[Association between physical activity and risk of stroke among adults aged 40 years and above: a prospective cohort study].

Objective: To examine the effect of physical activity (PA) on the incident risk of stroke among adults aged 40 years and above. Methods: The baseline data including PA and demographic characteristics were obtained from the Adult Chronic Disease Surveillance with population representativeness in Ningbo in 2015. The follow-up data of interested health outcomes from 2015 to 2019 were retrieved from a population-based Integrated Noncommunicable Disease Collaborative Management System in Ningbo. The two databases were matched to form a queue. PA was divided into three levels of low-intensity, moderate-intensity, and vigorous-intensity according to the metabolic equivalents (METs) spent per week. Cox regression model was used to calculate the hazard ratio (HR) and 95% confidence interval. Results: A total of 3 353 subjects were included at baseline survey in 2015. Until Dec 31, 2019, there had been 31 stroke events had occurred since then, with accumulative incidence rate of 242/100 000, and an average follow-up time of (50.28±2.54) months. When adjusted for gender, age, education level, smoking status, alcohol consumption, BMI and hypertension, multivariate Cox regression analysis showed that greater PA was associated with a 37.9% reduction of incidence of stroke (HR=0.621,95%CI:0.393-0.983). Compared with those who had low-intensity PA, those who were with vigorous-intensity. PA appeared associated with a 63.1% decrease in the incidence of stroke (HR=0.369, 95%CI: 0.139-0.976). However, there was no statistical significance with moderate-intensity PA (HR=0.712,95%CI:0.323-1.569), noticed. Conclusions: Greater PA is likely to reduce the incidence of stroke. Our findings indicated that people should be encouraged to increase the PA level and developing a healthy supportive environment in the community.

Clinical efficacy of palbociclib-based therapy in women with HR+/HER2- metastatic breast cancer in the real-world setting for Chinese women: a comparison with the IRIS study.

OBJECTIVE: This retrospective study aimed to explore the clinical efficacy of palbociclib with endocrine therapy (ET) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer in real-world practice. PATIENTS AND METHODS: This retrospective study analyzed the medical records of patients to determine treatment outcomes. Progression-free survival (PFS) curves were generated using log-rank tests with the Kaplan-Meier method. Treatment outcomes in Chinese patients were compared with those in patients from the USA, Argentina, Canada, and Europe in the IRIS study. RESULTS: In total, 69 patients were included in this study. The median PFS was 12.8 months (95% confidence interval: 10.1-15.5). A longer PFS was observed for patients with bone-only metastases, no liver metastases, no previous palliative chemotherapy, no previous palliative ET, and ET sensitivity. The overall response rate was 10.1%, and the clinical benefit rate was 78.3%. Nineteen patients (27.5%) received a reduced dose of palbociclib according to the decision of their physicians. Dose reduction did not affect the clinical efficacy of the combined treatment. Compared with those in the IRIS study, Chinese patients receiving palbociclib-based treatment were younger, and they had fewer bone-only metastases and more visceral and liver metastases. The clinical benefit rate and overall response rate for Chinese patients were lower than those observed for the patients in the IRIS study. CONCLUSIONS: ET combined with palbociclib treatment was effective and well-tolerated in HR+/HER2- metastatic breast cancer patients in the real-world setting. Earlier use of palbociclib-ET was associated with more clinical benefits in HR+/HER2- metastatic breast cancer.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

Organoid of ovarian cancer: genomic analysis and drug screening.

Ovarian cancer is the most common malignant tumors of the female reproductive system, and its standard treatments are cytoreductive surgery and platinum-based adjuvant chemotherapy. Great advances have been achieved in novel treatment strategies, including targeted therapy and immunotherapy. However, ovarian cancer has the highest mortality rate among gynecological tumors due to therapeutic resistance and the gap between preclinical data and actual clinical efficacy. Organoids are a 3D culture model that markedly affects gene analysis, drug screening, and drug sensitivity determination of tumors, especially when used in targeted therapy and immunotherapy. In addition, organoid can lead to advances in the preclinical research of ovarian cancer due to its convenient cultivation, good genetic stability, and high homology with primary tumors.

