Receipt of prostate-specific antigen test in Medicaid beneficiaries with and without HIV in 2001-2015 in 14 states.

Studies have reported lower incidence of prostate cancer in men living with HIV compared to men without HIV for reasons that remain unclear. Lower prostate cancer screening in men living with HIV could explain these findings. We describe receipt of prostate-specific antigen (PSA) test each calendar year by HIV status in Medicaid beneficiaries enrolled in 14 US states, 2001-2015. A total of 15,240,871 Medicaid beneficiaries aged 18-64 with ≥7 months of continuous enrollment were included in analyses. HIV diagnosis and PSA tests were identified using non-drug claims. Incidence rate ratios comparing receipt of PSA test by HIV status adjusted for age, race-ethnicity, state of residence, calendar year, comorbid conditions, benign prostatic conditions, and receipt of testosterone-replacement therapy were estimated using Poisson regression. Models were also stratified by state and estimates were pooled using random effects meta-analysis to account for heterogeneity by state. Models were additionally stratified by age and race-ethnicity. There were 42,503 PSA tests over 314,273 person-years and 1,669,835 PSA tests over 22,023,530 person-years observed in beneficiaries with and without HIV, respectively. Incidence of PSA test was slightly lower in men living with HIV than men without HIV (IRR=0.98; 95% CI: 0.97, 0.99) when adjusting for state. In the pooled estimate, the rate was higher among men living with HIV (IRR=1.11; 95% CI: 0.97, 1.27). Pooled estimates indicated approximately equal or higher rates of PSA test in men living with HIV compared to men without HIV across models stratified by age and race-ethnicity groups. Findings do not support the hypothesis that differences in prostate cancer screening explain differences in incidence by HIV status.

Incidence of Colon Cancer Among Medicaid Beneficiaries With or Without Human Immunodeficiency Virus Under Comparable Colorectal Cancer Screening Patterns.

Background: People with human immunodeficiency virus (HIV; PWH) in the United States have a lower incidence of colon cancer than the general population. The lower incidence may be explained by differences in receipt of screening. Thus, we sought to estimate colon cancer incidence under scenarios in which Medicaid beneficiaries, with or without HIV, followed the same screening protocols. Methods: We used data from 1.5 million Medicaid beneficiaries who were enrolled in 14 US states in 2001-2015 and aged 50-64 years; 72 747 beneficiaries had HIV. We estimated risks of colon cancer and death by age, censoring beneficiaries when they deviated from 3 screening protocols, which were based on Medicaid's coverage policy for endoscopies during the time period, with endoscopy once every 2, 4, or 10 years. We used inverse probability weights to control for baseline and time-varying confounding and informative loss to follow-up. Analyses were performed overall, by sex, and by race/ethnicity. Results: PWH had a lower incidence of colon cancer than beneficiaries without HIV. Compared with beneficiaries without HIV, the risk difference at age 65 years was -1.6% lower (95% confidence interval, -2.3% to -.7%) among PWH with the 2-year protocol and -0.8% lower (-1.3% to -.3%) with the 10-year protocol. Results were consistent across subgroup and sensitivity analyses. Conclusions: Our findings suggest that the lower risk of colon cancer that has been observed among PWH aged 50-64 years compared with those without HIV is not due to differences in receipt of lower endoscopy. Keywords: colon cancer, colorectal cancer screening, endoscopy, Medicaid, human immunodeficiency virus.

Clinical characteristics of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies.

BACKGROUND: An increasing number of cases of autoimmune encephalitis (AE) with co-existing multiple anti-neuronal antibodies have been reported in recent years. However, the clinical significance of the concurrent presence of multiple anti-neuronal antibodies in patients with AE remains unclear. METHODS: We retrospectively enrolled AE patients with multiple anti-neuronal antibodies treated at our center between August 2019 and February 2022. We also reviewed cases reported in multiple literature databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then the clinical and laboratory data of these cases were collected for review and summary. RESULTS: A total of 83 AE cases with multiple antibodies (9 cases from our center and 74 cases from the literatures reviewed) were identified. In our center, nine patients presented with encephalitis symptoms, clinically characterized as disturbed consciousness, seizures, cognitive impairment, and psychiatric disorders. Of the 83 cases, 73 cases had co-existence of 2 types of antibodies, 8 cases had 3 types, and 2 cases had 4 types. Thirty-nine cases (39/83, 46.9%) were confirmed or suspected of also having a tumor, of which the most common was lung cancer (28/83, 33.7%). Partial or complete recovery was achieved in 57 cases (57/83, 68.6%), while 26 cases (26/83, 31.3%) died during treatment or follow-up. CONCLUSIONS: AE with co-existing multiple anti-neuronal antibodies is a specific subgroup, that is increasingly recognized in clinical practice. The co-existence of multiple anti-neuronal antibodies has a major impact on clinical features, disease progression, and prognosis.

