Association between dietary fatty acids and urinary incontinence.

Background: Dietary nutrient intake contributes to urination; however, the association between dietary nutrient intake, especially that of fat, and urinary incontinence (UI) is not well understood. The most common types of UI include stress UI (SUI) and urgency UI (UUI). Objective: To investigate the potential effect(s) of dietary fat intake on UI and explore its mechanism of action in relation to body mass index (BMI). Methods: A cross-sectional survey of data from 15,121 individuals (20-85 years of age) from the National Health and Nutrition Examination Survey (2001-2008), a random population-based sample, was performed. Data regarding dietary nutrient intake were collected through 24 h dietary recall interviews. UI and covariate data were collected through in-person interviews. UI was assessed according to the American Urological Association Symptom Index. The odds ratio (OR) for SUI and UUI were calculated using multivariate logistic regression analysis. The mediation effect was estimated using observational mediation analysis. Results: Higher total fat intake was positively associated with increased odds for developing UI (OR 1.44 [95% confidence interval (CI) 1.08-1.93]). Females who consumed more saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were more likely to develop SUI. BMI partially explained the association between total fat, SFA, MUFA, and PUFA and SUI; the proportions of the mediation effect of BMI were 14.7%, 13.0%, 18.7%, and 16.3%, respectively. Conclusions: Results of this study emphasize the key role of dietary fat intake in the prevalence of UI. Higher fat intake was positively associated with UI and BMI partially mediated the effect of fat intake on SUI.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm with Orbital Tumor as the Initial Symptom.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.

Multianticoagulant Pseudothrombocytopenia in a Patient with Primary Carcinoma of the Liver with Hypersplenism.

BACKGROUND: Pseudothrombocytopenia (PTCP) is a relatively rare phenomenon in vitro, the mechanism is not completely clear, and there is no unified solution for it. How to identify and solve PTCP accurately is a challenge for laboratory personnel. METHODS: According to the patient's clinical manifestations, thrombocytopenia caused by hypersplenism was excluded. PTCP was confirmed by platelet volume histograms, scattergrams and platelet clumps on the blood smears. Commonly used alternative anticoagulants such as sodium citrate or heparin were used for platelet counting. The corrective effect of the platelet count was not good, so non-anticoagulant blood was collected and tested immediately, and blood smears were used to count platelets manually. RESULTS: The PTCP of the patient could not be solved using sodium citrate and heparin anticoagulation. By collecting non-anticoagulant blood and testing immediately, the platelet count returned to normal (180 x 109/L), which is consistent with the results of manual counting on the patient's blood smears (175 x 109/L). CONCLUSIONS: When PTCP is confirmed, commonly used alternative anticoagulants can be used. If these do not work, non-anticoagulant blood can be collected and tested immediately, and blood smears can be used to count platelets manually.

Acute Myeloid Leukemia Secondary to Treatment with Oxaliplatin Combined with Capecitabine for Colorectal Cancer.

BACKGROUND: Treatment-related acute myeloid leukemia (t-AML) is often secondary to some cytotoxic drugs or occurs after radiotherapy and immunosuppression therapy. As commonly used drugs in colorectal cancer chemotherapy, oxaliplatin and capecitabine have obvious cytotoxicity, which may also be an important factor causing t-AML. METHODS: In this study, we report the development of treatment-related acute myeloid leukemia in a pT4NIMO colorectal cancer patient after an approximate 16-month latency period following treatment with 6 cycles of oxali-platin (190 mg on Day 1) plus capecitabine (1.5 g orally twice daily on Days 1 - 14) in combination with recombinant human granulocyte-colony stimulating factor treatment. The patient developed severe anemia with thrombocytopenia after treatment. After a peripheral blood smear and bone marrow biopsy, the diagnosis of AML-M2a was confirmed. RESULTS: The patient was diagnosed with t-AML approximately 16 months after treatment. Our case illustrates the possibility of some cytotoxic drugs inducing t-AML after colorectal cancer treatment. CONCLUSIONS: We suggest that clinicians conduct long-term epidemiological follow-up and epidemiological investigations on patients treated with oxaliplatin and capecitabine. In addition, clinicians should carefully check the complete blood cell count on routine follow-ups and observe the morphological changes of white blood cells in peripheral blood smears, even for asymptomatic patients who have undergone chemotherapy. In this way, we can observe the possibility of its development into secondary leukemia.

ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner.

Background: N6-methyladenosine (m6A) is one of the most prevalent mRNA modifications in mammals, and it regulates the fate of modified RNA transcripts. In the current study, we aimed to elucidate the role of YTH m6A RNA-binding protein 1 (YTHDF1), a "reader" of m6A modification, in prostate cancer tumorigenesis. Methods: We employed a multi-omics approach to detect the direct target of YTHDF1 upon manipulation of YTHDF1 expression in prostate cancer cells. Expression of YTHDF1 was also evaluated in human prostate tumors and either adjacent or paired normal tissues. Additionally, in vivo tumor growth and metastasis experimental assays were performed to evaluate the role of YTHDF1 in tumorigenesis. Finally, luciferase reporter assays and Chromatin immunoprecipitation (ChIP) were conducted to elucidate the transcriptional regulators of YTHDF1. Results: We demonstrated that polo-like kinase 1 (PLK1) is a direct target of YTHDF1. YTHDF1 facilitated the translation efficiency of PLK1 in an m6A-dependent manner by identifying the m6A-modified PLK1 mRNA and subsequently promoted the hyperactivation of the PI3K/AKT signaling pathway. Moreover, our results indicated that YTHDF1 was upregulated in prostate cancer tissue and that high YTHDF1 expression was associated with adverse prognosis in patients with prostate cancer. Furthermore, upregulation of YTHDF1 promoted prostate cancer tumorigenesis and metastasis in vitro and in vivo. Additionally, dysregulation of ETS transcription factor ELK1 activated the transcription of YTHDF1 by directly binding to its promoter region. Conclusions: Collectively, our findings suggest that the ELK1/YTHDF1/PLK1/PI3K/AKT axis is critical for prostate cancer progression and may serve as a potential therapeutic target for prostate cancer treatment.

MAFG-AS1 is a prognostic biomarker and facilitates prostate cancer progression.

Long Noncoding RNAs (LncRNAs) have recently been identified as key regulator in tumor progression. The LncRNA MAFG-AS1 has been reported to facilitate the progression of multiple cancers, however, its role in prostate cancer is still unknown. Here, we reported that MAFG-AS1 was upregulated in prostate cancer. Importantly, high expression of MAFG-AS1 indicated advanced stage prostate cancer. Univariate and Multivariate Cox regression analyses showed that high MAFG-AS1 expression was independently correlated with poor progression-free interval (PFI). According to the result of The Cancer Genome Atlas (TCGA) database and tissue microarray, high MAFG-AS1 expression indicated a poor prognosis in prostate cancer patients. In addition, gene functional enrichment analysis revealed that MAFG-AS1 may be involved in ribosome biogenesis, ribonucleoprotein complex subunit organization, ribonucleoprotein complex assembly, rRNA metabolic process, structural constituent of ribosome, and ribonucleoprotein complex binding. Furthermore, MAFG-AS1 knockdown by siRNA markedly impaired prostate cancer cell proliferation, migration, and invasion.

Reprogramming hormone-sensitive prostate cancer to a lethal neuroendocrine cancer lineage by mitochondrial pyruvate carrier (MPC).

