EBF1-COX4I2 signaling axis promotes a myofibroblast-like phenotype in cancer-associated fibroblasts (CAFs) and is associated with an immunosuppressive microenvironment.

Immunotherapy has limited response rates in colorectal cancer (CRC) due to an immunosuppressive tumor microenvironment (TME). Combining transcriptome sequencing, clinical specimens, and functional experiments, we identified a unique group of CAF subpopulations (COX4I2 + ) with inhibited mitochondrial respiration and enhanced glycolysis. Through bioinformatics predictions and luciferase reporter assays, we determined that EBF1 can upstreamly regulate COX4I2 transcription. COX4I2 + CAFs functionally and phenotypically resemble myofibroblasts, are important for the formation of the fibrotic TME, and are capable of activating the M2 phenotype of macrophages. In vitro experiments demonstrated that COX4I2 + CAFs promote immunosuppressive TME by blocking CD8 + T cell infiltration and inducing CD8 + T cell dysfunction. Using multiple independent cohorts, we also found a strong correlation between the immunotherapy response rate of CRC patients and COX4I2 expression in their tumors. Our results identify a CAF subpopulation characterized by activation of the EBF1-COX4I2 axis, and this group of CAFs can be targeted to improve cancer immunotherapy outcomes.

Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer.

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.

Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent colitis-associated colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC. RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1ß, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

Textural differences based on apparent diffusion coefficient maps for discriminating pT3 subclasses of rectal adenocarcinoma.

BACKGROUND: The accuracy of discriminating pT3a from pT3b-c rectal cancer using high-resolution magnetic resonance imaging (MRI) remains unsatisfactory, although texture analysis (TA) could improve such discrimination. AIM: To investigate the value of TA on apparent diffusion coefficient (ADC) maps in differentiating pT3a rectal adenocarcinomas from pT3b-c tumors. METHODS: This was a case-control study of 59 patients with pT3 rectal adenocarcinoma, who underwent diffusion-weighted imaging (DWI) between October 2016 and December 2018. The inclusion criteria were: (1) Proven pT3 rectal adenocarcinoma; (2) Primary MRI including high-resolution T2-weighted image (T2WI) and DWI; and (3) Availability of pathological reports for surgical specimens. The exclusion criteria were: (1) Poor image quality; (2) Preoperative chemoradiation therapy; and (3) A different pathological type. First-order (ADC values, skewness, kurtosis, and uniformity) and second-order (energy, entropy, inertia, and correlation) texture features were derived from whole-lesion ADC maps. Receiver operating characteristic curves were used to determine the diagnostic value for pT3b-c tumors. RESULTS: The final study population consisted of 59 patients (34 men and 25 women), with a median age of 66 years (range, 41-85 years). Thirty patients had pT3a, 24 had pT3b, and five had pT3c. Among the ADC first-order textural differences between pT3a and pT3b-c rectal adenocarcinomas, only skewness was significantly lower in the pT3a tumors than in pT3b-c tumors. Among the ADC second-order textural differences, energy and entropy were significantly different between pT3a and pT3b-c rectal adenocarcinomas. For differentiating pT3a rectal adenocarcinomas from pT3b-c tumors, the areas under the curves (AUCs) of skewness, energy, and entropy were 0.686, 0.657, and 0.747, respectively. Logistic regression analysis of all three features yielded a greater AUC (0.775) in differentiating pT3a rectal adenocarcinomas from pT3b-c tumors (69.0% sensitivity and 83.3% specificity). CONCLUSION: TA features derived from ADC maps might potentially differentiate pT3a rectal adenocarcinomas from pT3b-c tumors.

Biparametric prostate MRI and clinical indicators predict clinically significant prostate cancer in men with "gray zone" PSA levels.

