[Value of PET/MRI in the diagnosis of malignant pleural effusion in comparison with PET/CT].

Objective: To investigate the diagnostic value of PET/MRI for malignant pleural effusion (MPE), and compare its diagnostic difference with PET/CT. Methods: The data of 57 patients with suspected MPE admitted into Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from October 2017 to January 2020 was analyzed. A total of 53 patients were included in the prospective study, and the whole body PET/CT and thoracic PET/MRI were performed on them respectively. Two physicians used a blind method to evaluate the morphological features of PET/CT and PET/MRI images, delineate the region of interest (ROI), obtain the maximum standard uptake value (SUVmax) of the ROI in the PET/CT and PET/MRI images. The target-to-background ratio (TBR) of the lesion was calculated. The diffusion-weighted imaging (DWI) characteristics of the pleura in PET/MRI images were analyzed. Taking pathological diagnosis as the gold standard, the diagnostic effect of PET/CT and PET/MRI on MPE were evaluated. Results: The 53 patients who were finally included were (62.8±1.7) years old, consisting of 31 males. Pathological results showed that 41 cases were MPE and 12 cases were benign pleural effusion (BPE). There were no statistical differences in age, gender and smoking history between the two groups (P>0.05). Bland-Altman analysis showed that the SUVmax of pleural lesions by PET/MRI was higher than that by PET/CT (6.4±0.6 vs 5.3±0.5, P<0.001). The TBR of PET/MRI was higher than that of PET/CT (2.2±0.2 vs 1.8±0.2, P<0.001). The sensitivity, specificity, and accuracy of PET/MRI in the diagnosis of MPE by combining imaging features such as SUVmax and DWI of pleural lesions were 75.6%, 100%, and 81.1%, respectively. The sensitivity, specificity, and accuracy of PET/CT combined with SUVmax and imaging features of pleural lesions in the diagnosis of MPE were 85.4%, 83.3%, and 77.4%, respectively. There was no statistically significant difference between PET/MRI and PET/CT in the area under the curve (AUC) for diagnosing MPE (0.934 vs 0.873, P>0.05). Conclusions: PET/MRI and PET/CT have the equivalent diagnostic efficiency for MPE. However, PET/MRI shows higher SUVmax and TBR for pleural lesions, and has specific pleural DWI imaging characteristics, which is worthy of further clinical research.

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. METHODS: CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. RESULTS: CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/ß-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. CONCLUSIONS: CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.

DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.

[Correlation between TNM staging of primary cholangiocarcinoma and the maximum standard uptake value of (18)F-2-deoxy-D-glucose positron emission tomography with computerized tomography].

Objective: To investigate the correlation between TNM staging of primary cholangiocarcinoma and the maximum standard uptake value (SUVmax) of (18)F-2-deoxy-D-glucose positron emission tomography with computerized tomography ((18)F-FDG PET/CT). Methods: A retrospective analysis of 36 patients with confirmed primary cholangiocarcinoma from October 2014 to July 2016 was carried out. All the patients underwent preoperative PET/CT in the Fifth Affiliated Hospital of Wenzhou Medical University from November 2014 to July 2016, the SUVmax was calculated by drawing region of interest around the primitive tumor area.According to the American Cancer Joint Committee (AJCC) guidelines for the clinical staging of intrahepatic and extrahepatic cholangiocarcinoma, the differences of SUVmax were compared in the patients with different age, gender and staging, and the correlation between TNM staging and SUVmax was determined.Data were compared with independent sample t test between groups. Results: The mean SUVmax of 36 patients with primary cholangiocarcinoma was 7.87±3.17 (2.1-14.6). The SUVmax values of patients with lymph node metastasis or distant metastasis were significantly higher than those without lymph node metastasis or distant metastasis (t=0.364, 0.343, both P<0.05), respectively. There was significant difference in SUVmax between patients with different TNM staging (F=1.352, P=0.021). There was no significant differences in SUVmax between patient with different gender, age (>70 years or<70 years) and T staging (t=1.058, 1.980, F=1.252, all P>0.05). Spearman correlation analyses showed that the TNB stage of primary cholangiocarcinoma was positively correlated with its SUVmax (r=0.658, P=0.007). Conclusion: The SUVmax is positively correlated with the TNM staging of primary cholangiocarcinoma, which is helpful for the clinical staging and prognosis of the patients.

[The clinical manifestations and risk factors in primary antiphospholipid syndrome with thrombocytopenia].

