Author: "Zhen Huang" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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811 results on '"Zhen Huang"'

1. Experimental study on bioaerosols behavior and purification measures in a subway compartment

Author: Renze Xu, Fan Wu, Lian Shen, Zhiqiang Fan, Jianci Yu, and Zhen Huang
Subjects: Subway compartment, Indoor air, Airborne transmission, Bioaerosol concentration, Air filter, Purification efficiency, Medicine, Science
Abstract: Abstract Bioaerosols in public transportation systems raise critical environmental concerns, seriously threatening passenger health and safety. In this study, we investigate the spread characteristics of bioaerosols in a standard type-B subway compartment using both air sampling and sediment sampling methods. Additionally, without compromising indoor passenger comfort, two self-designed air purification devices, based on intense field dielectric (IFD) and dielectric barrier discharge (DBD) technologies, respectively, are successfully applied for the improvement of the subway air quality. The results show that bioaerosols can propagate rapidly throughout the entire compartment in 5 min via airborne transmission. Under the effect of the symmetric air ducts and compartment structure, the difference in bioaerosol concentration in the air is less than 10% between both ends of the compartment. Concurrent substantial bioaerosol deposition on the ground, seats, and windows underscores the risk of contact transmission. Furthermore, the real-time purification rates of the two devices integrated into the air conditioning system reach 59.40% and 44.98%, respectively. With their demonstrated high efficiency in purifying bioaerosols and modular design featuring low energy consumption, easy cleaning, and reusability, these devices stand out as viable long-term solutions for large traffic vehicles. These research findings provide practical equipment recommendations and installation strategies for optimizing indoor air quality in subways and are applicable to other similar transportation systems.
Published: 2024
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2. Single-cell exome sequencing reveals polyclonal seeding and TRPS1 mutations in colon cancer metastasis

Author: Jianqiang Cai, Weilong Zhang, Yalan Lu, Wenjie Liu, Haitao Zhou, Mei Liu, Xinyu Bi, Jianmei Liu, Jinghua Chen, Yanjiang Yin, Yiqiao Deng, Zhiwen Luo, Yi Yang, Qichen Chen, Xiao Chen, Zheng Xu, Yueyang Zhang, Chaoling Wu, Qizhao Long, Chunyuan Huang, Changjian Yan, Yan Liu, Lei Guo, Weihua Li, Pei Yuan, Yucheng Jiao, Wei Song, Xiaobing Wang, Zhen Huang, Jianming Ying, and Hong Zhao
Subjects: Medicine, Biology (General), QH301-705.5
Abstract: Abstract Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.
Published: 2024
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3. AI models predicting breast cancer distant metastasis using LightGBM with clinical blood markers and ultrasound maximum diameter

Author: Yang Tan, Wen-hai Zhang, Zhen Huang, Qi-xing Tan, Yue-mei Zhang, Chang-yuan Wei, and Zhen-Bo Feng
Subjects: Medicine, Science
Abstract: Abstract Breast cancer metastasis significantly impacts women's health globally. This study aimed to construct predictive models using clinical blood markers and ultrasound data to predict distant metastasis in breast cancer patients, ensuring clinical applicability, cost-effectiveness, relative non-invasiveness, and accessibility of these models. Analysis was conducted on data from 416 patients across two centers, focusing on clinical blood markers (tumor markers, liver and kidney function indicators, blood lipid markers, cardiovascular biomarkers) and maximum lesion diameter from ultrasound. Feature reduction was performed using Spearman correlation and LASSO regression. Two models were built using LightGBM: a clinical model (using clinical blood markers) and a combined model (incorporating clinical blood markers and ultrasound features), validated in training, internal test, and external validation (test1) cohorts. Feature importance analysis was conducted for both models, followed by univariate and multivariate regression analyses of these features. The AUC values of the clinical model in the training, internal test, and external validation (test1) cohorts were 0.950, 0.795, and 0.883, respectively. The combined model showed AUC values of 0.955, 0.835, and 0.918 in the training, internal test, and external validation (test1) cohorts, respectively. Clinical utility curve analysis indicated the combined model's superior net benefit in identifying breast cancer with distant metastasis across all cohorts. This suggests the combined model's superior discriminatory ability and strong generalization performance. Creatine kinase isoenzyme (CK-MB), CEA, CA153, albumin, creatine kinase, and maximum lesion diameter from ultrasound played significant roles in model prediction. CA153, CK-MB, lipoprotein (a), and maximum lesion diameter from ultrasound positively correlated with breast cancer distant metastasis, while indirect bilirubin and magnesium ions showed negative correlations. This study successfully utilized clinical blood markers and ultrasound data to develop AI models for predicting distant metastasis in breast cancer. The combined model, incorporating clinical blood markers and ultrasound features, exhibited higher accuracy, suggesting its potential clinical utility in predicting and identifying breast cancer distant metastasis. These findings highlight the potential prospects of developing cost-effective and accessible predictive tools in clinical oncology.
Published: 2024
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4. DGPRI, a new liver fibrosis assessment index, predicts recurrence of AFP-negative hepatocellular carcinoma after hepatic resection: a single-center retrospective study