c-Met is a chimeric antigen receptor T-cell target for treating recurrent nasopharyngeal carcinoma.

BACKGROUND AIMS: Radiation therapy is the standard treatment for patients with nasopharyngeal carcinoma (NPC), but relapse occurs in 10% to 20% of patients. The treatment of recurrent nasopharyngeal carcinoma (rNPC) remains challenging. Chimeric antigen receptors (CAR)-T-cell therapy has achieved good outcomes in the treatment of leukemia and seems to be a promising therapeutic strategy for solid tumors. c-Met has been found to be highly expressed in multiple cancer types, and the activation of c-Met leads to the proliferation and metastasis of cancer cells. However, the expression of c-Met in rNPC tissues and whether it can be used as a target for CAR-T therapy in rNPC remain to be investigated. METHODS: We detected the expression of c-Met in 24 primary human rNPC tissues and three NPC cell lines and constructed two different antibody-derived anti-c-Met CARs, namely, Ab928z and Ab1028z. To estimate the function of these two different c-Met-targeted CAR-T cells, CD69 expression, cytotoxicity and cytokine secretion of CAR-T cells were assessed after coculture with target cells. A cell line-derived xenograft mouse model also was used to evaluate these two anti-c-Met CAR-T cells. Furthermore, we determined whether combination with an anti-EGFR antibody could promote the antitumor effect of CAR-T cells in a patient-derived xenograft mouse model. RESULTS: High c-Met expression was detected in 23 of 24 primary human rNPC tissues by immunohistochemistry staining and in three NPC cell lines by flow cytometry. Ab928z-T cells and Ab1028z-T cells showed significantly upregulated expression of CD69 after coculture with targeted cells. However, Ab1028z-T cells showed superior cytokine secretion and antitumor activity. Furthermore, Ab1028z-T cells effectively suppressed tumor growth compared with control CAR-T cells, and the combination with nimotuzumab further enhanced the tumor-clearing ability of Ab1028z-T cells. CONCLUSIONS: We found that c-Met is highly expressed in rNPC tissues and confirmed its potential as a CAR-T target for rNPC. Our study provides a new idea for the clinical treatment of rNPC.

Anoikis-related genes combined with single cell sequencing: Insights into model specification of lung adenocarcinoma and applicability for prognosis and therapy.

Background: Anoikis has therapeutic potential against different malignancies including lung adenocarcinoma. This study used anoikis and bioinformatics to construct a prognostic model for lung adenocarcinoma and explore new therapeutic strategies. Methods: Several bioinformatic algorithms (co-expression analysis, univariate Cox analysis, multivariate Cox analysis, and cross-validation) were used to screen anoikis-related genes (ARGs) to construct a risk model. Lung adenocarcinoma patients were divided into training and testing groups at a ratio of 1:1. The prognostic model was validated by risk score comparison between high- and low-risk groups using receiver operating characteristic curve (ROC), nomograms, independent prognostic analysis and principal component analysis. In addition, two anoikis-related genes patterns were classified utilizing consensus clustering method and were compared with each other in survival time, immune microenvironment, and regulation in pathway. Single cell sequencing was applied to analyze anoikis-related genes constructed the model. Results: This study demonstrated the feasibility of the model based on seven anoikis-related genes, as well as identifying axitinib, nibtinib and sorafenib as potential therapeutic strategies for LUAD. Risk score based on this model had could be used as an independent prognostic factor for lung adenocarcinoma (HR > 1; p < 0.001) and had the highest accuracy to predict survival compared with the clinical characteristics. Single cell sequencing analysis discovered Keratin 14 (KRT14, one of the seven anoikis-related genes) was mainly expressed in malignant cells in various cancers. Conclusion: We identified seven anoikis-related genes and constructed an accurate risk model based on bioinformatics analysis that can be used for prognostic prediction and for the design of therapeutic strategies in clinical practice.

