A Compound Mutation (c.953C<G and c.49G<A) Aggravates Functional Impairments of C1-INH in Hep G2 Cells

Ying-Yang Xu,Yu-Xiang Zhi 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.3

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Development and Validation of 18F-FDG PET/CT-Based Multivariable Clinical Prediction Models for the Identification of Malignancy-Associated Hemophagocytic Lymphohistiocytosis

Yang Xu,Lu Xia,Liu Jun,Kan Ying,Wang Wei,Zhang Shuxin,Liu Lei,Li Jixia,Yang Jigang 대한영상의학회 2022 Korean Journal of Radiology Vol.23 No.4

Objective: 18F-fluorodeoxyglucose (FDG) PET/CT is often used for detecting malignancy in patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), with acceptable sensitivity but relatively low specificity. The aim of this study was to improve the diagnostic ability of 18F-FDG PET/CT in identifying malignancy in patients with HLH by combining 18F-FDG PET/CT and clinical parameters. Materials and Methods: Ninety-seven patients (age ≥ 14 years) with secondary HLH were retrospectively reviewed and divided into the derivation (n = 71) and validation (n = 26) cohorts according to admission time. In the derivation cohort, 22 patients had malignancy-associated HLH (M-HLH) and 49 patients had non-malignancy-associated HLH (NM-HLH). Data on pretreatment 18F-FDG PET/CT and laboratory results were collected. The variables were analyzed using the Mann-Whitney U test or Pearson’s chi-square test, and a nomogram for predicting M-HLH was constructed using multivariable binary logistic regression. The predictors were also ranked using decision-tree analysis. The nomogram and decision tree were validated in the validation cohort (10 patients with M-HLH and 16 patients with NM-HLH). Results: The ratio of the maximal standardized uptake value (SUVmax) of the lymph nodes to that of the mediastinum, the ratio of the SUVmax of bone lesions or bone marrow to that of the mediastinum, and age were selected for constructing the model. The nomogram showed good performance in predicting M-HLH in the validation cohort, with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.686–0.971). At an appropriate cutoff value, the sensitivity and specificity for identifying M-HLH were 90% (9/10) and 68.8% (11/16), respectively. The decision tree integrating the same variables showed 70% (7/10) sensitivity and 93.8% (15/16) specificity for identifying M-HLH. In comparison, visual analysis of 18F-FDG PET/CT images demonstrated 100% (10/10) sensitivity and 12.5% (2/16) specificity. Conclusion: 18F-FDG PET/CT may be a practical technique for identifying M-HLH. The model constructed using 18F-FDG PET/CT features and age was able to detect malignancy with better accuracy than visual analysis of 18F-FDG PET/CT images.

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

( Hong-xu Yang ),( Yue Shang ),( Quan Jin ),( Yan-ling Wu ),( Jian Liu ),( Chun-ying Qiao ),( Zi-ying Zhan ),( Huan Ye ),( Ji-xing Nan ),( Li-hua Lian ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.4

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

Combined Effects of Curcumin and Triptolide on an Ovarian Cancer Cell Line

Cai, Ying-Ying,Lin, Wei-Ping,Li, Ai-Ping,Xu, Jian-Yang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

Zhang, Lin-Lin,Sun, Liang,Zhu, Xiao-Quan,Xu, Yong,Yang, Kuo,Yang, Fan,Yang, Yi-Ge,Chen, Guo-Qiang,Fu, Ji-Cheng,Zheng, Chen-Guang,Li, Ying,Mu, Xiao-Qiu,Shi, Xiao-Hong,Zhao, Fan,Wang, Fei,Yang, Ze,Wang, Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$, p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$, p=0.042/$OR_{recessive}=1.99$, p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$, $P_{tumorstage}=0.048$). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.

Deficiency of Follistatin-Like Protein 1 Accelerates the Growth of Breast Cancer Cells at Lung Metastatic Sites

Ying Zhang,Xiaozhou Xu,Ying Yang,Jie Ma,Lulu Wang,Xiangzhi Meng,Bing Chen,Ling Qin,Tao Lu,Yan Gao 한국유방암학회 2018 Journal of breast cancer Vol.21 No.3

Purpose: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been shown to play a role in various types of cancer. However, the clinical significance and function of FSTL1 in breast cancer have not been reported. We investigated the role of FSTL1 in breast cancer in this study. Methods: Enzyme-linked immunosorbent assays, western blot analysis, and reverse transcription polymerase chain reaction were used to monitor the expression of FSTL1 in breast cancer tissue and in serum samples from breast cancer patients. We employed a 4T1 breast cancer model and Fstl1+/− mice for in vivo studies. Hematoxylin and eosin staining, western blot analysis, and RNA sequencing were used to analyze the effect of FSTL1 on primary tumor growth and lung metastasis. Results: We demonstrated that the expression of FSTL1 is reduced in both the breast cancer tissue and the serum of breast cancer patients. We showed that reduced levels of FSTL1 in serum correlate with elevated expression of Ki-67 and epidermal growth factor receptor (EGFR) in cancer tissues. Moreover, lowered expression of FSTL1 was associated with decreased survival in breast cancer patients. Experiments on the Fstl1+/− mouse model established that FSTL1 deficiency had no effect on primary tumor growth, but increased the lung metastases of breast cancer cells, resulting in reduced survival of tumor-bearing mice. RNA sequencing found significantly reduced expression of Egln3 and increased expression of EGFR in Fstl1+/− mice. Thus, our results suggest that FSTL1 may affect the expression of EGFR through Egln3, inhibiting the proliferation of breast cancer cells at lung metastatic sites. Conclusion: In conclusion, we suggest a suppressor role of FSTL1 in breast cancer lung metastasis. Furthermore, FSTL1 may represent a potential prognostic biomarker and a candidate therapeutic target in breast cancer patients.

