Precise execution of personalized surgical planning using three-dimensional printed guide template in severe and complex adult spinal deformity patients requiring three-column osteotomy: a retrospective, comparative matched-cohort study.

BACKGROUND: The surgical treatment of severe and complex adult spinal deformity (ASD) commonly required three-column osteotomy (3-CO), which was technically demanding with high risk of neurological deficit. Personalized three dimensional (3D)-printed guide template based on preoperative planning has been gradually applied in 3-CO procedure. The purpose of this study was to compare the efficacy, safety, and precision of 3D-printed osteotomy guide template and free-hand technique in the treatment of severe and complex ASD patients requiring 3-CO. METHODS: This was a single-centre retrospective comparative cohort study of patients with severe and complex ASD (Cobb angle of scoliosis > 80° with flexibility < 25% or focal kyphosis > 90°) who underwent posterior spinal fusion and 3-CO between January 2020 to January 2023, with a minimum 12 months follow-up. Personalized computer-assisted three-dimensional osteotomy simulation was performed for all recruited patients, who were further divided into template and non-template groups based on the application of 3D-printed osteotomy guide template according to the surgical planning. Patients in the two groups were age- and gender- propensity-matched. The radiographic parameters, postoperative neurological deficit, and precision of osteotomy execution were compared between groups. RESULTS: A total of 40 patients (age 36.53 ± 11.98 years) were retrospectively recruited, with 20 patients in each group. The preoperative focal kyphosis (FK) was 92.72° ± 36.77° in the template group and 93.47° ± 33.91° in the non-template group, with a main curve Cobb angle of 63.35° (15.00°, 92.25°) and 64.00° (20.25°, 99.20°), respectively. Following the correction surgery, there were no significant differences in postoperative FK, postoperative main curve Cobb angle, correction rate of FK (54.20% vs. 51.94%, P = 0.738), and correction rate of main curve Cobb angle (72.41% vs. 61.33%, P = 0.101) between the groups. However, the match ratio of execution to simulation osteotomy angle was significantly greater in the template group than the non-template group (coronal: 89.90% vs. 74.50%, P < 0.001; sagittal: 90.45% vs. 80.35%, P < 0.001). The operating time (ORT) was significantly shorter (359.25 ± 57.79 min vs. 398.90 ± 59.48 min, P = 0.039) and the incidence of postoperative neurological deficit (5.0% vs. 35.0%, P = 0.018) was significantly lower in the template group than the non-template group. CONCLUSION: Performing 3-CO with the assistance of personalized 3D-printed guide template could increase the precision of execution, decrease the risk of postoperative neurological deficit, and shorten the ORT in the correction surgery for severe and complex ASD. The personalized osteotomy guide had the advantages of 3D insight of the case-specific anatomy, identification of osteotomy location, and translation of the surgical planning or simulation to the real surgical site.

U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression.

BACKGROUND: Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. METHODS: SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. RESULTS: SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. CONCLUSION: U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.

Impact of HER2 status on clinicopathological characteristics and pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: HER2-low triple-negative breast cancer (TNBC) accounted for up to 34%-39% of primary TNBC and 22.2%-32% of metastatic TNBC. Our study aims to explore the relationship between HER2 expression and clinicopathological characteristics, analyze the impact of HER2 expression on the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in TNBC. METHODS: This study involved 191 patients with TNBC who underwent operation after NAC from October 2021 to August 2022. Clinicopathological characteristics and the frequency of pCR were compared between HER2-low and HER2-0 TNBC. RESULTS: 42.2% (81/191) patients in our cohort were HER2-low. They exhibited differences in menopausal status, body mass index (BMI), androgen receptor (AR) expression, and histological grade (P < 0.05). Particularly, in HER2-low TNBC, AR was associated with tumor size, lymph node metastase, histological grade, and the incidence of multifocal disease (P < 0.05). The total pCR rate of entire cohor was 39.8%. Tumor size (P = 0.025), AR status (P = 0.033) and histological grade (P = 0.007) were significantly associated with the pCR rate of them, while the HER2 status did not exert a similar association. The multivariate analysis revealed that BMI (P = 0.004) and histological grade (P < 0.001) were associated with pCR of HER2-low TNBC, while tumor size (P = 0.034) and AR (P = 0.034) were associated with pCR of HER2-0 TNBC, respectively. CONCLUSIONS: In our cohort, HER2-low TNBC patients exhibits specific clinical characteristics and response features to NAC.

Cellular senescence in chronic lung diseases from newborns to the elderly: An update literature review.

