bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-139-5p Loss-Mediated WTAP Activation Contributes to Hepatocellular Carcinoma Progression by Promoting the Epithelial to Mesenchymal Transition
Authors: Liu Wenli , Gao Xuewei , Chen Xiaolong , Zhao Na , Sun Ying , Zou Yawen , Guan Yize , Yang Lin , Pei Xiaoxian , Wang Guozhen , Wang Bin , Li Mingcheng , Song Wengang 
Published: April 2021

Background: Hepatocellular carcinoma (HCC) is a primary aggressive gastrointestinal neoplasm that affects patients worldwide. It has been shown that Wilms' tumor 1-associating protein (WTAP) is frequently upregulated in various cancers. However, the potential role of WTAP in HCC remains largely unknown.Methods: The expression levels of WTAP in human HCC tissues were determined by the western blotting and immunohistochemical (IHC) staining. A correlation between the WTAP expression, clinicopathological features, and the HCC prognosis was analyzed. The WTAP expression was silenced by short hairpin RNA (shRNA), and effects of the knockdown of WTAP on the proliferation and invasion of HCC cells were assessed. The microRNAs (miRNAs) involved in the regulation of the WTAP expression were identified by a bioinformatics analysis and further confirmed by in vitro assays.Results: The expression levels of WTAP in liver cancer tissues were significantly elevated and compared with those in the adjacent normal tissues and significantly correlated with the clinical stage and prognosis in patients with HCC. Further investigation revealed that the knockdown of WTAP drastically suppressed HCC cell proliferation and invasion abilities. Luciferase reporter assay and validation experiments confirmed that WTAP was a direct target of miR-139-5p. Moreover, the overexpression of WTAP could partly abolish the inhibitory effects of miR-139-5p on the HCC cell growth and invasion. Mechanistically, we revealed that the miR-139-5p/WTAP axis regulated the HCC progression by controlling the epithelial to mesenchymal transition (EMT).Conclusions: In summary, the results indicate that WTAP is a potential oncogene in HCC and miR-139-5p negatively regulates the WTAP expression. MiR-139-5p/WTAP can be utilized as a potential therapeutic target for HCC.
Comparison of Diffusion Kurtosis Imaging and Amide Proton Transfer Imaging in the Diagnosis and Risk Assessment of Prostate Cancer
Authors: Yin Huijia , Wang Dongdong , Yan Ruifang , Jin Xingxing , Hu Ying , Zhai Zhansheng , Duan Jinhui , Zhang Jian , Wang Kaiyu , Han Dongming 
Published: April 2021

ObjectivesThis study aims to evaluate and compare the diagnostic value of DKI and APT in prostate cancer (PCa), and their correlation with Gleason Score (GS).Materials and MethodsDKI and APT imaging of 49 patients with PCa and 51 patients with benign prostatic hyperplasia (BPH) were collected and analyzed, respectively. According to the GS, the patients with PCa were divided into high-risk, intermediate-risk and low-risk groups. The mean kurtosis (MK), mean diffusion (MD) and magnetization transfer ratio asymmetry (MTRasym, 3.5 ppm) values among PCa, BPH, and different GS groups of PCa were compared and analyzed respectively. The diagnostic accuracy of each parameter was evaluated by using the receiver operating characteristic (ROC) curve. The correlation between each parameter and GS was analyzed by using Spearman’s rank correlation.ResultsThe MK and MTRasym (3.5 ppm) values were significantly higher in PCa group than in BPH group, while the MD value was significantly lower than in BPH group. The differences of MK/MD/MTRasym (3.5 ppm) between any two of the low-risk, intermediate-risk, and high-risk groups were all statistically significant (p &lt;0.05). The MK value showed the highest diagnostic accuracy in differentiating PCa and BPH, BPH and low-risk, low-risk and intermediate-risk, intermediate-risk and high-risk (AUC = 0.965, 0.882, 0.839, 0.836). The MK/MD/MTRasym (3.ppm) values showed good and moderate correlation with GS (r = 0.844, −0.811, 0.640, p &lt;0.05), respectively.ConclusionDKI and APT imaging are valuable in the diagnosis of PCa and demonstrate strong correlation with GS, which has great significance in the risk assessment of PCa.
A Nomogram Model to Predict Prognosis of Patients With Genitourinary Sarcoma
Authors: Li Linde , Liang Jiayu , Song Turun , Yin Saifu , Zeng Jun , Zhong Qiang , Feng Xiaobing , Jia Zihao , Fan Yu , Wang Xianding , Lin Tao 
Published: April 2021

