Abstract Background The prognostic role of the preoperative lymphocyte-to-monocyte ratio (LMR) in patients with gastric cancer (GC) remains unclear. The aim of this study was to explore the ...prognostic potential of the preoperative LMR in patients with resectable GC. Materials and methods The medical records of 926 consecutive patients with resectable GC between 2005 and 2010 were retrospectively reviewed and analyzed. Patients were stratified into two groups based on the preoperative LMR with a cutoff value of 4.8 (group 1: LMR ≤ 4.8; group 2: LMR > 4.8). Clinicopathologic factors potentially affecting patient outcomes were collected prospectively and analyzed. Results Compared to group 2, in group 1, there was a higher percentage of men, patients aged >48 y, total gastrectomy, tumor size > 4.8 cm, T4 lesions, N3 disease, metastatic tumors, advanced stage, ratio of metastatic to examined lymph nodes > 0.18, R1 resection, and occurrence of vascular or lymphatic invasion. Group 1 also had a higher 30-d surgical mortality rate (groups 1 versus 2 at 2.9% versus 0.5%; P = 0.006) and lower 3-y and 5-y overall survival (53.6% versus 71.9% and 46.4% versus 63.3%, respectively; P < 0.0001). Multivariate analysis showed that preoperative low LMR was an unfavorable prognostic factor for resectable GC. Conclusions Patients with lower LMR had more aggressive tumor behavior, higher surgical mortality rates, and worse long-term survival. The preoperative LMR may serve as an independent prognostic factor for prediction of surgical outcomes and for assisting clinicians in determining future treatment plans.
There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple ...therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin.
After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion.
A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure.
Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.
Clinical evidence suggests increased cancer stem cells (CSCs) in a tumor mass may contribute to the failure of conventional therapies because CSCs seem to be more resistant than differentiated tumor ...cells. Thus, unveiling the mechanism regulating CSCs and candidate target molecules will provide new strategy to cure the patients.
The stem-like cell properties were determined by a prostasphere assay and dye exclusion assay. To find critical stem cell marker and reveal regulation mechanism, basic biochemical and molecular biologic methods, such as quantitative real-time PCR, Western blot, reporter gene assay, and chromatin immunoprecipitation assay, were used. In addition, to determine the effect of combination therapy targeting both CSCs and its progeny, in vitro MTT assay and in vivo xenograft model was used.
We demonstrate immortalized normal human prostate epithelial cells, appeared nontumorigenic in vivo, become tumorigenic, and acquire stem cell phenotype after knocking down a tumor suppressor gene. Also, those stem-like cells increase chemoresistance to conventional anticancer reagent. Mechanistically, we unveil that Wnt signaling is a key pathway regulating well-known stem cell marker CD44 by directly interacting to the promoter. Thus, by targeting CSCs using Wnt inhibitors synergistically enhances the efficacy of conventional drugs. Furthermore, the in vivo mouse model bearing xenografts showed a robust inhibition of tumor growth after combination therapy.
Overall, this study provides strong evidence of CSC in castration-resistant prostate cancer. This new combination therapy strategy targeting CSC could significantly enhance therapeutic efficacy of current chemotherapy regimen only targeting non-CSC cells.
In this letter, we have investigated experimentally, for the first time, the feasibility of gate-all-around polycrystalline silicon (poly-Si) nanowire transistors with junctionless (JL) configuration ...by utilizing only one heavily doped poly-Si layer to serve as source, channel, and drain regions. In situ doped poly-Si material features high and uniform-doping concentration, facilitating the fabrication process. The developed JL device exhibits desirable electrostatic performance in terms of higher ON/OFF current ratio and lower source/drain series resistance as compared with the inversion-mode counterpart. Such scheme appears of great potential for future system-on-panel and 3-D IC applications.
Quantum dot (QD)-based RGB micro-LED technology is seen as one of the most promising approaches towards full color micro-LED displays. In this work, we present a novel nanoporous GaN (NP-GaN) ...structure that can scatter light and host QDs, as well as a new type of micro-LED array based on an NP-GaN embedded with QDs. Compared to typical QD films, this structure can significantly enhance the light absorption and stability of QDs. As a result, the green and red QDs exhibited light conversion efficiencies of 90.3% and 96.1% respectively, leading to improvements to the luminous uniformity of the green and red subpixels by 90.7% and 91.2% respectively. This study provides a viable pathway to develop high-uniform and high-efficient color conversion micro-LED displays.
Deep learning allows automatic segmentation of teeth on cone beam computed tomography (CBCT). However, the segmentation performance of deep learning varies among different training strategies. Our ...aim was to propose a 3.5D U-Net to improve the performance of the U-Net in segmenting teeth on CBCT. This study retrospectively enrolled 24 patients who received CBCT. Five U-Nets, including 2Da U-Net, 2Dc U-Net, 2Ds U-Net, 2.5Da U-Net, 3D U-Net, were trained to segment the teeth. Four additional U-Nets, including 2.5Dv U-Net, 3.5Dv5 U-Net, 3.5Dv4 U-Net, and 3.5Dv3 U-Net, were obtained using majority voting. Mathematical morphology operations including erosion and dilation (E&D) were applied to remove diminutive noise speckles. Segmentation performance was evaluated by fourfold cross validation using Dice similarity coefficient (DSC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). Kruskal-Wallis test with post hoc analysis using Bonferroni correction was used for group comparison. P < 0.05 was considered statistically significant. Performance of U-Nets significantly varies among different training strategies for teeth segmentation on CBCT (P < 0.05). The 3.5Dv5 U-Net and 2.5Dv U-Net showed DSC and PPV significantly higher than any of five originally trained U-Nets (all P < 0.05). E&D significantly improved the DSC, accuracy, specificity, and PPV (all P < 0.005). The 3.5Dv5 U-Net achieved highest DSC and accuracy among all U-Nets. The segmentation performance of the U-Net can be improved by majority voting and E&D. Overall speaking, the 3.5Dv5 U-Net achieved the best segmentation performance among all U-Nets.