PURPOSE: To predict clinically significant prostate cancer (cs-PCa) by combining the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score based on biparametric magnetic resonance imaging (bp-MRI) and clinical indicators in men with prostate-specific antigen (PSA) levels in the gray zone of 4-10 ng/mL. METHOD: We retrospectively analyzed 364 patients with elevated PSA levels in the gray zone who had pathologically confirmed disease and had undergone MRI examinations from January 2015 to October 2019; a training group (n = 255) and validation group (n = 109) were randomly established. Multivariate logistic regression analysis of the training group was performed to identify the independent predictors for cs-PCa, thereby establishing a predictive model that was evaluated in the training and validation groups by analyzing the receiver operating characteristic (ROC) curve. RESULTS: In the training group, the PI-RADS v2 score and prostate volume (PV) were independent predictors of cs-PCa (P < 0.05). The prediction model comprising the PI-RADS v2 score and PV had a larger AUC than the other predictors alone in the training group. The diagnostic sensitivity and specificity of the prediction model were 84.1 % and 83.4 %, respectively. The prediction model was indicated to have better predictive performance in the validation group. CONCLUSIONS: The prediction model exhibits a satisfactory predictive value for cs-PCa in men with PSA levels in the gray zone. PI-RADS v2 is the strongest univariate predictor for the detection of cs-PCa in men with PSA in the gray zone, but combining this with the PV can provide superior predictive ability.

Differentiating Transition Zone Cancers From Benign Prostatic Hyperplasia by Histogram Analysis of Apparent Diffusion Coefficient Maps With Standard and Ultrahigh b-value Diffusion-weighted MR Imaging.

OBJECTIVE: To compare the diagnostic performance of standard and ultrahigh b-value Diffusion-weighted Imaging (DWI) using volumetric histogram analysis in differentiating transition zone (TZ) cancer from benign prostatic hyperplasia (BPH). METHODS: 57 TZ cancer and 61 BPH patients received standard (1000 s/mm) and ultrahigh b-value (2000 s/mm) DWI. The diagnostic ability of ADC histogram parameters derived from two DWI for differentiating TZ cancer from BPH was determined by receiver operating characteristic curve. RESULTS: Median, minimum, the 10th, 25th percentile ADC in both ADC1000 and ADC2000 and skewness in ADC2000 had significant differences between TZ cancer and BPH (for all, P < 0.05).The 10th percentile ADC showed highest area under the ROC curve (AUC) in both ADC1000 and ADC2000.The 10th percentile ADC of ADC2000 showed significantly higher AUC than did ADC1000 (P = 0.0385). CONCLUSIONS: The 10th percentile ADC obtained from ultrahigh b-value DWI performed better for differentiating TZ cancer from BPH.

Preoperative diffusion-weighted imaging value of rectal cancer: preoperative T staging and correlations with histological T stage.

PURPOSE: To assess the ability of diffusion-weighted imaging (DWI) for evaluating T stage and correlation with histological T stage of rectal cancer. METHOD: The diagnostic accuracy, sensitivity, and specificity of T2WI and DWI combined with T2WI for T stage were evaluated. Mean tumor apparent diffusion coefficient (ADC) was compared with histological T stage. RESULT: There were no significant differences in the diagnostic accuracy, sensitivity, and specificity no matter what kind of T stage was concerned. The difference between ADC values and histological T stage were significantly different. CONCLUSION: DWI was useful for evaluating T stage of rectal cancer. The ADC may predict the histological grade.

Unusual features in an adult pancreatic hemangioma: CT and MRI demonstration.

Hemangiomas in the pancreas are very rare and only a few cases in adulthood have been reported in the literature. We describe a case of pancreatic hemangiomas in an adult with unique imaging findings. A 23-year-old woman visited the hospital for an incidentally detected pancreatic mass. CT and MRI revealed a multilocular cyst with fluid-fluid levels and no obvious enhancement. The patient underwent surgery and the mass was confirmed as a pancreatic hemangioma. The radiological features and differential diagnosis of this rare lesion are discussed.

Aggressive osteoblastoma of the temporal bone: a case report and review of the literature.

Osteoblastoma can take place in any part of the skeleton. Its occurrence in the calvarium is extremely rare. The aggressive form of osteoblastoma is a rare variant. To our knowledge, this is the second case of aggressive osteoblastoma arising in the temporal bone. We report an 18-year-old patient with aggressive osteoblastoma involving the left temporal bone. Computed tomography of temporal bone showed an osteolytic lesion with granular mineralization and mottled ossified density. Permanent histopathologic sections and immunohistochemical stains revealed an aggressive osteoblastoma.

