44 results on '"Wu, Xue"'
Search Results
2. Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer's disease.
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Xiao, Zhenxu, Wu, Xue, Wu, Wanqing, Yi, Jingwei, Liang, Xiaoniu, Ding, Saineng, Zheng, Li, Luo, Jianfeng, Gu, Hongchen, Zhao, Qianhua, Xu, Hong, and Ding, Ding
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COGNITIVE ability , *ALZHEIMER'S disease , *AMNESTIC mild cognitive impairment , *BIOMARKERS , *TAU proteins - Abstract
Background: Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer's disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. Methods: We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. Results: All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = −0.536, P < 0.0001), memory (r = −0.481, P < 0.0001), attention (r = −0.437, P < 0.0001), visuospatial function (r = −0.385, P < 0.0001), and language (r = −0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = −0.301, P < 0.001). Conclusions: Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Serum metabolomics in chickens infected with Cryptosporidium baileyi.
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Wu, Xue-Mei, Yang, Xin, Fan, Xian-Cheng, Chen, Xi, Wang, Yu-Xin, Zhang, Long-Xian, Song, Jun-Ke, and Zhao, Guang-Hui
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AMINO acid metabolism , *LIQUID chromatography-mass spectrometry , *METABOLOMICS , *MULTIVARIATE analysis , *LIPID metabolism , *CELLULAR aging , *CHICKENS , *METABOLITES - Abstract
Background: Cryptosporidium baileyi is an economically important zoonotic pathogen that causes serious respiratory symptoms in chickens for which no effective control measures are currently available. An accumulating body of evidence indicates the potential and usefulness of metabolomics to further our understanding of the interaction between pathogens and hosts, and to search for new diagnostic or pharmacological biomarkers of complex microorganisms. The aim of this study was to identify the impact of C. baileyi infection on the serum metabolism of chickens and to assess several metabolites as potential diagnostic biomarkers for C. baileyi infection. Methods: Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) and subsequent multivariate statistical analysis were applied to investigate metabolomics profiles in the serum samples of chickens infected with C. baileyi, and to identify potential metabolites that can be used to distinguish chickens infected with C. baileyi from non-infected birds. Results: Multivariate statistical analysis identified 138 differential serum metabolites between mock- and C. baileyi-infected chickens at 5 days post-infection (dpi), including 115 upregulated and 23 downregulated compounds. These metabolites were significantly enriched into six pathways, of which two pathways associated with energy and lipid metabolism, namely glycerophospholipid metabolism and sphingolipid metabolism, respectively, were the most enriched. Interestingly, some important immune-related pathways were also significantly enriched, including the intestinal immune network for IgA production, autophagy and cellular senescence. Nine potential C. baileyi-responsive metabolites were identified, including choline, sirolimus, all-trans retinoic acid, PC(14:0/22:1(13Z)), PC(15:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(16:1(9Z)/24:1(15Z)), phosphocholine, SM(d18:0/16:1(9Z)(OH)) and sphinganine. Conclusions: This is the first report on serum metabolic profiling of chickens with early-stage C. baileyi infection. The results provide novel insights into the pathophysiological mechanisms of C. baileyi in chickens. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Development of a tibial experimental non-union model in rats.
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Wu, Xue-Qiang, Wang, Dong, Liu, Yang, and Zhou, Jun-Lin
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UNUNITED fractures , *OSTEOTOMY , *ANIMAL experimentation , *CAUTERY , *TIBIA injuries , *FRACTURE fixation , *HISTOLOGICAL techniques , *DESCRIPTIVE statistics , *MICE , *FRACTURE healing - Abstract
Background: Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter. Methods: For this study, 96 female adult Sprague-Dawley (SD) rats were used. The rats underwent surgery to produce a tibial open fracture and were fixed with a 0.8-mm diameter Kirschner wire. In 48 of the rats, the periosteum proximal and distal to the fracture end was cauterized. Results: At 2, 4, 6, and 8 weeks after surgery, radiological and histological analysis showed typical physiological healing in the control group, and the healing rate was 100% at 6 weeks. But the non-union group was characterized by resorption of the fracture ends with few callus formations and no bridging callus formation, and the healing rate was 0% at 8 weeks. Conclusions: This method represents a reproducible model to create atrophic non-unions. This model provides a new option for studying the basic healing mechanisms and evaluating new therapies for bone regeneration and treatment of non-unions. [ABSTRACT FROM AUTHOR]
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- 2021
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5. The genome-wide supported CACNA1C gene polymorphisms and the risk of schizophrenia: an updated meta-analysis.
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Liu, Yong-ping, Wu, Xue, Xia, Xi, Yao, Jun, and Wang, Bao-jie
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GENETIC polymorphisms , *SCHIZOPHRENIA , *PUBLICATION bias , *22Q11 deletion syndrome , *GENOMICS - Abstract
Background: The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was an ancestral difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia. Methods: Pooled, subgroup, sensitivity, and publication bias analysis were conducted. Results: A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6007 cases, 6518 controls), and two rs4765905 studies (2435 cases, 2639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the ancestral-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in Europeans. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asians. Conclusions: Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asians and Europeans demonstrated both similarities and differences between the two ancestors. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Reduction of NgR in perforant path decreases amyloid-β peptide production and ameliorates synaptic and cognitive deficits in APP/PS1 mice.
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Jiang, Rong, Wu, Xue-Fei, Wang, Bin, Guan, Rong-Xiao, Lv, Lang-Man, Li, Ai-Ping, Lei, Lei, Ma, Ye, Li, Na, Li, Qi-Fa, Ma, Quan-Hong, Zhao, Jie, and Li, Shao
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AMYLOID beta-protein precursor , *CHONDROITIN sulfate proteoglycan , *TRANSGENIC mice , *ENTORHINAL cortex , *PROTEIN kinases , *AMYLOID plaque - Abstract
Background: Amyloid beta (Aβ) which is recognized as a main feature of Alzheimer's disease (AD) has been proposed to "spread" through anatomically and functionally connected brain regions. The entorhinal cortex and perforant path are the earliest affected brain regions in AD. The perforant path is the most vulnerable circuit in the cortex with respect to both aging and AD. Previous data show that the origins and terminations of the perforant path are susceptible to amyloid deposition at the younger age in AD. Nogo receptor (NgR) plays an essential role in limiting injury-induced axonal growth and experience-dependent plasticity in the adult brain. It has been suggested that NgR is involved in AD pathological features, but the results have been conflicting and the detailed mechanism needs further investigation. In this study, the effect of NgR in the perforant path on the pathological and functional phenotype of APP/PS1 transgenic mice was studied. Methods: To genetically manipulate NgR expression, adeno-associated virus (AAV) with short hairpin (shRNA) against NgR was injected into the perforant path of APP/PS1 transgenic mice, followed by an assessment of behavioral, synaptic plasticity and neuropathological phenotypes. NgR was overexpressed or knockdown in neuroblastoma N2a cells and APPswe/HEK293 cells to investigate the interaction between NgR and amyloid precursor protein (APP). Results: It is shown that reduction of NgR in the perforant path rescued cognitive and synaptic deficits in APP/PS1 transgenic mice. Concurrently, Aβ production in the perforant path and levels of soluble Aβ and amyloid plaques in the hippocampus were significantly decreased. There was a positive correlation between the total APP protein level and NgR expression both in transgenic mice and in cultured cells, where the α-secretase and β-secretase cleavage products both changed with APP level in parallel. Finally, NgR might inhibit APP degradation through lysosome by Rho/Rho-associated protein kinases (ROCK) signaling pathway. Conclusions: Our findings demonstrate that perforant path NgR plays an important role in regulating APP/Aβ level and cognitive functions in AD transgenic mice, which might be related to the suppression of APP degradation by NgR. Our study suggests that NgR in the perforant path could be a potential target for modulating AD progression. [ABSTRACT FROM AUTHOR]
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- 2020
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7. Metabolomic analysis for asymptomatic hyperuricemia and gout based on a combination of dried blood spot sampling and mass spectrometry technology.
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Liu, Shanshan, Liu, Yongting, Wu, Xue, and Liu, Zhengqi
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AMINO acid metabolism , *UREA metabolism , *GOUT diagnosis , *HYPERURICEMIA , *BIOMARKERS , *BLOOD chemical analysis , *METABOLOMICS , *BLOOD collection , *DIFFERENTIAL diagnosis , *METABOLISM , *MEDICAL screening , *RANDOM forest algorithms , *MASS spectrometry , *RESEARCH funding , *EARLY diagnosis , *ALGORITHMS , *METABOLITES , *FATTY acids , *OXIDATION-reduction reaction - Abstract
Background: Gout is the most common inflammatory arthritis and closely related to metabolic syndrome, leading to excruciating pain and the decline in quality of patients' life. However, the pathogenesis of gout is still unclear, and novel biomarkers are demanded for the early prediction and diagnosis of gout. Objective: This study aimed at profiling the dysregulated metabolic pathways in asymptomatic hyperuricemia (AHU) and gout and elucidating the associations between AHU, gout and metabolomics, which may aid in performing gout screening. Methods: A total of 300 participants, including 114 healthy controls, 92 patients with AHU, and 94 patients with gout, were analyzed by using a combination of dried blood spot (DBS) sampling and mass spectrometry (MS) technology. Multiple algorithms were applied to characterize altered metabolic profiles in AHU and gout. The mainly altered metabolites were identified by random forest analysis. Results: There were significant differences in AHU and gout compared with control group. The altered metabolites were involved in oxidation of fatty acids, carnitine synthesis, urea cycle, and amino acid metabolism in AHU and gout. Random forest classification of 16 metabolites yielded 3 important features to distinguish gout from AHU. Conclusions: Distinct metabolomic signatures were observed in AHU and gout. The selected metabolites may have the potential to improve the early detection of gout. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Long-term clinical outcomes in critically ill patients with sepsis and pre-existing low muscle mass: a retrospective cohort study.
