Preoperative neoadjuvant targeted therapy remodels intra-tumoral heterogeneity of clear-cell renal cell carcinoma and ferroptosis inhibition induces resistance progression.

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P<0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11(-) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.

Identification of prognostic stemness-related genes in kidney renal papillary cell carcinoma.

BACKGROUND: Kidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells and stemness-related genes (SRGs) are revealed to play important roles in the carcinogenesis and metastasis of various tumors. Consequently, we aim to investigate the underlying mechanisms of SRGs in KIRP. METHODS: RNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, based on which we calculated the mRNA expression-based stemness index (mRNAsi). Next, we selected the differentially expressed genes (DEGs) between low- and high-mRNAsi groups. Then, we utilized weighted gene correlation network analysis (WGCNA) and univariate Cox analysis to identify prognostic SRGs. Afterwards, SRGs were included in the multivariate Cox regression analysis to establish a prognostic model. In addition, a regulatory network was constructed by Pearson correlation analysis, incorporating key genes, upstream transcription factors (TFs), and downstream signaling pathways. Finally, we used Connectivity map analysis to identify the potential inhibitors. RESULTS: In total, 1124 genes were characterized as DEGs between low- and high-RNAsi groups. Based on six prognostic SRGs (CCKBR, GPR50, GDNF, SPOCK3, KC877982.1, and MYO15A), a prediction model was established with an area under curve of 0.861. Furthermore, among the TFs, genes, and signaling pathways that had significant correlations, the CBX2-ASPH-Notch signaling pathway was the most significantly correlated. Finally, resveratrol might be a potential inhibitor for KIRP. CONCLUSIONS: We suggested that CBX2 could regulate ASPH through activation of the Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.

Logistic regression model predicts early surgical site infection after spinal fusion: a retrospective cohort study.

OBJECTIVE: This study aimed to develop a diagnostic model for predicting early surgical site infection based on postoperative inflammatory markers after spinal fusion surgery. METHODS: In this retrospective study, we analysed the trends of inflammatory markers between surgical site infection (SSI) group and non-SSI group. The data were randomly divided into training cohort and validation cohort (ratio 7:3). The variables for SSI were analysed using stepwise logistic regression to develop prediction model. To evaluate the model, we analysed its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), as well as the area under curve (AUC) in the validation cohort. Calibration plots and decision curve analysis (DCA) were employed to assess the calibration and clinical usefulness of the model. RESULTS: We observed significant changes in inflammatory markers on the seventh day after surgery. The prediction model included four variables on the seventh day after surgery: body temperature, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil counts. After binary processing of these data, the simplified model achieved an AUC of 0.86 (CI 95%: 0.81-0.92) in the training cohort and 0.9 (CI 95%: 0.82-0.98) in the validation cohort. Calibration plots and DCA demonstrated that the proposed model was effective for the diagnosis of SSI. CONCLUSION: We developed and validated a prediction model for diagnosing early infection after spinal fusion.

Immunogenic Material Vaccine for Cancer Immunotherapy by Structure-Dependent Immune Cell Trafficking and Modulation.

Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination is reported. The immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod-like bacteria) is precisely manipulated. The results reveal that innate immune cells accurately sense and respond to the architectures, of which two outperformed material candidates (151 nm hollow spheres and hollow microrods with an aspect ratio of 4.5) show higher competence in creating local proinflammatory environment with promoted innate immune cell influx and stimulation on dendritic cells (DCs). In combination with viral peptides, model proteins, or cell lysate antigens, the outperformed microrod material remarkably primes antigen-specific CD8 cytolytic T cells. In prophylactic and therapeutic regimens, the microrod adjuvanted vaccines display optimal aptitude in tumor suppression in four aggressive murine tumor models, by promoting the infiltration of heterogeneous cytolytic effector cells while decreasing suppressive immunoregulatory populations in tumors. This study demonstrates that a rationally selected architecture of immunogenic materials potentially advances the clinical reality of cancer vaccination.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.

Novel model of pyroptosis-related molecular signatures for prognosis prediction of clear cell renal cell carcinoma patients.

