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.

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.

Landscape of peripheral immunity in patients with upper urinary tract urolithiasis and the underlying correlations with renal function.

INTRODUCTION: Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function. METHODS: Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group. RESULTS: Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups. CONCLUSIONS: Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore.

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.

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.

GBP2 serves as a novel prognostic biomarker and potential immune microenvironment indicator in renal cell carcinoma.

Since the application of immune checkpoint therapy (ICT) has gradually become a new strategy for clear cell renal cell carcinoma (ccRCC) treatment, biomarkers that predict the individual response to ICT is needed. This study aimed to identify a new clinical indicator for postoperative surveillance of ccRCC and prediction of ICT response. We investigated the GBP2 expression and its relation with immune cell infiltration in tumor microenvironment using public databases, clinical specimens and ccRCC cell lines. Bioinformatic analysis using public database revealed that GBP2 expression is higher in cancer tissues than in adherent normal tissues among different cancer types including ccRCC, and the same results were acquired from clinical tissue samples tested by Western Blot and PCR. In ccRCC cell lines, CCk-8 proliferation assay and apoptosis assessment suggested GBP2 facilitates the malignancy of ccRCC. 286 ccRCC patients were randomly divided into a training or validation cohort, and immunohistochemistry (IHC) and Kaplan-Meier analysis revealed that higher GBP2 expression is related to worse prognosis. C-index analysis implied that integrating GBP2 expression with TNM stage improved the accuracy in predicting prognosis of ccRCC patients compared to the solitary use of either. Bioinformatic analysis implied a relation between GBP2 and immunity, and GBP2 expression is positively related with suppressive immune markers in ccRCC microenvironment. Taken together, our study demonstrated the potential of GBP2 to sever as a prognostic predictor of ccRCC, and an association between GBP2 and tumor-infiltrating lymphocytes in ccRCC was observed, making it a promising indicator of ICT response.

FCER1G positively relates to macrophage infiltration in clear cell renal cell carcinoma and contributes to unfavorable prognosis by regulating tumor immunity.

BACKGROUND: Tumor-associated macrophages (TAMs) are closely related to unfavorable prognosis of patients with clear cell renal cell carcinoma (ccRCC). However, the important molecules in the interaction between ccRCC and TAMs are unclear. METHODS: TCGA-KIRC gene expression data of tumor tissues and normal tissues adjacent to tumor were compared to identify differentially expressed genes in ccRCC. TAMs related genes were discovered by analyzing the correlation between these differentially expressed genes and common macrophage biomarkers. Gene set enrichment analysis was performed to predict functions of TAMs related gene. The findings were further validated using RNA sequencing data obtained from the CheckMate 025 study and immunohistochemical analysis of samples from 350 patients with ccRCC. Kaplan-Meier survival curve, Cox regression analysis and Harrell's concordance index analysis were used to determine the prognostic significance. RESULTS: In this study, we applied bioinformatic analysis to explore TAMs related differentially expressed genes in ccRCC and identified 5 genes strongly correlated with all selected macrophage biomarkers: STAC3, LGALS9, TREM2, FCER1G, and PILRA. Among them, FCER1G was abundantly expressed in tumor tissues and showed prognostic importance in patients with ccRCC who received treatment with Nivolumab; however, it did not exhibit prognostic value in those treated with Everolimus. We also discovered that high expression levels of FCER1G are related to T cell suppression. Moreover, combination of FCER1G and macrophage biomarker CD68 can improve the prognostic stratification of patients with ccRCC from TCGA-KIRC. Based on the immunohistochemical analysis of samples from patients with ccRCC, we further validated that FCER1G and CD68 are both highly expressed in tumor tissue and correlate with each other. Higher expression of CD68 or FCER1G in ccRCC tissue indicates shorter overall survival and progression-free survival; patients with high expression of both CD68 and FCER1G have the worst outcome. Combining CD68 and FCER1G facilitates the screening of patients with a worse prognosis from the same TNM stage group. CONCLUSIONS: High expression of FCER1G in ccRCC is closely related to TAMs infiltration and suppression of T cell activation and proliferation. Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC.