5-methyladenosine regulators play a crucial role in development of chronic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis.

5-methyladenosine (m5C) modification regulates gene expression and biological functions in oncologic areas. However, the effect of m5C modification in chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remains unknown. Expression data for 12 significant m5C regulators were obtained from the interstitial lung disease dataset. Five candidate m5C regulators, namely tet methylcytosine dioxygenase 2, NOP2/Sun RNA methyltransferase 5, Y-box binding protein 1, tRNA aspartic acid methyltransferase 1, and NOP2/Sun RNA methyltransferase 3 were screened using random forest and nomogram models to predict risks of pulmonary fibrosis. Next, we applied the consensus clustering method to stratify the samples with different m5C patterns into two groups (cluster A and B). Finally, we calculated immune cell infiltration scores via single-sample gene set enrichment analysis, then compared immune cell infiltration, related functions as well as the expression of programmed cell death 1 (PD-1, PDCD1) and programmed death protein ligand-1 (PD-L1, CD274) between the two clusters. Principal component analysis of m5C-related scores across the 288 samples revealed that cluster A had higher immune-related expression than B. Notably, T helper cell (Th) 2 type cytokines and Th1 signatures were more abundant in clusters A and B, respectively. Our results suggest that m5C is associated with and plays a crucial role in development of pulmonary fibrosis. These m5C patterns could be potential biomarkers for identification of CHP and IPF, and guide future development of immunotherapy or other new drugs strategies for pulmonary fibrosis.

Diagnosis and Prognosis of Non-small Cell Lung Cancer based on Machine Learning Algorithms.

BACKGROUND: Non-small cell lung cancer (NSCLC) has been the subject of intense scholarly debate. We aimed to identify the potential biomarkers via bioinformatics analysis. METHODS: Three datasets were downloaded from gene expression omnibus database (GEO). R software was applied to screen differentially expressed genes (DEGs)and analyze immune cell infiltrates. Gene set enrichment analysis (GSEA) showed significant function and pathway in two groups. The diagnostic markers were further investigated by multiple machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)). Various online analytic platforms were utilized to explore the expression and prognostic value of differential genes. Furthermore, western blotting was performed to test the effects of genes on cell proliferation in vitro. RESULTS: We identified 181 DEGs shared by two datasets and selected nine diagnostic markers. Those genes were also significantly overexpressed in the third dataset. Topoisomerase II alpha (TOP2A) is overexpressed in lung cancer and associated with a poor prognosis, which was confirmed using immunohistochemistry (IHC) and Western blotting. Additionally, TOP2A showed a negative correlation with immune cells, such as CD8+ T cells, eosinophils and natural killer (NK) cell. CONCLUSION: Collectively, for the first time, we applied multiple machine learning algorithms, online databases and experiments in vitro to show that TOP2A is a potential biomarker for lung adenocarcinoma and could facilitate the development of new treatment strategies.

An Analysis of BMP1 Associated with m6A Modification and Immune Infiltration in Pancancer.

Background: This research explores the underlying link between diagnosis and therapy between bone morphogenetic protein 1 (BMP1) and various cancers. Methods: Three immunotherapeutic cohorts, by the composition of IMvigor210, GSE35640, and GSE78220 were obtained from previously published articles and the Gene Expression Omnibus database. The different expressions of BMP1 in various clinical parameters were conducted, and prognostic analysis was executed utilizing Cox proportional hazard regression and Gene Expression Profiling Interactive Analysis. Moreover, the correlation between BMP1 and tumor microenvironment was analyzed using ESTIMATE and CIBERSORT algorithms. Tumor mutational burden and microsatellite instability were also included. The correlation between m6A modification and the gene expression level was analyzed using Tumor IMmune Estimation Resource, the University of Alabama at Birmingham Cancer data analysis portal. Gene Set Cancer Analysis analyzed the correlation of BMP1 expression level with copy number variations and methylation. Furthermore, the correlation between BMP1 and therapeutic response after antineoplastic drug use was illustrated for further discussion. Results: BMP1 expression had significant differences in 14 cancers. It presented an intimate relationship with immune-relevant biomarkers. A variation analysis indicated that BMP1 had a significant association with immunotherapeutic response. The expression level of BMP1 was closely associated with insulin-like growth factor binding protein 3, an m6A modification relative gene. Except for a few cancer types, methylation negatively correlated with BMP1, and copy number variations positively correlated with BMP1. Notably, low BMP1 expression was connected with immunotherapeutic response in the cohorts, and its expression was related to increased sectional sensitivity of drugs. Conclusion: BMP1 may serve as a potential biomarker for prognostic prediction and immunologic infiltration in diversified cancers, providing a new thought approach for oncotherapy.

