osteosarcoma. Silencing the ATG7 gene promoted the proliferation and migration in osteosarcoma cells, suppressing the oxidative stress and ferroptosis process. Conclusions: A novel FRG signature was developed in this study to predict the prognosis of osteosarcoma patients. The results indicated that ATG7 might regulate the process of oxidative stress and ferroptosis in osteosarcoma cells and could be used as a potential target to develop therapeutic strategies for treating osteosarcoma.

Sacral Ewing sarcoma with rib, lung, and multifocal skull metastases: A rare case report and review of treatments.

Ewing sarcoma (ES) rarely derives from the sacrum or mobile spine. The discovery of primary ES with multimetastatic involvements is exceedingly less frequent in clinical practice. A 23-year-old man with initial primary sacral ES developed metastases of rib, lung, and multifocal skull after receiving surgical intervention and series of adjuvant therapies. We provide this very rare case consisting of its clinical features, imaging findings, treatments, and outcomes. Therapeutic modalities of ES are also reviewed in previous published articles. The prognosis of metastatic ES remains dismal; effective therapeutic modalities for ES require multidisciplinary collaboration, with more high-quality clinical trials to promote the optimal protocols.

A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma.

The therapeutic strategy of Ewing sarcoma (EWS) remains largely unchanged over the past few decades. Hypoxia is reported to have an impact on tumor cell progression and is regarded as a novel potential therapeutic target in tumor treatment. This study aimed at developing a prognostic gene signature based on hypoxia-related genes (HRGs). EWS patients from GSE17674 in the GEO database were analyzed as a training cohort, and differently expressed HRGs between tumor and normal samples were identified. The univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used in this study. A total of 57 EWS patients from the International Cancer Genome Consortium (ICGC) database were set as the validation cohort. A total of 506 differently expressed HRGs between tumor and normal tissues were identified, among which 52 were associated with the prognoses of EWS patients. Based on 52 HRGs, EWS patients were divided into two molecular subgroups with different survival statuses. In addition, a prognostic signature based on 4 HRGs (WSB1, RXYLT1, GLCE and RORA) was constructed, dividing EWS patients into low- and high-risk groups. The 2-, 3- and 5-years area under the receiver operator characteristic curve of this signature was 0.913, 0.97 and 0.985, respectively. It was found that the survival rates of patients in the high-risk group were significantly lower than those in the low-risk group (p < 0.001). The risk level based on the risk score could serve as an independent clinical factor for predicting the survival probabilities of EWS patients. Additionally, antigen-presenting cell (APC) related pathways and T cell co-inhibition were differently activated in two risk groups, which may result in different prognoses. CTLA4 may be an effective immune checkpoint inhibitor to treat EWS patients. All results were verified in the validation cohort. This study constructed 4-HRGs as a novel prognostic marker for predicting survival in EWS patients.

Peoniflorin Preconditioning Protects Against Myocardial Ischemia/Reperfusion Injury Through Inhibiting Myocardial Apoptosis: RISK Pathway Involved.

Preconditioning with Peoniflorin, a component of traditional Chinese prescriptions, was proposed to be a potential strategy for cardioprotection against ischemia/reperfusion (I/R) injury. However, the cardioprotective effect of Peoniflorin preconditioning has not been thoroughly confirmed, and the underlying mechanism remains unclear. Here, we examined the cardioprotective effect and its mechanism of Peoniflorin preconditioning against myocardial I/R injury. Rats were subjected to 30 min of transient ischemia followed by 2 h of reperfusion with or without Peoniflorin (100 mg/kg) prior to reperfusion. Peoniflorin preconditioning significantly limited myocardial infarct size and reperfusion arrhythmias, as well as obviously attenuated the histomorphological and micromorphological damages induced by I/R injury. The reduced myocardial injury was also associated with the anti-apoptotic effect of Peoniflorin, as evidence by decreased TUNEL-positive cells, upregulation of BCL-2 expression, and downregulation of Bax and caspase-3 expression. In an effort to evaluate the mechanism responsible for the observed cardioprotective and anti-apoptotic effect, Western blot of phosphorylated protein was performed after 20 min of reperfusion. Results showed that Peoniflorin preconditioning activated both the Akt and ERK1/2 arm of the reperfusion injury salvage kinase (RISK) pathway. To further confirm this mechanism, the PI3K signaling inhibitor LY294002 and ERK1/2 signaling inhibitor PD98059 were administered in vivo. The cardioprotective and anti-apoptotic effects of Peoniflorin preconditioning were diminished but not abolished by pretreatment with LY294002 or PD98059. Taken together, these results indicate that Peoniflorin preconditioning protects the myocardial against I/R injury and inhibits myocardial apoptosis via the activation of the RISK pathway, highlighting the potential therapeutic effects of Peoniflorin on reducing myocardial I/R injury.

Acute spinal cord infarction after multilevel en bloc corpectomy: a case report and literature review.