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Darden, Nola, Sharma, Sonakshi, Wu, Xue, Mancini, Benjamin, Karamchandani, Kunal, and Bonavia, Anthony S.
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SKELETAL muscle physiology , *STATURE , *CONFIDENCE intervals , *CRITICALLY ill , *MULTIVARIATE analysis , *AGE distribution , *HEALTH outcome assessment , *PATIENTS , *DISEASES , *MEDICAL care costs , *RETROSPECTIVE studies , *TERTIARY care , *REGRESSION analysis , *SEPSIS , *HOSPITAL mortality , *RISK assessment , *SEVERITY of illness index , *DESCRIPTIVE statistics , *RESEARCH funding , *COMPUTED tomography , *LONGITUDINAL method , *ABDOMINAL radiography , *PELVIS , *DISCHARGE planning , *PROPORTIONAL hazards models - Abstract
Purpose: Critically ill patients with sepsis account for significant disease morbidity and healthcare costs. Low muscle mass has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear. Methods: Retrospective cohort analysis of patients treated at a quaternary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with low muscle mass defined by ≤ 5th percentile skeletal muscle index, measured at the L3 lumbar level (L3SMI) on Computed-Tomography (CT) scan (≤ 41.6 cm2/m2 for males and ≤ 32.0 cm2/m2 for females). L3SMI was calculated by normalizing the CT-measured skeletal muscle area to the square of the patient's height (in meters). Measurements were taken from abdominal/pelvic CT scan obtained within 7 days of sepsis onset. The prevalence of low muscle mass and its association with clinical outcomes, including in-hospital and one-year mortality, and post-hospitalization discharge disposition in survivors, was analyzed. Unfavorable post-hospitalization disposition was defined as discharge to a location other than the patient's home. Results: Low muscle mass was present in 34 (23%) of 150 patients, with mean skeletal muscle indices of 28.0 ± 2.9 cm2/m2 and 36.8 ± 3.3 cm2/m2 in females and males, respectively. While low muscle mass was not a significant risk factor for in-hospital mortality (hazard ratio 1.33; 95% CI 0.64 – 2.76; p = 0.437), it significantly increased one-year mortality after adjusting for age and illness severity using Cox multivariate regression (hazard ratio 1.9; 95% CI 1.1 – 3.2; p = 0.014). Unfavorable post-hospitalization discharge disposition was not associated with low muscle mass, after adjusting for age and illness severity in a single, multivariate model. Conclusion: Low muscle mass independently predicts one-year mortality but is not associated with in-hospital mortality or unfavorable hospital discharge disposition in critically ill patients with sepsis. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Dual effect of aucubin on promoting VEGFR2 mediated angiogenesis and reducing RANKL-induced bone resorption.
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He, Yulin, Kam, Hiotong, Wu, Xue, Chen, Qian, and Lee, Simon Ming Yuen
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IN vitro studies , *IN vivo studies , *BONE growth , *HETEROCYCLIC compounds , *BONE resorption , *GROWTH factors , *PLANTS , *CELL proliferation , *RESEARCH funding , *MOLECULAR structure - Abstract
Background: Angiogenesis is regarded as a critical role in bone repair and regeneration, involving in pathological bone disorders such as osteoporosis. Aucubin, an iridoid glycoside primarily derived from Eucommia ulmoides, is reported to inhibit osteoclast activity, enhance bone formation and promote angiogenesis in osteoporosis models. Our study is to further investigate the anti-osteoporosis effect of aucubin in transgenic medaka, and the pro-angiogenic effect of aucubin and its mechanism of action both in vivo and in vitro. Methods: The anti-osteoporosis effect of aucubin was confirmed by using RANKL-stimulated bone resorption transgenic medaka. The pro-angiogenic effect of aucubin in vivo was investigated using vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor II (VRI)-induced vascular insufficient transgenic zebrafish model. Furthermore, endothelial cell proliferation, migration, tube formation and the mechanisms were evaluated to identify the pro-angiogenic effect of aucubin in normal and su5416-injured human umbilical vein endothelial cells (HUVECs). Results: Aucubin decreased the resorption of the mineralized bone matrix and centra degradation in heat-shocked transgenic col10α1:nlGFP/rankl:HSE:CFP medaka. Moreover, aucubin reversed VRI-induced vascular insufficiency in zebrafish through regulating flt1, kdr, kdrl, vegfaa, ang-1, ang-2, tie1 and tie2 mRNA expressions in Tg(fli1a:EGFP)y1 or AB wild type zebrafish. Aucubin promoted cell proliferation by upregulating p-mTOR, p-Src, p-MEK, p-Erk1/2, p-Akt and p-FAK in HUVECs. Furthermore, aucubin exhibited a pro-angiogenic effect on su5416-injured HUVECs by promoting their proliferation, migration, and tube formation through regulating the phosphorylation of VEGFR2, MEK, ERK and the ratio of Bcl2-Bax. Conclusion: Aucubin could reduce bone resorption in RANKL-induced osteoporosis medaka by live imaging. Meanwhile, aucubin exhibited a protective effect in VRI-induced vascular insufficient zebrafish by regulating VEGF-VEGFR and Ang-Tie signaling pathways. Additionally, aucubin promoted the proliferation, migration and tube formation of HUVECs probably by mediating VEGFR2/MEK/ERK, Akt/mTOR and Src/FAK signalling pathways. This study further indicated the dual effect of aucubin on angiogenesis and osteogenesis which may be beneficial to its treatment of osteoporosis. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Mechanisms underlying neutrophils adhesion to triple-negative breast cancer cells via CD11b-ICAM1 in promoting breast cancer progression.
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Yang, Chenghui, Li, Lili, Ye, Zhiqiang, Zhang, Anqi, Bao, Yunjia, Wu, Xue, Ren, Guohong, Jiang, Chao, Wang, Ouchen, and Wang, Zhen
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TRIPLE-negative breast cancer , *CELL adhesion , *BREAST cancer , *CANCER cells , *NEUTROPHILS , *CANCER invasiveness - Abstract
Background: Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood. Methods: Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC. Results: TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin. Conclusions: Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.
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Yu, Pengfei, Chen, Ping, Wu, Min, Ding, Guangyu, Bao, Hua, Du, Yian, Xu, Zhiyuan, Yang, Litao, Fang, Jingquan, Huang, Xingmao, Lai, Qian, Wei, Jia, Yan, Junrong, Yang, Shanshan, He, Peng, Wu, Xue, Shao, Yang, Su, Dan, and Cheng, Xiangdong
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CIRCULATING tumor DNA , *EARLY detection of cancer , *WHOLE genome sequencing , *STOMACH cancer , *MONTE Carlo method , *CELL-free DNA - Abstract
Background: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. Methods: We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. Results: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. Trial registration: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022. [ABSTRACT FROM AUTHOR]
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- 2024
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12. An Unsupervised, Model-Free, Machine-Learning Combiner for Peptide Identifications from Tandem Mass Spectra.
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Edwards, Nathan, Wu, Xue, and Tseng, Chau-Wen
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MASS spectrometry , *MACHINE learning , *PEPTIDES , *FALSE discovery rate , *SUPERVISED learning , *MASS spectrometers , *SEARCH engines - Abstract
As the speed of mass spectrometers, sophistication of sample fractionation, and complexity of experimental designs increase, the volume of tandem mass spectra requiring reliable automated analysis continues to grow. Software tools that quickly, effectively, and robustly determine the peptide associated with each spectrum with high confidence are sorely needed. Currently available tools that postprocess the output of sequence-database search engines use three techniques to distinguish the correct peptide identifications from the incorrect: statistical significance re-estimation, supervised machine learning scoring and prediction, and combining or merging of search engine results. We present a unifying framework that encompasses each of these techniques in a single model-free machine-learning framework that can be trained in an unsupervised manner. The predictor is trained on the fly for each new set of search results without user intervention, making it robust for different instruments, search engines, and search engine parameters. We demonstrate the performance of the technique using mixtures of known proteins and by using shuffled databases to estimate false discovery rates, from data acquired on three different instruments with two different ionization technologies. We show that this approach outperforms machine-learning techniques applied to a single search engine's output, and demonstrate that combining search engine results provides additional benefit. We show that the performance of the commercial Mascot tool can be bested by the machine-learning combination of two open-source tools X!Tandem and OMSSA, but that the use of all three search engines boosts performance further still. The Peptide identification Arbiter by Machine Learning (PepArML) unsupervised, model-free, combining framework can be easily extended to support an arbitrary number of additional searches, search engines, or specialized peptide–spectrum match metrics for each spectrum data set. PepArML is open-source and is available from http://peparml.sourceforge.net. [ABSTRACT FROM AUTHOR]
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- 2009
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13. The enrichment of Fanconi anemia/homologous recombination pathway aberrations in ATM/ATR-mutated NSCLC was accompanied by unique molecular features and poor prognosis.