Background: Pyroptosis is a programmed death mode of inflammatory cells, which is closely related to tumor progression and tumor immunity. Clear cell renal cell carcinoma (ccRCC) is the major pathological type of renal cell carcinoma (RCC) with poor prognosis. Many theories have tried to clarify the mechanism in the development of ccRCC, but the role of pyroptosis in ccRCC has not been well described. The main purpose of this study is to explore the role of pyroptosis in ccRCC and establish a novel prognosis prediction model of pyroptosis-related molecular signatures for ccRCC. Methods: In the present study, we made a systematical analysis of the association between ccRCC RNA transcriptome sequencing data from The Cancer Genome Atlas (TCGA) database [which included 529 ccRCC patients who were randomized in a training cohort (n=265) and an internal validation cohort (n=264)] and 40 pyroptosis-related genes (PRGs), from which four genes (CASP9, GSDME, IL1B and TIRAP) were selected to construct a molecular prediction model of PRGs for ccRCC. In addition, a cohort of 114 ccRCC patients from Shanghai Eastern Hepatobiliary Surgery Hospital (EHSH) was used as external data to verify the effectiveness of the model by immunohistochemistry. Moreover, the biological functions of the four PRGs were also verified in ccRCC 786-O and 769-P cells by Western blot (WB), CCK-8 cell proliferation, and Transwell invasion assays. Results: The model was able to differentiate high-risk patients from low-risk patients, and this differentiation was consistent with their clinical survival outcomes. In addition, the four PRGs also affected the ability of cell proliferation and invasion in ccRCC. Conclusion: The prediction model of pyroptosis-related molecular markers developed in this study may prove to be a novel understanding for ccRCC.

LRP5 competes for SPOP binding to enhance tumorigenesis mediated by Daxx and PD-L1 in prostate cancer.

Genetic factors coordinate with environmental factors to drive the pathogenesis of prostate adenocarcinoma (PRAD). SPOP is one of the most mutated genes and LRP5 mediates lipid metabolism that is abnormally altered in PRAD. Here, we investigated the potential cross-talk between SPOP and LRP5 in PRAD. We find a negative correlation between SPOP and LRP5 proteins in PRAD. SPOP knockdown increased LRP5 protein while SPOP overexpression resulted in LRP5 reduction that was fully rescued by proteasome inhibitors. LRP5 intracellular tail has SPOP binding site and the direct interaction between LRP5 and SPOP was confirmed by Co-IP and GST-pulldown. Moreover, LRP5 competed with Daxx for SPOP-mediated degradation, establishing a dynamic balance among SPOP, LRP5 and Daxx. Overexpression of LRP5 tail could shift this balance to enhance Daxx-mediated transcriptional inhibition, and inhibit T cell activity in a co-culture system. Further, we generated human and mouse prostate cancer cell lines expressing SPOP variants (F133V, A227V, R368H). SPOP-F133V and SPOP-A227V have specific effects in up-regulating the protein levels of PD-1 and PD-L1. Consistently, SPOP-F133V and SPOP-A227V show robust inhibitory effects on T cells compared to WT SPOP in co-culture. This is further supported by the mouse syngeneic model showing that SPOP-F133V and SPOP-A227V enhance tumorigenesis of prostate cancer in in-vivo condition. Taken together, our study provides evidence that SPOP-LRP5 crosstalk plays an essential role, and the genetic variants of SPOP differentially modulate the expression and activity of immune checkpoints in prostate cancer.

Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories.

Previous bulk RNA sequencing or whole genome sequencing on clear cell renal cell carcinoma (ccRCC) subtyping mainly focused on ccRCC cell origin or the complex tumor microenvironment (TME). Based on the single-cell RNA sequencing (scRNA-seq) data of 11 primary ccRCC specimens, cancer stem-cell-like subsets could be differentiated into five trajectories, whereby we further classified ccRCC cells into three groups with diverse molecular features. These three ccRCC subgroups showed significantly different outcomes and potential targets to tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). Tumor cells in three differentiation directions exhibited distinct interactions with other subsets in the ccRCC niches. The subtyping model was examined through immunohistochemistry staining in our ccRCC cohort and validated the same classification effect as the public patients. All these findings help gain a deeper understanding about the pathogenesis of ccRCC and provide useful clues for optimizing therapeutic schemes based on the molecular subtype analysis.

Omnidirectional (Flexible) Ureteral Access Sheath: Safety, Efficacy, and Initial Experience Report.