The role of cellular senescence in age-related diseases has been fully recognized. In various age-related-chronic lung diseases, the function of alveolar epithelial cells (AECs) is impaired and alveolar regeneration disorders, especially in bronchopulmonary dysplasia，pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), cancer, etc. Except for age-related-chronic lung diseases, an increasing number of studies are exploring the role of cellular senescence in developmental chronic lung diseases, which typically originate in childhood and even in the neonatal period. This review provides an overview of cellular senescence and lung diseases from newborns to the elderly, attempting to draw attention to the relationship between cellular senescence and developmental lung diseases.

The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

Effects of food-grade iron(III) oxide nanoparticles on cecal digesta- and mucosa-associated microbiota and short-chain fatty acids in rats.

Although iron(III) oxide nanoparticles (IONPs) are widely used in diverse applications ranging from food to biomedicine, the effects of IONPs on different locations of gut microbiota and short-chain fatty acids (SCFAs) are unclear. So, a subacute repeated oral toxicity study on Sprague Dawley (SD) rats was performed, administering low (50 mg/kg·bw), medium (100 mg/kg·bw), and high (200 mg/kg·bw) doses of IONPs. In this study, we found that a high dose of IONPs increased animal weight, and 16S rRNA sequencing revealed that IONPs caused intestinal flora disorders in both the cecal digesta- and mucosa-associated microbiota. However, only high-dose IONP exposure changed the abundance and composition of the mucosa-associated microbiota. IONPs increased the relative abundances of Firmicutes, Ruminococcaceae_UCG-014, Ruminiclostridium_9, Romboutsia, and Bilophila and decreased the relative abundance of Bifidobacterium, and many of these microorganisms are associated with weight gain, obesity, inflammation, diabetes, and mucosal damage. Functional analysis showed that changes in the gut microbiota induced by a high dose of IONPs were mainly related to metabolism, infection, immune, and endocrine disease functions. IONPs significantly elevated the levels of valeric, isobutyric, and isovaleric acid, promoting the absorption of iron. This is the first description of intestinal microbiota dysbiosis in SD rats caused by IONPs, and the effects and mechanisms of action of IONPs on intestinal and host health need to be further studied and confirmed.

Evaluation of bone mineral density in adolescent idiopathic scoliosis using a three-dimensional finite element model: a retrospective study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is often accompanied by osteopenia and osteoporosis, which can cause serious complications. The aim of this study was to determine the specific bone mineral density (BMD) of each vertebral body in patients with AIS using biomechanical finite element modeling based on three-dimensional (3D) reconstruction. METHODS: This retrospective study involved 56 patients with AIS. Computed tomography (CT) and radiography were performed. Spinal vertebrae were segmented from the spinal CT images of patients with AIS to reconstruct 3D vertebral models. The vertebral models were meshed into tetrahedral finite elements to assess the BMD. RESULTS: The mean main curve Cobb angle was 88.6 ± 36.7°, and the mean kyphosis angle was 36.8 ± 31.5°. The mean BMD of the global spine was 0.83 ± 0.15 g/cm2. The highest BMD was measured on the concave side of the apex (0.98 ± 0.16 g/cm2). Apical vertebral BMD was negatively correlated with age and height (r = - 0.490, p = 0.009 and r = - 0.478, p = 0.043, respectively). There were no significant differences in BMD values between the concave and convex sides (p > 0.05). CONCLUSIONS: The 3D finite element modeling of BMD in patients with AIS is a reliable and accurate BMD measurement method. Using this method, the overall BMD of patients with AIS was shown to gradually decrease from the top to the bottom of the spine. Our findings provide valuable insights for surgical planning, choice of screw trajectories, and additional biomechanical analyzes using finite element models in the context of scoliosis.

Case Report: Non-negligible Epstein-Barr virus-associated posttransplant lymphoproliferative disorders in a lung transplant recipient.