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Wei, Wei, Shi, Fangfang, Xu, Yang, Jiao, Yang, Zhang, Ying, Ou, Qiuxiang, Wu, Xue, Yang, Lingyi, and Lai, Jinhuo
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FANCONI'S anemia , *DNA repair , *NON-small-cell lung carcinoma , *NONSENSE mutation , *FRAMESHIFT mutation - Abstract
Background: ATM and ATR are two critical factors to regulate DNA damage response (DDR), and their mutations were frequently observed in different types of cancer, including non-small cell lung cancer (NSCLC). Given that the majority of identified ATM/ATR mutations were variants of uncertain significance, the clinical/molecular features of pathogenic ATM/ATR aberrations have not been comprehensively investigated in NSCLC. Methods: Next-generation sequencing (NGS) analyses were conducted to investigate the molecular features in 191 NSCLC patients who harbored pathogenic/likely pathogenic ATM/ATR mutations and 308 NSCLC patients who did not have any types of ATM/ATR variants. The results were validated using an external cohort of 2727 NSCLC patients (including 48 with ATM/ATR pathogenic mutations). Results: Most pathogenic ATM/ATR genetic alterations were frameshift and nonsense mutations that disrupt critical domains of the two proteins. ATM/ATR-mutated patients had significantly higher tumor mutational burdens (TMB; P < 0.001) and microsatellite instabilities (MSI; P = 0.023), but not chromosomal instabilities, than those without any ATM/ATR variations. In particular, KRAS mutations were significantly enriched in ATM-mutated patients (P = 0.014), whereas BRCA2 mutations (P = 0.014), TP53 mutations (P = 0.014), and ZNF703 amplification (P = 0.008) were enriched in ATR-mutated patients. Notably, patients with ATM/ATR pathogenic genetic alterations were likely to be accompanied by mutations in Fanconi anemia (FA) and homologous recombination (HR) pathways, which were confirmed using both the study (P < 0.001) and validation (P < 0.001) cohorts. Furthermore, the co-occurrence of FA/HR aberrations could contribute to increased TMB and MSI, and patients with both ATM/ATR and FA/HR mutations tended to have worse overall survival. Conclusions: Our results demonstrated the unique clinical and molecular features of pathogenic ATM/ATR mutations in NSCLC, which helps better understand the cancerous involvement of these DDR regulators, as well as directing targeted therapies and/or immunotherapies to treat ATM/ATR-mutated NSCLC, especially those with co-existing FA/HR aberrations. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Characterization and functional analyses of the human HTR1A gene: 5' regulatory region modulates gene expression in vitro.
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Wu, Xue, Xu, Feng-ling, Ding, Mei, Zhang, Jing-jing, Yao, Jun, and Wang, Bao-jie
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GENE expression , *SEROTONIN , *NEUROBEHAVIORAL disorders , *NEUROTRANSMITTER receptors , *GENETIC regulation , *CHEMILUMINESCENCE , *TRANSCRIPTION factors - Abstract
Background: The serotonin neurotransmitter (5-HT) and its receptors have important roles in neuropsychiatric disorders such as schizophrenia. The aim of this study was to investigate the functional sequences of the 5′ regulation region of the human HTR1A gene to explore the effects on the expression of the 5-HT1A receptor. Methods: Fourteen recombinant pGL3-basic vectors containing deletion fragments of the HTR1A gene regulatory region were transfected with HEK-293 and SK-N-SH cells. The relative chemiluminescence intensities of different length fragments were analyzed. The JASPAR software was used for the prediction of transcription factors. Results: In the HEK-293 cells, the relative chemiluminescence intensity of the − 1649 bp to − 1550 bp (ATG + 1) fragment was significantly different. Two inhibitory activity regions were found in the − 1409 bp to − 1381 bp and − 1196 bp to − 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. In addition, the fragments located from − 1124 bp to − 1064 bp and from − 908 bp to − 722 bp up-regulated protein expression. Only the sequence from − 1550 bp to − 1409 bp demonstrated a difference in luciferase expression in the both cell lines. According to the results of the 5'-UTR truncated vectors, there was a repression region at the distal end of the 5'-UTR, an enhancer region might be present at the proximal end of the transcription start site. Conclusions: Although the functional sequences of the HTR1A gene regulatory region were confirmed, the regulatory factors and functional components require further investigation. [ABSTRACT FROM AUTHOR]
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- 2018
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15. Coexisting of bone marrow fibrosis, dysplasia and an X chromosomal abnormality in chronic neutrophilic leukemia with CSF3R mutation: a case report and literature review.
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Wu, Xue Bin, Wu, Wei Wei, Zhou, Yue, Wang, Xuan, Li, Jia, and Yu, Yang
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TREATMENT of chronic myeloid leukemia , *BONE marrow , *CELL receptors , *CHROMOSOME abnormalities , *CHROMOSOMES , *COMBINED modality therapy , *GENETIC mutation , *MYELOFIBROSIS , *PROGNOSIS , *CHRONIC myeloid leukemia , *TREATMENT effectiveness , *DISEASE complications , *DIAGNOSIS - Abstract
Background: Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) with less than 40 cases of patients being reported or clinically suspected meeting with 2008 World Health Organization ("WHO") diagnostic criteria. The current diagnosis of CNL remains to exclude other diseases. Recently, a new biomarker of CSF3R mutations that is almost invariably present in CNL has been identified. There is no effective treatment for CNL, therefore prognosis of the disease is poor, but it may be attributed to the presence of both SETBP1 and CSF3R gene mutations. The presence or absence of CSF3R mutation did not affect survival, whereas a trend for shortened survival was observed among patients with SETBP1-mutation.Case Presentation: Here we report a 65-year old woman patient who presented with leukocytosis without sign of fever and tumors. Bone marrow aspirates showed a markedly hypercellular feature with 76%-92% myeloid and the dysplastic changes were found in about 7% of neutrophils cells. The bone marrow biopsy demonstrated marrow fibrosis with Gomori staining positive (+++~++++). Cytogenetic analysis showed 46,X,del (X) (q22). No molecular markers of BCR/ABL1 rearrangement (P210, P230, P190 and variably), JAK2V617F, FIP1L1-PDGFRA, TEL-PDGFRB, ZNF198-FGFR1 and SETBP1 mutations were identified, however, the CSF3R gene membrane proximal mutation (c.1853C > T/p.T618I sites) was detected by PCR techniques. The patient was diagnosed with CNL and died in about 2 months after disease diagnosis.Conclusion: In clinical course, the CNL concurrently with severe bone marrow fibrosis and dysplastic features as well as X chromosomal abnormality may predict a worsening prognosis regardless of SETBP1 mutation status. [ABSTRACT FROM AUTHOR]- Published
- 2018
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16. Rare mutation-dominant compound EGFR-positive NSCLC is associated with enriched kinase domain-resided variants of uncertain significance and poor clinical outcomes.
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Zhao, Weixin, Song, Ailing, Xu, Yang, Wu, Qian, Liu, Cuicui, Yin, Jiani C., Ou, Qiuxiang, Wu, Xue, Shao, Yang, and Zhao, Xinmin
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EPIDERMAL growth factor receptors , *NON-small-cell lung carcinoma , *PROTEIN-tyrosine kinase inhibitors , *TREATMENT effectiveness - Abstract
Background: Compound epidermal growth factor receptor (EGFR) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated. Methods: We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). Prognosis and drug resistance to first-line TKIs were analyzed in 174 and 95 patients, respectively. Results: Compound EGFR mutations were enriched with EGFR exon 21 p.L858R and rare mutations, but not 19-Del (P < 0.001). The common + rare and rare + rare subtypes had fewer concurrent mutations in the PI3K pathway (P = 0.032), while the rare + rare and common + VUSs subtypes showed increased association with smoking- and temozolomide-related mutational signatures, respectively (P < 0.001). The rare mutation-dominant subtypes (rare + VUSs and rare + rare) had the worst clinical outcomes to first-line TKIs (P < 0.001), which was further confirmed using an external cohort (P = 0.0066). VUSs in the rare + VUSs subtype selectively reside in the EGFR kinase domain (P < 0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain. Conclusions: Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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17. Forkhead box P3 gene polymorphisms predispose to type 2 diabetes and diabetic nephropathy in the Han Chinese populations: a genetic-association and gender-based evaluation study.
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Wang, Xiaorong, Liu, Zejing, Zhang, Shangdi, Yang, Yinfeng, Wu, Xue, and Liu, Xinyue
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TYPE 2 diabetes , *FORKHEAD transcription factors , *DIABETIC nephropathies , *GENETIC polymorphisms , *REGULATORY T cells , *SINGLE nucleotide polymorphisms - Abstract
Background: Functional mutations or polymorphisms affecting forkhead box P3 (FOXP3) can lead to their abnormal FOXP3 gene expression and/or defective Treg cells generation, thus resulting in autoimmune disease and inflammatory disorders. FOXP3 also plays a key role in Type 2 diabetes mellitus (T2DM) and its complications, because the disease usually involves chronic low-grade inflammatory disorders and is associated with long-term immune system imbalance. This study aimed to investigate the association between FOXP3 polymorphisms and the susceptibility to T2DM and type 2 diabetes nephropathy (T2DN) within the Han Chinese populations. Methods: Polymorphisms in rs3761548C/A and rs2294021C/T were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis. Results: The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548C/A was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021C/T; in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 C/A-rs2294021C/T) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect. Conclusions: This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Associations of MRI-visible perivascular spaces with longitudinal cognitive decline across the Alzheimer's disease spectrum.
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Wang, Ming-Liang, Zou, Qiao-Qiao, Sun, Zheng, Wei, Xiao-Er, Li, Peng-Yang, Wu, Xue, and Li, Yue-Hua
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ALZHEIMER'S disease , *MILD cognitive impairment , *COGNITION disorders , *PROPORTIONAL hazards models , *MINI-Mental State Examination , *DISEASE progression - Abstract
Objective: To investigate the characteristics and associations of MRI-visible perivascular spaces (PVS) with clinical progression and longitudinal cognitive decline across the Alzheimer's disease spectrum. Methods: We included 1429 participants (641 [44.86%] female) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. PVS number and grade in the centrum semiovale (CSO-PVS), basal ganglia (BG-PVS), and hippocampus (HP-PVS) were compared among the control (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD) groups. PVS were tested as predictors of diagnostic progression (i.e., CN to MCI/AD or MCI to AD) and longitudinal changes in the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog 13), Mini-Mental State Examination (MMSE), memory (ADNI-MEM), and executive function (ADNI-EF) using multiple linear regression, linear mixed-effects, and Cox proportional hazards modeling. Results: Compared with CN subjects, MCI and AD subjects had more CSO-PVS, both in number (p < 0.001) and grade (p < 0.001). However, there was no significant difference in BG-PVS and HP-PVS across the AD spectrum (p > 0.05). Individuals with moderate and frequent/severe CSO-PVS had a higher diagnostic conversion risk than individuals with no/mild CSO-PVS (log-rank p < 0.001 for all) in the combined CN and MCI group. Further Cox regression analyses revealed that moderate and frequent/severe CSO-PVS were associated with a higher risk of diagnostic conversion (HR = 2.007, 95% CI = 1.382–2.914, p < 0.001; HR = 2.676, 95% CI = 1.830–3.911, p < 0.001, respectively). A higher CSO-PVS number was associated with baseline cognitive performance and longitudinal cognitive decline in all cognitive tests (p < 0.05 for all). Conclusions: CSO-PVS were more common in MCI and AD and were associated with cognitive decline across the AD spectrum. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Quantitative assessment of the microstructure of the mesorectum with different prognostic statuses by intravoxel incoherent motion diffusion-weighed magnetic resonance imaging.