Background: Recently a novel omnidirectional (OD) ureteral access sheath (UAS) has been developed. By retrospectively reviewing and comparing the flexible ureteroscopic lithotripsy (FURL) cases in our institution with either a conventional Cook UAS or an OD UAS in the past year, we shared our experience of the safety, efficacy, and relevant issues on the usage of OD UAS. Materials and Methods: The medical history and surgery details of 199 patients with kidney stones or ureterojunctional stones who underwent FURL in Xinhua Hospital, including 61 Cook UAS and 138 OD UAS, were reviewed and compared. The maximal deflection angle was measured by steering four different types of ureteroscopes to bend the OD UAS in different states. Result: The deflection angle of OD UAS was ∼110° to 130° free load, and 90° to 130° when loaded with different instruments. The stone burden and position were similar in two groups. Given a similar prestent ratio and operation time, the OD UAS group achieved a higher single-session stone-free rate (SFR) (63.9% vs 94.2%, p < 0.0001) at 1-month follow-up evaluated by a CT scan. Conclusion: OD UAS is a novel device with high safety and efficacy. The unique flexible design allows it to bend with the ureteroscope and enter renal calices and be set close to the stone. Combined with the suction port, OD UAS contributes greatly to dealing with large-burden kidney stones, shortens operation time, and improves single-session SFR.

Biomarkers for patients with Wilms tumor: a review.

Wilms tumor, originating from aberrant fetal nephrogenesis, is the most common renal malignancy in childhood. The overall survival of children is approximately 90%. Although existing risk-stratification systems are helpful in identifying patients with poor prognosis, the recurrence rate of Wilms tumors remains as high as 15%. To resolve this clinical problem, diverse studies on the occurrence and progression of the disease have been conducted, and the results are encouraging. A series of molecular biomarkers have been identified with further studies on the mechanism of tumorigenesis. Some of these show prognostic value and have been introduced into clinical practice. Identification of these biomarkers can supplement the existing risk-stratification systems. In the future, more biomarkers will be discovered, and more studies are required to validate their roles in improving the detection rate of occurrence or recurrence of Wilms tumor and to enhance clinical outcomes.

Glycolysis-related biomarker TCIRG1 participates in regulation of renal cell carcinoma progression and tumor immune microenvironment by affecting aerobic glycolysis and AKT/mTOR signaling pathway.

BACKGROUND: Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC). METHODS: Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments. RESULTS: It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4+T cell Th1, CD8+T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines. CONCLUSIONS: Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.

PUS1 is a novel biomarker for evaluating malignancy of human renal cell carcinoma.

Renal cell carcinoma (RCC) is one of the most common malignancies. Despite the rapid development of the oncology research and surgical treatment, the prognosis of RCC has not significantly improved. Thus, exploration of the pathological molecular mechanism and development of new therapeutic targets of RCC are of great importance. Herein, by bioinformatic analysis and in vitro cell experiments, we report that, the expression of pseudouridine synthase 1 (PUS1), belonging to the family of PUS enzymes that participate in RNA modifications, is closely associated with RCC progression. In addition, the upregulated PUS1 expression results in the elevated RCC cancer cell viability, migration, invasion and colony formation ability, whereas the decreased PUS1 expression exerts the opposite effects on RCC cells. Thus, our findings show the potential role of PUS1 in RCC cells, providing with evidence that PUS1 is involved in RCC progression, which may help contribute to RCC diagnosis and intervention in clinic.

Construction and validation of a prognostic model for predicting clear cell renal cell carcinoma based on complement-related genes.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous tumor and is the most common subtype of renal cell carcinoma (RCC). Surgery is used to cure most early ccRCC, but the 5-year overall survival (OS) of ccRCC patients is far from satisfactory. Thus, new prognostic features and therapeutic targets for ccRCC need to be identified. Since complement factors can influence tumor development, we aimed to develop a model to predict the prognosis of ccRCC through complement-related genes. Methods: Differentially expressed genes were screened from an International Cancer Genome Consortium (ICGC) data set, and the genes associated with prognosis were screened by univariate regression and least absolute shrinkage and selection operator-Cox regression, and column line plots were generated using the rms R package to predict OS. The C-index was used to show the accuracy of the survival prediction and the prediction effects were verified using a data set from The Cancer Genome Atlas (TCGA). An immuno-infiltration analysis was performed with CIBERSORT analysis, and a drug sensitivity analysis was performed using the Gene Set Cancer Analysis (GSCA) (http://bioinfo.life.hust.edu.cn/GSCA/#/) database. Results: We identified 5 complement-related genes (i.e., A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4) for risk-score modeling to predict OS at 1, 2, 3, and 5 years, and the C-index of the prediction mode was 0.795. In addition, the model was successfully validated in TCGA data set. The CIBERSORT analysis showed that M1 macrophages were downregulated in the high-risk group. The GSCA database analysis showed that DOCK4, COL4A2, and A2M were positively correlated with the half maximal inhibitory concentration (IC50) of 10 drugs and small molecules, and COL4A2, NOTCH4, A2M, and APOBEC3G were negatively correlated with the IC50 of dozens of different drugs and small molecules. Conclusions: We developed and validated a survival prognostic model based on 5 complement-related genes for ccRCC. We also elucidated the relationship with tumor immune status and developed a new predictive tool for clinical purposes. In addition, our results showed that A2M, APOBEC3G, COL4A2, DOCK4, and NOTCH4 may be potential targets for the treatment of ccRCC in the future.

Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway.

BACKGROUND: Cartilage endplate (CEP) degeneration is an important initiating factor leading to intervertebral disc degeneration (IVDD). Astaxanthin (Ast) is a natural lipid-soluble and red-orange carotenoid which possesses various biological activities, including antioxidant, anti-inflammatory, and anti-aging effects in multiple organisms. However, the effects and mechanism of Ast on endplate chondrocytes remain largely unknown. The objective of the current study was to investigate the effects and of Ast on CEP degeneration and its underlying molecular mechanisms. METHODS: Tert-butyl hydroperoxide (TBHP) was used to mimic the IVDD pathological environment. We investigated the effects of Ast on the Nrf2 signaling pathway and damage-associated events. The IVDD model was constructed by surgical resection of L4 posterior elements to explore the role of Ast in vivo. RESULTS: We found that the activation of the Nrf-2/HO-1 signaling pathway was enhanced by Ast, thus promoted mitophagy process, inhibited oxidative stress and CEP chondrocytes ferroptosis, eventually ameliorated extracellular matrix (ECM) degradation, CEP calcification and endplate chondrocytes apoptosis. Knockdown of Nrf-2 using siRNA inhibited Ast induced mitophagy process and its protective effect. Moreover, Ast inhibited oxidative stimulation-induced NF-κB activity and could ameliorate the inflammation response. The results also were confirmed by experiments in vivo, Ast alleviated IVDD development and CEP calcification. CONCLUSIONS: Ast could protect vertebral cartilage endplate against oxidative stress and degeneration via activating Nrf-2/HO-1 pathway. Our results imply that Ast may serve as a potential therapeutic agent for IVDD progression and treatment.

PTEN inhibitor VO-OHpic protects endplate chondrocytes against apoptosis and calcification via activating Nrf-2 signaling pathway.

Cartilage endplate (CEP) degeneration and calcification is an important contributor to the onset and pathogenesis of intervertebral disc degeneration (IDD). However, the underlying mechanisms of CEP degeneration remain elusive, let alone according treatment strategies to prevent CEP degeneration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that promotes cell apoptosis, and recent studies indicated that PTEN is overexpressed in degenerated intervertebral disc. However, whether direct inhibition of PTEN attenuates CEP degeneration and IDD development remains largely unknown. In the present study, our in vivo experiments demonstrated that VO-OHpic could attenuate IDD progression and CEP calcification. We also found that VO-OHpic inhibited oxidative stress induced chondrocytes apoptosis and degeneration by activating Nrf-2/HO-1 pathway, thus promoted parkin mediated mitophagy process and inhibited chondrocytes ferroptosis, alleviated redox imbalance and eventually improved cell survival. Nrf-2 siRNA transfection significantly reversed the protective effect of VO-OHpic on endplate chondrocytes. In conclusion, our study demonstrated that inhibition of PTEN with VO-OHpic attenuates CEP calcification and IDD progression. Moreover, VO-OHpic protects endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 mediated mitophagy process and ferroptosis inhibition. Our results suggest that VO-OHpic may be a potential effective medicine for IDD prevention and treatment.

A Novel Method for Predicting Ideal Postoperative Upper Instrumented Vertebra Tilt to Prevent Lateral Shoulder Imbalance after Scoliosis Correction Surgery.

Lateral shoulder imbalance (LSI) is reflected radiologically by the clavicle angle (CA). How to achieve postoperative lateral shoulder balance (LSB) after scoliosis correction surgery remains unclear. In the current study, by using the preoperative upper instrumented vertebra (UIV) tilt, the CA, the flexibility between T1 and the UIV, and the ideal postoperative UIV tilt was predicted based on the following formula: ideal postoperative UIV tilt = preoperative UIV tilt-the flexibility between T1 and UIV-preoperative CA. The reliability of the formula was verified through a retrospective analysis, and 76 scoliosis patients were enrolled. The feasibility of this method was verified through a prospective analysis, and 13 scoliosis patients were enrolled. In the retrospective study, there was a significant correlation between the difference in the actual and ideal postoperative UIV tilt values and the postoperative CA, with correlation coefficients in the whole, LSI, and LSB groups of 0.981, 0.982, and 0.953, respectively (p < 0.001). In the prospective study, all patients achieved satisfactory LSB. Using the formula preoperatively to predict an ideal postoperative UIV tilt and controlling the intraoperative UIV tilt with the improved crossbar technique may be an effective digital method for achieving postoperative LSB and has important clinical significance.