Transfect bone marrow stromal cells with pcDNA3.1-VEGF to construct tissue engineered bone in defect repair.

BACKGROUND: We previously showed that nano-hydroxyapatite/carboxymethyl chitosan (n-Ha/CMCS) displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicity. The aim of this study was to determine the effect of the same composite with vascular endothelial growth factor (VEGF)- transfected bone marrow stromal cells (BMSCs) in a rabbit radial defect model. METHODS: The nano-hydroxyapatite was produced through co-precipitation. The n-HA/CMCS scaffold was produced by particle filtration and lyophilization followed by genipin crosslinking. Total RNA from rabbit bone was reverse-transcribed to synthesize VEGF165-pcDNA3.1 that was transfected into the BMSCs. The composite was implanted into a rabbit radial defect model, and the osteogenic activity examined by gross morphology, X-ray examination and hematoxylin and eosin (HE) staining. RESULTS: The microstructure and mechanical property of the n-HA/CMCS scaffold resembled natural cancellous bone. Compared with glutaric dialdehyde crosslinked scaffolds, the genipin crosslinked scaffold was less toxic, and displayed a higher capacity to promote cell adhesion and proliferation. Spontaneous fluorescence of the composite permitted visualization of the composite-bone interface and the adhesion behavior of cells on the scaffold under laser scanning confocal microscopy. The scaffold with VEGF-transfected BMSCs bridged the bony defect and promoted healing, with most of the implanted material being replaced by natural bone over time with little residual implant. Using X-ray, we noted obvious callus formation and recanalization of the bone marrow cavity. Furthermore, HE stained sections showed new cortical bone formation. CONCLUSIONS: The n-HA/CMCS scaffold composite with VEGF-trasnfected BMSCs is biocompatible, nontoxic, promotes the infiltration and formation of the microcirculation, and stimulates bone defect repair. Furthermore, the degradation rate of the composite matched that of growing bone. Overall, this composite material is potentially useful for bone defect repair.

Localized Castleman disease of plasma cell type in the abdomen.

Castleman disease is a relatively rare entity, with the hyaline-vascular type the predominant form. Although the plasma cell type is uncommon, it still comprises approximately 10% of cases of localized diseases. In addition, the abdomen is a rare site for involvement and localized Castleman disease of the plasma cell type in the abdomen is rare. The radiologic features of localized plasma cell type in the abdomen are mostly limited to case reports. In addition to the conventional imaging findings, we present some new imaging findings of localized plasma cell type in the abdomen.

[Ultrasound guided transrectal prostate biopsy: 11-year experience].

OBJECTIVE: To summarize the experience in ultrasound guided transrectal prostate biopsy and analyze the influencing factors of the biopsy results. METHODS: 687 patients with prostate specific antigen (PSA) > 4 microg, tubercles in prostate detected by digital rectal examination and/or prostate abnormality detected by magnetic resonance imaging, aged (70 +/- 8), underwent ultrasound guided transrectal 6 - 12 core prostate biopsy 1996 - 2007. Since 2006 the criteria for biopsy included PSA of 4 - 10 microg/ml, free PSA/total PSA ratio (F/T ratio) 0.15. RESULTS: 269 of the 687 cases, with the mean age of (72 +/- 8), were diagnosed as with prostate cancer. 294 and 121 of the 687 patients (42.8% and 17.6% respectively) accepted prostate biopsy because of elevated PSA or abnormality of DRE. The number of patients accepting prostate biopsy increased yearly (10 cases in 1996 to 98 cases in 2007). The positive biopsy rate was 39.8%, with the highest rate of 60.0% in 1999 and lowest rate of 30.4% in 2005. The highest number of prostate cancer diagnosed was the highest (42 cases) in 2007 and the lowest (4 cases) in 1996. PSA level was positively co-related with positive biopsy rate. The application of F/T ratio improved the positive biopsy rate in the patient with the PSA of 4 - 10 microg/ml. The incidence rates of the main complications hematuria, bloody stool, and fever were 46.3%, 8.7%, and 1.9% respectively. CONCLUSION: Elevated PSA has become the most common reason for prostate biopsy. The combination with PSA, F/T ratio, and increased biopsy core number improve the positive biopsy rate. The ultrasound guided transrectal prostate biopsy is efficient and safe in the diagnosis of prostate cancer.