[Preliminary application of endoscopic titanium clip localization combined with three-dimensional CT reconstruction in the determination of resection margin of gastric central cancer under laparoscopy].

Objective: To evaluate the accuracy of endoscopic titanium clip localization combined with CT three-dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods: A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6± 7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three-dimensional (3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three-dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results: The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion: The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to 2 gastric central cancer.

Peroxisome proliferator-activated receptor delta regulates lipid droplet formation and transport in goat mammary epithelial cells.

Even though recent evidence in goat mammary epithelial cells (GMEC) suggest a role of peroxisome proliferator-activated receptor delta (PPARD) in regulating lipid homeostasis, its role is not fully understood. Our hypothesis was that PPARD regulates lipid transport processes in GMEC and, thus, plays a crucial role in regulating fat formation. The PPARD was overexpressed using an adenovirus system (Ad-PPARD) with recombinant green fluorescent protein (Ad-GFP) as the control. Results revealed that overexpression of PPARD markedly upregulated the mRNA abundance of PPARD. Compared with the control (Ad-GFP+dimethyl sulfoxide), overexpression of PPARD alone had no effect on mRNA expression of CD36, SCD1, FABP4, ACSL1, and ADRP. The cultures overexpressing PPARD with the PPARD ligand GW0742 (GW) upregulated the expression of CD36, FABP3, FABP4, ACSL1, and ADRP. Overexpression of PPARD in GMEC plus GW increased the concentration of 16:1 and 18:1-trans and was associated with upregulation of SCD1. Compared with the control (Ad-GFP+dimethyl sulfoxide), the decrease of triacylglycerol concentration coupled with upregulation of genes related to lipid droplet secretion (e.g., ADRP and ACSL1) induced by PPARD overexpression suggests a role in lipid droplet (LD) secretion. Luciferase assay revealed that GW increased the ADRP promoter activity in a dose-dependent manner. Knockdown of PPARD impaired the increase of ADRP promoter activity induced by GW, whereas GW enhanced the activity of ADRP promoter in GMEC overexpressing PPARD. Data with the ADRP 5'-flanking truncated luciferase reporter suggest a core region (-1,444 to -990 bp) response element for the induction of GW. This core region contains a known PPARG response element (PPRE) at -1,003 to -990 bp. When the PPRE was mutated, the overexpression of PPARD had no effect on ADRP promoter activity. Collectively, these results reveal a novel role for PPARD in lipid homeostasis via promoting fatty acid transport and LD formation through a mechanism of direct binding to the promoter of key genes. Hence, PPARD activity may contribute to fatty acid transport and LD formation during lactation.

[The relationship of preoperativelymphocyte-monocyte ratio and the clinicopathological characteristics and prognosis of patients with epithelial ovarian cancer].

Objective: To investigate the relationship of preoperative lymphocyte-monocyte ratio (LMR) and the clinicopathological characteristics and prognosis of patients with epithelial ovarian cancer (EOC). Methods: Clinical data of 364 cases of EOC patients with initial treatment were collected in Harbin Medical University Cancer Hospital from 2005-2011 and analyzed retrospectively.The optimal cut-off points of preoperative LMR to predict the postoperative survival period of EOC patients were determined by the establishment of receiver operating characteristic (ROC) curve. The patients were divided into low LMR group and high LMR group according to the optimal cut-off points, and the relationship of LMR and the clinicopathological factors and prognosis of EOC patients were analyzed. Results: The best cut-off point of preoperative LMR to predict the postoperative survival period of EOC patients was 3.84. The preoperative LMR of EOC patients was significantly associated with the postoperative FIGO stage, ascites and CA125 level (all P<0.05). The median follow-up time was 37 months, the median progression-free survival (PFS) time of low LMR group was 56 months, significantly shorter than 88 months of high LMR group (P<0.01). And the median overall survival (OS) time of low LMR group was 69 months, significantly shorter than 100 months of high LMR group (P<0.01). The univariate analysis showed that the postoperative FIGO stage, pathological grade, ascites, lymph node metastasis, CA125 level, adjuvant therapy, preoperative LMR were all significantly associated with PFS (all P<0.05). In addition, the age, postoperative FIGO stage, pathological grade, ascites, lymph node metastasis, CA125 level, adjuvant therapy, preoperative LMR were all significantly associated with OS (all P<0.05). Cox multivariate analysis showed that postoperative FIGO stage Ⅲ-Ⅳ, low differentiation, positive lymph node metastasis, without postoperative adjuvant therapy and LMR≤3.84were independent risk factors of PFS and OS of EOC patients (P<0.05). Conclusion: The preoperative LMR is an independent influence factor of PFS and OS of EOC patients, and can be used to evaluate the prognosis of patients with EOC.