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Lu, Bao-Lan, Chen, Yan, Wen, Zi-Qiang, Liu, Yi-Yan, Ma, Yu-Ru, Que, Yu-Tao, Zhang, Zhi-Wen, Wu, Xue-Han, and Yu, Shen-Ping
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MAGNETIC resonance imaging , *DIFFUSION magnetic resonance imaging , *RECTAL cancer , *SURGICAL margin - Abstract
Background: The mesorectum surrounding the rectum provides an ideal substrate for tumour spread. However, preoperative risk assessment is still an issue. This study aimed to investigate the microstructural features of mesorectum with different prognostic statuses by intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI).Methods: Patients with pathologically proven rectal adenocarcinoma underwent routine high-resolution rectal magnetic resonance imaging (MRI) and IVIM DWI sequences were acquired. The MRI-detected circumferential resection margin (mrCRM) and extramural vascular invasion (mrEMVI) were evaluated. IVIM parameters of the mesorectum adjacent to (MAT) and distant from (MDT) the tumour were measured and compared between and within the prognostic factor groups.Results: The positive mrCRM (pMAT < 0.001; pMDT = 0.013) and mrEMVI (pMAT = 0.001; pMDT < 0.001) groups demonstrated higher D values in the MAT and MDT than the corresponding negative groups. Conversely, the positive mrCRM (p = 0.001) and mrEMVI (p < 0.001) groups both demonstrated lower f values in the MAT. Similarly, in the self-comparison between the MAT and MDT in the above subgroups, D showed a significant difference in all subgroups (p < 0.001 for all), and f showed a significant difference in the positive mrCRM (p = 0.001) and mrEMVI (p = 0.002) groups. Moreover, the MAT displayed a higher D* in the positive mrCRM (p = 0.014), negative mrCRM (p = 0.009) and negative mrEMVI groups (p < 0.001).Conclusion: The microstructure of the mesorectum in patients with rectal cancer with poor prognostic status shows changes based on IVIM parameters. IVIM parameters might be promising imaging biomarkers for risk assessment of tumour spread in mesorectum preoperatively. [ABSTRACT FROM AUTHOR]- Published
- 2022
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20. Homologous recombination deficiency in diverse cancer types and its correlation with platinum chemotherapy efficiency in ovarian cancer.
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Wen, Hao, Feng, Zheng, Ma, Yutong, Liu, Rui, Ou, Qiuxiang, Guo, Qinhao, Shen, Yi, Wu, Xue, Shao, Yang, Bao, Hua, and Wu, Xiaohua
- Abstract
Background: Homologous recombination deficiency (HRD) is a molecular biomarker for administrating PARP inhibitor (PARPi) or platinum-based (Pt) chemotherapy. The most well-studied mechanism of causing HRD is pathogenic BRCA1/2 mutations, while HRD phenotype is also present in patients without BRCA1/2 alterations, suggesting other unknown factors.Methods: The targeted next-generation sequencing (GeneseeqPrime® HRD) was used to evaluate the HRD scores of 199 patients (Cohort I). In Cohort II, a total of 85 Pt-chemotherapy-treated high-grade serous ovarian cancer (HGSOC) patients were included for investigating the role of HRD score in predicting treatment efficacy. The concurrent genomic features analyzed along HRD score evaluation were studied in a third cohort with 416 solid tumor patients (Cohort III).Results: An HRD score ≥ 38 was predefined as HRD-positive by analyzing Cohort I (range: 0-107). Over 95% of the BRCA1/2-deficient cases of Cohort I were HRD-positive under this threshold. In Cohort II, Pt-sensitive patients have significantly higher HRD scores than Pt-resistant patients (median: 54 vs. 34, p = 0.031) and a significantly longer PFS was observed in HRD-positive patients (median: 548 vs. 343 days, p = 0.003). Furthermore, TP53, NCOR1, and PTK2 alterations were enriched in HRD-positive patients. In Cohort III, impaired homologous recombination repair pathway was more frequently observed in HRD-positive patients without BRCA1/2 pathogenic mutations. The alteration enrichment of TP53, NCOR1, and PTK2 observed in Cohort II was also validated by the ovarian subgroup in Cohort III.Conclusions: Using an in-house HRD evaluation method, our findings show that overall HRR gene mutations account for a significant part of HRD in the absence of BRCA1/2 aberrations, and suggest that HRD positive status might be a predictive biomarker of Pt-chemotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2022
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21. Heterozygous FMN2 missense variant found in a family case of premature ovarian insufficiency.
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Li, Jie, Peng, Tianliu, Wang, Le, Long, Panpan, Quan, Ruping, Tan, Hangjing, Zeng, Minghua, Wu, Xue, Yang, Junting, Xiao, Hongmei, and Shi, Xiaobo
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PREMATURE ovarian failure , *MISSENSE mutation , *GENETIC variation , *OVARIAN reserve , *DNA repair , *PATIENT-family relations - Abstract
Background: Premature ovarian insufficiency (POI) plagues 1% of women under 40, while quite a few remain an unknown cause. The development of sequencing has helped find pathogenic genes and reveal the relationship between DNA repair and ovarian reserve. Through the exome sequencing, our study targets screening out the possible POI pathogenic gene and variants in a Chinese family and 20 sporadic POI patients, preliminarily exploring the functional impact and finding out potential linkages between the gene and POI. Results: The whole exome sequencing suggested a novel FMN2 heterozygous variant c.1949C > T (p.Ser650Leu) carried by all three patients in a Chinese family and another c.1967G > A(p.Arg656His) variant in a sporadic case. Since no FMN2 missense mutation is reported for causing human POI, we preliminarily assessed p.Ser650Leu variant via cross-species alignment and 3D modeling and found it possibly deleterious. A series of functional evidence was consistent with our hypothesis. We proved the expression of FMN2 in different stages of oocytes and observed a statistical difference of chromosomal breakages between the POI patient carrying p.Arg656His variant and the health control (p = 0.0013). Western Blot also suggested a decrease in FMN2 and P21 in the mutant type and an associated increase in H2AX. The p.Arg656His variant with an extremely low frequency also indicated that the gene FMN2 might play an essential role in the genetic etiology of POI. To the best of our knowledge, this is the first POI report on missense variants of FMN2. Conclusion: This finding indicates a novel gene possibly related to POI and sheds lights on the study of FMN2. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Tea and tea drinking: China's outstanding contributions to the mankind.
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Pan, Si-Yuan, Nie, Qu, Tai, Hai-Chuan, Song, Xue-Lan, Tong, Yu-Fan, Zhang, Long-Jian-Feng, Wu, Xue-Wei, Lin, Zhao-Heng, Zhang, Yong-Yu, Ye, Du-Yun, Zhang, Yi, Wang, Xiao-Yan, Zhu, Pei-Li, Chu, Zhu-Sheng, Yu, Zhi-Ling, and Liang, Chun
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TEA -- History , *CULTURE , *FOOD habits , *HERBAL medicine , *DRINKING (Physiology) , *HEALTH attitudes , *IMMUNITY , *HEALTH behavior , *DRINKING behavior , *LONGEVITY , *TEA , *CHINESE medicine , *HISTORY - Abstract
Background: Tea trees originated in southwest China 60 million or 70 million years ago. Written records show that Chinese ancestors had begun drinking tea over 3000 years ago. Nowadays, with the aging of populations worldwide and more people suffering from non-communicable diseases or poor health, tea beverages have become an inexpensive and fine complementary and alternative medicine (CAM) therapy. At present, there are 3 billion people who like to drink tea in the world, but few of them actually understand tea, especially on its development process and the spiritual and cultural connotations. Methods: We searched PubMed, Google Scholar, Web of Science, CNKI, and other relevant platforms with the key word "tea", and reviewed and analyzed tea-related literatures and pictures in the past 40 years about tea's history, culture, customs, experimental studies, and markets. Results: China is the hometown of tea, tea trees, tea drinking, and tea culture. China has the oldest wild and planted tea trees in the world, fossil of a tea leaf from 35,400,000 years ago, and abundant tea-related literatures and art works. Moreover, tea may be the first Chinese herbal medicine (CHM) used by Chinese people in ancient times. Tea drinking has many benefits to our physical health via its antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, and anti-obesity activities. At the moment, COVID-19 is wreaking havoc across the globe and causing severe damages to people's health and lives. Tea has anti-COVID-19 functions via the enhancement of the innate immune response and inhibition of viral growth. Besides, drinking tea can allow people to acquire a peaceful, relaxed, refreshed and cheerful enjoyment, and even longevity. According to the meridian theory of traditional Chinese medicine, different kinds of tea can activate different meridian systems in the human body. At present, black tea (fermented tea) and green tea (non-fermented tea) are the most popular in the world. Black tea accounts for over 90% of all teas sold in western countries. The world's top-grade black teas include Qi Men black in China, Darjeeling and Assam black tea in India, and Uva black tea in Sri Lanka. However, all top ten famous green teas in the world are produced in China, and Xi Hu Long Jing tea is the most famous among all green teas. More than 700 different kinds of components and 27 mineral elements can be found in tea. Tea polyphenols and theaflavin/thearubigins are considered to be the major bioactive components of black tea and green tea, respectively. Overly strong or overheated tea liquid should be avoided when drinking tea. Conclusions: Today, CAM provides an array of treatment modalities for the health promotion in both developed and developing countries all over the world. Tea drinking, a simple herb-based CAM therapy, has become a popular man-made non-alcoholic beverage widely consumed worldwide, and it can improve the growth of economy as well. Tea can improve our physical and mental health and promote the harmonious development of society through its chemical and cultural elements. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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23. The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification.