[Detection of urological and male genital tumors diagnosed in Beijing Hospital 1995 - 2004].

OBJECTIVE: To investigate the diagnostic condition of urological and male genital tumors in Beijing Hospital during the period 1995 - 2004. METHODS: The clinical data of 1245 patients diagnosed as with urological and male genital tumors that were hospitalized in the Department of Urology, Beijing Hospital from 1 January 1995 to 31 December 2004, 957 males and 288 females, were analyzed retrospectively. RESULTS: The 1245 with urological and male genital tumors accounted for 20.96% of the patients hospitalized in the Department of Urology of this hospital in the same period. The commonest malignancies included transitional cell carcinoma of bladder (n = 387), carcinoma of prostate (n = 271), and clear cell carcinoma of kidney (n = 250). The detected numbers of cases of these three kinds of malignancies increased year by year. The ratio of metastatic carcinoma in prostate and kidney decreased with each passing year. Before 1999 75.48% of the patients with prostate carcinoma visited the hospital because of low urinary tract symptom (LUTS), and only 12.48% because of abnormalities discovered during physical examination, However, after 2000 the percentage of the prostate carcinoma patients who visited the hospital because of LUST deceased to 54.44%, and those because of abnormalities discovered during physical examination increased to 40.99% (P < 0.01). CONCLUSION: The improvement of diagnostic methods has changed the condition of tumor diagnosis in recent years.

[Evaluation of gastric lavage treatment for severe acute organophosphorus pesticides poisoning complicated by respiratory failure requiring mechanical ventilation].

OBJECTIVE: To discuss the measures of gastric lavage for severe acute organophosphorus pesticides poison (AOPP) patients complicated with respiratory failure and treated with mechanical ventilation. METHODS: 92 cases of respiratory failure due to severe AOPP treated with mechanical ventilation were treated for gastric lavage with nasal gastric tube or gastrotomy. Patients of each gastric lavage method were divided into fasting toxicosis group (fasting group) and post-meal toxicosis group (post-meal group). RESULTS: When treated for lavage with nasal gastric tube, the duration of coma, the time for reaching atropinization and the dosage of atropine needed, the total dosage of atropine used, the mechanical ventilation time, the time for restoring 50% of the normal value of choline esterase, the hospitalization time and charges, the relapse rate, the rate of atropine toxicosis and mortality were respectively: 13 (3 - 24) h, 180 (60 - 290) min, 150 (80 - 310) mg, 300 (90 - 870) mg, 17 (4 - 52) h, (5.0 +/- 2.3) d, 9 (7 - 18) d, (8080 +/- 2570) yuans, 0, 0, and 4.76% in the fasting groups; all the figures were superior to those of the post-meal group with the same treatment: 26 (4 - 55) h, 380 (110 - 690) min, 360 (90 - 730) mg, 3610 (1100 - 9070) mg, 36 (6 - 110) h, (7.8 +/- 3.6) d, 12 (9 - 35) d, (10 720 +/- 3350) yuans, 45%, 30%, and 30.00% (P < 0.01 or P < 0.05). There was no obvious difference between the fasting group and the post-meal group in curative effect, complication occurrence rate and mortality except for the charges when treated with gastrotomy. For the post-meal toxicosis patients gastrotomy showed a better effect than the nasal gastric tube and there was no difference in charges. CONCLUSIONS: It is suggested that severe AOPP patients complicated with respiratory failure and treated with mechanical ventilation should hare lavage with nasal gastric tube, if they were poisoned in fasting state, but they should be washed through gastrotomy if poisoned after meal.