Urine cytological study in patients with clinicopathologically confirmed neuronal intranuclear inclusion disease.

Objective: The diagnosis of neuronal intranuclear inclusion disease (NIID) is currently based on CGG repeat expansion in the 5'UTR of the NOTCH2NLC gene, or p62-positive intranuclear inclusions in skin biopsy. The purpose of this study is to explore the value of non-invasive pathological findings in urine sediment cells from NIID patients. Materials and methods: Ten patients with clinically suspected NIID were enrolled for skin biopsy and gene screening. Morning urine (500 ml) was collected from each patient, and cell sediment was obtained by centrifugation. Urine cytology, including Giemsa staining, p62 immunostaining, and electron microscopic examination, were conducted on cell sediment. Results: The main clinical symptoms of 10 patients included episodic disturbance of consciousness, cognitive impairment, tremor, limb weakness, and so on. Cerebral MRI showed that 9 patients had linear DWI high signal in the corticomedullary junction. Genetic testing found that the number of CGG repeat ranged from 96 to 158 in the NOTCH2NLC gene. Skin biopsy revealed that all patients showed p62-positive intranuclear inclusions in 18.5 ± 6.3% of the duct epithelial cells of sweat gland. In contrast, urine sediment smears revealed that only 3 patients had p62 positive intranuclear inclusions in 3.5 ± 1.2% of the sedimentary cells. Ultrastructural examinations showed that intranuclear inclusions were also identified in the cell sediment of the 3 patients. Conclusion: Urine cytology may be a new and non-invasive pathological diagnosis technique for some NIID patients, although the positive rate is not as high as that of skin biopsy, which is a sensitive and reliable pathological method for NIID.

Machine Learning Algorithm Guiding Local Treatment Decisions to Reduce Pain for Lung Cancer Patients with Bone Metastases, a Prospective Cohort Study.

INTRODUCTION: As life expectancy increases for lung cancer patients with bone metastases, the need for personalized local treatment to reduce pain is expanding. METHODS: Patients were treated by a multidisciplinary team (MDT), and local treatment including surgery, percutaneous osteoplasty, or radiation. Visual analog scale (VAS) and quality of life (QoL) scores were analyzed. VAS at 12 weeks after treatment was the main outcome. We developed and tested machine learning models to predict which patients should receive local treatment. Model discrimination was evaluated by the area under curve (AUC), and the best model was used for prospective decision-making accuracy validation. RESULTS: Under the direction of MDT, 161 patients in the training set, 32 patients in the test set, and 36 patients in the validation set underwent local treatment. VAS in surgery, percutaneous osteoplasty, and radiation groups decreased significantly to 4.78 ± 1.28, 4.37 ± 1.36, and 5.39 ± 1.31 at 12 weeks, respectively (p < 0.05), with no significant differences among the three datasets, and improved QoL was also observed (p < 0.05). A decision tree (DT) model that included VAS, bone metastases character, Frankel classification, Mirels score, age, driver gene, aldehyde dehydrogenase 2, and enolase 1 expression had a best AUC in predicting whether patients would receive local treatment of 0.92 (95% CI 0.89-0.94) in the training set, 0.85 (95% CI 0.77-0.94) in the test set, and 0.88 (95% CI 0.81-0.96) in the validation set. CONCLUSION: Local treatment provided significant pain relief and improved QoL. There were no significant differences in reducing pain and improving QoL among training, test, and validation sets. The DT model was best at determining whether patients should receive local treatment. Our machine learning model can help guide clinicians to make local treatment decisions to reduce pain. TRIAL REGISTRATION: Trial registration number ChiCRT-ROC-16009501.