Author: Bolun Zhang, Junshuai Xue, Bowen Xu, Jianping Chang, Xin Li, Zhen Huang, Hong Zhao, and Jianqiang Cai
Subjects: Alpha-fetoprotein-negative hepatocellular carcinoma, Liver fibrosis, Postoperative recurrence, Gamma-glutamyl transpeptidase-to-platelet ratio, Direct bilirubin, Medicine, Science
Abstract: Abstract Although patients with alpha-fetoprotein-negative hepatocellular carcinoma (AFPNHCC) have a favorable prognosis, a high risk of postoperative recurrence remains. We developed and validated a novel liver fibrosis assessment index, the direct bilirubin-gamma-glutamyl transpeptidase-to-platelet ratio (DGPRI). DGPRI was calculated for each of the 378 patients with AFPNHCC who underwent hepatic resection. The patients were divided into high- and low-score groups using the optimal cutoff value. The Lasso-Cox method was used to identify the characteristics of postoperative recurrence, followed by multivariate Cox regression analysis to determine the independent risk factors associated with recurrence. A nomogram model incorporating the DGPRI was developed and validated. High DGPRI was identified as an independent risk factor (hazard ratio = 2.086) for postoperative recurrence in patients with AFPNHCC. DGPRI exhibited better predictive ability for recurrence 1–5 years after surgery than direct bilirubin and the gamma-glutamyl transpeptidase-to-platelet ratio. The DGPRI-nomogram model demonstrated good predictive ability, with a C-index of 0.674 (95% CI 0.621–0.727). The calibration curves and clinical decision analysis demonstrated its clinical utility. The DGPRI nomogram model performed better than the TNM and BCLC staging systems for predicting recurrence-free survival. DGPRI is a novel and effective predictor of postoperative recurrence in patients with AFPNHCC and provides a superior assessment of preoperative liver fibrosis.
Published: 2024
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5. Risk and prosocial behavioural cues elicit human-like response patterns from AI chatbots

Author: Yukun Zhao, Zhen Huang, Martin Seligman, and Kaiping Peng
Subjects: Medicine, Science
Abstract: Abstract Emotions, long deemed a distinctly human characteristic, guide a repertoire of behaviors, e.g., promoting risk-aversion under negative emotional states or generosity under positive ones. The question of whether Artificial Intelligence (AI) can possess emotions remains elusive, chiefly due to the absence of an operationalized consensus on what constitutes 'emotion' within AI. Adopting a pragmatic approach, this study investigated the response patterns of AI chatbots—specifically, large language models (LLMs)—to various emotional primes. We engaged AI chatbots as one would human participants, presenting scenarios designed to elicit positive, negative, or neutral emotional states. Multiple accounts of OpenAI's ChatGPT Plus were then tasked with responding to inquiries concerning investment decisions and prosocial behaviors. Our analysis revealed that ChatGPT-4 bots, when primed with positive, negative, or neutral emotions, exhibited distinct response patterns in both risk-taking and prosocial decisions, a phenomenon less evident in the ChatGPT-3.5 iterations. This observation suggests an enhanced capacity for modulating responses based on emotional cues in more advanced LLMs. While these findings do not suggest the presence of emotions in AI, they underline the feasibility of swaying AI responses by leveraging emotional indicators.
Published: 2024
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6. Chinese expert consensus on the overall management of liver function in conversion therapy for liver cancer (2022 edition)

Author: Qinghua Meng, Zhengqiang Yang, Zhenyu Zhu, Juan Li, Xinyu Bi, Xiao Chen, Chunyi Hao, Zhen Huang, Fei Li, Xiao Li, Guangming Li, Yinmo Yang, Yefan Zhang, Haitao Zhao, Hong Zhao, Xu Zhu, Jiye Zhu, Jianqiang Cai, The Liver Tumor Branch of the China International Exchange and Promotive Association for Medical and Healthcare (CPAM), The Gastrointestinal Cancer Multidisciplinary Cooperation Group of Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, The Liver Cancer Professional Committee of Chinese Medical Doctor Association, and Yuanyuan Ji
Subjects: Medicine
Published: 2023
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7. Genomic and transcriptomic characterization of pre-operative chemotherapy response in patients with osteosarcoma

Author: Yongkun Yang, Zhen Huang, Mingming Yuan, Jinqiu Rui, Rongrong Chen, Tao Jin, Yang Sun, Zhiping Deng, Huachao Shan, Xiaohui Niu, and Weifeng Liu
Subjects: Medicine, Science
Abstract: Abstract Osteosarcoma is a heterogeneous disease with regard to its chemotherapy response and clinical outcomes. This study aims to investigate the genomic and transcriptomic characteristics related to pre-operative chemotherapy response. Samples from 25 osteosarcoma patients were collected to perform both whole exome and transcriptome sequencing. Osteosarcoma had significant amount of chromosomal copy number variants (CNVs). Chemotherapy responders showed the higher chromosomal CNV burden than non-responders (p = 0.0775), but the difference was not significant. The percentage of COSMIC signature 3, associated with homologous recombination repair deficiency, was higher in responders (56%) than in non-responders (45%). Transcriptomic analysis suggested that 11 genes were significantly up-regulated in responders and 18 genes were up-regulated in non-responders. Both GSEA and KEGG enrichment analysis indicted that four pathways related to cardiomyopathy were up-regulated in responders, while neuroactive ligand − receptor interaction was up-regulated in non-responders. Finally, a previously published chemoresistant model was validated using our dataset, with the area under the curve of 0.796 (95% CI, 0.583–1.000). Osteosarcoma had the heterogeneous mutational profile with frequent occurrence of CNVs. Transcriptomic analysis identified several signaling pathways associated with chemotherapy responsiveness to osteosarcoma. Transcriptomic signatures provides a potential research direction for predicting the chemotherapy response.
Published: 2023
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8. Study on Cynodon dactylon root system affecting dry–wet cracking behavior and shear strength characteristics of expansive soil