Performances of Prognostic Models in Stratifying Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy: a Validation Study in a Chinese Cohort

Xu, Hui,Zhang, Xiaopeng,Wu, Zhijun,Feng, Ying,Zhang, Cheng,Xie, Minmin,Yang, Yahui,Zhang, Yi,Feng, Chong,Ma, Tai The Korean Gastric Cancer Association 2021 Journal of gastric cancer Vol.21 No.3

Purpose: While several prognostic models for the stratification of death risk have been developed for patients with advanced gastric cancer receiving first-line chemotherapy, they have seldom been tested in the Chinese population. This study investigated the performance of these models and identified the optimal tools for Chinese patients. Materials and Methods: Patients diagnosed with metastatic or recurrent gastric adenocarcinoma who received first-line chemotherapy were eligible for inclusion in the validation cohort. Their clinical data and survival outcomes were retrieved and documented. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive ability of the models. Kaplan-Meier curves were plotted for patients in different risk groups divided by 7 published stratification tools. Log-rank tests with pairwise comparisons were used to compare survival differences. Results: The analysis included a total of 346 patients with metastatic or recurrent disease. The median overall survival time was 11.9 months. The patients were different into different risk groups according to the prognostic stratification models, which showed variability in distinguishing mortality risk in these patients. The model proposed by Kim et al. showed relative higher predicting abilities compared to the other models, with the highest χ² (25.8) value in log-rank tests across subgroups, and areas under the curve values at 6, 12, and 24 months of 0.65 (95% confidence interval [CI]: 0.59-0.72), 0.60 (0.54-0.65), and 0.63 (0.56-0.69), respectively. Conclusions: Among existing prognostic tools, the models constructed by Kim et al., which incorporated performance status score, neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, and tumor differentiation, were more effective in stratifying Chinese patients with gastric cancer receiving first-line chemotherapy.

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

Xu, Chao-Yang,Jiang, Zhi-Nong,Zhou, Ying,Li, Jia-Jia,Huang, Li-Ming Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

A Novel Interleaving Control Scheme for Boost Converters Operating in Critical Conduction Mode

Yang, Xu,Ying, Yanping,Chen, Wenjie The Korean Institute of Power Electronics 2010 JOURNAL OF POWER ELECTRONICS Vol.10 No.2

Interleaving techniques are widely used to reduce input/output ripples and to increase the power capacity of boost converters operating in critical conduction mode. Two types of phase-shift control schemes are studied in this paper, the turn-on time shifting method and the turn-off time shifting method. It is found that although the turn-off time shifting method exhibits better performance, it suffers from sub-harmonic oscillations at high input voltages. To solve this problem, an intensive quantitative analysis of the sub-harmonic oscillation phenomenon is made in this paper. Based upon that, a novel modified turn off time shifting control scheme for interleaved boost converters operating in critical conduction mode is proposed. An important advantage of this scheme is that both the master phase and the slave phase can operate stably in critical conduction mode without any oscillations in the full input voltage range. This method is implemented with a FPGA based digital PWM control platform, and tests were carried out on a two-phase interleaved boost PFC converter prototype. Experimental results demonstrated the feasibility and performance of the proposed phase-shift control scheme.

Expression of PGDH Correlates with Cell Growth in Both Esophageal Squamous Cell Carcinoma and Adenocarcinoma

Yang, Guo-Tao,Wang, Juan,Xu, Tong-Zhen,Sun, Xue-Fei,Luan, Zi-Ying Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Esophageal cancer represents the fourth most common gastrointestinal cancer and generally confers a poor prognosis. Prostaglandin-producing cyclo-oxygenase has been implicated in the pathogenesis of esophageal cancer growth. Here we report that prostaglandin dehydrogenase, the major enzyme responsible for prostaglandin degradation, is significantly reduced in expression in esophageal cancer in comparison to normal esophageal tissue. Reconstitution of PGDH expression in esophageal cancer cells suppresses cancer cell growth, at least in part through preventing cell proliferation and promoting cell apoptosis. The tumor suppressive role of PGDH applies equally to both squamous cell carcinoma and adenocarcinoma, which enriches our understanding of the pathogenesis of esophageal cancer and may provide an important therapeutic target.