A Retrospective Study of predicting risk of Metastasis among FDG-avid Bone Lesions in 18F-FDG PET/CT.

Purpose: We evaluated the imaging and clinical features for discriminating the possibility of metastasis among FDG-avid bone lesions in 18F-FDG PET/CT in patients who have received bone biopsy. Methods: The retrospective study included patients who underwent both 18F-FDG PET/CT and bone biopsy for FDG-avid bone lesions. Bone lesions maximum standardized uptake value (SUVmax), CT findings, alongside with common clinical features were analyzed. Results: From the 338 patients enrolled in the final study, all of them were received bone biopsy. Biopsies confirm metastasis in 256 cases (75.74%) and benign tissue in 82 cases (24.26%). Metastasis group had higher bone SUVmax than benign group (median 7.9 vs 4.5, p <0.001). A cutoff bone SUVmax of 5 achieved an AUC of 0.748 in all patients. Lytic CT feature and higher age were more likely frequent in metastasis group. Moreover, in patients without obvious CT abnormality (45, 13.31%), the AUC was 0.743 by a SUVmax cutoff of 5.38, whilst in patients with a solitary bone lesion (74, 21.89%), the AUC was 0.803 by a SUVmax cutoff of 4.3. Conclusions: SUVmax is a promising and valuable metabolic indicator for predicting risk of metastasis among FDG-avid bone lesions in 18F-FDG PET/CT, ancillary clinical and imaging features may increase the probability of a metastatic bone lesion.

Value of combining PET/CT and clinicopathological features in predicting EGFR mutation in Lung Adenocarcinoma with Bone Metastasis.

Purpose: Epidermal growth factor receptor (EGFR) mutation is the most common target for precision treatment in metastatic lung adenocarcinoma. We investigated the predictive role of 18F-FDG PET/CT and clinicopathological features for EGFR mutations in lung adenocarcinoma with bone metastasis. Methods: Seventy-five lung adenocarcinoma patients with histologically confirmed bone metastasis were included. They all received EGFR status test and PET/CT before systemic treatment. The differences of maximum standardized uptake value (SUVmax) in primary tumor (pSUVmax), regional lymph node (nSUVmax) and bone metastasis (bmSUVmax) between different EGFR status groups were compared, alongside with common clinicopathological features. Multivariate logistic regression analysis was performed to evaluate predictors of EGFR mutations. Results: EGFR mutations were found in 37 patients (49.3%). EGFR mutations were more common in females, non-smokers, expression of Thyroid Transcription Factor-1 (TTF-1) and NaspinA. Low bmSUVmax was significantly associated with EGFR mutations, while no significant difference was observed in pSUVmax and nSUVmax. Multivariate analysis showed that bmSUVmax ≤7, non-smoking, expression of TTF-1 were predictors of EGFR mutations. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.84 for the combination of the three factors. Conclusion: Low bmSUVmax is more frequently in EGFR mutations, and bmSUVmax is an independent predictor of EGFR mutations. Combining bmSUVmax with other clinicopathological features could forecast the EGFR status in lung adenocarcinoma with unavailable EGFR gene testing.

Methylation-Induced Silencing of ALDH2 Facilitates Lung Adenocarcinoma Bone Metastasis by Activating the MAPK Pathway.