Author: Yingzi Xu, Yanyan Guo, Zhen Huang, Dezhi Liu, Quanen Huang, and Hong Tang
Subjects: Medicine, Science
Abstract: Abstract Expansive soil exhibits remarkable characteristics of water absorption expansion and water loss shrinkage, rendering it susceptible to cracking under the alternating dry–wet environments of nature. The generation and development of cracks in expansive soil can result in catastrophic engineering accidents such as landslides. Vegetation protection is an important approach to stabilizing expansive soil slopes and fulfilling ecological protection requirements. In this study, through indoor experiments and theoretical analysis methods, the effects of Cynodon dactylon roots on the crack development and shear strength of expansive soil subjected to dry–wet cycles were analyzed, and the relationship between the crack development and shear strength decay in root-doped expansive soil was explored. Furthermore, the mechanism of vegetative root system action was elucidated. The results show that the Cynodon dactylon root system exerts a significant inhibitory effect on crack development in expansive soil. The crack indexes of root-doped expansive soil exhibit significant phase characteristics during the process of dry–wet cycles. The crack-blocking and reinforcing effect of the root system becomes pronounced as the root-to-soil mass ratio increases and the root diameter decreased. Moreover, the process of crack development in expansive soil is accompanied by a decrease in soil shear strength. The quantitative relationship between crack development and shear strength decay can serve as a basis for predicting the stability of slope soil. Overall, the results highlight the potential of vegetation-based approaches in protecting slopes with expansive soils and have practical implications for ecological protection and engineering design in areas with expansive soils.
Published: 2023
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9. Research on local sound field intensity control technique in metasurface based on deep neural networks.

Author: Huanlong Zhao, Qiang Lv, Zhen Huang, Wei Chen, and Guoqiang Hao
Subjects: Medicine, Science
Abstract: The use of tunable metasurface technology to realize the underwater tracking function of submarines, which is one of the hotspots and difficulties in submarine design. The structure-to-sound-field metasurface design approach is a highly iterative process based on trial and error. The process is cumbersome and inefficient. Therefore, an inverse design method was proposed based on parallel deep neural networks. The method took the global and local target sound field feature information as input and the metasurface physical structure parameters as output. The deep neural network was trained using a kernel loss function based on a radial basis kernel function, which established an inverse mapping relationship between the desired sound field to the metasurface physical structure parameters. Finally, the sound field intensity modulation at a localized target range was achieved. The results indicated that within the regulated target range, this method achieved an average prediction error of less than 5 dB for 92.9% of the sample data.
Published: 2024
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10. IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis

Author: Jian Liao, Qing-hong Qin, Fa-you Lv, Zhen Huang, Bin Lian, Chang-yuan Wei, Qin-guo Mo, and Qi-xing Tan
Subjects: Medicine, Science
Abstract: Abstract IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from a retrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.
Published: 2023
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11. Alterations in the human oral microbiota in systemic lupus erythematosus

Author: Jinyan Guo, Guangying Cui, Wei Huang, Zhaohui Zheng, Tianfang Li, Guanmin Gao, Zhen Huang, Yuwei Zhan, Suying Ding, Shengyun Liu, Zujiang Yu, and Zhigang Ren
Subjects: Systemic lupus erythematosus, Oral microbiota, Characteristics, Diagnostic biomarker, Disease activity, Medicine
Abstract: Abstract Background Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota. Methods We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized. Results The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848–0.9483, p
Published: 2023
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12. Urotensin II promotes the proliferation and secretion of vascular endothelial growth factor in rat dermal papilla cells by activating the Wnt-β-catenin signaling pathway

Author: Congjuan Liao, Zhen Huang, Liuting Chen, Xiaorong Fan, Jun Peng, Xiaoqing Tan, Jianshe Yang, and Xusheng Zhang
Subjects: Urotensin II, rat dermal papilla cells, proliferation, VEGF, Wnt/β-catenin pathway, Medicine
Abstract: Introduction. Urotensin II (U II) is a kind of active peptide with a variety of biological effects, such as promoting cell proliferation and endocrine effects. The aim of this study is to investigate the effect of urotensin II on the proliferation and secretion of vascular endothelial growth factor (VEGF) in cultured rat dermal papilla cells (DPCs), and to explore its molecular mechanism. Materials and Methods. We used the DPCs isolated from the thoracic aortas of Wistar-Kyoto rats to run the CCK8 and ELISA assay, RC-PCR and Western blotting techniques to identify the effect of Urotensin II on the proliferation and secretion of VEGF in DPCs, data were analyzed by one-way ANOVA or t-test. Results. U II can increase the mRNA expression of proliferation markers Ki67 and PCNA. In addition, the Wnt/β-catenin pathway was activated by U II, but Wnt inhibitor DKK1 reversed the effect of U II. Conclusions. U II promoted the proliferation and secretion of VEGF in rat DPCs through activation of the Wnt-β-catenin signaling pathway.
Published: 2023
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13. RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy

Author: Yalan Lu, Rong Huang, Jianming Ying, Xingchen Li, Tao Jiao, Lei Guo, Haitao Zhou, Han Wang, Amannisa Tuersuntuoheti, Jianmei Liu, Qichen Chen, Yanhong Wang, Luying Su, Changyuan Guo, Fu Xu, Ziyi Wang, Yan Lu, Kai Li, Junbo Liang, Zhen Huang, Xiao Chen, Jinjie Yao, Hanjie Hu, Xiaowen Cheng, Yufeng Wan, Xinyan Chen, Ning Zhang, Shiying Miao, Jianqiang Cai, Linfang Wang, Changzheng Liu, Wei Song, and Hong Zhao
Subjects: Medicine, Biology (General), QH301-705.5
Abstract: Abstract Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138−/− mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.
Published: 2022
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14. A Retrospective Observational Study on Disease Characteristics and Treatment Patterns of Giant Cell Tumor of the Bone in China

Author: Hairong Xu, Yuan Li, Tao Wang, Weifeng Liu, Ke Ma, Yongkun Yang, Zhen Huang, Chuang Li, and Xiaohui Niu
Subjects: Medicine
Abstract: Aims. Giant cell tumor of the bone (GCTB) is associated with considerable morbidity. As GCTB epidemiological data for China are limited, this study is aimed at describing the disease characteristics of GCTB in China and establishing the historical context for its treatment before recent advances in treatment options. Methods. The disease characteristics, treatment patterns, and local GCTB recurrence rate after primary surgery for GCTB were evaluated in this single-center, retrospective, noninterventional, observational study of patients treated for GCTB at Ji Shui Tan Hospital, Beijing, from 2009 to 2016 based on medical chart review. Patients with unmet need were defined as those whose surgical treatment was difficult or who had to undergo high-morbidity surgery. Results. Among the 668 patients with a primary GCTB diagnosis, 578 (86.5%) of target lesions were in the extremities, and 89 (13.3%) were in the pelvic or axial bone. Of these, 173 (25.9%) were characterized as having an unmet need. Almost all GCTB patients received surgical treatment at both primary diagnosis (666/668 (99.7%)) and last disease recurrence (196/200 (98.0%)). Additionally, about one-third of patients received nonsurgical treatment at primary diagnosis (205/668 (30.7%)) and disease recurrence (67/200 (33.5%)), with neoadjuvant therapy being the most common treatment. The rate of high-morbidity surgery increased for recurrent disease (65/200 (32.5%)) compared with primary diagnosis (111/668 (16.6%)). The 2-year cumulative incidence of postoperative disease recurrence was 29.2%, in line with rates observed in prior studies. Conclusion. As many patients with primary and recurrent disease received high-morbidity surgery, more effective treatments are needed.
Published: 2023
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15. Rapidly developable therapeutic-grade equine immunoglobulin against the SARS-CoV-2 infection in rhesus macaques

Author: Xiaolei Liu, Yi Liu, Xuemin Jin, Zhanlong He, Zhen Huang, Shumin Sun, Yuwei Gao, Jingyu Li, Qin Ning, Zhongping Xie, Ningyi Jin, and Mingyuan Liu
Subjects: Medicine, Biology (General), QH301-705.5
Published: 2022
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16. Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort

Author: Dandan Tan, Lin Ge, Yanbin Fan, Xingzhi Chang, Shuang Wang, Cuijie Wei, Juan Ding, Aijie Liu, Shuo Wang, Xueying Li, Kai Gao, Haipo Yang, Chengli Que, Zhen Huang, Chunde Li, Ying Zhu, Bing Mao, Bo Jin, Ying Hua, Xiaoli Zhang, Bingbing Zhang, Wenhua Zhu, Cheng Zhang, Yanjuan Wang, Yun Yuan, Yuwu Jiang, Anne Rutkowski, Carsten G. Bönnemann, Xiru Wu, and Hui Xiong
Subjects: Natural history, Genotype, LAMA2, Muscular dystrophy, Rare diseases, Medicine
Abstract: Abstract Background LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype–phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy. Methods Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed. Results One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0–36.0 months), 11.0 months (range 6.0–36.0 months), and 27.0 months (range 18.0–84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0–20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6–9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029). Conclusions This study provides better understandings of natural history and genotype–phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.
Published: 2021
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17. Clinical study of diabetic peripheral neuropathy screening by retinal vascular geometric parameters