Cell lineage reprogramming is the main approach for cancer cells to acquire drug resistance and escape targeted therapy. The use of potent targeted therapies in cancers has led to the development of highly aggressive carcinoma, including neuroendocrine prostate cancer (NEPC). Although metabolic reprogramming has been reported to be essential for tumor growth and energy production, the relationship between metabolic reprogramming and lineage differentiation which can cause hormone therapy resistance has never been reported in prostate cancer (PCa). Moreover, as there is still no efficient therapy for NEPC, it is urgent to reverse this lineage differentiation during the hormone therapy. Here for the first time, we used in vitro and in vivo human PCa models to study the effect of metabolic reprogramming on the lineage differentiation from the androgen receptor (AR)-dependent adenocarcinoma to AR-independent NEPC. This lineage differentiation leads to antiandrogen drug resistance and tumor development. This phenotype is enabled by the loss of mitochondrial pyruvate carrier (MPC), the gate for mitochondrial pyruvate influx, and can be reversed by MPC overexpression. Morphologic and cellular studies also demonstrate that the pyruvate kinase M2 (PKM2) involved epithelium-mesenchymal transition process mediated this lineage alteration. Its inhibition is a potential treatment for MPC-lo tumors. All of these results suggest that metabolic rewiring can act as a starter for increased cellular plasticity which leads to antiandrogen therapy resistance through lineage differentiation. This study provides us with a potent treatment target for therapy-induced, enzalutamide-resistant NE-like prostate cancer.

E2F transcription factor 2-activated DLEU2 contributes to prostate tumorigenesis by upregulating serum and glucocorticoid-induced protein kinase 1.

Long noncoding RNAs (lncRNAs) participate in biological processes in multiple types of tumors. However, the regulatory patterns of lncRNAs in prostate cancer remain largely unclear. Here, we evaluated the expression and roles of the lncRNA DLEU2 in prostate cancer. Our results showed that DLEU2 was upregulated in advanced prostate cancer tissues. Patients with prostate cancer displaying high expression of DLEU2 had a poor prognosis. Moreover, we demonstrated that overexpression of DLEU2 facilitated the proliferation, migration, and invasion of prostate cancer in vitro. Mechanistically, DLEU2 promoted serum and glucocorticoid-induced protein kinase 1 (SGK1) expression by acting as an miR-582-5p sponge, and the transcription of DLEU2 was activated by the dysregulation of E2F transcription factor 2 (E2F2) expression in prostate cancer. Furthermore, knockdown of DLEU2 attenuated prostate cancer tumorigenesis in vivo. Notably, these findings suggested that E2F2-activated DLEU2 may function as a competing endogenous RNA to facilitate prostate cancer progression by targeting the miR-582-5p/SGK1 axis.

Screening to Identify an Immune Landscape-Based Prognostic Predictor and Therapeutic Target for Prostate Cancer.

OBJECTIVES: Existing prognostic risk assessment strategies for prostate cancer (PCa) remain unsatisfactory. Similar treatments for patients at the same disease stage can lead to different survival outcomes. Thus, we aimed to explore a novel immune landscape-based prognostic predictor and therapeutic target for PCa patients. METHODS: A total of 490 PCa patients from The Cancer Genome Atlas Project (TCGA) cohort were analyzed to obtain immune landscape-based prognostic features. Then, analyses at different levels were performed to explore the relevant survival mechanisms, prognostic predictors, and therapeutic targets. Finally, experimental verification was performed using a tissue microarray (TMA) from 310 PCa patients. Furthermore, a nomogram was constructed to provide a quantitative approach for predicting the prognosis of patients with PCa. RESULTS: The immune landscape-based risk score (ILBRS) was obtained. Then, VAV1, which presented a significant positive correlation with Treg infiltration and ILBRS, was screened and identified to be significantly related to the prognosis of PCa. Finally, experimental verification confirmed the prognostic value of VAV1 for PCa prognosis at the protein level. CONCLUSIONS: VAV1 has the potential to be developed as an immune landscape-based PCa prognostic predictor and therapeutic target and will help improve prognosis by enabling the selection of individualized, targeted therapy.

Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism.

Background and Objectives: Defects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation. Methods: Two hundred and seventy-three patients with primary CH were screened for mutations in SLC5A5 using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in SLC5A5. The functional activity of the mutants was further examined in vitro. Results: In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in SLC5A5 were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. In vitro experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired. Conclusion: The undescribed compound heterozygous mutation of SLC5A5 was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of SLC5A5 in CH pathogenesis.