Background: Posttransplant lymphoproliferative disorders (PTLDs) are uncommon but serious complications in patients following solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is a risk factor for the development of PTLD, especially early-onset PTLD, in EBV-negative recipients. To date, however, there are no specific guidelines on the threshold of EBV-DNA load for therapeutic intervention, the source for measurement (e.g., blood, bronchoalveolar fluid), or the use of antiviral agents as prophylaxis for early PTLD prevention in EBV-mismatched patients. Methods: The present study describes a 56-year-old male lung transplant recipient diagnosed with EBV-associated PTLD. Results: This patient had a history of invasive fungal disease and Mucor and Aspergillus fumigatus infections in the early post-transplant period, necessitating antifungal therapy throughout the course of the disease. The patient was EBV-positive 15 days after transplantation, with lung CT showing multiple bilateral nodules of varying sizes beginning 98 days after transplantation. A lung biopsy showed PTLD, and next-generation sequencing (NGS) revealed EBV. This patient, however, did not receive any antiviral therapy for early PTLD prevention or any PTLD-related treatment. He died 204 days after lung transplantation. Conclusion: The present study describes a lung transplant recipient who developed EBV-associated PTLD, a non-negligible disease, after solid organ transplantation. Monitoring EBV-DNA load is important, as a sudden increase may be a sensitive indicator of PTLD. An earlier diagnosis may increase the likelihood of successful treatment.

Activation of kappa opioid receptor (KOR) inhibits estrogen receptor (ER)-positive breast cancer through the KOR-ER-XBP1 pathway.

Opioids are commonly used in patients with breast cancer (BC), both for perioperative analgesia and for the relief of chronic cancer pain. Studies have suggested a potential association of opioid receptors (ORs) with the prognosis of BC patients. However, the exact roles of different ORs remain poorly understood. In this study, we found that κ opioid receptor (KOR) was the only OR (among the four types of ORs) that was significantly decreased in BC tumor tissues compared with peritumoral normal tissues. In addition, decreased expression of KOR correlated with poor clinical outcomes in patients with estrogen receptor (ER)-positive BC. In vitro studies confirmed the anti-tumor effects of KOR agonists in ER-positive MCF-7 and T47D cells by showing that activation of KOR significantly inhibited cellular proliferation and promoted apoptosis. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network (PPI) analysis, we found that KOR-ER-XBP1 was the potential downstream signaling pathway mediating the anti-tumor effects of KOR agonist. Finally, the role of XBP1 was confirmed as KOR activation-induced increase in the proliferative and monoclonal formation abilities of ER-positive BC cells were both significantly abolished after silencing of XBP1. These findings provide us a better understanding of the roles of different ORs in BC, identifying KOR agonists as better opioids than traditional µ opioid receptor (MOR) agonists for providing analgesia in ER-positive BC patients owing to their association with better prognosis.

Evaluation of Pulmonary Function After Halo-Pelvic Traction for Severe and Rigid Kyphoscoliosis Utilizing CT with 3D Reconstruction.

BACKGROUND: The purpose of the present study was to evaluate changes in pulmonary function, caused by preoperative halo-pelvic traction (HPT) for the treatment of extremely severe and rigid kyphoscoliosis, with use of 3-dimensional computed tomography (3D-CT) reconstruction and pulmonary function tests (PFTs). METHODS: Twenty-eight patients with severe and rigid scoliosis (Cobb angle, >100°) underwent preoperative HPT and staged posterior spinal fusion. CT, radiographic assessment, and PFT were performed during pre-traction and post-traction visits. The changes in total lung volume were evaluated with use of 3D-CT reconstruction, and the changes in pulmonary function were evaluated with PFTs at each time point. Differences were analyzed with use of 2-tailed paired Student t tests, and correlations were analyzed with use of Spearman rank tests. RESULTS: None of the patients had pulmonary complications during traction, and all radiographic spinal measurements improved significantly after HPT. The main Cobb angle was corrected from 143.30° ± 20.85° to 62.97° ± 10.83° between the pre-traction and post-traction evaluations. Additionally, the C7-S1 distance was lengthened from 280.48 ± 39.99 to 421.26 ± 32.08 mm between the pre-traction and post-traction evaluations. Furthermore, 3D lung reconstruction demonstrated a notable increase in total lung volume (TLV) (from 1.30 ± 0.25 to 1.83 ± 0.37 L) and maximum lung height (from 176.96 ± 27.44 to 202.31 ± 32.45 mm) between the pre-traction and post-traction evaluations. Moreover, PFTs showed that total lung capacity (TLC) improved between the pre-traction and post-traction evaluations (from 2.06 ± 0.32 to 2.98 ± 0.82 L) and that the changes in T1-T12 distance and maximum lung height were correlated with changes in TLV (p = 0.0288 and p = 0.0007, respectively). CONCLUSIONS: The application of HPT is a safe and effective method for improving pulmonary function in patients with extremely severe and rigid scoliosis before fusion surgery. The TLV as measured with CT-based reconstruction was greatly increased after HPT, mainly because of the changes in thoracic height. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Suppression of Secondary Electron Emission from Nickel Surface by Graphene Composites Based on First-Principles Method.