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Yang, Yefan, Ding, Ying, Gong, Yuxi, Zhao, Sha, Li, Mingna, Li, Xiao, Song, Guoxin, Zhai, Boya, Liu, Jin, Shao, Yang, Zhu, Liuqing, Pang, Jiaohui, Ma, Yutong, Ou, Qiuxiang, Wu, Xue, and Zhang, Zhihong
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PANCREATIC duct , *PANCREATIC cancer , *DNA mismatch repair , *DISEASE risk factors , *GENETIC mutation , *RAS oncogenes , *PANCREATIC tumors , *ASIANS - Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is the major subtype of pancreatic cancer and head PDACs show distinct characteristics from body/tail PDACs. With limited studies based on Asian population, the mutational landscape of Asian PDAC remains unclear.Methods: One hundred fifty-one Chinese patients with head PDAC were selected and underwent targeted 425-gene sequencing. Genomic alterations, tumor mutational burden, and microsatellite instability were analyzed and compared with a TCGA cohort.Results: The genomic landscape of Chinese and Western head PDAC had identical frequently-mutated genes including KRAS, TP53, SMAD4, and CDKN2A. KRAS hotspot in both cohorts was codon 12 but Chinese PDACs containing more G12V but fewer G12R variants. Potentially pathogenic fusions, CHD2-BRAF and KANK1-MET were identified in two KRAS wild-type patients. Serum cancer antigens CA125 and CA19-9 were positively associated with SMAD4 alterations while high CEA was enriched in wild-type CDKN2A subgroup. The probability of vascular invasion was lower in patients with RNF43 alterations. The nomogram developed including histology grade, the mutation status of SMAD4, TGFBR2, and PREX2 could calculate the risk score of prognoses validated by Chinese and TCGA cohort.Conclusions: Chinese head PDAC contained more KRAS G12V mutation than Western population. The well-performed nomogram may improve post-operation care in real-world practice. [ABSTRACT FROM AUTHOR]- Published
- 2022
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24. Nurses' turnover intention, hope and career identity: the mediating role of job satisfaction.
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Hu, Huiling, Wang, Chongkun, Lan, Yue, and Wu, Xue
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OCCUPATIONAL roles , *STRUCTURAL equation modeling , *NURSES' attitudes , *RESEARCH methodology , *CROSS-sectional method , *MULTIPLE regression analysis , *TERTIARY care , *LABOR turnover , *HOPE , *PROFESSIONAL identity , *NURSES , *JOB satisfaction , *DESCRIPTIVE statistics , *INTENTION , *STATISTICAL sampling , *STATISTICAL correlation - Abstract
Background: A high turnover rate has become a critical issue in the field of nursing and how to tackle the problem of nursing turnover has received increased attention worldwide. Hope, career identity, job satisfaction may be useful for reducing turnover. The aim of this study is to explore the relationships among career identity, hope, job satisfaction, and the turnover intention of nurses, and to test the mediating role of job satisfaction on the associations of hope and career identity with turnover intention. Methods: A descriptive cross-sectional design was used. A total of 500 nurses were recruited from five comprehensive tertiary hospitals using convenience sampling. The questionnaire included items about sociodemographic information as well as the Adult Dispositional Hope Scale, Nursing Career Identity Scale, Job Satisfaction Index Scale, and Nurse Turnover Intention Scale. Pearson's correlation, multiple linear regression, and structural equation modeling were used to analyze the data. We describe the study in accordance with the STROBE statement. Results: Hope (r = − 0.227, p < 0.001) and career identity (r = − 0.342, p < 0.001) were negatively correlated with turnover intention. Job satisfaction played a completely mediating role on the associations of hope and career identity with turnover intention (β1 = − 0.09, β2 = − 0.33). Conclusions: Job satisfaction mediated the associations of career identity and hope with turnover intention. Thus, effective measures can be taken to enhance nurses' hope and career identity in order to improve their job satisfaction and thereby reduce their turnover intention. Providing nurses with more support, helping them find a spiritual foundation, and holding mindful activities that stimulate positive emotions are helpful. In addition, colleges should pay more attention to instilling nursing students with career identity and nursing values. [ABSTRACT FROM AUTHOR]
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- 2022
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25. Clinical utility of cerebrospinal fluid-derived circular RNAs in lung adenocarcinoma patients with brain metastases.
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Wang, Zhen, Yu, Ruoying, Chen, Xiaoxi, Bao, Hua, Cao, Ran, Li, An-Na, Ou, Qiuxiang, Tu, Hai-Yan, Zhou, Qing, Wu, Xue, Lin, Zhi-Bo, and Wu, Yi-Long
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CIRCULAR RNA , *BRAIN metastasis , *LUNGS , *BLOOD-brain barrier , *CEREBROSPINAL fluid , *WNT signal transduction , *ADENOCARCINOMA , *RESEARCH , *RESEARCH methodology , *RNA , *LUNG tumors , *EVALUATION research , *BRAIN tumors , *COMPARATIVE studies , *RESEARCH funding - Abstract
Background: Free circular RNAs(circRNAs) escaping from primary lesion of cancer to brain are strictly regulated by blood-brain barrier and therefore cerebrospinal fluid (CSF) circRNAs have potential advantage in exploring biomarkers and mechanism of brain metastasis in lung cancer.Methods: We collected paired cerebrospinal fluid, plasma and tumor tissues from 21 lung adenocarcinoma (ADC) patients with brain metastases (BM) and performed RNA sequencing.Results: Compared to tumor tissue and plasma, circRNAs in CSF were characterized by lower number of spieces but higher abundance. Notably, CSF-circRNAs displayed high heterogeneity among different BM lung ADC patients. A total of 60 CSF-circRNAs was identified and associated with shorten overall survival. The circRNA-miRNA-mRNA network analysis revealed that the 60 CSF-circRNAs involved in cancer-associated pathways, and five of them showed strong association with WNT signaling pathway. Validation by RT-PCR of CSF and in vitro experiments of the five candidate circRNAs support their potential roles in cell proliferation and invasion.Conclusions: In summary, our results depicted the heterogenous CSF-circRNAs profiles among BM lung ADC and implied that CSF-circRNAs may be promising prognosis-related biomarkers. [ABSTRACT FROM AUTHOR]- Published
- 2022
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26. Circular RNA ciRS-7 affects the propagation of Cryptosporidium parvum in HCT-8 cells by sponging miR-1270 to activate the NF-κB signaling pathway.
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Yin, Yan-Ling, Liu, Ting-Li, Yao, Qian, Wang, Yu-Xin, Wu, Xue-Mei, Wang, Xue-Ting, Yang, Xin, Song, Jun-Ke, and Zhao, Guang-Hui
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CELLULAR signal transduction , *CIRCULAR RNA , *CRYPTOSPORIDIUM parvum , *GENE expression , *CRYPTOSPORIDIOSIS , *ANIMAL diseases , *ZOONOSES - Abstract
Background: Cryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals. However, the molecular mechanisms underlying host and Cryptosporidium interactions are still not clear. Methods: To study the roles of circRNAs in host cells during Cryptosporidium infection, the expression profiles of circRNAs in HCT-8 cells infected with C. parvum were investigated using a microarray assay, and the regulatory role of a significantly upregulated circRNA, ciRS-7, was investigated during C. parvum infection. Results: C. parvum infection caused notable alterations in the expression profiles of circRNAs in HCT-8 cells, and a total of 178 (including 128 up- and 50 downregulated) circRNAs were significantly differentially expressed following C. parvum infection. Among them, ciRS-7 was significantly upregulated and regulated the NF-κB signaling pathway by sponging miR-1270 during C. parvum infection. Furthermore, the ciRS-7/miR-1270/relA axis markedly affected the propagation of C. parvum in HCT-8 cells. Conclusions: Our results revealed that ciRS-7 would promote C. parvum propagation by regulating the miR-1270/relA axis and affecting the NF-κB pathway. To the best of our knowledge, this is the first study to investigate the role of circRNA during Cryptosporidium infection, and the findings provide a novel view for implementing control strategies against Cryptosporidium infection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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27. Multi-dimensional fragmentomic assay for ultrasensitive early detection of colorectal advanced adenoma and adenocarcinoma.
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Ma, Xiaoji, Chen, Yikuan, Tang, Wanxiangfu, Bao, Hua, Mo, Shaobo, Liu, Rui, Wu, Shuyu, Bao, Hairong, Li, Yaqi, Zhang, Long, Wu, Xue, Cai, Sanjun, Shao, Yang, Liu, Fangqi, and Peng, Junjie
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FECAL occult blood tests , *ADENOMA , *CELL-free DNA , *SENSITIVITY & specificity (Statistics) , *NUCLEOTIDE sequencing - Abstract
Previous studies on liquid biopsy-based early detection of advanced colorectal adenoma (advCRA) or adenocarcinoma (CRC) were limited by low sensitivity. We performed a prospective study to establish an integrated model using fragmentomic profiles of plasma cell-free DNA (cfDNA) for accurately and cost-effectively detecting early-stage CRC and advCRA. The training cohort enrolled 310 participants, including 149 early-stage CRC patients, 46 advCRA patients and 115 healthy controls. Plasma cfDNA samples were prepared for whole-genome sequencing. An ensemble stacked model differentiating healthy controls from advCRA/early-stage CRC patients was trained using five machine learning models and five cfDNA fragmentomic features based on the training cohort. The model was subsequently validated using an independent test cohort (N = 311; including 149 early-stage CRC, 46 advCRA and 116 healthy controls). Our model showed an area under the curve (AUC) of 0.988 for differentiating advCRA/early-stage CRC patients from healthy individuals in an independent test cohort. The model performed even better for identifying early-stage CRC (AUC 0.990) compared to advCRA (AUC 0.982). At 94.8% specificity, the sensitivities for detecting advCRA and early-stage CRC reached 95.7% and 98.0% (0: 94.1%; I: 98.5%), respectively. Promisingly, the detection sensitivity has reached 100% and 97.6% in early-stage CRC patients with negative fecal occult or CEA blood test results, respectively. Finally, our model maintained promising performances (AUC: 0.982, 94.4% sensitivity at 94.8% specificity) even when sequencing depth was down-sampled to 1X. Our integrated predictive model demonstrated an unprecedented detection sensitivity for advCRA and early-stage CRC, shedding light on more accurate noninvasive CRC screening in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. Circular RNA ciRS-7 affects the propagation of Cryptosporidium parvum in HCT-8 cells by sponging miR-1270 to activate the NF-κB signaling pathway.