Objectives: To cross-sectionally analyze the clinical characteristics of primary antiphospholipid syndrome (PAPS) patients with thrombocytopenia, risk factors associated with thrombocytopenia, and risk of symptom recurrence in these patients. Methods: The inpatients with PAPS were retrospectively analyzed in Peking Union Medical College Hospital from 2009 to 2019. Using the collected clinical and laboratory data, the clinical characteristics and risk of symptom recurrence in the PAPS patients with thrombocytopenia were compared with those in the PAPS patients with normal platelet counts. Univariate and multivariate logistic regression analyses were performed to screen the risk factors for thrombocytopenia. Results: In this study, 127 patients with PAPS were enrolled, of which 36 (28.3% ) had thrombocytopenia, with a median age of 38 years, and 63.9% were female. In the thrombocytopenia group, the average platelet count was (58.9±27.0) ×10(9)/L, and the prevalence of thrombosis and morbid pregnancy was not significantly different from that in the normal platelet group. However, the thrombocytopenia group had higher incidence rate of autoimmune hemolytic anemia (19.4% vs 3.3% ) , livedo reticularis (16.7% vs 3.3% ) , chronic kidney disease (25% vs 8.8% ) and antiphospholipid antibodies triple positiveness (61.1% vs 37.4% ) , lower complement levels (C3 of 0.87 g/L vs 1.07 g/L, C4 of 0.12 g/L vs 0.18 g/L, P<0.05) , and higher adjusted Global APS Score (median score of 13 vs 9, P=0.037) than the normal platelet group. In multivariate logistic regression analysis, hypocomplementemia (OR value 5.032, 95% CI 3.118-22.095) is an independent risk factor for thrombocytopenia. Conclusions: In patients with PAPS, thrombocytopenia is mostly mild to moderate. Hypocomplementemia may be the independent risk factor for thrombocytopenia in PAPS patients. The PAPS patients with thrombocytopenia may have a higher risk of symptom recurrence.

[Analysis of the clinical characteristics and prognosis of 36 cases of newly diagnosed multiple myeloma patients with bone marrow monoclonal plasma cell ratio of less than 10].

Objective: To improve the understanding of newly diagnosed multiple myeloma (NDMM) patients with bone marrow (BM) monoclonal plasma cell ratio of less than 10%. Methods: The clinical characteristics, laboratory examination, response to treatment, and prognosis of 36 NDMM patients with BM plasma cell ratio of less than 10% at Peking Union Medical College Hospital from January 2009 to December 2017 were summarized retrospectively. In the same period, other age- and gender-matched 72 NDMM patients were selected as the control group, whose BM plasma cell ratio was equal to or greater than 10%. Results: First, the patients in the study group accounted for 4.4% of the whole MM population (36/818) , among which only 11 (30.6%) were classified as International Staging System (ISS) Ⅲ, which was significantly lower than that in the control group[45 (62.5%) ] (P=0.002) . Extramedullary disease (EMD) was more common in the study group (33.3%vs 5.6%, P<0.001) . The median quantity of serum M protein (g/L) in the less than 10% group was 1.04 (0-50.10) , which was significantly lower than that in the control group [4.50 (0-63.10) ] (P=0.016) , similar to the median quantity of 24-h urinary light chain (510 mg vs 2800 mg, respectively, P=0.023) . Second, the median progression-free survival (PFS) times of front-line regimen in the study and control groups were 26.4 and 19.9 months, respectively (HR=1.703, 95%CI 0.167-0.233, P=0.002) . In addition, the overall survival (OS) times were 65.8 and 46.2 months, respectively (HR=2.626, 95%CI 0.439-0.541, P=0.058) . Third, the study group was reclassified based on the quantity of M protein. The median OS times in patients with low/high tumor load were 66.4 and 24.0 months, respectively (HR=2.349, 95%CI 0.603-0.696, P=0.046) . The median PFS times were 33.1 and 15.5 months, respectively (HR=1.806, 95%CI 0.121-0.399, P=0.077) . Bortezomib-based regimens did not affect the clinical outcomes. Conclusion: The subpopulation of patients with MM with BM monoclonal plasma cell ratio less than 10% has specific clinical characteristics, including an early disease stage and a lower overall tumor load. Although more patients of this minor group presented with an extramedullary disease, their response rate to the initial treatment and survival outcome are better than those of patients with BM monoclonal plasma cell ratio more than 10%.

[Short-term outcomes of single incision plus one port laparoscopic surgery for colorectal cancer].