Secondary electron emission (SEE) is a fundamental phenomenon of particle/surface interaction, and the multipactor effect induced by SEE can result in disastrous impacts on the performance of microwave devices. To suppress the SEE-induced multipactor, an Ni (111) surface covered with a monolayer of graphene was proposed and studied theoretically via the density functional theory (DFT) method. The calculation results indicated that redistribution of the electron density at the graphene/Ni (111) interface led to variations in the work function and the probability of SEE. To validate the theoretical results, experiments were performed to analyze secondary electron yield (SEY). The measurements showed a significant decrease in the SEY on an Ni (111) surface covered with a monolayer of graphene, accompanied by a decrease in the work function, which is consistent with the statistical evidence of a strong correlation between the work function and SEY of metals. A discussion was given on explaining the experimental phenomenon using theoretical calculation results, where the empty orbitals lead to an electron trapping effect, thereby reducing SEY.

Carbon intensity of global crude oil trading and market policy implications.

The energy mix transition has accelerated the need for more accurate emissions reporting throughout the petroleum supply chain. Despite increasing environmental regulations and pressure for emissions disclosure, the low resolution of existing carbon footprint assessment does not account for the complexity of crude oil trading. The lack of source crude traceability has led to poor visibility into the "well-to-refinery-entrance" carbon intensities at the level of granular pathways between producers and destination markets. Using high-fidelity datasets, optimization algorithms to facilitate supply chain traceability and bottom-up, physics-based emission estimators, we show that the variability in global "well-to-refinery-entrance" carbon intensities at the level of crude trade pathways is significant: 4.2-214.1 kg-CO2-equivalent/barrel with a volume-weighted average of 50.5 kg-CO2-equivalent/barrel. Coupled with oil supply forecasts under 1.5 °C scenarios up to 2050, this variability translates to additional CO2-equivalent savings of 1.5-6.1 Gigatons that could be realized solely by prioritizing low-carbon supply chain pathways without other capital-intensive mitigation measures.

UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy.

Autophagy have critical implications in the proliferation and metastasis of HCC. In the current study, we aimed to explore the underlying mechanisms of UHRF2 regulates HCC cells autophagy and HCC progression. We initially determined the relationship between UHRF2 and HCC autophagy, oncogenicity and patient survival through GSEA database and TCGA database. We mainly investigated the effect of UHRF2 on HCC development and autophagy through western blot, electron microscopy, and immunofluorescence. Functionally, UHRF2 was positively involved in the autophagy activation. Overexpression of UHRF2 reduced apoptosis in HCC cells, and promoted the malignancy phenotype of HCC both in vitro and in vivo. Mechanistically, PRDX1 bound to UHRF2 and upregulated its protein expression to facilitate the biological function of UHRF2 in HCC. Meanwhile, UHRF2 bound to autophagy-related protein PARP1 and upregulated PARP1 protein level. The results showed that UHRF2 promoted autophagy and contributed to the malignant phenotype of HCC by regulating PARP1 protein level. In summary, a novel interaction between PRDX1, UHRF2, and PARP1 was revealed, suggesting that UHRF2 could inspire a potential biomarker and potential therapeutic target for HCC.

HIF-1α/MMP-9 promotes spinal cord central sensitization in rats with bone cancer pain.

Bone cancer pain (BCP) is one of the most prevalent and serious symptoms of patients with cancer. Currently, the medical interventions used for the treatment of BCP do not act with optimal safety and efficacy. In this study, we appraised whether the hypoxia-inducible factor 1α (HIF-1α)/metalloproteinase-9 (MMP9) axis activates the PI3K/AKT pathway, resulting in elevated spinal cord central sensitization and aggravated BCP. BCP rats were established by tibial injection of Walker 256 cells, followed by different interventions in rats using HIF-1ɑ inhibitor LW6 or antibody treatments. After treatment with LW6 or antibody against HIF-1α, central sensitization in the spinal cord tissues of rats was inhibited, and pain perception in rats was reduced. Moreover, the activation of glial cells in the spinal cord tissues was ameliorated. The expression of MMP9 was remarkably suppressed in spinal cord tissues after inhibition of HIF-1ɑ activity, and the activity of the PI3K/AKT signaling pathway was inhibited. Further activation of MMP9 expression suppressed the alleviating effect of HIF-1ɑ inhibitor LW6 or antibody on pain perception in rats inoculated with tumors. Taken together, our studies suggest a HIF-1α/MMP9-mediated activation of PI3K/AKT in the spinal cord tissues, resulting in increased pain perception in a rat model with BCP.