Author: Guotao Hu, Hongmei Wu, Lei Kuang, Benny Chung-Ying Zee, Ying Huang, Zhen Huang, Li He, Yuanhong Zeng, Yongbo Gao, and Hailan Wang
Subjects: Medicine, Science
Abstract: Abstract To investigate the relationship between geometrical changes of retinal vessels and diabetic peripheral neuropathy (DPN), and to determine the effectiveness of retinal vascular geometry analysis and vibration perception threshold (VPT) for DPN assessment. Type 2 diabetes patients (n = 242) were categorized by stage of DPN. VPT and fundus photography was performed to obtain retinal vascular geometry parameters. The risk factors for DPN and the correlation between DPN stages were analyzed. The efficiency of the retinal vascular geometric parameters obtained with VPT as a diagnostic tool for DPN was examined. Stages of DPN showed a linear correlation with VPT (r = 0.818), central retinal vein equivalent (CRVE) (r = 0.716), and fractal dimension arterioles (DFa) (r = − 0.769). VPT, CRVE, DFa, and fractal dimension veins (DFv) showed high sensitivity (80%, 55%, 82%, and 67%, respectively) and specificity (92%, 93%, 82%, and 80%, respectively) for DPN diagnosis. Good agreement was observed between combined use of geometric parameters (CRVE, DFa and DFv) and VPT (Kappa value 0.430). The detection rate of DPN with combined use of geometric parameters of retinal vessels (64.88%) was significantly higher than that with use of VPT (47.52%). Retinal vascular geometry changes demonstrated significant correlation with DPN severity. VPT, CRVE, DFa, and DFv may provide insights for understanding DPN.
Published: 2021
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18. Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis

Author: Chengxin Luo, Guixian Wu, Xiangtao Huang, Yanni Ma, Yali Zhang, Qiuyue Song, Mingling Xie, Yanni Sun, Yarui Huang, Zhen Huang, Yu Hou, Shuangnian Xu, Jieping Chen, and Xi Li
Subjects: Medicine, Science
Abstract: Abstract Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel–Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73–0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13–1.48, P
Published: 2021
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19. An on-board 2G HTS magnets system with cooling-power-free and persistent-current operation for ultrahigh speed superconducting maglevs

Author: Fangliang Dong, Zhen Huang, Luning Hao, Xiaoyong Xu, Zhijian Jin, and Nan Shao
Subjects: Medicine, Science
Abstract: Abstract Introduction of superconductor to magnetic levitation (maglev) trains greatly enhances the performances compared to those of normal conductor maglevs, e.g. from 430 km/h of the Transrapid (in Shanghai) to 603 km/h of the L0 Series in Japan. However, one of the important constraints on development of superconducting maglevs is limited wireless feeding power for on-board superconducting magnets and cryogenic cooling. In this paper, a persistent-current superconducting magnets system with solid nitrogen (SN2) cooling preservation is proposed for liberation of its demanding on-board power feeding requirement. The magnets are optimally designed with no-insulation technique guaranteeing a safe operation with magnetic field over 0.8 T. Lasting time of persistent current (at 96.5% magnetic field retained) and SN2 cooling preservation (up to 40 K) is all >9 h, covering a maglev traveling distance of >5400 km at average designed speed of >600 km/h. The magnets have anti-vibration ability of 15 g (147 m/s2) up to 350 Hz, which has covered the vibratory motion range in maglevs. This work is intended to provide a reference for superconducting maglev developments.
Published: 2019
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20. Integrated analysis of immune-related long noncoding RNAs as diagnostic biomarkers in psoriasis

Author: Feixiang Fan, Zhen Huang, and Yongfeng Chen
Subjects: Biomarker, Dermatosis, lncRNA, Psoriasis, Immune cell, Medicine, Biology (General), QH301-705.5
Abstract: Background Psoriasis is a chronic immune-mediated inflammatory dermatosis. Long noncoding RNAs (lncRNAs) play an important role in immune-related diseases. This study aimed to identify potential immune-related lncRNA biomarkers for psoriasis. Methods We screened differentially expressed immune-related lncRNAs biomarkers using GSE13355 (skin biopsy samples of 180 cases) from Gene Expression Omnibus (GEO). Moreover, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to explore biological mechanisms in psoriasis. In addition, we performed LASSO logistic regression to identify potential diagnostic lncRNAs and further verify the diagnostic value and relationship with drug response using two validation sets: GSE30999 (skin biopsy samples of 170 cases) and GSE106992 (skin biopsy samples of 192 cases). Furthermore, we estimated the degree of infiltrated immune cells and investigated the correlation between infiltrated immune cells and diagnostic lncRNA biomarkers. Results A total of 394 differentially expressed genes (DEGs) were extracted from gene expression profile. GO and KEGG analysis of target genes found that immune-related lncRNAs were primarily associated with epidermis development, skin development, collagen-containing extracellular matrix, and glycosaminoglycan binding and mainly enriched in cytokine-cytokine receptor interaction and influenza A and chemokine signaling pathway. We found that LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1, CARMN, CCDC18-AS1, EPB41L4A-AS, and LINC01214 exhibited well diagnostic efficacy. The ROC and ROC CI were 0.944 (0.907–0.982), 0.953 (0.919–0.987), 0.822 (0.758–0.887), 0.854 (0.797–0.911), 0.957(0.929–0.985), 0.894 (0.846–0.942), and 0.964 (0.937–0.991) for LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1,CARMN, CCDC18-AS1, EPB41L4A-AS1, and LINC01214. LINC01137, LINC01215, and LINC01214 were correlated with drug response. LINC01137, CCDC18-AS1, and CARMN were positively correlated with activated memory CD4 T cell, activated myeloid dendritic cell (DC), neutrophils, macrophage M1, and T follicular helper (Tfh) cells, while negatively correlated with T regulatory cell (Treg). LINC01215, MAPKAPK5-AS1, TPT1-AS1, EPB41L4A-AS, and LINC01214 were negatively correlated with activated memory CD4 T cell, activated myeloid DC, neutrophils, macrophage M1, and Tfh, while positively correlated with Treg. Conclusions These findings indicated that these immune-related lncRNAs may be used as potential diagnostic and predictive biomarkers for psoriasis.
Published: 2021
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21. TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice

Author: Xiaolong Tu, Yuanyuan Zhang, Xiuxiu Zheng, Jia Deng, Huanan Li, Zhiqian Kang, Zhipeng Cao, Zhen Huang, Zhi Ding, Lei Dong, Jiangning Chen, Yuhui Zang, and Junfeng Zhang
Subjects: Medicine, Science
Abstract: Abstract Hepatocyte death, as well as the following inflammatory and fibrogenic signaling cascades, is the key trigger of liver fibrosis. Here, we isolated hepatocytes from CCl4-induced fibrotic liver and found that hepatocyte lincRNA-p21 significantly increased during liver fibrosis. The increase of hepatocyte lincRNA-p21 was associated with the loss of miR-30, which can inhibit TGF-β signaling by targeting KLF11. We revealed that lincRNA-p21 modulated miR-30 availability by acting as a competing endogenous RNA (ceRNA). The physiological significance of this interaction is highlighted by the feedback loop, in which lincRNA-p21 works as a downstream effector of the TGF-β signaling to strengthen TGF-β signaling and mediate its role in promoting liver fibrosis by interacting with miR-30. In vivo results showed that knockdown of hepatocyte lincRNA-p21 greatly reduced CCl4-induced liver fibrosis and inflammation, whereas ectopic expression of miR-30 in hepatocyte exhibited the similar results. Mechanistic studies further revealed that inhibition of miR-30 impaired the effects of lincRNA-p21 on liver fibrosis. Additionally, lincRNA-p21 promoted hepatocyte apoptosis in vitro and in vivo, whereas the proliferation rate of hepatocyte was suppressed by lincRNA-p21. The pleiotropic roles of hepatocyte lincRNA-p21 suggest that it may represent an unknown paradigm in liver fibrosis and serve as a potential target for therapy.
Published: 2017
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22. Prognostic Analysis of 102 Patients with Synchronous Colorectal Cancer and Liver Metastases Treated with Simultaneous Resection

Author: Ye-Fan Zhang, Rui Mao, Xiao Chen, Jian-Jun Zhao, Xin-Yu Bi, Zhi-Yu Li, Jian-Guo Zhou, Hong Zhao, Zhen Huang, Yong-Kun Sun, and Jian-Qiang Cai
Subjects: Colorectal Cancer, Liver Metastases, Prognosis, Simultaneous Resection, Medicine
Abstract: Background: The liver is the most common site for colorectal cancer (CRC) metastases. Their removal is a critical and challenging aspect of CRC treatment. We investigated the prognosis and risk factors of patients with CRC and liver metastases (CRCLM) who underwent simultaneous resections for both lesions. Methods: From January 2009 to August 2016, 102 patients with CRCLM received simultaneous resections of CRCLM at our hospital. We retrospectively analyzed their clinical data and analyzed their outcomes. Overall survival (OS) and disease-free survival (DFS) were examined by Kaplan-Meier and log-rank methods. Results: Median follow-up time was 22.7 months; no perioperative death or serious complications were observed. Median OS was 55.5 months; postoperative OS rates were 1-year: 93.8%, 3-year: 60.7%, and 5-year: 46.4%. Median DFS was 9.0 months; postoperative DFS rates were 1-year: 43.1%, 3-year: 23.0%, and 5-year 21.1%. Independent risk factors found in multivariate analysis included carcinoembryonic antigen ≥100 ng/ml, no adjuvant chemotherapy, tumor thrombus in liver metastases, and bilobar liver metastases for OS; age ≥60 years, no adjuvant chemotherapy, multiple metastases, and largest diameter ≥3 cm for DFS. Conclusions: Simultaneous surgical resection is a safe and effective treatment for patients with synchronous CRCLM. The main prognostic factors are pathological characteristics of liver metastases and whether standard adjuvant chemotherapy is performed.
Published: 2017
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23. Harnessing region-specific neurovascular signaling to promote germinal matrix vessel maturation and hemorrhage prevention

