Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.
Adult ; Aged ; Aged, 80 and over ; Anemia, Macrocytic ; Humans ; Lenalidomide ; Middle Aged ; Myelodysplastic Syndromes ; Retrospective Studies ; Thalidomide

Background: MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. Methods: Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. Results: Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375. Conclusions The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.
14-3-3 Proteins ; metabolism ; Carcinoma, Renal Cell ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms ; pathology ; MicroRNAs ; physiology ; Phenotype

Aseptic loosening, ascribes to particle induced osteolysis, is the most common reason for total joint arthroplasty failure. Wear particles, liberated from the surface of prostheses, mediate the expression of inflammatory cytokines in macrophages and increase the osteoclastogenesis. However, it remains unclear how macrophages can recognize wear particles and be induced by wear particles. Recently, a number of studies have demonstrated that Toll like receptors and inflammasome may play a critical role in osteolysis. However, the mechanism of activation of Toll like receptors and the relationship between TLR pathway and downstream signaling pathways still remain unclear. It will be beneficial to understand the pathogenesis of aseptic loosening by exploring these mechanisms. This article highlights the role of Toll like receptors and inflammasome in aseptic loosening, which is helpful to the development of therapies that prevent wear particle induced aseptic loosening.

OBJECTIVETo analyze the clinical features, diagnosis and treatment of lung cancer associated paraneoplastic limbic encephalitis (PLE).

METHODSThe clinical data of 7 cases of patients with lung cancer associated PLE out of 8927 patients of lung cancer from January 2000 to May 2010 was analyzed retrospectively. All the patients were male, aging from 41 to 54 years with a mean of 48 years. The data including history, physical examination, laboratory tests, diagnosis, treatment and follow-up were collected and analyzed.

RESULTSAll the 7 patients had smoking history. All 7 patients had varying short-term memory loss, 6 had epilepsy, 4 had different degrees of mental disorders, and 2 had syndrome of inappropriate secretion of antidiuretic hormone. Malignancies were screened and detected by chest X-ray or CT scan, while the pathological diagnoses were obtained through biopsy or transbronchial needle aspiration through electronic bronchoscope (5/7), biopsy of supraclavicular lymph nodes (1/7) and open pulmonary lobectomy (1/7). The pathological diagnosis included small cell lung cancer in 6 cases, adenocarcinoma of lung in 1 case. During the follow-up, 1 patient was lost, and the mean time of follow-up of the remaining 6 patients was about 11.5 months (ranged from 4 to 21 months). Four patients received early immunosuppressive treatment in terms of corticosteroids, only slight relief of neurological symptoms was seen in 2 patients. However, after chemotherapy (6/6), radiation (3/6), or surgical removal of the tumor (1/6), complete remission (3/6, with negative anti-Hu antibody) or partial remission (3/6, 2 of whom with positive anti-Hu antibody) of neurological symptoms were observed. Till October 2010, 3 patients with poorer tumor stag died ( survival were 4, 10, and 14 months respectively), while the other 3 patients with negative anti-Hu antibody and relative better tumor stag were still in the follow-up (the period were 5, 15, and 21 months).

CONCLUSIONSPLE is a rare disease. In comparison with immunosuppressive therapy, chemotherapy, radiation or surgical removal of the tumor could provide better remission of the neurological symptoms. Positive serum anti-Hu antibody, poorer tumor stag, and together with poorer response to treatments seem to indicate a poorer prognosis.

Adult ; Carcinoma, Small Cell ; complications ; Humans ; Limbic Encephalitis ; etiology ; therapy ; Lung Neoplasms ; complications ; Male ; Middle Aged ; Retrospective Studies

Aged ; Coronary Angiography ; Coronary Artery Disease ; Coronary Disease ; diagnostic imaging ; pathology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Tomography, Emission-Computed, Single-Photon

BACKGROUNDA recent genome-wide association study in Caucasians revealed that three loci (rs174547 in fatty acid desaturase 1 (FADS1), rs2338104 near mevalonate kinase/methylmalonic aciduria, cobalamin deficiency, cblB type (MVK/MMAB) and rs10468017 near hepatic lipase (LIPC)) influence the plasma concentrations of high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG). However, there are few reports on the associations between these polymorphisms and plasma lipid concentrations in Chinese individuals. This study aimed to evaluate the associations between these three polymorphisms with HDL-C and TG concentrations, as well as coronary heart disease (CHD) susceptibility in Chinese individuals.

METHODSWe conducted a population-based case-control study in Chinese individuals to evaluate the associations between these three polymorphisms and HDL-C and TG concentrations, and also evaluated their associations with susceptibility to CHD. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism assays and TaqMan genotyping assays.

RESULTSWe found significant differences in TG and HDL-C concentrations among the TT, TC and CC genotypes of FADS1 rs174547 (P=0.017 and 0.003, respectively, multiple linear regression). The CC variant of rs174547 was significantly associated with hyperlipidemia compared with the TT variant (adjusted odds ratio (OR)=1.71, 95% confidence intervals (CI): 1.16-2.54). The FADS1 rs174547 CC variant was also associated with significantly increased CHD risk compared with the TT and TC variant (adjusted OR=1.53, 95%CI: 1.01-2.31), and the effect was more evident among nonsmokers and females. The polymorphisms rs2338104 and rs10468017 did not significantly influence HDL-C or TG concentrations in this Chinese population.

CONCLUSIONrs174547 in FADS1 may contribute to the susceptibility of CHD by altering HDL-C and TG levels in Chinese individuals.

Aged ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Cholesterol, HDL ; blood ; Coronary Disease ; blood ; epidemiology ; genetics ; Fatty Acid Desaturases ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Triglycerides ; blood