[A screening system for anti-metastatic small-molecule compounds based on perinucleolar compartment prevalence in liver cancer cells].

Objective: To establish a screening system for anti-metastatic small-molecule compounds based on perinucleolar compartment (PNC) prevalence in liver cancer cells and to investigate its validity. Methods: Polypyrimidine tract-binding protein (PTB) monoclonal antibody was used to measure the PNC prevalence in HepG2, HepG2M, and Huh7 cells, and wound healing assay and transwell assay were used to analyze the migration and invasion abilities of hepatoma cells. HepG2M cells were used as the model for the screening of anti-metastatic small-molecule compounds, and after the treatment with the compounds A1, A4, and E696, qPCR was used to measure the expression of metastasis-related miRNAs (miR-141 and miR-200c). A one-way analysis of variance was used for comparison of data between multiple groups. Results: PTB immunofluorescence assay showed that HepG2M cells had the highest PNC prevalence, followed by Huh7 and HepG2 cells, and PNC prevalence was positively correlated with the metastasis and invasion abilities of hepatoma cells. The PNC prevalence of HepG2M cells was reduced to 22.88% ±4.61% by A1, 14.22% ± 3.05% by A4, and 26.12% ± 4.94% by E696. Wound healing assay showed that the 48-hour scratch ratio increased from 17.70% ± 3.34% to 64.50% ± 2.65%, 83.40% ± 5.10%, and 57.20% ± 3.06% (F = 171.1, P < 0.01), respectively. Transwell assay showed that the number of invasive cells was reduced from 264.33 ± 30.50 to 104.33 ± 13.50, 58.00 ± 11.00, and 111.33 ± 19.50 (F = 59.87, P < 0.01), respectively. The anti-metastatic effect of these three compounds was positively correlated with their ability to destroy PNC. A4 upregulated the expression of miR-141 and miR-200c in a dose-dependent manner, and after HepG2M cells were treated with A4 at a concentration of 5 µM, 10 µM, or 20 µM, the level of miR-141 was increased to 3.61 ± 0.78, 8.12 ± 1.15, and 18.24 ± 2.44 folds (F = 88.01, P < 0.01), respectively, and that of miR-200c was increased to 2.82 ± 0.43, 4.82 ± 0.89, and 10.74 ± 1.22 folds (F = 87.94, P < 0.01), respectively. Conclusion: The screening system for anti-metastatic small-molecule compounds based on PNC prevalence can provide an effective technical platform for research and development of anti-metastatic drugs for liver cancer.

Synergism between RIZ1 gene therapy and paclitaxel in SiHa cervical cancer cells.

RIZ1 is a tumor suppressor gene. The purpose of the present study was to investigate the inhibitory effect of RIZ1 gene therapy on the growth of SiHa cervical cancer cells and its synergism with paclitaxel. The expression levels of RIZ1 were examined by real-time PCR and western blotting before and after transfection of RIZ1. The effects of paclitaxel or pcDNA3.1(+)-RIZ1 alone or in combination, on the proliferation of SiHa cells were evaluated by MTT method. The inhibitory effect on the proliferation of SiHa cells was more significant in the pcDNA3.1(+)-RIZ1 combined with paclitaxel group than in the pcDNA3.1(+)-RIZ1 or paclitaxel groups (P<0.05). The expression level of RIZ1 in SiHa cells increased after treatment with paclitaxel, which indicated a synergism between them. RIZ1 gene therapy combined with paclitaxel showed stronger cell inhibition than paclitaxel alone, which indicated a synergism between them.