Bone metastasis (BM) dramatically reduces the quality of life and life expectancy in lung adenocarcinoma (LUAD) patients. There is an urgent need to identify potential biomarkers for application in the treatment of this deadly disease. We compared patient BM, LUAD, and para-LUAD tissues using proteomic analysis and identified aldehyde dehydrogenase 2 (ALDH2), which can detoxify acetaldehyde to acetic acid, as one of the key regulators in lung tumor metastasis. Both the mRNA and protein levels of ALDH2 were significantly lower in tumor tissues than in normal tissues and were lowest in BM tissues with increased migratory capacity. Also, ALDH2 was upregulated following treatment with 5-azacitidine, a DNA methyltransferase inhibitor, in H1299, H460, and HCC827 cells. Further, we identified a potential methylated CpG island 3, with the longest methylated CpG island area in ALDH2, and performed bisulfite genomic sequencing of these sites. An average of 78.18% of the sites may be methylated in CpG island 3. Knockdown of DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and methylated CpG binding protein 4 (MBD4) upregulated ALDH2 expression. ALDH2 functions as a mitogen-activated protein kinase (MAPK) upstream to inhibit cell proliferation and migration, promote cell apoptosis, and alter the epithelial-mesenchymal transition (EMT) by elevating E-cadherin and attenuating vimentin. Cell proliferation and migration were inhibited after the addition of the JNK inhibitor SP600125. In the multivariate analysis, M stage (p = 0.003), ALDH2 (p = 0.008), and phospho-c-Jun N-terminal kinase (p-JNK) (p = 0.027) expression were independent prognostic factors for overall survival in patients with BM. In vivo experiments also showed that ALDH2 expression could suppress tumor formation. In summary, we found that ALDH2 expression is a prognostic factor for BM in LUAD and that DNMT3A and MBD4 repression of ALDH2 via a MAPK-dependent pathway alters the EMT process, indicating that these proteins could act as potential biomarkers or therapeutic targets for LUAD metastasis.

TRIM58 Interacts with Pyruvate Kinase M2 to Inhibit Tumorigenicity in Human Osteosarcoma Cells.

BACKGROUND: Tripartite motif containing 58 (TRIM58), an E3 ubiquitin ligase, is reported as a suppressor gene in certain human tumors. However, the biological function of TRIM58 in osteosarcoma (OS) is still less identified. METHODS: In the present study, TRIM58 induced silencing and overexpression in OS cells using RNA interference (RNAi) and lentiviral-mediated vector, respectively. Cell proliferation profiles were analyzed using cell counting kit-8 (CCK-8) assay. Cell apoptosis profiles were determined using a flow cytometer. qRT-PCR and western blot were used to determine gene expression. Coimmunoprecipitation (Co-IP) assay was used to examine protein interaction. RESULTS: Our results demonstrated TRIM58 was downregulated in human OS tissues. Overexpression of TRIM58 remarkably suppressed the growth of OS cells and decreased glucose transportation and lactate secretion. These results indicated that TRIM58 involved in the regulation of energy metabolism in OS cells. Importantly, TRIM58 interacted with pyruvate kinase M2 (PKM2) in OS cells. Moreover, TRIM58 might inhibit the activity of PKM2 through enhancing its polyubiquitination in OS cells. CONCLUSIONS: This analysis not only explored a deep understanding of the biological function of TRIM58 but also indicated its signaling pathway in OS cells.

Diagnostic Value of Whole-Body DWI With Background Body Suppression Plus Calculation of Apparent Diffusion Coefficient at 3 T Versus 18F-FDG PET/CT for Detection of Bone Metastases.

OBJECTIVE. The purpose of this study is to evaluate the diagnostic performance of whole-body (WB) DWI with background body suppression (DWIBS) combined with calculation of the apparent diffusion coefficient (ADC) value at 3 T compared with the diagnostic performance of 18F-FDG PET/CT for detecting bone metastases in patients with malignant tumors. SUBJECTS AND METHODS. Thirty-nine consecutive patients with suspected bone metastases underwent both WB DWIBS and FDG PET/CT. Imaging findings were independently interpreted using qualitative and quantitative analyses. Pathologic findings or clinical or radiologic follow-up data were used as the diagnostic reference standard. The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value of both modalities were calculated. The ADCs of benign lesions and metastases were compared. RESULTS. A total of 213 metastatic bone segments were confirmed among 39 patients. The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value were 93.0%, 87.8%, 89.6%, 79.8%, and 96.0%, respectively, for WB DWIBS and 92.5%, 92.0%, 92.1%, 85.7% and 95.9%, respectively, for FDG PET/CT. The specificity of WB DWIBS in detecting bone metastases was significantly lower than that of FDG PET/CT (p < 0.05), whereas the sensitivity, overall accuracy, positive predictive value, and negative predictive value in detecting bone metastases were not significantly different between WB DWIBS and FDG PET/CT (p > 0.05). The ADCs for benign lesions were significantly higher than those for metastases (p < 0.001). In ROC curve analysis, the AUC value was 0.901. A cutoff ADC value of 920.5 × 10-6 mm2s-1 distinguished benign lesions from bone metastases with a sensitivity of 92.9% and a specificity of 73.4%. CONCLUSION. WB DWIBS coupled with ADC analysis at 3 T is effective for detecting bone metastases.