Comparison of the effects of extrinsic compression on the drainage performance of three ureteric stents.

OBJECTIVES: To share our centre's experience dealing with ureteric obstruction, in particular malignant obstructions, by investigating the deformation and flow velocity of three commonly used, readily accessible ureteric stents under at different compression levels and surface change at three time points (new, 1 month and 3 months after implantation). SUBJECTS AND METHODS: Scanning electron microscope (SEM) analysis was conducted on ureteric JJ stents, including the Cook Universa Soft, the Kang Yi Bo (KYB) antireflux and the Urovision Visiostar ESWL JJ stents. Deformation caused by compression was measured using a digital force gauge. Intraluminal flow velocity was tested with the stents subject to different compression levels. RESULTS: The Urovision Visiostar JJ stent demonstrated significantly better anti-compression capability. The Cook Universa Soft and KYB antireflux JJ stents showed favourable draining velocity without compression, but the velocity dropped substantially on compression. The velocity of the KYB antireflux JJ stent reduced substantially after 3 months of implantation, while the Urovision Visiostar achieved the best draining effect when under compression at all three time points. CONCLUSION: The Urovision Visiostar JJ stent demonstrated significantly greater resistance to compression than the other two JJ stents, as well as better drainage under compression. Patients with benign or malignant ureteric compression might benefit from use of the Urovision Visiostar stent. Large prospective clinical trials are needed to confirm these findings.

Predictive formulae of ideal lumbar lordosis determined by individual pelvic incidence and thoracic kyphosis in asymptomatic adults.

BACKGROUND: The precise prediction of ideal lumbar lordosis (LL) has become increasingly important in clinical practice. The aim of this study was to explore the regulatory mechanisms of sagittal spinopelvic alignment and to predict ideal LL based on individual pelvic incidence (PI) and thoracic kyphosis (TK) parameters in asymptomatic adults. METHODS: A total of 233 asymptomatic subjects older than 18 years were consecutively enrolled in our study between April 2017 and December 2019. A full-spine, standing X-ray was performed for each subject. The following parameters were measured in the sagittal plane: the apex of lumbar lordosis (LLA), the distance between the plumb line of the lumbar apex (LAPL) and the gravity plumb line, the inflection point (IP), LL, the upper arc and lower arc of lumbar lordosis (LLUA and LLLA, respectively), PI and TK. Stepwise multiple linear regressions were conducted, and the statistical significance level was P < 0.05. RESULTS: Both PI and TK were two important predictive variables for LLA, LAPL, IP and LL. In addition, the LLUA was mainly explained by TK, while the LLLA was explained by PI. The corresponding predictive models are listed as follows: LLA = 17.110 - 0.040∗PI + 0.023∗TK (R2 = 0.380), LAPL = 31.296 + 0.467∗PI - 0.126∗TK (R2 = 0.309), IP = 10.437 + 0.091∗TK - 0.029∗PI (R2 = 0.227), LL = 2.035 + 0.618∗PI + 0.430∗TK (R2 = 0.595), LLUA = 0.893 + 0.418∗TK (R2 = 0.598), LLLA = 3.543 + 0.576∗PI (R2 = 0.433). CONCLUSION: The specific sagittal lumbar profile should be regulated by both pelvic and thoracic morphology. Such predictive models for lumbar parameters determined by individual PI and TK parameters have been established, which are meaningful for surgeons to better understand the regulatory mechanisms of sagittal spinopelvic alignment and reconstruct a satisfactory lumbar alignment.

The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.

Iron overload is common in elderly people which is implicated in the disease progression of osteoarthritis (OA), however, how iron homeostasis is regulated during the onset and progression of OA and how it contributes to the pathological transition of articular chondrocytes remain unknown. In the present study, we developed an in vitro approach to investigate the roles of iron homeostasis and iron overload mediated oxidative stress in chondrocytes under an inflammatory environment. We found that pro-inflammatory cytokines could disrupt chondrocytes iron homeostasis via upregulating iron influx transporter TfR1 and downregulating iron efflux transporter FPN, thus leading to chondrocytes iron overload. Iron overload would promote the expression of chondrocytes catabolic markers, MMP3 and MMP13 expression. In addition, we found that oxidative stress and mitochondrial dysfunction played important roles in iron overload-induced cartilage degeneration, reducing iron concentration using iron chelator or antioxidant drugs could inhibit iron overload-induced OA-related catabolic markers and mitochondrial dysfunction. Our results suggest that pro-inflammatory cytokines could disrupt chondrocytes iron homeostasis and promote iron influx, iron overload-induced oxidative stress and mitochondrial dysfunction play important roles in iron overload-induced cartilage degeneration.