Pre-embedding Double-Label Immunoelectron Microscopy of Chemically Fixed Tissue Culture Cells.

Localization of specific proteins within cells at the nanometer level of resolution is central to understanding how these proteins function in cell processes such as motility and intracellular trafficking. Such localization can be achieved by combining transmission electron microscopy (TEM) with immunogold labeling. Here we describe a pre-embedding, indirect gold immunolabeling approach to localize two different proteins of interest with secondary antibodies labeled with gold particles of different sizes in cells grown on cover slips. In this protocol, the cells are immunolabeled prior to being embedded in an epoxy resin for ultrathin sectioning. The protocol also includes strategies for optimizing the balance between ultrastructure and antigen preservation, steps to minimize nonspecific antibody binding, and steps to optimize antibody penetration.

Hepatic Steatosis as a Predictive Factor of Antiviral Effect of Pegylated Interferon Therapy in Patients With Hepatitis B.

BACKGROUND AND AIMS: This study sought to evaluate the impact of hepatic steatosis, a common hepatocyte change in nonalcoholic fatty liver disease, upon response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB). METHODS: Eighty-nine consecutive CHB patients from the Affiliated Hospital of Hangzhou Normal University receiving 48 weeks of PEG-IFN therapy were enrolled in this study, and 56 patients were followed up for 48 weeks among subjects with completed therapy. Baseline characteristics, end-of-treatment response (ETR), and sustained viral response (SVR) to PEG-IFN therapy were evaluated. Univariate analysis and multivariate logistic regression were applied to find independent factors of hepatic steatosis and PEG-IFN treatment failure. RESULTS: Steatosis was present in 34.5% (31 of 89) of liver biopsy samples. ETR to PEG-IFN therapy was 56.17% (50 of 89) at 48 weeks, and SVR to PEG-IFN therapy was 57.6% (32 of 56) at 96 weeks. There was no significant difference in ETR between the patients with hepatic steatosis and those without hepatic steatosis at 48 weeks (P > .05), whereas SVR was higher in patients without hepatic steatosis than in those with hepatic steatosis at 96 weeks (P < .05). Multivariate analysis showed that the sustained response rate was independently associated with steatosis, fibrosis, aspartate aminotransferase, C-reactive protein, and ferritin. Hepatic steatosis was a prediction factor with the sustained response. CONCLUSIONS: Hepatic steatosis may be a predictive factor of response to PEG-IFN therapy in patients with CHB.

Good survival in a patient with recurrent transitional cell carcinoma of the ovary: A case report of PET-CT for detection and follow-up.

Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian cancer. The present study reports the case of a 55-year-old patient from The Affiliated Tumor Hospital of Harbin Medical University (Harbin, Heilongjiang, China) who underwent successful surgery for recurrence of a TCC of the ovary with rectum metastases following the initial surgery and chemotherapy. Positron emission tomography/computed tomography (PET-CT) was used in the pre-operative detection of the tumor and the post-operative follow-up of the patient. To date, the patient has experienced 8 years of disease-free survival. The aim of the present study was to convey the good survival rate of the patient following recurrent TCC of the ovary, and the role of PET-CT in detection and follow-up, in order to aid in the future selection of appropriate diagnostic methods and therapies for this disease.

Human placenta mesenchymal stem cells expressing exogenous kringle1-5 protein by fiber-modified adenovirus suppress angiogenesis.

Anti-angiogenesis gene therapy is considered a promising treatment for excessive vascularization. Mesenchymal stem cell (MSC)-based gene therapy may enhance the effect of anti-angiogenesis by maintaining a long therapeutic period in vivo. However, transduction efficiencies and transgene expression in MSC-based gene therapy should be improved. Here we report human placenta-derived MSC (HPMSC)-based gene therapy using a fiber-modified adenoviral vector carrying the kringle1-5 gene to maintain long-term survival and effectively suppress angiogenesis both in vitro and in vivo. HPMSCs infected by the adenoviral vector were transduced at high efficiency with a low multiplicity of infection, and the infected HPMSCs expressed exogenous kringle1-5 protein in vitro and in vivo. Infected HPMSCs were detected at 2 weeks in vivo by fluorescence imaging and immunohistochemistry of reporter gene expression. Importantly, the microvessel growth of aortic rings in vitro was inhibited by administration of infected HPMSCs expressing kringle1-5 protein (K1-5-HPMSCs) at day 6. In Matrigel plugs combined with K1-5-HPMSCs, microvessel density was decreased as detected by immunohistochemistry and blood flow was decreased as detected by the power Doppler contrast enhanced at day 14. The fiber-modified adenovirus is an effective gene vector for HPMSC-based gene therapy, which may be a promising strategy for cancer anti-angiogenesis.