Clinical Characteristics of Minimal Lumbar Disc Herniation and Efficacy of Percutaneous Endoscopic Lumbar Discectomy via Transforaminal Approach: A Retrospective Study.

OBJECTIVE: To define the characteristics of Mini LDH, develop new diagnostic references and examine the clinical efficacy of percutaneous endoscopic lumbar discectomy via a transforaminal approach (TF-PELD) for it. METHODS: A total of 72 patients who underwent TF-PELD with Mini LDH from September 2019 to October 2022 were enrolled in this retrospective study. The patients' basic information, symptoms, number of outpatient visits, duration of conservative treatment, physical examination findings and so on were obtained from the medical records. Clinical effects of TF-PELD for Mini LDH were assessed by means of the following: the Visual Analog Scale (VAS) for low back pain (LBP) and leg pain, Oswestry Disability Index (ODI) for functional status assessment and Modified Mac Nab criteria for patient satisfaction. RESULTS: Mini LDH have specific clinical characteristics and imaging features. All included patients achieved obvious pain relief after TF-PELD surgery. Pain scores were repeated at postoperative day 1 and 1, 3, 6, 12 and 24 months later. Results were statistically analyzed. The average VAS-Back, VAS-Leg and ODI scores were all significantly reduced at the first postoperative day and gradually decreased with the follow-up time continuing. In total, 66 out of 72 patients received an excellent or good recovery and no poor result was reported according to the Modified Mac Nab criteria. CONCLUSIONS: Mini LDH is a type of LDH with special characteristics and in need of correct diagnosis and active treatment in clinical work. TF-PELD was also found to be an effective procedure for the treatment of Mini LDH.

Specific foraminal changes originate from degenerative spondylolisthesis on computed tomographic images.

PURPOSE: Operative treatment for degenerative spondylolisthesis (DS) is accompanied by the high incidence of nerve injury. Foraminal structures, especially the hypertrophied facet joints, have significant impacts on the adjacent nerve. This study aims to identify the specific foraminal changes relating to DS and nerve injury. METHODS: The CT images of 70 patients with DS and 50 patients without lumbar disease were collected. The length and height of the foraminal structure were measured horizontally and vertically on sagittally reconstructed images. Horizontal stenosis, meaning to pending compression to nerve root after complete reduction, was evaluated on the image located to the middle of the foramen. Chi-square test or T-test were carried out using SPSS 26.0. RESULTS: The hyperplasia of the superior articular process (SAP) and articular capsule (Ac) incidence rates in DS group was significantly more common than that of the control group (9.2 vs 0.0%, 42.9 vs 2.0%). The height and width of the SAP and Ac in vertical and horizontal directions were significantly greater than those in the control group (4.95 mm vs - 0.47 mm, P < 0.0001; 3.28 vs 0.02 mm, P < 0.0001; 5.27 vs3.44 mm, P < 0.0001; 2.60 vs 0.37 mm, P < 0.0001). In the DS group, hyperplasia of the SAP and Ac accounted for 9 and 43% respectively, 85 and 45% of which were accompanied by horizontal stenosis of the intervertebral foramen. CONCLUSION: DS is usually characterized of excessive hyperplasia of the SAP and Ac, both of which are possible elements of nerve root injury after complete reduction in operation and should be focused on during surgery.

Glycolysis drives STING signaling to facilitate dendritic cell antitumor function.

Activation of STING signaling in DCs promotes antitumor immunity. Aerobic glycolysis is a metabolic hallmark of activated DCs, but how the glycolytic pathway intersects with STING signaling in tumor-infiltrating DCs remains elusive. Here, we show that glycolysis drives STING signaling to facilitate DC-mediated antitumor immune responses. Tumor-infiltrating DCs exhibited elevated glycolysis, and blockade of glycolysis by DC-specific Ldha/Ldhb double deletion resulted in defective antitumor immunity. Mechanistically, glycolysis augmented ATP production to boost STING activation and STING-dependent DC antitumor functions. Moreover, DC-intrinsic STING activation accelerated HIF-1α-mediated glycolysis and established a positive feedback loop. Importantly, glycolysis facilitated STING-dependent DC activity in tissue samples from patients with non-small cell lung cancer. Our results provide mechanistic insight into how the crosstalk of glycolytic metabolism and STING signaling enhances DC antitumor activity and can be harnessed to improve cancer therapies.