Combining UBR5 and CD163+ tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients.

PURPOSE: Identification of reliable postoperative indicators for accurately evaluating prognosis of clear cell renal cell carcinoma (ccRCC) patients remains an important clinical issue. This study determined the prognostic value of UBR5 expression in ccRCC patients by combining with CD163+ tumor-associated macrophages (TAMs) and the established clinical parameters. METHODS: The expression of UBR5 was analyzed in ccRCC patients from TCGA databases. A total of 310 ccRCC patients were randomly divided into the training and validation cohorts at a 3:2 or 1:1 ratio, and immunohistochemistry (IHC) and statistical analyses were performed to examine the prognostic value of UBR5 and CD163+ TAMs. RESULTS: UBR5 expression was commonly downregulated in human ccRCC specimens, which was associated with TNM stage, SSIGN, WHO/ISUP Grading and poor prognosis of ccRCC patients. In addition, UBR5 expression was negatively correlated with CD163 expression (a TAM marker) in ccRCC tissues, and combining expressions of UBR5 and CD163 better predicted worse overall survival and progression-free survival of ccRCC patients. Even after multivariable adjustment, UBR5, CD163, TNM stage and SSIGN appeared to be independent risk factors. By time-dependent c-index analysis, the integration of intratumoral UBR5 and CD163 achieved higher c-index value than UBR5, CD163, TNM stage or SSIGN alone in predicting ccRCC patients' prognosis. Moreover, the incorporation of both UBR5 and CD163 into the clinical indicators TNM stage or SSIGN exhibited highest c-index value. CONCLUSIONS: Integrating intratumoral UBR5 and CD163+ TAMs with the current clinical parameters achieves better accuracy in predicting ccRCC patients' postoperative prognosis.

USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-A165b alternative splicing via regulating SRSF1 and SRPK1.

BACKGROUND: The benefit of targeted therapy for renal cell carcinoma (RCC) is largely crippled by drug resistance. Rapid disease progression and poor prognosis occur in patients with drug resistance. New treatments demand prompt exploration for clinical therapies. Ubiquitin-specific peptidase 39 (USP39) serves as the pro-tumor factor in several previous studies of other malignant tumors. To investigate the function and mechanism of USP39 in promoting malignant proliferation and angiogenesis of RCC. METHODS: We applied ONCOMINE database to analyze the correlation between USP39 expression level and the clinical characteristics of RCC. USP39 knockdown or overexpression plasmids were transfected into 786-O and ACHN cells. The HUVEC received cell supernatants of 786-O and ACHN cells with knockdown or overexpression USP39.The effect of USP39 on RCC was evaluated by MTT assay, cell cycle analysis, colony formation assay and tubule formation assay. The interaction between USP39 and VEGF-A alternative splicing was assessed by affinity purification and mass spectrometry, co-immunoprecipitation and Western blot assays. RESULTS: The mRNA expression level of USP39 in RCC was significantly higher than that in normal renal tissue (P < 0.001), and negatively correlated with the survival rate of RCC patients (P < 0.01). Silencing of USP39 in 786-O and ACHN cells inhibited cell proliferation and colony formation, and induced S phase arrest. USP39 overexpression significantly increased the number of tubules (P < 0.05) and branches (P < 0.01) formed by HUVEC cells, and USP39 knockdown produced an opposite effect (P < 0.05). The USP39 (101-565) fragment directly mediated its binding to SRSF1 and SRPK1, and promoted the phosphorylation of SRSF1 to regulate VEGF-A alternative splicing. USP39 knockdown upregulated the expression of VEGF-A165b, and USP39 overexpression downregulated the expression of VEGF-A165b significantly (both P < 0.05). CONCLUSION: USP39 acted as a pro-tumor factor by motivating the malignant biological processes of RCC, probably through inhibiting VEGF-A165b alternative splicing and regulating SRSF1 and SRPK1. USP39 may prove to be a potential therapeutic target for RCC.

TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC. MATERIALS AND METHODS: TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays. RESULTS: TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC. CONCLUSIONS: Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.

Integrating HECW1 expression into the clinical indicators exhibits high accuracy in assessing the prognosis of patients with clear cell renal cell carcinoma.

BACKGROUND: Although many intratumoral biomarkers have been reported to predict clear cell renal cell carcinoma (ccRCC) patient prognosis, combining intratumoral and clinical indicators could predict ccRCC prognosis more accurately than any of these markers alone. This study mainly examined the prognostic value of HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) expression in ccRCC patients in combination with established clinical indicators. METHODS: The expression level of HECW1 was screened out by data-independent acquisition mass spectrometry (DIA-MS) and analyzed in ccRCC patients from the The Cancer Genome Atlas (TCGA) database and our cohort. A total of 300 ccRCC patients were stochastically divided into a training cohort and a validation cohort, and real-time PCR, immunohistochemistry (IHC) and statistical analyses were employed to examine the prognostic value of HECW1 in ccRCC patients. RESULTS: The expression level of HECW1 usually decreased in human ccRCC specimens relative to control specimens in TCGA (p < 0.001). DIA-MS, Real-time PCR, and IHC analyses also showed that the majority of ccRCCs harbored decreased HECW1 expression compared with that in normal adjacent tissues (p < 0.001). Additionally, HECW1 expression was reduced in ccRCC cell lines compared with the normal renal cell line HK-2 (p < 0.001). Moreover, lower HECW1 expression was found in ccRCC patients with a higher tumor node metastasis (TNM) stage, bone metastasis, or first-line targeted drug resistance (p < 0.001). Low HECW1 expression indicated higher TNM stage, SSIGN (Stage, Size, Grade, and Necrosis) score and WHO/ISUP grade and poor prognosis in ccRCC patients (p < 0.05). Even after multivariable adjustment, HECW1, TNM stage, and SSIGN score served as independent risk factors. The c-index analysis showed that integrating intratumoral HECW1 expression into TNM stage or SSIGN score resulted in a higher c-index value than these indicators alone for predicting ccRCC patient prognosis. CONCLUSION: HECW1 is a novel prognostic biomarker and therapeutic target in ccRCC, and integrating intratumoral HECW1 expression with established clinical indicators yields higher accuracy in assessing the postoperative prognosis of ccRCC patients.

A diagnostic model for differentiating tuberculous spondylitis from pyogenic spondylitis on computed tomography images.

OBJECTIVES: To develop and evaluate a logistics regression diagnostic model based on computer tomography (CT) features to differentiate tuberculous spondylitis (TS) from pyogenic spondylitis (PS). METHODS: Demographic and clinical features were collected from the Electronic Medical Record System. Data of bony changes seen on CT images were compared between the PS (n = 61) and TS (n = 51) groups using the chi-squared test or t test. Based on features that were identified to be significant, a diagnostic model was developed from a derivation set (two thirds) and evaluated in a validation set (one third). The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: The width of bone formation around the vertebra and sequestrum was greater in the TS group. There were significant differences between the two groups in the horizontal and longitudinal location of erosion and the morphology of axial bone destruction and sagittal residual vertebra. Kyphotic deformity and overlapping vertebrae were more common in the TS group. A diagnostic model that included eight predictors was developed and simplified to include the following six predictors: width of the bone formation surrounding the vertebra, longitudinal location, axial-specific erosive morphology, specific morphology of the residual vertebra, kyphotic deformity, and overlapping vertebrae. The simplified model showed good sensitivity, specificity, and total accuracy (85.59%, 87.80%, and 86.50%, respectively); the AUC was 0.95, indicating good clinical predictive ability. CONCLUSIONS: A diagnostic model based on bone destruction and formation seen on CT images can facilitate clinical differentiation of TS from PS. KEY POINTS: • We have developed and validated a simple diagnostic model based on bone destruction and formation observed on CT images that can differentiate tuberculous spondylitis from pyogenic spondylitis. • The model includes six predictors: width of the bone formation surrounding the vertebra, longitudinal location, axial-specific erosive morphology, specific morphology of the residual vertebra, kyphotic deformity, and overlapping vertebrae. • The simplified model has good sensitivity, specificity, and total accuracy with a high AUC, indicating excellent predictive ability.

Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures Associated with Spinal Canal Encroachment without Neurological Symptoms.

BACKGROUND Percutaneous kyphoplasty (PKP) has been widely used for osteoporotic vertebral compression fractures (OVCFs). However, whether this approach is suitable for osteoporotic vertebral fractures with spinal canal encroachment remains controversial. MATERIAL AND METHODS Of 526 patients who underwent PKP at our hospital, 40 had conditions associated with spinal canal encroachment, and were enrolled in the study. Detailed physical, neurological, and radiological examinations were performed on each patient before and after surgery and at the followup. A visual analog scale (VAS) and the Oswestry Disability Index (ODI) were used for the clinical assessment. The vertebral body height, the local kyphosis, and the spinal canal width were used for the radiological evaluation. RESULTS There were 11 male and 29 female patients, with a mean age of 71±8 years. The VAS score decreased from 6.4±0.7 preoperatively to 1.6±0.7 postoperatively and to 2.3±1.5 at the last followup visit. The ODI score was 78±9.5 before surgery, declined to 24±11.3 after surgery, and was 27.6±12.5 at the last followup visit. The vertebral body height increased from 11.7±4.3 mm to 14.6±4.4 mm. The local kyphosis decreased from 15.0±10.7 degrees preoperatively to 8.5±11.3 degrees postoperatively. The spinal canal width remained stable, at 8.5±2.0 mm before PKP and 8.7±1.9 after PKP. CONCLUSIONS PKP effectively relieved back pain in OVCF patients with spinal canal encroachment. Their social function improved as well.

Mechanical loading induces HIF-1α expression in chondrocytes via YAP.

OBJECTIVES: To investigate the role of YAP in cyclic mechanical stress induced up-regulation of HIF-1α in rat cartilage chondrocytes. RESULTS: Our in vitro and in vivo experiments demonstrated that cyclic mechanical stress promoted HIF-1α and YAP proteins expression in a magnitude dependent manner. Cyclic mechanical stress at 4000µ strain exhibited most significant effect in promoting HIF-1α and YAP up-regulation. Activation of YAP using LPA significantly promoted HIF-1α stabilization and expression, while YAP siRNA treatment suppressed the up-regulation of HIF-1α induced by cyclic mechanical stress. CONCLUSION: Our results indicated that cyclic mechanical stress promoted HIF-1α stabilization and YAP is involved in mechanical stress induced HIF-1α up-regulation.

Computed tomography imaging characteristics help to differentiate pyogenic spondylitis from brucellar spondylitis.

PURPOSE: Both pyogenic spondylitis (PS) and brucellar spondylitis (BS) can cause deformities and permanent neurologic deficits without prompt diagnosis and treatment. However, differential diagnosis is challenging. The aim of this study was to compare the computed tomography (CT) imaging features of PS with those of BS. METHODS: Thirty-two patients with PS and 44 with BS were enrolled in the study. CT images were obtained in all cases. Data on bone destruction and formation, vertebral wall destruction, and osteosclerotic changes were collected and compared using the Chi-square test or t test. A P value < 0.01 was considered statistically significant. Positive predictive values (PPV) for detecting PS or BS were reported. RESULTS: Involvement of the lumbar vertebrae and multiple spinal levels was more common in the BS group than in the PS group. Bone destruction was significantly greater in the PS group than in the BS group (30.8 vs 18.0%; t = 3.920, P = 0.000), with more extensive destruction of the vertebral body (35.8 vs 12.5%, χ2 = 12.672, P = 0.002, PPV = 63.16%). In the BS group, there was more osteosclerosis around erosions (70.5 vs 43.3%, χ2 = 11.59, P = 0.001, PPV = 67.74%) and fan-shaped osteosclerosis (27.3 vs 19.4%, χ2 = 18.556, P = 0.006, PPV = 64.86%), more bone formation around the vertebra (77.2 vs 34.3%, χ2 = 33.608, P = 0.000, PPV = 76.83%), more bone formation under the anterior longitudinal ligament (63.6 vs 19.4%, χ2 = 30.133, P = 0.000, PPV = 76.09%), more longer anterior bone formation (3.55 vs 0.78 mm, t = 3.997, P = 0.000), and more anterior and closed-bone formation with local erosion (42.0 vs 9.0%, χ2 = 74.243, P = 0.000, PPV = 74.36%). CONCLUSIONS: CT images have unique advantages of revealing the morphology of erosions, osteosclerosis, and bone formation around the vertebra and help to differentiate PS from BS. These slides can be retrieved under Electronic Supplementary Material.