ObjectivesThe aim of this study is to evaluate the significant factors influencing the overall survival (OS) and recurrence free survival (RFS) and make an attempt to develop a nomogram for predicting the prognosis of patients with genitourinary sarcoma (GS).MethodsData on adult GS from 1985 to 2010 were collected. The impact of clinical factors on OS and RFS were estimated by Kaplan–Meier (KM) analysis, and differences between groups were analyzed by the log-rank test. To establish a nomogram, all patients were randomly divided into a training set (n = 125) and a testing set (n = 63). Cox proportion hazard model was utilized to assess the prognostic effect of variables. Then, a nomogram was established to estimate 1-, 3-, and 5-year OS based on Cox regression model. Subsequently, the nomogram was validated by a training set and a validation set.ResultsA total of 188 patients were enrolled into our study. Male patients with bladder sarcoma had better OS rather than RFS when stratified by gender (P = 0.022). According to histological subtypes, patients with leiomyosarcoma (LMS) undergoing chemotherapy were associated with favorable OS (P = 0.024) and RFS (P = 0.001). Furthermore, LMS in kidney sarcoma were associated with lower recurrence rate in comparison to rhabdomyosarcoma (RMS) (P = 0.043). Margin status after surgical excision markedly influenced the OS and RFS of GS patients and negative margins presented optimal prognosis. Chemotherapy was associated with improved OS for patients without surgery (P = 0.029) and patients with positive margins (P = 0.026). Based on the multivariate analysis of the training cohort, age, gender, surgery status, histological subtype, and chemotherapy were included in our nomogram for prediction of OS. The nomogram had sufficient power with concordance index (C-index) of OS: 0.770, 95%CI: 0.760–0.772 and area under curve (AUC) of OS: 0.759, 95%CI: 0.658–0.859 in the training set and with C-index of OS: 0.741, 95%CI: 0.740–0.765, and AUC of OS: 0.744, 95%CI: 0.576–0.913 in the validation set.ConclusionsAdults GS is a group of extremely rare tumors with poor prognosis. Of all histological types, LMS is sensitive to chemotherapy. We highlighted the cardinal role of surgical resection and the importance of achieving negative margins. We identified the efficacy of chemotherapy for patients with positive margins and those without surgery as well. A nomogram is validated as an effective tool predicting short-term outcomes.
A Novel Prognostic Model and Practical Nomogram for Predicting the Outcomes of Colorectal Cancer: Based on Tumor Biomarkers and Log Odds of Positive Lymph Node Scheme
Authors: Zhu Jun , Hao Jun , Ma Qian , Shi Tingyu , Wang Shuai , Yan Jingchuan , Chen Rujie , Xu Dong , Jiang Yu , Zhang Jian , Li Jipeng 
Published: April 2021

BackgroundEmerging evidence shows that serum tumor biomarkers (TBs) and log odds of positive lymph node scheme (LODDS) are closely associated with the prognosis of colorectal cancer (CRC) patients. The aim of our study is to validate the predictive value of TBs and LODDS clinically and to develop a robust prognostic model to predict the overall survival (OS) of patients with CRC.MethodsCRC patients who underwent radical resection and with no preoperative chemotherapy were enrolled in the study. The eligible population were randomized into training (70%) and test (30%) cohorts for the comprehensive evaluation of the prognostic model. Clinical implications of serum biomarkers and LODDS were identified by univariate and multivariate Cox proportion regression analysis. The predictive ability and discriminative performance were evaluated by Kaplan–Meier (K–M) curves and receiver operating characteristic (ROC) curves. Clinical applicability of the prognostic model was assessed by decision curve analysis (DCA), and the corresponding nomogram was constructed based on the above factors.ResultsA total of 1,202 eligible CRC patients were incorporated into our study. Multivariable COX analysis demonstrated that CA199 (HR = 1.304), CA125 (HR = 1.429), CEA (HR = 1.307), and LODDS (HR = 1.488) were independent risk factors for OS (all P &lt; 0.0001). K–M curves showed that the high-risk group possessed a shorter OS than the low-risk counterparts. The area under curves (AUCs) of the model for 1-, 3- and 5-year OS were 86.04, 78.70, and 76.66% respectively for the train cohort (80.35, 77.59, and 74.26% for test cohort). Logistic DCA and survival DCA confirmed that the prognostic model displayed more clinical benefits than the conventional AJCC 8th TNM stage and CEA model. The nomograms were built accordingly, and the calibration plot for the probability of survival at 3- or 5-years after surgery showed an optimal agreement between prediction and actual observation.ConclusionsPreoperative serum TBs and LODDS have significant clinical implications for CRC patients. A novel prognostic model incorporating common TBs (CA199, CA125, and CEA) and LODDS displayed better predictive performance than both single factor and the TNM classification. A novel nomogram incorporating TBs and LODDS could individually predict OS in patients with CRC.
Chlorpromazine Sensitizes Progestin-Resistant Endometrial Cancer Cells to MPA by Upregulating PRB
Authors: Cui Yunxia , Wu Huiwen , Yang Linlin , Huang Ting , Li Jian , Gong Xiaodi , Li Lijuan , Sun Xiao , Mao Fei , Wang Yudong 
Published: April 2021