LXRα-mediated downregulation of FOXM1 suppresses the proliferation of hepatocellular carcinoma cells.

Liver X receptors (LXRs), including LXRα and LXRß isoforms, have important roles in the metabolic regulation of glucose, cholesterol and lipid. Moreover, activation of LXRs also represses the expression of cyclin D1 and cyclin B1, and thus suppresses the proliferation of multiple cancer cells, but the relevant mechanism is not well known. Forkhead box M1 (FOXM1) is a proliferation-specific member of forkhead box family, which is highly expressed in proliferating normal cells and numerous cancer cells. FOXM1 directly activates transcription of cyclin D1 and cyclin B1, resulting in the enhancement of cell cycle progression and cell proliferation. However, it is unclear whether LXRs are involved in the regulation of FOXM1. In this study, we demonstrated that specific LXRs agonists downregulated expression of FOXM1, cyclin D1 and cyclin B1 in hepatocellular carcinoma (HCC) cells, which led to cell cycle and cell proliferation arrest. Knockdown of FOXM1 significantly alleviated LXRs activation-mediated cell cycle arrest and cell growth suppression. Reporter assays showed that the activation of LXRs significantly reduced the transcriptional activity of FOXM1 promoter. Electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that LXRα but not LXRß could bind to an inverted repeat IR2 (-52CCGTCAcgTGACCT-39) in the promoter region of FOXM1 gene. Moreover, the xenograft tumor growth and the corresponding FOXM1 expression in nude mice were dramatically repressed by LXRs agonists. Taken together, we conclude that LXRα but not LXRß functions as a transcriptional repressor for FOXM1 expression. The pathway 'LXRα-FOXM1-cyclin D1/cyclin B1' is a novel mechanism by which LXRs suppress the proliferation of HCC cells, suggesting that the pathway may be a novel target for HCC treatment.

miR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis.

Human cancers often exhibit attenuated microRNA (miRNA) biogenesis and global underexpression of miRNAs; thus, targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy. Here, we report that miR-26a enhances miRNA biogenesis, which acts as a common mechanism partially accounting for miR-26a function in diverse cancers including melanoma, prostate and liver cancer. miR-26a was broadly reduced in multiple cancers, and overexpression of miR-26a significantly suppressed tumor growth and metastasis both in vitro and in vivo, including melanoma, prostate and liver cancers. Notably, miR-26a overexpression was accompanied by global upregulation of miRNAs, especially let-7, and let-7 expression was concordant with miR-26a expression in cancer cell lines, xenograft tumors and normal human tissues, underscoring their biological relevance. We showed that miR-26a directly targeted Lin28B and Zcchc11-two critical repressors of let-7 maturation. Furthermore, we have demonstrated that Zcchc11 promoted tumor growth and metastasis, and it was prominently overexpressed in human cancers. Our findings thus provide a novel mechanism by which a miRNA acts as a modulator of miRNA biogenesis. These results also define a role of the miR-26a and Zcchc11 in tumorigenesis and metastasis and have implications to develop new strategies for cancer therapy.