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Yin, Yan-Ling, Liu, Ting-Li, Yao, Qian, Wang, Yu-Xin, Wu, Xue-Mei, Wang, Xue-Ting, Yang, Xin, Song, Jun-Ke, and Zhao, Guang-Hui
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CRYPTOSPORIDIUM parvum , *CIRCULAR RNA , *CRYPTOSPORIDIOSIS , *ANIMAL diseases , *ZOONOSES , *CRYPTOSPORIDIUM - Abstract
Background: Cryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals. However, the molecular mechanisms underlying host and Cryptosporidium interactions are still not clear. Methods: To study the roles of circRNAs in host cells during Cryptosporidium infection, the expression profiles of circRNAs in HCT-8 cells infected with C. parvum were investigated using a microarray assay, and the regulatory role of a significantly upregulated circRNA, ciRS-7, was investigated during C. parvum infection. Results: C. parvum infection caused notable alterations in the expression profiles of circRNAs in HCT-8 cells, and a total of 178 (including 128 up- and 50 downregulated) circRNAs were significantly differentially expressed following C. parvum infection. Among them, ciRS-7 was significantly upregulated and regulated the NF-κB signaling pathway by sponging miR-1270 during C. parvum infection. Furthermore, the ciRS-7/miR-1270/relA axis markedly affected the propagation of C. parvum in HCT-8 cells. Conclusions: Our results revealed that ciRS-7 would promote C. parvum propagation by regulating the miR-1270/relA axis and affecting the NF-κB pathway. To the best of our knowledge, this is the first study to investigate the role of circRNA during Cryptosporidium infection, and the findings provide a novel view for implementing control strategies against Cryptosporidium infection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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29. Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol.
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Li, Xin-Yu, Li, Jia-Qiang, Luo, Xue-Qun, Wu, Xue-Dong, Sun, Xin, Xu, Hong-Gui, Li, Chang-Gang, Liu, Ri-Yang, Sun, Xiao-Fei, Chen, Hui-Qin, Lin, Yu-Deng, LI, Chi-kong, and Fang, Jian-Pei
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LYMPHOBLASTIC leukemia , *ACUTE leukemia , *BONE marrow , *GROUP psychotherapy , *MEDICAL centers - Abstract
Background: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL.Methods: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs.Results: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129).Conclusions: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification. [ABSTRACT FROM AUTHOR]- Published
- 2021
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30. Functional polymorphisms and transcriptional analysis in the 5′ region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders.
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Xia, Xi, Ding, Mei, Xuan, Jin-feng, Xing, Jia-xin, Yao, Jun, Wu, Xue, and Wang, Bao-jie
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SEROTONIN receptors , *GENETIC regulation , *MENTAL illness , *GENE expression , *REGULATOR genes - Abstract
Background: The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5′ regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. Methods: Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5′ regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. Results: Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from − 1587 to − 1371 bp (TSS, + 1), − 1149 to − 894 bp, − 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions − 603 to − 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. Conclusions: HTR1B 5′ regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions − 1587 to − 1371 bp, − 1149 to − 894 bp, − 603 to − 316 bp, − 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression. [ABSTRACT FROM AUTHOR]
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- 2020
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31. Integrative analysis of the common genetic characteristics in ovarian cancer stem cells sorted by multiple approaches.
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Zhang, Xiaoxiao, Su, Yue, Wu, Xue, Xiao, Rourou, Wu, Yifan, Yang, Bin, Wang, Zhen, Guo, Lili, Kang, Xiaoyan, and Wang, Changyu
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CANCER stem cells , *OVARIAN cancer , *GENE expression profiling , *EXTRACELLULAR matrix , *GENITALIA - Abstract
Background: Ovarian cancer is the second fatal malignancy of the female reproductive system. Based on the cancer stem cell (CSC) theory, its poor prognosis of ovarian cancer attributed to tumor recurrence caused by CSCs. A variety of cell surface-specific markers have been employed to identify ovarian cancer stem cells (OCSCs). In this study, we attempted to explore the common feature in ovarian cancer stem cells sorted by multiple approaches. Methods: We collected the gene expression profiles of OCSCs were from 5 public cohorts and employed R software and Bioconductor packages to establish differently expressed genes (DEGs) between OCSCs and parental cells. We extracted the integrated DEGs by protein-protein interaction (PPI) network construction and explored potential treatment by the Cellminer database. Results: We identified and integrated the DEGs of OCSCs sorted by multiple isolation approaches. Besides, we identified OCSCs share characteristics in the lipid metabolism and extracellular matrix changes. Moreover, we obtained 16 co-expressed core genes, such as FOXQ1, MMP7, AQP5, RBM47, ETV4, NPW, SUSD2, SFRP2, IDO1, ANPEP, CXCR4, SCNN1A, SPP1 and IFI27 (upregulated) and SERPINE1, DUSP1, CD40, and IL6 (downregulated). Through correlation analysis, we screened out ten potential drugs to target the core genes. Conclusion: Based on the comprehensive analysis of the genomic datasets with different sorting methods of OCSCs, we figured out the common driving genes to regulating OCSC and obtained ten new potential therapies for eliminating ovarian cancer stem cells. Hence, the findings of our study might have potential clinical significance. [ABSTRACT FROM AUTHOR]
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- 2020
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32. Effects of HTR1B 3′ region polymorphisms and functional regions on gene expression regulation.
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Xia, Xi, Ding, Mei, Xuan, Jin-feng, Xing, Jia-xin, Pang, Hao, Yao, Jun, Wu, Xue, and Wang, Bao-jie
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GENETIC regulation , *BINDING sites , *HAPLOTYPES , *REGULATOR genes , *REPORTER genes , *GENE expression - Abstract
Background: The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3′ regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3′ region of HTR1B. Results: We found that the haplotype, A-G-Del-C-T-Ins-A, enhanced the expression level compared to the main haplotype; A-G-Del-C-G-Ins-A; G-G-Del-C-G-Ins-G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that + 2440 ~ + 2769 bp and + 1953 ~ + 2311 bp regions both had negative effects on gene expression. Conclusions: The 3′ region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3′ region includes several effector binding sites that induce an inhibitory effect on gene expression. [ABSTRACT FROM AUTHOR]
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- 2020
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33. Quantitative characterization of tumor cell-free DNA shortening.
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Guo, Juntang, Ma, Kefeng, Bao, Hua, Ma, Xiangyuan, Xu, Yang, Wu, Xue, Shao, Yang W., Jiang, Mei, and Huang, Jin
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CELL-free DNA , *SOMATIC mutation - Abstract
Background: Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application. Results: Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166 bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150 bp). Less than 1% of cfDNA samples were found to be peaked at 134/144 bp and independent of tumor cfDNA purity. Using whole-genome sequencing of cfDNA, we discovered a positive correlation between cfDNA shortening and the magnitude of chromatin inaccessibility, as measured by transcription, DNase I hypersensitivity, and histone modifications. Tumor cfDNA shortening occurred simultaneously at both 5′ and 3′ ends of the DNA wrapped around nucleosomes. Conclusions: Tumor cfDNA shortening exhibited two distinctive modes. Tumor cfDNA purity and chromatin inaccessibility were contributing factors but insufficient to trigger a global transition from 166 bp dominant to 134/144 bp dominant phenotype. [ABSTRACT FROM AUTHOR]
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- 2020
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34. Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis.
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Meng, Yifan, Lu, Wanrong, Guo, Ensong, Liu, Jia, Yang, Bin, Wu, Ping, Lin, Shitong, Peng, Ting, Fu, Yu, Li, Fuxia, Wang, Zizhuo, Li, Yuan, Xiao, Rourou, Liu, Chen, Huang, Yuhan, Lu, Funian, Wu, Xue, You, Lixin, Ma, Ding, and Sun, Chaoyang
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HOSPITAL patients , *COVID-19 , *CANCER-related mortality , *PROPENSITY score matching , *BLOOD sedimentation - Abstract
Background: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. Methods: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. Results: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76–5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients. Conclusions: We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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35. Mannose-binding lectin 2 gene polymorphisms and their association with tuberculosis in a Chinese population.
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Zhang, Jun-Xian, Gong, Wen-Ping, Zhu, Dong-Lin, An, Hui-Ru, Yang, You-Rong, Liang, Yan, Wang, Jie, Tang, Jing, Zhao, Wei-guo, and Wu, Xue-Qiong
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CHINESE people , *GENETIC polymorphisms , *SINGLE nucleotide polymorphisms , *GENETIC models , *TUBERCULOSIS - Abstract
Background: Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population. Methods: We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis. Results: We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152–1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055–1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349–0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087–1.793) effect against the development of TB. Conclusions: This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future. [ABSTRACT FROM AUTHOR]
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- 2020
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36. Genome-wide analysis of differentially expressed profiles of mRNAs, lncRNAs and circRNAs in chickens during Eimeria necatrix infection.