Medroxyprogesterone acetate (MPA) is the main conservative treatment for endometrial cancer (EC) patients desirable to preserve fertility and those who cannot suffer from surgery. Considering the high incidence of progestin resistance and recurrence of MPA treatment, we reproposed antipsychotics chlorpromazine (CPZ) as a new strategy for both progestin-sensitive and -resistant endometrial cancer. Cytobiology experiments indicated that CPZ could significantly suppress proliferation, migration/invasion and induce apoptosis in Ishikawa (ISK) and KLE EC cell lines. And xenograft mouse models were constructed to validate the antitumor effect and toxicity of CPZ in-vivo. CPZ inhibited the growth at a low dose of 3mg/kg and the mice exhibited no signs of toxicity. Next, concomitant treatment and sequential treatment with CPZ and MPA were proceeded to analysis the synergistic effect in EC cells. Concomitant treatment only performed a limited synergistic effect on apoptosis in ISK and KLE cells. Nevertheless, sequential treatment showed favorable synergistic effects in progestin-resistant KLE cells. Finally, a stable MPA-resistant cell line shRNA was established to explore the mechanism of CPZ reversing progestin resistance. Immunoblot data showed that CPZ inhibited the activation of PI3K/AKT signal in ISK and KLE cells and upregulated PRB expression in progestin-resistant cells, by which CPZ overcame progestin resistance to MPA. Thus, CPZ might act as a candidate drug for conservative treatment and sequential treatment with CPZ and MPA could be a suitable therapeutic option for progestin resistant patients.
Chinese Herbal Medicine Usage Reduces Overall Mortality in HIV-Infected Patients With Osteoporosis or Fractures
Authors: Ho Mao-Wang , Li Te-Mao , Li Ju-Pi , Chiou Jian-Shiun , Chiu Mu-Lin , Chen Chao-Jung , Cheng Chi-Fung , Tsai Fuu-Jen , Wu Yang-Chang , Lin Ting-Hsu , Liao Chiu-Chu , Huang Shao-Mei , Lin Yu-Ning , Chou Chen-Hsing , Liang Wen-Miin , Lin Ying-Ju 
Published: April 2021

The survival of patients with HIV has greatly improved, due to Anti-Retroviral Therapy (ART). However, long-term HIV survivors often develop serious bone abnormalities, possibly due to the interplay of osteoblasts, osteoclasts, HIV ad ART. We evaluated in a nation-wide study in Taiwan the effect of Chinese herbal medicine (CHM) on overall mortality in HIV patients with osteoporosis or fractures. Enrollment period was between 1998 and 2011. Patients with osteoporosis or fractures before the HIV infection, and those with less than 14 days CHM use, were excluded. This left 498 patients, 160 CHM users, 338 without CHM. Univariate Kaplan-Meier and multivariate Cox regression analysis were used to compare the overall mortality in these 2 groups. Due to the nature of Chinese medicine, CHMs inevitably varied. We therefore also used rule mining and network analysis to determine which major CHM clusters were prescribed to the patients. CHM users had a much Lower mortality (hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.24–0.77, p &lt; 0.005) and higher survival (p = 0.004, log-rank test). Although the CHMs greatly varied, network analysis identified one main cluster of strongly related CHM combinations (Chuan-Xiong-Cha-Tiao-San (CXCTS), Gan-Cao (GC; Glycyrrhiza uralensis Fisch.), Liu-He-Tang (LHT), Huang-Qin-Tang (HQT), Jia-Wei-Ping-Wei-San (JWPWS), and Dang-Gui-Long-Hui-Wan (DGLHuiW)). CHM as an additional treatment strongly improves overall survival in HIV-infected patients with osteoporosis and fractures.
Cystic Fibrosis Lung Disease in the Aging Population
Authors: Künzi Lisa , Easter Molly , Hirsch Meghan June , Krick Stefanie 
Published: April 2021