Spinal cord infarction (SCI) is a catastrophic neurologic deficit following spine surgery. Because of the opposite management regimens used for SCI and acute epidural hematoma, accurate diagnosis of SCI is of great importance to maximally reserve neurologic functions and improve outcomes. A 21-year-old man developed acute paralysis and sensory deficits of the bilateral lower limbs shortly after undergoing two-stage combined posterior and anterior multilevel en bloc corpectomy. An emergency second-look surgery revealed wide-spectrum blackness of the thecal sac with no signs of an epidural hematoma. The patient underwent anticoagulation therapy, ventilation support, microcirculation perfusion, and fluid optimization. He regained an ambulatory status without other severe complications. Upon discharge, his muscle strength had returned to grade 4 and his Eastern Cooperative Oncology Group performance score had decreased to 0. At the final 48-month follow-up, the implants were in good position without local recurrence, and the patient was able to lead an independent life and work in his full capacity. An epidural hematoma did not appear to be the cause of SCI after spinal tumor surgery in this case; however, SCI was a possible reason for the acute paralysis. Anticoagulation treatment with adjuvant therapies may be an effective option in managing SCI.

Refractory recurrent spinal chondrosarcoma: What is the role of salvage surgery?

BACKGROUND: The spinal chondrosarcoma has high risk of recurrence if the initial surgery is not performed in an en bloc fashion. It remains technically demanding to surgically manage the refractory recurrent spinal chondrosarcoma (RRSC). This study is to assess the clinical features and investigate the prognostic factors for patients with RRSCs. METHODS: forty-nine patients with RRSCs underwent salvage surgeries in our institution, and the clinical characteristics were collected and recorded by two independent reviewers. Univariate and multivariate analyses were performed to investigate the independent prognostic factors of recurrence-free survival (RFS) and overall survival (OS) for patients with RRSCs. RESULTS: During the mean follow-up of 31.7 ± 21.04 months (Range 9-93), the 3-year RFS and OS rate was 24.5% and 34.5%, respectively. According to the Cox proportional hazards regression model, wide excision with tumor-free margin (>4 mm) was associated with both better RFS and OS for patients with RRSCs. Meanwhile, the number of recurrences ≤2 was beneficial to RFS, while high pathological grade was correlated with worse OS. CONCLUSIONS: Wide excision with tumor-free margin (>4 mm) is recommendable if appropriate in the salvage surgery for patients with RRSCs. Patients with number of recurrences ≤ 2 and lower pathological grade may have better RFS and OS, respectively.

Identifying the Risk Factors and Estimating the Prognosis in Patients with Pelvis and Spine Ewing Sarcoma: A Population-Based Study.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: The study was designed to: (1) figure out risk factors of metastasis; (2) explore prognostic factors and develop a nomogram for pelvis and spine Ewing sarcoma (PSES). SUMMARY OF BACKGROUND DATA: Tools to predict survival of PSES are still insufficient. Nomogram has been widely developed in clinical oncology. Moreover, risk factors of PSES metastasis are still unclear. METHODS: The data were collected and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff values of continuous variables were identified by X-tile software. The prognostic factors of survival were performed by Kaplan-Meier method and multivariate Cox proportional hazards modeling. Nomograms were further constructed for estimating 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) by using R with rms package. Meanwhile, Pearson χ2 test or Fisher exact test, and logistic regression analysis were used to analyze the risk factors for the metastasis of PSES. RESULTS: A total of 371 patients were included in this study. The 3- and 5-year CSS and OS rate were 65.8 ±â€Š2.6%, 55.2 ±â€Š2.9% and 64.3 ±â€Š2.6%, 54.1 ±â€Š2.8%, respectively. The year of diagnosis, tumor size, and lymph node invasion were associated with metastasis of patients with PSES. A nomogram was developed based on identified factors including: age, tumor extent, tumor size, and primary site surgery. The concordance index (C-index) of CSS and OS were 0.680 and 0.679, respectively. The calibration plot showed the similar trend of 3-year, 5-year CSS, and OS of PSES patients between nomogram-based prediction and actual observation, respectively. CONCLUSION: PSES patients with earlier diagnostic year (before 2010), larger tumor size (>59 mm), and lymph node invasion, are more likely to have metastasis. We developed a nomogram based on age, tumor extent, tumor size, and surgical treatments for determining the prognosis for patients with PSES, while more external patient cohorts are warranted for validation.Level of Evidence: 3.

Longitudinal Deformation of Deep Shield Tunnels Caused by Upper Load Reduction.

Above-crossing excavations may cause uplift damages on existing shield tunnels. Therefore, to accurately calculate the deformation of shield tunnels is very necessary for geotechnical engineers. At present, the single-sided elastic foundation beam model is usually used in longitudinal deformation calculations for shield tunnels, which overestimates the uplift of deep shield tunnels. Because of the existence of the ground arch, deep shield tunnels are subjected to two-sided foundation reaction forces. Therefore, this paper proposes a partial missing double-sided elastic foundation beam model and the related fourth-order partial differential equations. In this model, the shield tunnel is subjected to double Winkler foundation springs and is simply considered a Euler-Bernoulli beam. A two-stage analysis method is used to solve the problem. First, the vertical unloading stress due to the above-crossing tunnelling at the tunnel location is calculated through Mindlin's solution. Second, the deformation response of the beam subjected to an unloading stress is calculated by the finite difference method. Two engineering cases are used to verify the research. The results indicate that the proposed model is more accurate than traditional models in predicting the maximum uplift value, which is basically consistent with the observations. Due to the existence of segment staggering, the longitudinal influence range of the calculation by two models is larger than the actual measurement.