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Fan, Xian-Cheng, Liu, Ting-Li, Wang, Yi, Wu, Xue-Mei, Wang, Yu-Xin, Lai, Peng, Song, Jun-Ke, and Zhao, Guang-Hui
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EIMERIA , *CHICKENS , *CHICKEN diseases , *CIRCULAR RNA , *SMALL intestine , *NON-coding RNA , *LINCRNA - Abstract
Background: Eimeria necatrix, the most highly pathogenic coccidian in chicken small intestines, can cause high morbidity and mortality in susceptible birds and devastating economic losses in poultry production, but the underlying molecular mechanisms in interaction between chicken and E. necatrix are not entirely revealed. Accumulating evidence shows that the long-non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are key regulators in various infectious diseases. However, the expression profiles and roles of these two non-coding RNAs (ncRNAs) during E. necatrix infection are still unclear. Methods: The expression profiles of mRNAs, lncRNAs and circRNAs in mid-segments of chicken small intestines at 108 h post-infection (pi) with E. necatrix were analyzed by using the RNA-seq technique. Results: After strict filtering of raw data, we putatively identified 49,183 mRNAs, 818 lncRNAs and 4153 circRNAs. The obtained lncRNAs were classified into four types, including 228 (27.87%) intergenic, 67 (8.19%) intronic, 166 (20.29%) anti-sense and 357 (43.64%) sense-overlapping lncRNAs; of these, 571 were found to be novel. Five types were also predicted for putative circRNAs, including 180 exonic, 54 intronic, 113 antisense, 109 intergenic and 3697 sense-overlapping circRNAs. Eimeria necatrix infection significantly altered the expression of 1543 mRNAs (707 upregulated and 836 downregulated), 95 lncRNAs (49 upregulated and 46 downregulated) and 13 circRNAs (9 upregulated and 4 downregulated). Target predictions revealed that 38 aberrantly expressed lncRNAs would cis-regulate 73 mRNAs, and 1453 mRNAs could be trans-regulated by 87 differentially regulated lncRNAs. Additionally, 109 potential sponging miRNAs were also identified for 9 circRNAs. GO and KEGG enrichment analysis of target mRNAs for lncRNAs, and sponging miRNA targets and source genes for circRNAs identified associations of both lncRNAs and circRNAs with host immune defense and pathogenesis during E. necatrix infection. Conclusions: To the best of our knowledge, the present study provides the first genome-wide analysis of mRNAs, lncRNAs and circRNAs in chicken small intestines infected with E. necatrix. The obtained data will offer novel clues for exploring the interaction mechanisms between chickens and Eimeria spp. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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37. Wogonin as a targeted therapeutic agent for EBV (+) lymphoma cells involved in LMP1/NF-κB/miR-155/PU.1 pathway.
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Xue Wu, Ping Liu, Haijun Zhang, Yuan Li, Mohammad Salmani, Jumah Masoud, Fei Wang, Ke Yang, Rong Fu, Zhewei Chen, Baoan Chen, Wu, Xue, Liu, Ping, Zhang, Haijun, Li, Yuan, Salmani, Jumah Masoud Mohammad, Wang, Fei, Yang, Ke, Fu, Rong, Chen, Zhewei, and Chen, Baoan
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LYMPHOMAS , *THERAPEUTICS , *ANTI-inflammatory agents , *CELL proliferation , *TUMOR growth , *ANIMAL experimentation , *ANIMALS , *ANTINEOPLASTIC agents , *B cell lymphoma , *CELL lines , *CELL physiology , *CELLULAR signal transduction , *EPSTEIN-Barr virus diseases , *GENES , *MICE , *PROTEINS , *RNA , *DNA-binding proteins , *FLAVANONES , *PHARMACODYNAMICS - Abstract
Background: Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future.Methods: Cell proliferation was studied by CCK8. Flow cytometry was used to analyze the apoptosis and the cycle arrest of cells. Further, we also used immunofluorescent staining to detect the morphologic changes of the apoptotic cells. The expression of LMP1/miR-155/p65/pp65/PU.1 was evaluated by quantitative real-time PCR (qRT-PCR) and western blot, while that of NF-κB was analyzed by EMSA. At last, immunohistochemical staining was applied to assess the expression of target proteins and relevant molecules.Results: In vitro, wogonin induced the apoptosis of Raji cells by downregulating the expression of NF-κB through LMP1/miR-155/NF-κB/PU.1 pathway, which was in a dose and time-dependent manner. In vivo, wogonin could suppress tumor growth, associated with the downregulation of ki67, p65 and upregulation of PU.1.Conclusions: Wogonin could suppress tumor growth and induce cell apoptosis by inhibiting the expression of NF-κB. Taken these findings, we concluded that wogonin could be a potential targeted therapeutic agent for EBV-positive lymphoma with the expression of LMP1 through the pathway of LMP1/NF-κB/miR-155/PU.1. [ABSTRACT FROM AUTHOR]- Published
- 2017
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38. Prediction of miscarriage in first trimester by serum estradiol, progesterone and β-human chorionic gonadotropin within 9 weeks of gestation.
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Deng, Wenhui, Sun, Rui, Du, Jun, Wu, Xue, Ma, Lijie, Wang, Min, and Lv, Qiubo
- Abstract
Purpose: To predict miscarriage outcome within 12 weeks of gestational age by evaluating values of serum estradiol, progesterone and β-human chorionic gonadotropin (β-HCG) within 9 weeks of gestation.Methods: One hundred sixty-five women with singleton pregnancies were retrospectively studied. Estradiol, progesterone and β-HCG levels were measured at 5-6 weeks of gestation and the measurements were repeated at 7-9 weeks. According to pregnancy outcome at 12 weeks of gestation, 71 cases were categorized into miscarriage group, and 94 cases into group of normal pregnancy. Each group was further divided into 5-6 and 7-9 weeks of gestation sub-group. Predictive values of estradiol, progesterone and β- HCG levels at 5-6 weeks and 7-9 weeks of gestation were analyzed with receiver operating characteristic (ROC) curves and logistic regression.Results: Serum levels of estradiol at 7-9 weeks identified miscarriage with an area under the ROC curve (AUC) of 0.866 (95% CI 0. 793 ~ 0.938, P = 0.000), diagnostic cutoff value of 576 pg/ml, sensitivity of 0.804, and specificity of 0.829 respectively at the optimal threshold, according to Youden index. Progesterone levels at 7-9 weeks were with AUC of 0.766 (95% CI 0. 672 ~ 0.861, P = 0.000), cutoff value of 15.27 ng/ml, sensitivity of 0.921, and specificity of 0.558, respectively; Estradiol at 5-6 weeks were with AUC of 0.709 (95% CI 0. 616 ~ 0.801, P < 0.001), the diagnostic cutoff value of 320 pg/ml, sensitivity of 0.800, and specificity of 0.574, respectively. The performance of the dual markers of estradiol and progesterone analysis (AUC 0.871, CI 0.793-0.950), three-markers analysis (AUC 0.869, CI 0.759-0.980)were slightly better than the single marker at 7-9 weeks. β-HCG or progesterone provide additional utility of estradiol prediction at 5-6 weeks with AUC 0.770 (0.672-0.869) for β-HCG and estradiol, AUC0.768(CI 0.670-0.866) for β-HCG, estradiol and progesterone and AUC 0.739 (CI 0.651-0.827) for progesterone and estradiol.Conclusions: Low serum levels such as dual of estradiol and progesterone or estradiol alone at 7-9 weeks, β-HCG or progesterone combing estradiol at 5-6 weeks of gestation can be used better to predict miscarriage in first trimester. [ABSTRACT FROM AUTHOR]- Published
- 2022
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39. Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endometrial carcinoma.
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Li, Yuan, Li, Jiaqi, Guo, Ensong, Huang, Jia, Fang, Guangguang, Chen, Shaohua, Yang, Bin, Fu, Yu, Li, Fuxia, Wang, Zizhuo, Xiao, Rourou, Liu, Chen, Huang, Yuhan, Wu, Xue, Lu, Funian, You, Lixin, Feng, Ling, Xi, Ling, Wu, Peng, and Ma, Ding
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BIOLOGICAL evolution , *CHROMOSOME segregation , *OPERATIVE surgery , *PATHOLOGY , *CARCINOMA , *MOLECULAR pathology - Abstract
Background: Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Histopathological risk stratification lacks reproducibility, neglects heterogeneity and contributes little to surgical procedures. Existing molecular stratification is useless in patients with specific pathological or molecular characteristics and cannot guide postoperative adjuvant radiotherapies. Chromosomal instability (CIN), the numerical and structural alterations of chromosomes resulting from ongoing errors of chromosome segregation, is an intrinsic biological mechanism for the evolution of different prognostic factors of histopathology and molecular pathology and may be applicable to the risk stratification of EC. Results: By analyzing CIN25 and CIN70, two reliable gene expression signatures for CIN, we found that EC with unfavorable prognostic factors of histopathology or molecular pathology had serious CIN. However, the POLE mutant, as a favorable prognostic factor, had elevated CIN signatures, and the CTNNB1 mutant, as an unfavorable prognostic factor, had decreased CIN signatures. Only if these two mutations were excluded were CIN signatures strongly prognostic for outcomes in different adjuvant radiotherapy subgroups. Integrating pathology, CIN signatures and POLE/CTNNB1 mutation stratified stageIendometrioid EC into four groups with improved risk prognostication and treatment recommendations. Conclusions: We revealed the possibility of integrating histopathology and molecular pathology by CIN for risk stratification in early-stage EC. Our integrated risk model deserves further improvement and validation. [ABSTRACT FROM AUTHOR]
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- 2020
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40. Study on cyanidin metabolism in petals of pink-flowered strawberry based on transcriptome sequencing and metabolite analysis.