Author: Devi Santhosh, Joe Sherman, Shafi Chowdhury, and Zhen Huang
Subjects: germinal matrix hemorrhage, mouse model, tgfβ signaling, brain neurovascular biology, Medicine, Pathology, RB1-214
Abstract: Germinal matrix hemorrhage (GMH), affecting about 1 in 300 births, is a major perinatal disease with lifelong neurological consequences. Yet despite advances in neonatal medicine, there is no effective intervention. GMH is characterized by localized bleeding in the germinal matrix (GM), due to inherent vessel fragility unique to this developing brain region. Studies have shown that reduced TGFβ signaling contributes to this vascular immaturity. We have previously shown that a region-specific G-protein-coupled receptor pathway in GM neural progenitor cells regulates integrin β8, a limiting activator of pro-TGFβ. In this study, we use mice to test whether this regional pathway can be harnessed for GMH intervention. We first examined the endogenous dynamics of this pathway and found that it displays specific patterns of activation. We then investigated the functional effects of altering these dynamics by chemogenetics and found that there is a narrow developmental window during which this pathway is amenable to manipulation. Although high-level activity in this time window interferes with vessel growth, moderate enhancement promotes vessel maturation without compromising growth. Furthermore, we found that enhancing the activity of this pathway in a mouse model rescues all GMH phenotypes. Altogether, these results demonstrate that enhancing neurovascular signaling through pharmacological targeting of this pathway may be a viable approach for tissue-specific GMH intervention. They also demonstrate that timing and level are likely two major factors crucial for success. These findings thus provide critical new insights into both brain neurovascular biology and the intervention of GMH.
Published: 2019
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24. Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

Author: Mu-Xing Li, Xin-Yu Bi, Hong Zhao, Zhen Huang, Yue Han, Dong-Bin Zhao, Jian-Jun Zhao, and Jian-Qiang Cai
Subjects: Colorectal Cancer, Excision Repair Cross-complementation Group 1, Prognosis, Medicine
Abstract: Background: Conflicting results about the association between expression level of excision repair cross-complementation group 1 (ERCC1) and clinical outcome in patients with colorectal cancer (CRC) receiving chemotherapy have been reported. Thus, we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC. Methods: A thorough literature search using PubMed (Medline), Embase, Cochrane Library, Web of Science databases, and Chinese Science Citation Database was conducted to obtain the relevant studies. Pooled hazard ratios (HR s) or odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the results. Results: A total of 11 studies were finally enrolled in this meta-analysis. Compared with patients with lower ERCC1 expression, patients with higher ERCC1 expression tended to have unfavorable overall survival (OS) (HR = 2.325, 95% CI: 1.720–3.143, P < 0.001), progression-free survival (PFS) (HR = 1.917, 95% CI: 1.366–2.691, P < 0.001) and poor response to chemotherapy (OR = 0.491, 95% CI: 0.243–0.990, P = 0.047). Subgroup analyses by treatment setting, ethnicity, HR extraction, detection methods, survival analysis, and study design demonstrated that our results were robust. Conclusions: ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy, OS, and PFS. Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC1's prognostic value.
Published: 2016
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25. Evaluation of Eight Different Clinical Staging Systems Associated with Overall Survival of Chinese Patients with Hepatocellular Carcinoma

Author: Jian-Jun Zhao, Tao Yan, Hong Zhao, Jian-Guo Zhou, Zhen Huang, Ye-Fan Zhang, Yuan Li, Zhi-Yu Li, Xin-Yu Bi, and Jian-Qiang Cai
Subjects: Chinese Population, Clinical Staging Ssystem, Hepatocellular Carcinoma, Survival, Medicine
Abstract: Background: Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients. Methods: This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic. Results: The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7 th (TNM 7 th ) (AIC = 2899.980), TNM 6 th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389). Conclusions: BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.
Published: 2015
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26. A unified approach for determining the ultimate strength of RC members subjected to combined axial force, bending, shear and torsion.

Author: Pu Wang and Zhen Huang
Subjects: Medicine, Science
Abstract: This paper uses experimental investigation and theoretical derivation to study the unified failure mechanism and ultimate capacity model of reinforced concrete (RC) members under combined axial, bending, shear and torsion loading. Fifteen RC members are tested under different combinations of compressive axial force, bending, shear and torsion using experimental equipment designed by the authors. The failure mechanism and ultimate strength data for the four groups of tested RC members under different combined loading conditions are investigated and discussed in detail. The experimental research seeks to determine how the ultimate strength of RC members changes with changing combined loads. According to the experimental research, a unified theoretical model is established by determining the shape of the warped failure surface, assuming an appropriate stress distribution on the failure surface, and considering the equilibrium conditions. This unified failure model can be reasonably and systematically changed into well-known failure theories of concrete members under single or combined loading. The unified calculation model could be easily used in design applications with some assumptions and simplifications. Finally, the accuracy of this theoretical unified model is verified by comparisons with experimental results.
Published: 2017
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27. Driving style recognition method using braking characteristics based on hidden Markov model.