Construction of HBV-HCC prognostic model and immune characteristics based on potential genes mining through protein interaction networks.

OBJECTIVE: To search for human protein-coding genes related to hepatocellular carcinoma (HCC) in the context of hepatitis B virus (HBV) infection, and perform prognosis risk assessment. METHODS: Genes related to HBV-HCC were selected through literature screening and protein-protein interaction (PPI) network database analysis. Prognosis potential genes (PPGs) were identified using Cox regression analysis. Patients were divided into high-risk and low-risk groups based on PPGs, and risk scores were calculated. Kaplan-Meier plots were used to analyze overall survival rates, and the results were predicted based on clinicopathological variables. Association analysis was also conducted with immune infiltration, immune therapy, and drug sensitivity. Experimental verification of the expression of PPGs was done in patient liver cancer tissue and normal liver tissue adjacent to tumors. RESULTS: The use of a prognosis potential genes risk assessment model can reliably predict the prognosis risk of patients, demonstrating strong predictive ability. Kaplan-Meier analysis showed that the overall survival rate of the low-risk group was significantly higher than that of the high-risk group. There were significant differences between the two subgroups in terms of immune infiltration and IC50 association analysis. Experimental verification revealed that CYP2C19, FLNC, and HNRNPC were highly expressed in liver cancer tissue, while UBE3A was expressed at a lower level. CONCLUSION: PPGs can be used to predict the prognosis risk of HBV-HCC patients and play an important role in the diagnosis and treatment of liver cancer. They also reveal their potential role in the tumor immune microenvironment, clinical-pathological characteristics, and prognosis.

Dexmedetomidine ameliorates liver injury and maintains liver function in patients with hepatocellular carcinoma after hepatectomy: a retrospective cohort study with propensity score matching.

Background: Although dexmedetomidine (DEX) is widely used during the perioperative period in patients with hepatocellular carcinoma (HCC), its clinical effects on liver function and postoperative inflammation are unclear. This study aimed to explore effects of DEX on postoperative liver function and inflammation in patients with HCC after hepatectomy. Methods: A retrospective cohort study with propensity score matching was performed. A total of 494 patients who underwent hepatectomy from June 2019 to July 2020 and fulfilled the eligibility criteria were included in this study. Baseline data, liver function indexes and inflammation-related biomarkers were collected and compared between the two groups. Survival analysis was conducted to investigate the effects of DEX on the overall survival (OS) of patients. Propensity score matching (PSM) was used to minimize bias between the two groups. Results: The study cohort comprised 189 patients in the DEX-free group and 305 patients in the DEX group. Patients in the DEX group had lower levels of alanine transaminase (ALT, P = 0.018) and lactate dehydrogenase (LDH, P = 0.046) and higher level of serum albumin (ALB, P < 0.001) than patients in the DEX-free group before discharge. A total of 107 pairs of patients were successfully matched by PSM. Results consistently suggested that ALT and LDH levels were significantly lower (P = 0.044 and P = 0.046, respectively) and ALB levels were significantly higher (P = 0.002) in the DEX group than in the DEX-free group in the early postoperative period. No significant differences of inflammation-related biomarkers were observed between two groups after PSM. Neither the Kaplan-Meier survival analysis nor the multiple Cox regression survival analysis identified DEX as a contributing factor that would affect the OS of patients after PSM. Conclusion: DEX exerts protective effects on liver function while has little effects on inflammation-related biomarkers in the early postoperative period in patients undergoing hepatectomy due to HCC.

Copper and cuproptosis-related genes in hepatocellular carcinoma: therapeutic biomarkers targeting tumor immune microenvironment and immune checkpoints.

Background: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear. Methods: We investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram. Results: A total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients' characteristics and risk scores. Conclusion: CRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.