Relationship between vascular endothelial growth factor -2578C > a gene polymorphism and lung cancer risk: a meta-analysis.

BACKGROUND: Several reports were published on the relationship between the vascular endothelial growth factor (VEGF) -2578C > A gene polymorphism and lung cancer risk; however, the results are debatable. This meta-analysis was conducted to assess the relationship between VEGF -2578C > A gene polymorphism and lung cancer risk. METHODS: The associated literatures were identified on the 1st of September 2018 from CBM-disc (China Biological Medicine Database) and PubMed. RESULT: A total of 14 reports were recruited into our meta-analysis to assess the association between VEGF -2578C > A gene polymorphism and lung cancer susceptibility. There was a marked association between VEGF -2578C > A A allele / CC genotype and lung cancer risk in overall and Asian populations (overall populations: A allele: OR = 1.26, 95% CI: 1.08-1.46, P = 0.003; CC genotype: OR = 0.72, 95% CI: 0.54-0.95, P = 0.02; Asians: A allele: OR = 1.33, 95% CI: 1.15-1.55, P = 0.0002; CC genotype: OR = 0.68, 95% CI: 0.50-0.93, P = 0.01). However, VEGF -2578C > A gene polymorphism was not associated with the risk of lung cancer in Caucasians. CONCLUSION: VEGF -2578C > A A allele / CC genotype is associated with the lung cancer susceptibility in Asians and in overall populations.

Association of glutathione S-transferase P1 gene polymorphism with the risk of small-cell carcinoma of lung cancer.

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of small-cell carcinoma of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of small-cell carcinoma of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Ten reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and small-cell carcinoma of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of small-cell carcinoma in overall populations, East-Asians and Turkish population. However, there was an association between GG genotype with the risk of small-cell carcinoma in Caucasians. In conclusion, GG genotype was associated with the risk of small-cell carcinoma in Caucasian patients with lung cancer. However, GSTP1 A/G gene polymorphism is not associated with the susceptibility of small-cell carcinoma in overall populations, East-Asians and Turkish population.

Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus.

Relationship between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the type 2 diabetes mellitus (T2DM) susceptibility is still conflicting at present. This meta-analysis was conducted to assess the association between VDR BsmI gene polymorphism and the risk of T2DM. The association studies were identified from PubMed, and Cochrane Library on 1 January 2014, and eligible investigations were included and synthesized using meta-analysis method. Eleven reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T2DM susceptibility. In overall populations, B allele, BB genotype and bb genotype were not associated with T2DM risk. VDR BsmI gene polymorphism was also not associated with the T2DM risk in Asians and Caucasians. In conclusion, VDR BsmI gene polymorphism was also not associated with T2DM risk in overall populations, Asians and Caucasians. However, more studies should be conducted to confirm it.

Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of renal cell carcinoma from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphism and the risk of renal cell carcinoma using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR gene polymorphism with renal cell carcinoma susceptibility. In this meta-analysis, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphism were not associated with the risk of renal cell carcinoma in overall populations and in Caucasians. In conclusion, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, more studies should be conducted to confirm it.

Adiponectin inhibits lymphotoxin-ß receptor-mediated NF-κB signaling in human umbilical vein endothelial cells.

Adiponectin exerts anti-diabetic and anti-atherogenesis properties through its 2 receptors (AdipoR1 and AdipoR2). However, the signaling pathways responsible for the anti-inflammatory effects of adiponectin are largely unknown. In this study, we identified the lymphotoxin (LT)-ß receptor (LTBR) as an interacting partner of human AdipoR1 by using a yeast two-hybrid screening. The interaction between LTBR and AdipoR1 was confirmed by co-immunoprecipitation and co-localization analysis. Furthermore, adiponectin incubation inhibited lymphotoxin-induced NF-κB activation and the expression of adhesion molecules in human umbilical vein endothelial cells. These results indicated that AdipoR1 interacted with LTBR and mediated the inhibition of LTBR-activated NF-κB pathway.