The demographics of the population with cystic fibrosis (CF) is continuously changing, with nowadays adults outnumbering children and a median predicted survival of over 40 years. This leads to the challenge of treating an aging CF population, while previous research has largely focused on pediatric and adolescent patients. Chronic inflammation is not only a hallmark of CF lung disease, but also of the aging process. However, very little is known about the effects of an accelerated aging pathology in CF lungs. Several chronic lung disease pathologies show signs of chronic inflammation with accelerated aging, also termed “inflammaging”; the most notable being chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In these disease entities, accelerated aging has been implicated in the pathogenesis via interference with tissue repair mechanisms, alterations of the immune system leading to impaired defense against pulmonary infections and induction of a chronic pro-inflammatory state. In addition, CF lungs have been shown to exhibit increased expression of senescence markers. Sustained airway inflammation also leads to the degradation and increased turnover of cystic fibrosis transmembrane regulator (CFTR). This further reduces CFTR function and may prevent the novel CFTR modulator therapies from developing their full efficacy. Therefore, novel therapies targeting aging processes in CF lungs could be promising. This review summarizes the current research on CF in an aging population focusing on accelerated aging in the context of chronic airway inflammation and therapy implications.
Health Impact and Cost-Effectiveness of Implementing Gender-Neutral Vaccination With the 9-Valent Human Papillomavirus Vaccine in Belgium
Authors: Simoens Steven , Bento-Abreu Andre , Merckx Barbara , Joubert Sophie , Vermeersch Steve , Pavelyev Andrew , Varga Stefan , Morais Edith 
Published: April 2021

Background: Routine human papillomavirus (HPV) immunization in Belgium is currently regionally managed, with school-aged girls receiving the 9-valent HPV (9vHPV) vaccine in Flanders and Wallonia-Brussels with a national catch-up program for females only. This study will assess whether expanding these programs to gender-neutral vaccination (GNV) with the 9vHPV vaccine is a cost-effective strategy in Belgium.Methods: A validated HPV-type transmission dynamic model estimated the potential health and economic impact of regional vaccination programs, comparing GNV versus female-only vaccination (FOV) with the 9vHPV vaccine in individuals aged 11–12 years in Flanders, GNV with the 9vHPV vaccine versus FOV with the 2-valent HPV (2vHPV) vaccine in individuals aged 12–13 years in Wallonia-Brussels, and national catch-up GNV versus FOV with the 9vHPV vaccine for those aged 12–18 years. Vaccination coverage rates of 90, 50, and 50% in both males and females were used in the base cases for the three programs, respectively, and sensitivity analyses were conducted. All costs are from the third-party payer perspective, and outcome measures were reported over a 100-year time horizon.Results: GNV with the 9vHPV vaccine was projected to decrease the cumulative incidence of HPV 6/11/16/18/31/33/45/52/58-related diseases relative to FOV in both Flanders and Wallonia-Brussels. Further reductions were also projected for catch-up GNV with the 9vHPV vaccine, including reductions of 6.8% (2,256 cases) for cervical cancer, 7.1% (386 cases) and 18.8% (2,784 cases) for head and neck cancer in females and males, respectively, and 30.3% (82,103 cases) and 44.6% (102,936 cases) for genital warts in females and males, respectively. As a result, a GNV strategy would lead to reductions in HPV-related deaths. Both regional and national catch-up GNV strategies were projected to reduce cumulative HPV-related disease costs and were estimated to be cost-effective compared with FOV with incremental cost-effectiveness ratios of €8,062, €4,179, and €6,127 per quality-adjusted life-years in the three programs, respectively. Sensitivity analyses were consistent with the base cases.Conclusions: A GNV strategy with the 9vHPV vaccine can reduce the burden of HPV-related disease and is cost-effective compared with FOV for both regional vaccination programs and the national catch-up program in Belgium.
Comparison of Rifamycins for Efficacy Against Mycobacterium avium Complex and Resistance Emergence in the Hollow Fiber Model System
Authors: Boorgula Gunavanthi D. , Jakkula Laxmi U. M. R. , Gumbo Tawanda , Jung Bockgie , Srivastava Shashikant 
Published: April 2021