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Xue, Li, Wang, Jian, Zhao, Jun, Zheng, Yang, Wang, Hai-Feng, Wu, Xue, Xian, Cheng, Lei, Jia-Jun, Zhong, Chuan-Fei, and Zhang, Yun-Tao
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ANTHOCYANINS , *METABOLITE analysis , *STRAWBERRIES , *SEQUENCE analysis , *GENE expression profiling - Abstract
Background: Pink-flowered strawberry is a promising new ornamental flower derived from intergeneric hybridization (Fragaria × Potentilla) with bright color, a prolonged flowering period and edible fruits. Its flower color ranges from light pink to red. Pigment compounds accumulated in its fruits were the same as in cultivated strawberry fruits, but different from that in its flowers. However, the transcriptional events underlying the anthocyanin biosynthetic pathway have not been fully characterized in petal coloration. To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify the key genes, we performed an integrated analysis of the transcriptome and metabolome in petals of pink-flowered strawberry. Results: The main pigments of red and dark pink petals were anthocyanins, among which cyanidins were the main compound. There were no anthocyanins detected in the white-flowered hybrids. A total of 50,285 non-redundant unigenes were obtained from the transcriptome databases involved in red petals of pink-flowered strawberry cultivar Sijihong at three development stages. Amongst the unigenes found to show significant differential expression, 57 were associated with anthocyanin or other flavonoid biosynthesis, in which they were regulated by 241 differentially expressed members of transcription factor families, such as 40 MYBs, 47 bHLHs, and 41 NACs. Based on a comprehensive analysis relating pigment compounds to gene expression profiles, the mechanism of flower coloration was examined in pink-flowered strawberry. A new hypothesis was proposed to explain the lack of color phenotype of the white-flowered strawberry hybrids based on the transcriptome analysis. The expression patterns of FpDFR and FpANS genes corresponded to the accumulation patterns of cyanidin contents in pink-flowered strawberry hybrids with different shades of pink. Moreover, FpANS, FpBZ1 and FpUGT75C1 genes were the major factors that led to the absence of anthocyanins in the white petals of pink-flowered strawberry hybrids. Meanwhile, the competitive effect of FpFLS and FpDFR genes might further inhibit anthocyanin synthesis. Conclusions: The data presented herein are important for understanding the molecular mechanisms underlying the petal pigmentation and will be powerful for integrating novel potential target genes to breed valuable pink-flowered strawberry cultivars. [ABSTRACT FROM AUTHOR]
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- 2019
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41. Molecular genetic characterization reveals linear tumor evolution in a pulmonary sarcomatoid carcinomas patient with a novel PHF20-NTRK1 fusion: a case report.
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Ge, Jianjun, Yao, Bin, Huang, Jia, Wu, Xue, Bao, Hua, Ou, Qiuxiang, Shao, Yang W., and Chen, Jun
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CARCINOMA , *TUMORS , *THERAPEUTICS , *BIOLOGICAL evolution , *ADJUVANT treatment of cancer - Abstract
Background: Pulmonary sarcomatoid carcinoma (SC) consists of both carcinomatous and sarcomatous tumors with high degree of malignancy, rapid progression, and poor prognosis. However, little is known regarding how pulmonary SC develops and progresses.Case Presentation: A 66-year-old male was initially diagnosed with stage IIIa lung cancer containing both adenocarcinoma (ADC) and SC. Adjuvant chemotherapy was administrated post-surgery, however, recurrence with SC only soon followed. Mutation profiling of the patient's microdissected ADC and SC components of the primary lesion and recurrent tumor was performed by targeted next-generation sequencing (NGS) of 416 cancer-relevant genes. Our data showed that primary SC/ADC and the recurrent SC shared multiple gene mutations including EGFR, NF1, TP53, CDKN2B, and SMARCA4, while both primary and recurrent SCs had a unique TP53 exon 4 splicing mutation frequently observed in sarcoma. Interestingly, a novel PHF20-NTRK1 fusion was acquired in the recurrent SC, which may be a potential driver for SC recurrence.Conclusions: The molecular genetic characteristics of tumor tissues at different stages reveals a linear tumor evolution model in this case, and support that the primary SC derived from the original lung ADC during the evolution of the tumor. We also identified a novel PHF20-NTRK1 fusion, which may contribute to the disease recurrence, and that can be potentially targeted with NTRK1 inhibitors for treatment. [ABSTRACT FROM AUTHOR]- Published
- 2019
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42. A new less invasive surgical technique in the management of acute Achilles tendon rupture through limited-open procedure combined with a single-anchor and “circuit” suture technique.
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Zhang, Hao, Liu, Pei-Zhao, Zhang, Xin, Ding, Chen, Cui, Hao-Chen, Ding, Wen-Bin, Wang, Ren-Kai, Wu, Da-Jiang, Wei, Qiang, Qin, Sheng, Wu, Xue-Lin, Tong, Da-Ke, Wang, Guang-Chao, Tang, Hao, and Ji, Fang
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ENDOSCOPIC surgery , *RANGE of motion of joints , *RESEARCH funding , *SUTURING , *RETROSPECTIVE studies , *DATA analysis software , *DESCRIPTIVE statistics , *ACHILLES tendon rupture - Abstract
Background: Traditional incision repair and minimally invasive repair for acute Achilles tendon repair have limitations. This study aimed to present our series of 23 patients with acute Achilles tendon rupture that was repaired using two small incisions to assist the anchor repair of the tear and a new “circuit” suture technique. Methods: This was a retrospective study of 23 patients with acute Achilles tendon rupture treated with the new technique at Changhai Hospital between January 2015 and December 2016 and followed up for 14–33 months. Clinical outcome was assessed using the AOFAS, Leppilahti, and Arner-Lindholm scores. Complications, range of motion (ROM), and time to return to work and light sport activity were assessed. Results: The AOFAS score was 85–96 at 3 months and 92–100 at 12 months. The 3-month ROM was 27°–37°, and the 12-month ROM was 36°–48°. The Leppilahti score was 85–95 at 3 months and 90–100 at 12 months. The recovery time of the patients was 10–18 weeks. The postoperative recovery time to exercise was 16–24 weeks. There was only one case of deep venous thrombosis. According to the Arner-Lindholm assessment criteria, patient outcomes were rated as excellent in 20 (87.0%) cases, good in three (13.0%) cases, and poor in 0 cases. The excellent-to-good rate was 100%. Conclusion: The limited-open procedure combined with a single-anchor and “circuit” suture technique could be used to repair torn Achilles sites, with a low occurrence of complications. This new and minimally invasive technique could be an alternative in the management of acute Achilles tendon rupture. [ABSTRACT FROM AUTHOR]
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- 2018
- Full Text
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43. SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients.
- Author
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Mei, Zhu, Shao, Yang W, Lin, Peinan, Cai, Xiaomin, Wang, Biao, Ding, Yan, Ma, Xiangyuan, Wu, Xue, Xia, Yewei, Zhu, Dongqin, Shu, Yongqian, Fu, Zan, and Gu, Yanhong
- Abstract
Background: Cetuximab, an anti-EGFR monoclonal antibody, is used in combination with chemotherapy in clinic to enhance the outcome in metastatic colorectal cancer (mCRC) patients with only ~ 20% response rate. To date only activating mutations in KRAS and NRAS have been identified as poor prognosis biomarkers in cetuximab-based treatment, which makes an urgent need for identification of novel prognosis biomarkers to precisely predict patients' response in order to maximize the benefit.Methods: In this study, we analysed the mutation profiles of 33 Chinese mCRC patients using comprehensive next-generation sequencing (NGS) targeting 416 cancer-relevant genes before cetuximab treatment. Upon receiving cetuximab-based therapy, patients were evaluated for drug response, and the progression-free survival (PFS) was monitored. The association of specific genetic alterations and cetuximab efficacy was analyzed.Results: Patients carrying SMAD4 mutations (SMAD4mut, n = 8) or NF1 mutations (NF1mut, n = 4) had significantly shorter PFS comparing to those carrying wildtype SMAD4 (SMAD4wt, n = 25) (P = 0.0081) or wildtype NF1 (NF1wt, n = 29) (P = 0.0028), respectively. None of the SMAD4mut or NF1mut patients showed response to cetuximab when assessed at 12-week post-treatment. Interestingly, two patients carrying both SMAD4mut and NF1mut showed the shortest PFS among all the patients.Conclusions: Our results demonstrated that SMAD4 and NF1 mutations can serve as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese mCRC patients. [ABSTRACT FROM AUTHOR]- Published
- 2018
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44. Targeted next generation sequencing identified clinically actionable mutations in patients with esophageal sarcomatoid carcinoma.
- Author
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Lu, Hongyang, Yang, Shifeng, Zhu, Huineng, Tong, Xiaoling, Xie, Fajun, Qin, Jing, Han, Na, Wu, Xue, Fan, Yun, Shao, Yang W., and Mao, Weimin
- Subjects
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ESOPHAGEAL tumors , *CARCINOMA , *GENETIC mutation , *PROTEIN-tyrosine kinases , *HISTONE acetyltransferase - Abstract
Background: Esophageal sarcomatoid carcinoma (ESC) is a rare disease with a mixture of both carcinomatous and sarcomatous components in the tumor. Its genetic background and mechanisms of oncogenesis remain largely unknown.Methods: Here we performed targeted next generation sequencing (NGS) on a pan-cancer gene panel in 15 ESC tumors to explore their genetic alterations, and aimed to identify clinically actionable mutations for future treatment instructions.Results: TP53 alterations were identified in all patients. Alterations in receptor tyrosine kinases (RTK) were identified in 10 out of 15 patients. Members of downstream RAS and PI3-kinase pathways are also mutated in 10 patients, and PIK3CA is the top mutated gene in these pathways. In addition, we identified mutations on histone modification genes in 5 patients, including histone acetyltransferase gene EP300 and its homologue CREBBP, lysine methyltransferase genes KMT2A and KMT2B, and lysine demethylase gene KDM5A. Finally, mismatch repair (MMR) genes and proofreading gene POLE all together were mutated in one third of the ESC patients.Conclusions: This is the first study to unravel the mutational profile of ESC tumors. Our findings could match 9 patients to the targeted therapies currently available in clinical practice or in active clinical trials, suggesting the potential utility of targeted therapies for this rare disease in the future. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
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