C7 sacral tilt (C7ST): a novel spinopelvic parameter reveals the relationship between pelvic parameters and global spinal sagittal balance and converts pelvic parameters into spinal parameters.

PURPOSE: The aim is to propose a novel spinopelvic parameter C7 sacral tilt (C7ST), of which its sum with global tilt (GT) is equal to pelvic incidence (PI), from a geometrical point of view. METHODS: A cohort of 198 patients was recruited and the whole lateral spine and pelvic radiographs were performed. The following sagittal parameters were measured: sagittal vertical axis (SVA), C7 vertical tilt (C7VT), sacral slope (SS), pelvic tilt (PT), PI, GT and C7ST. The correlations between them were analyzed using the Pearson or Spearman correlation coefficient, and simple linear regressions were simultaneously conducted. P < 0.05 was set as the level of significance. RESULTS: Geometric construction by complementary angles revealed that PI = C7ST + GT, GT = PT + C7VT, and C7ST = SS - C7VT. Both C7ST and GT were moderately correlated with PI (R = 0.52 and 0.596, respectively), strongly correlated with SS and PT, respectively (SS = 0.9 * C7ST + 1.15, R = 0.955; PT = 0.87 * GT + 3.86, R = 0.96). The correlation coefficients of the SVA and C7VT, SVA and SS - C7ST, and SVA and GT - PT were 0.935, 0.925 and 0.863, respectively. CONCLUSION: The novel proposed spinopelvic parameter C7ST has the advantages of convenient measurement, reduced error, and extrapolation of other parameters. The greatest significance of proposing C7ST is that pelvic parameters (PI, PT and SS) are converted into spinal parameters (C7ST and GT), which is very helpful for a more intuitive understanding of the progression of spinal sagittal imbalance.

Factors Associated with Perioperative Serum Calcium Levels in Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fracture: A Prospective Clinical Study.

BACKGROUND Long-term hypocalcemia can result in osteoporotic vertebral compression fracture (OVCF). Transient paralysis and tetraplegia due to hypocalcemia is a rare but severe complication after kyphoplasty. The aims of this prospective clinical study were to investigate the clinical factors associated with serum calcium levels in patients undergoing percutaneous kyphoplasty (PKP). MATERIAL AND METHODS Sixty-eight patients with OVCF were clinically evaluated before and after PKP. Serum calcium was measured before surgery and 24 hours after surgery. Clinical information included the time between vertebral fracture and surgery, the number of involved vertebral bodies, the dose of bone cement required during surgery, and bone mineral density. Correlation coefficient and simple linear regression analysis were performed to identify the clinical factors associated with serum calcium levels. RESULTS Peri-operative serum calcium levels were significantly and positively associated with the dose of bone cement required during PKP and the number of affected vertebral bodies. There was a significant and negative correlation between the time from vertebral fracture to surgery and bone mineral density, which were shown by linear regression analysis to have a predictive value of 5.8% and 47.3%, respectively. CONCLUSIONS For patients undergoing PKP, the amount of bone cement required and the number of affected vertebral bodies were associated with low serum calcium levels. Surgeons should be aware of the importance of measuring and monitoring serum calcium levels in this patient group.