[Mechanism of cardioprotection induced by noninvasive limb ischemic preconditioning].

OBJECTIVE: To verify the inhibitory effect of mitochondrial calcium uniporter in remote preconditioning-induced cardioprotection. METHODS: By occlusion and reperfusion of left anterior descending artery, the rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vivo. Thus the ischemic reperfusion model was established. The rats were randomly assigned to undergo one of the following maneuvers: (1) remote preconditioning; (2) ruthenium red (an inhibitor of mitochondrial calcium uniporter); (3) spermine or SB202190 (an opener of mitochondrial calcium uniporter). Remote preconditioning was elicited by three cycles of 5 min of right femoral artery occlusion interspersed with 5 min of reperfusion. The mean arterial blood pressure, heart rate and lactate dehydrogenase released in plasma were measured during reperfusion but the infarct size was measured after reperfusion. RESULTS: In comparison with I/R group, remote preconditioning limited infarct size [(20.4 +/- 2.5)% vs (51.0 +/- 6.0)%] and lactate dehydrogenase release [(271 +/- 9) U/L vs (339 +/- 39)U/L] during reperfusion. On the contrary, spermine or SB202190 attenuated the reduction of infarct size and lactate dehydrogenase release induced by remote preconditioning. The group of spermine was [(40.8 +/- 9.2)% vs (20.4 +/- 2.5)%] and [(383 +/- 43) U/L vs (271 +/- 9) U/L] while the group of SB202190 was [(44.3 +/- 6.8)% vs (20.4 +/- 2.5)%] and [(356 +/- 26) U/L vs (271 +/- 9) U/L]. CONCLUSION: Inhibition of mitochondrial calcium uniporter opening is involved in the remote preconditioning-induced cardioprotection.

Effect of hepatocyte growth-promoting factors on myocardial ischemia during exercise in patients with severe coronary artery disease.

Hepatocyte growth-promoting factor (pHGF) has the greatest potential as a therapeutic agent for vascular growth factor. The aim of this study was to investigate the effect of pHGF on myocardial ischemia and exercise capacity in patients with severe coronary artery disease (CAD). Forty-nine patients were enrolled for a two week treatment period. Treadmill graded exercise tests with gas analysis were conducted before and after therapy. Serum levels of HGF were significantly elevated after therapy. The degrees of exercise-induced ST segment depression were decreased more significantly in the pHGF group. Similar differences were also found in the maximum heart rate and the maximum heart rate when the ST segment was depressed 1 mm while undergoing the treadmill graded exercise test. Both were increased more significantly in the pHGF group. Total exercise time, systolic blood pressure in the peak of exercise, the length of time that ST segment depression of 1 mm is needed, and total work all were increased in both groups after intervention. Furthermore, total exercise time and total work were increased more significantly in the pHGF group. The levels of HGF increased significantly after pHGF treatment. pHGF could favorably improve exercise-induced myocardial ischemia and enhance exercise capacity in patients with severe CAD.

Receptor for activated C-kinase 1, a novel binding partner of adiponectin receptor 1.

Adiponectin is an adipose tissue derived hormone with anti-diabetic and insulin-sensitizing properties. Two adiponectin receptors, AdipoR1 and AdipoR2, have recently been identified, yet the signaling pathways triggered through adiponectin receptors remain to be elucidated. Using a yeast two-hybrid screen, we identified an adaptor protein, receptor for activated protein kinase C1 (RACK1), as an interacting partner of human AdipoR1. RACK1 was confirmed to interact with AdipoR1 by co-immunoprecipitation and co-localization analysis in mammalian cells. The interaction was enhanced by adiponectin stimulation. In addition, the knockdown of RACK1 by RNA interference inhibited adiponectin-stimulated glucose uptake in HepG2 cells. These results suggest that RACK1 may act as a key bridging factor in adiponectin signaling transduction through interacting with AdipoR1.