Predictive value of systemic inflammatory markers for recurrence of papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of differentiated thyroid cancer. Early identification of patients at higher risk of recurrence may allow to improve relevant follow-up strategies and plan tailored treatment. Inflammation play an important role in the prognosis of cancer. We aimed to explore the predictive value of systemic inflammatory markers in PTC recurrence. METHODS: We retrospectively enrolled 200 consecutive patients who were diagnosed with PTC and underwent curative resection at Lianyungang Oriental Hospital between January 2006 and December 2018. Clinicopathological characteristics, preoperative hematologic results were analyzed. The optimal cutoff values were calculated using x-tile software. The multivariate logistic regression and univariable survival analysis were performed by SPSS. RESULTS: Multivariable analysis showed that lymph node metastases (odds ratio [OR] = 2.506, 95% confidence interval [CI]: 1.226-5.119, p = 0.012) and higher monocyte-to-lymphocyte ratio (MLR) (OR = 2.100, 95% CI: 1.042-4.233, p = 0.038) were independent prognostic factors for tumor recurrence. The cutoff value 0.22 of MLR significantly predicted recurrence at 53.3% sensitivity and 67.9% specificity. Patients with MLR ≥ 0.22 exhibited significantly poor long-term prognosis (46.8%) compared to the counterpart (76.8%, p = 0.0004). CONCLUSIONS: Preoperative MLR significantly predicted PTC recurrence after curative resection, which may provide clues for early identification of patients at higher risk of PTC recurrence.

Effect of K­line on posterior cervical surgery versus anterior cervical surgery in patients with multi-level ossification of posterior longitudinal ligament.

PURPOSE: To evaluate the influence of K-line on the outcome of open-door laminoplasty versus anterior cervical corpectomy decompression and fusion (ACCF) for patients with more than two levels of ossification of the posterior longitudinal ligament (OPLL). METHODS: 60 patients undergoing open-door laminoplasty and 62 patients undergoing ACCF from January 2013 to January 2020 with more than 2 years of follow-up were included. Eighty-four cases with the ossification mass not beyond the K-line were grouped as K-line (+), while thirty-eight cases were grouped as K-line (-). The operation time, intraoperative blood loss, hospital stay, preoperative, postoperative, and last follow-up JOA scores, and postoperative complications were investigated. RESULTS: The improvement rate of JOA scores after posterior approaches in cases of group K-line (+) and K-line (-) was 72.4% and 53.1%, respectively, which showed a significant difference (P < 0.01). In group K-line (+), the improvement of JOA scores for open-door laminoplasty was 73.4% and 71.8% for ACCF, which showed no significant difference (P > 0.05). In group K-line (-), the improvement of JOA scores for ACCF was 52.1% and 42.9% for open-door laminoplasty, which showed a significant difference (P < 0.05). The incidence of C5 palsy was significantly lower in cases with ACCF than in cases with open-door laminoplasty (P < 0.05). CONCLUSION: For patients with more than two levels of OPLL, preoperative K-line (+) predicates a better outcome than K-line (-). For cases with K-line (-), ACCF provides better neurologic function recovery. For patients with K-line (+), open-door laminoplasty provides the same neurologic function recovery of ACCF.

Clinical Application of Personalized Digital Surgical Planning and Precise Execution for Severe and Complex Adult Spinal Deformity Correction Utilizing 3D Printing Techniques.

(1) Background: The three-dimensional printing (3DP) technique has been reported to be of great utility in spine surgery. The purpose of this study is to report the clinical application of personalized preoperative digital planning and a 3DP guidance template in the treatment of severe and complex adult spinal deformity. (2) Methods: eight adult patients with severe rigid kyphoscoliosis were given personalized surgical simulation based on the preoperative radiological data. Guidance templates for screw insertion and osteotomy were designed and manufactured according to the planning protocol and used during the correction surgery. The perioperative, and radiological parameters and complications, including surgery duration, estimated blood loss, pre- and post-operative cobb angle, trunk balance, and precision of osteotomy operation with screw implantation were collected retrospectively and analyzed to evaluate the clinical efficacy and safety of this technique. (3) Results: Of the eight patients, the primary pathology of scoliosis included two adult idiopathic scoliosis (ADIS), four congenital scoliosis (CS), one ankylosing spondylitis (AS), and one tuberculosis (TB). Two patients had a previous history of spinal surgery. Three pedicle subtraction osteotomies (PSOs) and five vertebral column resection (VCR) osteotomies were successfully performed with the application of the guide templates. The main cobb angle was corrected from 99.33° to 34.17°, and the kyphosis was corrected from 110.00° to 42.00°. The ratio of osteotomy execution and simulation was 97.02%. In the cohort, the average screw accuracy was 93.04%. (4) Conclusions: The clinical application of personalized digital surgical planning and precise execution via 3D printing guidance templates in the treatment of severe adult rigid deformity is feasible, effective, and easily generalizable. The preoperative osteotomy simulation was executed with high precision, utilizing personalized designed guidance templates. This technique can be used to reduce the surgical risk and difficulty of screw placement and high-level osteotomy.