Rifamycins are integral part of the combination regimen for treatment of pulmonary Mycobacterium avium-complex [MAC] infection, but different practitioners prefer different rifamycins. The objective of the study was to compare microbial kill and resistance emergence of rifamycins using principles of pharmacokinetics/pharmacodynamics. First, we identified rifamycin MICs in 20 MAC isolates from patients followed by concentration-response studies in test-tubes. Next, we examined efficacy and resistance suppression of three doses of each rifamycin in the hollow fiber system model of pulmonary MAC [HFS-MAC], mimicking human like concentration-time profile of the drugs. HFS-MAC units were repetitively sampled for total and drug-resistant MAC burden and for drug concentration measurements. Inhibitory sigmoid E max model, linear regression, and analysis of variance was used for data analysis. For rifabutin 90% of isolates had MIC ≤ 0.125 mg/L while for both rifampin and rifapentine this was ≤2.0 mg/L. There was no statistically significant difference (p &gt; 0.05) in maximal kill and effective concentration mediating 50% of the bacterial kill among three rifamycins in the static concentration experiment. In the HFS-MAC, the bactericidal kill (day 0–4) for rifampin was 0.89 (95% Confidence Interval (CI): 0.43–1.35), for rifapentine was 1.05 (95% CI: 0.08–1.23), and for rifabutin was 0.92 (95% CI: 0.61–1.24) log10 CFU/ml, respectively. Rifamycins monotherapy failed after just 4-days of treatment and entire MAC population was drug resistant on day 26 of the study. There was no dose dependent difference in MAC kill or resistance suppression among the three rifamycins tested in the HFS-MAC. Therefore, replacing one rifamycin, due to emergence of drug-resistance, with other may not be beneficial in clinical setting.
Dose-Related Urinary Metabolic Alterations of a Combination of Quercetin and Resveratrol-Treated High-Fat Diet Fed Rats
Authors: Zhuang Tongxi , Liu Xinhua , Wang Wen , Song Jing , Zhao Le , Ding Lili , Yang Li , Zhou Mingmei 
Published: April 2021

Most herbal polyphenols and flavonoids reveals multiple ameliorative benefits for obesity caused by chronic metabolic disorders. Accumulated studies have revealed that preferable therapeutic effects can be obtained through clinical combination of these two kinds of natural compounds for obesity improvement. The typical representative research was the combination of quercetin and resveratrol (CQR), in which the ratio of quercetin and resveratrol is 2:1, demonstrating a synergistic effect in anti-obesity process. Although there exists reports clarifying the mechanism of the combination of two to improve obesity from the perspective of improving adipose tissue inflammation or modulating the composition of intestinal flora, there are few further studies on the mechanism of drug action from the perspective of metabolites transformation. In this research, we mainly focused on the alterations of endogenous metabolites in rats, and analyzed the urine metabolites of obese and intervention model. Therefore, a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach was applied to assess the potential effects and mechanisms of CQR at different dosages (45, 90, and 180 mg/kg) in high fat diet (HFD)-induced obesity rats. Body weight gain and visceral fat weight were reduced by CQR, as well as blood lipid and inflammatory factor levels were increased by CQR in a dose-related manner. Urinary metabolomics revealed 22 differential metabolites related to the HFD-induced obesity, which were reversed in a dose-dependent manner by CQR, of which 8 were reversed in the 45 mg/kg CQR group, 15 were reversed in the 90 mg/kg CQR group, and 18 were reversed in the 180 mg/kg CQR group. Combined with bioinformatics and pattern recognition, the results demonstrated that the key differential metabolites were basically involved in amino acid metabolism, galactose metabolism, pantothenate and CoA biosynthesis, pyruvate metabolism and lysine degradation. In summary, our results showed significant therapeutic action by CQR administration and remarkable metabolomic changes after HFD feeding and CQR intervention. Urinary metabolomic analysis was highlighted on account of providing holistic and comprehensive insights into the pathophysiological mechanisms of the HFD-induced obesity, which also supplied clues for the future mechanism studies of CQR’s anti-obesity effects.