Symptomatic spinal metastases from neuroendocrine neoplasms: surgical outcomes and prognostic analysis.

OBJECTIVES: In this article, we investigated the efficiency of surgery in treating symptomatic spinal metastases from neuroendocrine neoplasms and performed univariate analysis for identification of possible prognostic factors. METHODS: A retrospective study was performed, enrolling a total of 19 patients who received surgeries in our center for symptomatic spinal metastases from neuroendocrine neoplasms (NEN). The Kaplan-Meier method was adopted to estimate overall survival (OS) and recurrence free survival (RFS). Univariate analysis was performed for identification of possible prognostic factors. RESULTS: All patients recruited displayed stable recovery after surgical intervention, with a median OS of 27.3 months (95% Confidence Interval: 16.4-38.1 months) and a median RFS of 23.0 months (95% Confidence Interval: 12.1-33.8 months). Postoperatively, 15 patients exhibited improved neurological function based on the Frankel classification, while 16 patients experienced significant pain relief, with mean visual analog scale (VAS) score decreasing from 7.47 ± 2.32-2.47 ± 1.25 (p < 0.05). Univariate analysis revealed that the presence of visceral metastases (p = 0.034) and extraspinal bone metastases (p = 0.016) are both related with poor prognosis. Additionally, well histologic differentiation (p = 0.010) and administration of postoperative octreotide (p = 0.041) or bisphosphonate (p = 0.023) are all indicators for better outcome. CONCLUSIONS: Surgery is an efficient option for treating symptomatic spinal metastases from NEN due to its immediate and assured benefits in pain alleviation, restoration of function and stability reconstruction.

Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade.

Aberrant energy status contributes to multiple metabolic diseases, including obesity, diabetes, and cancer, but the underlying mechanism remains elusive. Here, we report that ketogenic-diet-induced changes in energy status enhance the efficacy of anti-CTLA-4 immunotherapy by decreasing PD-L1 protein levels and increasing expression of type-I interferon (IFN) and antigen presentation genes. Mechanistically, energy deprivation activates AMP-activated protein kinase (AMPK), which in turn, phosphorylates PD-L1 on Ser283, thereby disrupting its interaction with CMTM4 and subsequently triggering PD-L1 degradation. In addition, AMPK phosphorylates EZH2, which disrupts PRC2 function, leading to enhanced IFNs and antigen presentation gene expression. Through these mechanisms, AMPK agonists or ketogenic diets enhance the efficacy of anti-CTLA-4 immunotherapy and improve the overall survival rate in syngeneic mouse tumor models. Our findings reveal a pivotal role for AMPK in regulating the immune response to immune-checkpoint blockade and advocate for combining ketogenic diets or AMPK agonists with anti-CTLA4 immunotherapy to combat cancer.

Interdisciplinary Surgical Treatments and Long-Term Outcomes of Lumbar Spinal Tumors With Retroperitoneal Involvements: A Retrospective Case Series Study.

PURPOSE: Surgical treatments are technically challenging for lumbar spinal tumor (LST) with extensive retroperitoneal involvements. Our study aimed to report the experience and outcomes concerning interdisciplinary surgical collaborations in managing such LSTs. PATIENTS AND METHODS: Nine patients underwent interdisciplinary surgical treatments which were performed by specialists, namely, spinal, vascular, and urinary surgeries. Data on clinical characteristics were collected, and the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association Score (JOAS) were used in the evaluation before and after surgery. The postoperative complications and the long-term outcomes were reported as well. RESULTS: The interdisciplinary work included double J catheter indwelling (n = 9), nephrostomy (n = 5), replacement of the common iliac vein (n = 2), abdominal aorta repair (n = 3), and vital vessel repair (n = 8). The early-stage complications included complaints of moderate low back pain and slight implant shift (n = 1, 11.1%) and tardive ureterodialysis (n = 1, 11.1%). The 3- and 5-year disease-free survival rates were 76.2 ± 14.8 and 50.8 ± 23.0%, respectively, during the mean follow-up of 34.6 ± 17.9 months (range, 9.5-68.7). Besides this, more blood loss was associated with recurrent and metastatic tumor status (p = 0.043) and surgery time >5 h (p = 0.023). Remarkable pain relief and favorable quality of life were achieved based on the postoperative VAS (3.3 ± 0.9, p < 0.001) and JOAS (16.6 ± 0.5, p < 0.001). CONCLUSIONS: The treatments of LSTs with wide-range retroperitoneal involvements require interdisciplinary surgical collaborations to lower the risks and improve the long-term outcomes. High-quality prospective cohort studies with large samples are warranted to establish general surgical protocols in managing LSTs with extensive retroperitoneal involvements.