Validation of the inoue method for camera-based glomerular filtration rate determination in Filipinos

A study was conducted to validate the Inoue protocol in determining the glomerular filtration rate (GFR) of Filipinos. Dynamic posterior planar kidney images of 402 consecutive Filipino patients referred for in vitro GFR determination were reprocessed using the Inoue protocol. Regression and Bland-Altman analyses were done on surface area normalized glomerular filtration rates (GFRSAnorm) generated using the Inoue linear regression model of the sample, Gates' method, and original regression formula published by Inoue, using respective two-point plasma concentration (in vitro) GFRSAnorm values as reference standards. GFRSAnorm results from the three camera-based techniques had strong correlation with those obtained using the in vitro method (i.e. r values of 0.9349, 0.8922 and 0.9349, respectively). However, agreement analysis showed lack of both bias and precision in the results of the Inoue linear regression model of the sample, and presence of bias and lack of precision in the results of both the Gates' method and the original linear regression model published by Inoue when compared to their corresponding in vitro GFRSAnorm results (standard error of 0.6209, 0.8379 and 0.9473, respectively). Thus, the linear regression model of the Inoue protocol is superior to the Gates' method for camera-based GFR estimation, and is population-specific, but is not robust enough to be a replacement for the in vitro technique.

TNFAIP8 as a predictor of metastasis and a novel prognostic biomarker in patients with epithelial ovarian cancer.

BACKGROUND: Tumour necrosis factor-α-induced protein 8 (TNFAIP8) has been recently documented in various malignancies, but its role in epithelial ovarian cancer (EOC) remains unknown. METHODS: Tumour necrosis factor-α-induced protein 8 expression was determined by real-time reverse transcription PCR and western blot analysis. Tumour tissues, consisting of serous, mucinous, endometrioid and clear cell histotypes, from 202 EOC patients (International Federation of Gynecologists and Obstetricians I-IV) who underwent primary cytoreduction were collected. Then, we examined the immunohistochemical expression of TNFAIP8 and evaluated its clinical significances. RESULTS: Tumour necrosis factor-α-induced protein 8 overexpression was significantly associated with high histologic grade (P=0.005), large residual tumour size (P=0.014), recurrence (P=0.024) and response to chemotherapy (P<0.001). Multivariate analysis showed that TNFAIP8 overexpression was independently correlated with the presence of lymph node (odds ratio (OR): 4.129; 95% confidence interval (CI): 1.491-11.435; P=0.006) and intraperitoneal metastasis (OR: 2.209; 95% CI: 1.174-4.156; P=0.014). Moreover, results revealed that the status of TNFAIP8 expression was an independently prognostic factor for both cancer-specific survival (hazard ratio (HR): 1.852; 95% CI: 1.322-2.594; P<0.001) and disease-free survival (HR: 1.724; 95% CI: 1.235-2.407; P=0.001) in patients with EOC. CONCLUSION: The present data provide evidence that TNFAIP8 predicts EOC metastasis and poor survival, highlighting its potential function as a therapeutic target for EOCs.

Intranasal administration of TAT-haFGF(14₋154) attenuates disease progression in a mouse model of Alzheimer's disease.

Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 µg/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced ß-amyloid protein(1-42) (Aß(1-42)) deposits as well as the levels of Aß soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Aß pathology and oxidative stress.

Involvement of the NF-κB pathway in multidrug resistance induced by HBx in a hepatoma cell line.

It is widely believed that hepatocellular cancer (HCC), especially HBV associated HCC, is highly resistant to chemotherapy. To investigate the molecular influence of HBx protein on multidrug resistance (MDR) in HCC and the potential role of the NF-κB pathway in this process. We established HBx-expressing cells by liposome-mediated transfection of the HBx into the HepG2 cell line. We found that HBx expression in HCC cells induces drug resistance against multiple drugs, a significantly lower apoptosis ratio in HepG2-HBx and HepG2.2.15 cells, compared with HepG2 and HepG2-3.1 cells (P < 0.05) after treating with 5-FU or adriamycin. And compared with the control group, the HBx-transfected cells showed a higher expression of MDR-associated and anti-apoptotic genes. Furthermore, we found that the NF-κB activity was remarkably high in the HBx-expressing cells as measured by p65 nuclear localization. In addition, the upregulated anti-apoptotic genes, Gadd45b and Survivin, in HBx-expressing HCC cells were downregulated by IMD-0354 treatment, which is the NF-κB pathway inhibitor. Taken together, these results suggest that HBx protein might be one of the causes for the occurrence of MDR in HCC, and the NF-κB pathway might be involved in this change.