Objective: Although single port laparoscopic surgery has achieved good clinical results, many surgeons are discouraged by the difficulties of operation, conflict of instruments, lack of antagonistic traction, and straight-line perspective. Therefore, some surgeons have proposed a single incision plus one hole laparoscopic surgery (SILS+1) surgical method. This study explored the safety and feasibility of SILS+1 for radical resection of colorectal cancer. Methods: A descriptive cohort study was carried out. The clinical data, including the operation, pathology and recovery situation, of 178 patients with colorectal cancer undergoing SILS+1 at Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2018 to January 2019 were prospectively collected and retrospectively analyzed. Clavien-Dindo criteria was used for postoperative complication evaluation and visual analog scale was used for pain standard. Follow-up studies were conducted through outpatient service or telephone and the follow-up period was up to May 2019. Results: A total of 178 patients with colorectal cancer underwent SILS+1, including 111 male patients (62.4%) with an average age of 59 years. Eleven (6.2%) patients received added 1-3 operation ports during operation, and 1 patient was converted to open surgery due to ileocolic artery hemorrhage. The operative time was (135.2±42.3) minutes. The intraoperative blood loss was (34.6±35.5) ml. The number of harvested lymph nodes was 33.1±17.6. The distal margin was (4.7±17.8) cm. The proximal margin was (10.2±5.3) cm. Operation-related complications were observed in 16 patients (9.0%) within 30 days after the operation, of whom 6 had Clavien-Dindo III complications (3.4%). The postoperative pain scores were lower than 3. The average postoperative hospital stay was (5.6±2.6) days. Three patients (1.7%) returned to hospital within 30 days after operation due to intestinal obstruction and infection around stoma. The cosmetic evaluation of all the patients was basically satisfied. Conclusion: SILS+1 is safe and feasible in the treatment of colorectal cancer, and can reduce the postoperative pain.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in colorectal cancer.

Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated inhibition of cell growth and survival in response to IR. Importantly, miR-214 was highly expressed in radiosensitive CRC specimens and negatively correlated with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in radioresistant CRC specimens. Our study elucidates that miR-214 promotes radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly, miR-214 is a determinant of CRC irradiation response and may serve as a potential therapeutic target in CRC treatment.

The value of dual time point (18)F-FDG PET imaging for the differentiation between malignant and benign lesions.

AIM: To assess the clinical value of dual time point 2-[(18)F]-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG PET) imaging for the differentiation between malignant and benign lesions. MATERIALS AND METHODS: Ninety-six patients (28 patients with primary lung cancer, 18 patients with digestive system carcinoma, 13 patients with other malignant tumours, and 37 patients with benign lesions) underwent FDG-PET/CT at two time points: examination 1 at 45-55 min and examination 2 at 160+/-24 (150-180) min after the intravenous injection of 233+/-52 (185-370)MBq (18)F-FDG. Reconstructed images were evaluated qualitatively and quantitatively. The maximum standardized uptake values (SUVmax) of the lesions were calculated for both time points. An increase was considered to have occurred if the SUVs at examination 2 had increased by >10% as compared with those at the examination 1. RESULTS: The lesions in 24 of 28 (86%) patients with primary lung cancer had an SUVmax > or = 2.5 at examination 1. Of these, SUVmax values increased in 23 patients, but had not changed in one patient, at examination 2. The lesions in the other four patients with primary lung tumour had SUVmax values between 1.5 and 2.5 at examination 1, which were considered as suspected positive, increased SUVmax values were observed in three of these patients at examination 2. The malignant lesions in 17 of 18 patients with digestive system carcinoma showed SUVmax values > or = 2.5 and only one patient had an SUVmax value < 1.5 at examination 1; all lesions showed an increase in SUVmax values at examination 2. In 13 patients with other malignant tumours, all lesions had SUVmax values > or = 2.5 at examination 1 and the SUVmax values were further increased at examination 2. Therefore, the malignant lesions in 54/59 (92%) of patients had SUVmax values > or = 2.5 at examination 1 and showed a further increase in SUVmax value at examination 2. Only 12 of 37 (32%) patients with benign lesions showed SUVmax values > or = 2.5 at examination 1 and nine patients with benign lesions had SUVmax values > or = 2.5 in examination 2. The sensitivity, specificity, accuracy, positive and negative predictive values for the early and delayed imaging were 91.5, 67.6, 82.3, 81.8, and 83.3%, and 98.3, 75.7, 89.6, 86.6, and 96.6%, respectively. CONCLUSION: The results of the present study provide further evidence that dual time point (18)F-FDG PET imaging is an important noninvasive method for the differentiation of malignant and nonmalignant lesions.