Postoperative redislocation of the hip in a patient with congenital insensitivity to pain with anhidrosis: A case report and review of literature.

Pelvic osteotomy is commonly used to adjust acetabula dysplasia for congenital dislocation of the hip, whereas congenital insensitivity to pain with anhidrosis (CIPA) is a rare hereditary disease that often has the characteristics of joint development deformity and easy fracture. This article reports the case involving a CIPA patient who was surgically treated by Chiari pelvic osteotomy and proximal femoral rotation osteotomy for congenital dislocation of the left hip joint and was provided long-term follow-up for redislocation and bilateral femoral head absorption.

Differentially expressed and survival-related proteins of lung adenocarcinoma with bone metastasis.

Despite recent advances in targeted and immune-based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. First, two-dimensional gel electrophoresis (2-DE) was used to identify proteins that were differentially expressed in LUAD with BM, and then matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify these proteins. Second, the Cancer Genome Atlas (TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan-Meier plotter (KM Plotter) was used to generate survival curves for the analyzed cases. Immunohistochemistry (IHC) was used to check the expression of proteins in 28 patients with BM and nine patients with LUAD. Lastly, the results were analyzed with respect to clinical features and patient's follow-up. We identified a number of matched proteins from 2-DE. High expression of enolase 1 (ENO1) (HR = 1.67, logrank P = 1.9E-05), ribosomal protein lateral stalk subunit P2 (RPLP2) (HR = 1.77, logrank P = 2.9e-06), and NME/NM23 nucleoside diphosphate kinase 2 (NME1-NME2) (HR = 2.65, logrank P = 3.9E-15) was all significantly associated with poor survival (P < 0.05). Further, ENO1 was upregulated (P = 0.0004) and calcyphosine (CAPS1) was downregulated (P = 5.34E-07) in TCGA LUAD RNA-seq expression data. IHC revealed that prominent ENO1 staining (OR = 7.5, P = 0.034) and low levels of CAPS1 (OR = 0.01, P < 0.0001) staining were associated with BM incidence. Finally, we found that LUAD patients with high expression of ENO1 and RPLP2 had worse overall survival. This is the first instance where the genes ENO1, RPLP2, NME1-NME2 and CAPS1 were associated with disease severity and progression in LUAD patients with BM. Thus, with this study, we have identified potential biomarkers and therapeutic targets for this disease.

The possible mechanism of Parkinson's disease progressive damage and the preventive effect of GM1 in the rat model induced by 6-hydroxydopamine.

The progressive pathogenesis and prevention of Parkinson's disease (PD) remains unknown at present. Therefore, the present study aimed to investigate the possible progressive pathogenesis and prevention of PD. Our study investigated the content of glutamate, mitochondria calcium, calmodulin, malonaldehyde and trace elements in striatum, cerebral cortex and hippocampus tissues; and the expression of bcl-2, bax and neuronal nitric oxide synthase (nNOS) in substantia nigra and striatum; and the change of apomorphine induced rotation behavior; and the treatmental effect of monosialotetrahexosylganglioside (GM1) intraperitoneal administration for 14 days in a PD rat model induced by 6-hydroxydopamine. The results revealed that the content of glutamate significantly decreased, and that of mitochondria calcium, calmodulin, malonaldehyde and ferrum significantly increased in striatum, cerebral cortex and hippocampus tissues; the content of magnesium significantly decreased, and that of cuprum and zinc significantly increased in cerebral cortex; the expression of bcl-2 significantly decreased, and that of bax and nNOS significantly increased in substantia nigra and striatum in PD rat. GM1 can partially improve the apomorphine induced rotation behavior and changes of glutamate, mitochondria calcium, calmodulin content in striatum of PD rat. Data suggested that dysfunction of excitatory amino acids neurotransmitter, calcium homeostasis disorder, abnormal metabolism of oxygen free radicals, abnormal trace elements distribution and/or deposition and excessive apoptosis participated in the progressive process of PD, and that GM1 could partially prevent the progressive damage.