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have ...not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3. BDL rats showed increased hepatic NF-κB/AP-1 activities, inflammatory cell infiltration/accumulation, and cytokine production, and these signs of hepatic inflammation were ameliorated by rosmarinic acid. Mechanistic study revealed an inhibitory effect of rosmarinic acid on the axis of the high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) in BDL rats. Results of cultured hepatic stellate cells further showed the impacts of rosmarinic acid which attenuated TGF-β1-induced stellate cell mitogenic and fibrogenic activation. Our findings support the concept that rosmarinic acid could serve as a hepatoprotective agent, and dietary rosmarinic acid supplementation may be beneficial in terms of improving cholestasis-related liver injury via mechanisms involving resolution of oxidative burden and down-regulation of HMGB1/TLR4, NF-κB, AP-1, and TGF-β1/Smad signaling.
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•Bile duct ligation caused extrahepatic cholestasis in rodents.•Rosmarinic acid showed improvement effects against cholestasis.•Rosmarinic acid attenuated hepatic TGF-β1 signaling in BDL rats.•Rosmarinic acid attenuated hepatic NF-κB/AP-1 activities in BDL rats.•Rosmarinic acid attenuated hepatic HMGB1/TLR4 signaling in BDL rats.
The incidence and mortality rates of colorectal cancer (CRC) have been high in recent years. Prevention and early detection are crucial for decreasing the death rate. Therefore, this study aims to ...characterize the alteration patterns of mothers against decapentaplegic homolog 3 (
) in patients with CRC and its applications in early detection by using a genome-wide methylation array to identify an aberrant hypomethylation site in the intron position of the
gene. Quantitative methylation-specific polymerase chain reaction showed that hypomethylated
occurred in 91.4% (501/548) of Taiwanese CRC tissues and 66.6% of benign tubular adenoma polyps. In addition,
hypomethylation was observed in 94.7% of patients with CRC from The Cancer Genome Atlas dataset. A decrease in circulating cell-free methylation
was detected in 70% of CRC patients but in only 20% of healthy individuals.
mRNA expression was low in 42.9% of Taiwanese CRC tumor tissues but high in 29.4% of tumors compared with paired adjacent normal tissues. Hypomethylated
was found in cancers of the digestive system, such as liver cancer, gastric cancer, and colorectal cancer, but not in breast cancer, endometrial cancer, and lung cancer. In conclusion,
hypomethylation is a potential diagnostic marker for CRC in Western and Asian populations.
Primary cilium is a microtubule-based organelle that projects from the surfaces of most mammalian cell types and protrudes into the extracellular milieu as an antenna-like sensor to senses ...extracellular physical and biochemical signals, and then transmits signals into cytoplasm or nucleus to regulate numerous physical and developmental processes. Therefore, loss of primary cilia is associated to multiple cancer progression, including skin, breast, pancreas, ovarian, prostate, and kidney cancers. Our previous studies demonstrate that high prevalent loss of DAB2 Interacting Protein (DAB2IP) is associated with renal cell carcinoma, and we found a kinesin-like protein, kinesin family member 3A (KIF3a), was significantly increased in DAB2IP-interacting protein fraction. KIF3 is one of the most abundant kinesin-2 family proteins expressed in cells, and it is necessary for ciliogenesis. In this study, we observed that loss of DAB2IP in normal kidney epithelial cell significantly impair primary cilia formation. We unveiled a new mechanism of primary cilia stability via DAB2IP and KIF3a physical interaction at DAB2IP-PH domain. Furthermore, we found that KIF3a also act as a tumor suppressor in renal cell carcinoma, affect tumor development and patient survival.
The etiology of sudden sensorineural hearing loss (SSNHL) remains unclear. Possible causes of SSNHL include vascular diseases, viral infection, and autoimmune disorders. Therefore, we investigated ...whether hepatitis virus infection is correlated with the risk of SSNHL. Using data from the Taiwan Longitudinal Health Insurance Database, we conducted a retrospective matched-cohort study to compare patients diagnosed with hepatitis B or C virus (HBV/HCV) infections from January 1, 2000, to December 31, 2010, (N = 170,942) with frequency-matched controls (N = 512,826) at a ratio of 1:3 by sex, age, and index year. We followed each patient until the end of 2010 and evaluated the incidence of SSNHL. At the end of the follow-up period, 647 (0.38%, 647/170,942) patients developed SSNHL in the HBV/HCV group compared with 978 (0.19%, 978/512,826) in the control groups, with a statistical significance of P < 0.001 (using the log-rank test). The incidence rate ratio of SSNHL was 5.743-fold higher in the HBV/HCV group than in the control group (283.17 vs. 49.31 per 100,000 person-years, P < 0.001). The risk of SSNHL increased with HBV/HCV infection, and an adjusted hazard ratio of 5.103 (95% CI, 4.585-5.678) was determined using Cox proportional hazards regression. This study contributes to the awareness of the increased risk of SSNHL in HBV/HCV-infected populations. Our findings suggest that an underlying viral infection contributes to the development of SSNHL.
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