Author: Chao Deng, Chaozhong Wu, Nengchao Lyu, and Zhen Huang
Subjects: Medicine, Science
Abstract: Since the advantage of hidden Markov model in dealing with time series data and for the sake of identifying driving style, three driving style (aggressive, moderate and mild) are modeled reasonably through hidden Markov model based on driver braking characteristics to achieve efficient driving style. Firstly, braking impulse and the maximum braking unit area of vacuum booster within a certain time are collected from braking operation, and then general braking and emergency braking characteristics are extracted to code the braking characteristics. Secondly, the braking behavior observation sequence is used to describe the initial parameters of hidden Markov model, and the generation of the hidden Markov model for differentiating and an observation sequence which is trained and judged by the driving style is introduced. Thirdly, the maximum likelihood logarithm could be implied from the observable parameters. The recognition accuracy of algorithm is verified through experiments and two common pattern recognition algorithms. The results showed that the driving style discrimination based on hidden Markov model algorithm could realize effective discriminant of driving style.
Published: 2017
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28. Gua Sha, a press-stroke treatment of the skin, boosts the immune response to intradermal vaccination

Author: Tingting Chen, Ninghua Liu, Jinxuan Liu, Xiaoying Zhang, Zhen Huang, Yuhui Zang, Jiangning Chen, Lei Dong, Junfeng Zhang, and Zhi Ding
Subjects: Gua Sha, Skin immune system, Skin scrape, Intradermal vaccination, Physical adjuvant, Surface microcirculation, Medicine, Biology (General), QH301-705.5
Abstract: Objective The skin is an important immunological barrier of the body as well as an optimal route for vaccine administration. Gua Sha, which involves press-stroke treatment of the skin, is an effective folk therapy, widely accepted in East Asia, for various symptoms; however, the mechanisms underlying its therapeutic effects have not been clarified. We investigated the influence of Gua Sha on the immunological features of the skin. Methods Gua Sha was performed on BALB/c mice and the effects were evaluated using anatomical, histological, and cytometric methods as well as cytokine determination locally and systemically. The effect on intradermal vaccination was assessed with antigen-specific subtype antibody responses. Results Blood vessel expansion, erythrocyte extravasation, and increased ratios of immune active cells were observed in the skin tissue following the treatment. Pro-inflammatory cytokines were up-regulated, and immunosuppressive cytokines, down-regulated, in the treated and untreated skin and systemic circulation; no obvious variations were detected in case of anti-inflammatory cytokines. Interestingly, intradermal delivery of a model vaccine following Gua Sha induced about three-fold higher IgG titers with a more Th1-biased antibody subtype profile. Conclusion Gua Sha treatment can up-regulate the innate and adaptive immune functions of the skin and boost the response against intradermal antigens. Thus, Gua Sha may serve as a safe, inexpensive, and independent physical adjuvant for intradermal vaccination.
Published: 2016
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29. Identification of Genome-Wide Variants and Discovery of Variants Associated with Brassica rapa Clubroot Resistance Gene Rcr1 through Bulked Segregant RNA Sequencing.

Author: Fengqun Yu, Xingguo Zhang, Zhen Huang, Mingguang Chu, Tao Song, Kevin C Falk, Abhinandan Deora, Qilin Chen, Yan Zhang, Linda McGregor, Bruce D Gossen, Mary Ruth McDonald, and Gary Peng
Subjects: Medicine, Science
Abstract: Clubroot, caused by Plasmodiophora brassicae, is an important disease on Brassica species worldwide. A clubroot resistance gene, Rcr1, with efficacy against pathotype 3 of P. brassicae, was previously mapped to chromosome A03 of B. rapa in pak choy cultivar "Flower Nabana". In the current study, resistance to pathotypes 2, 5 and 6 was shown to be associated with Rcr1 region on chromosome A03. Bulked segregant RNA sequencing was performed and short read sequences were assembled into 10 chromosomes of the B. rapa reference genome v1.5. For the resistant (R) bulks, a total of 351.8 million (M) sequences, 30,836.5 million bases (Mb) in length, produced 120-fold coverage of the reference genome. For the susceptible (S) bulks, 322.9 M sequences, 28,216.6 Mb in length, produced 109-fold coverage. In total, 776.2 K single nucleotide polymorphisms (SNPs) and 122.2 K insertion / deletion (InDels) in R bulks and 762.8 K SNPs and 118.7 K InDels in S bulks were identified; each chromosome had about 87% SNPs and 13% InDels, with 78% monomorphic and 22% polymorphic variants between the R and S bulks. Polymorphic variants on each chromosome were usually below 23%, but made up 34% of the variants on chromosome A03. There were 35 genes annotated in the Rcr1 target region and variants were identified in 21 genes. The numbers of poly variants differed significantly among the genes. Four out of them encode Toll-Interleukin-1 receptor / nucleotide-binding site / leucine-rich-repeat proteins; Bra019409 and Bra019410 harbored the higher numbers of polymorphic variants, which indicates that they are more likely candidates of Rcr1. Fourteen SNP markers in the target region were genotyped using the Kompetitive Allele Specific PCR method and were confirmed to associate with Rcr1. Selected SNP markers were analyzed with 26 recombinants obtained from a segregating population consisting of 1587 plants, indicating that they were completely linked to Rcr1. Nine SNP markers were used for marker-assisted introgression of Rcr1 into B. napus canola from B. rapa, with 100% accuracy in this study.
Published: 2016
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30. Enhancing Protein Expression in HEK-293 Cells by Lowering Culture Temperature.

Author: Chi-Yen Lin, Zhen Huang, Wei Wen, Andrew Wu, Congzhou Wang, and Li Niu
Subjects: Medicine, Science
Abstract: Animal cells and cell lines, such as HEK-293 cells, are commonly cultured at 37°C. These cells are often used to express recombinant proteins. Having a higher expression level or a higher protein yield is generally desirable. As we demonstrate in this study, dropping culture temperature to 33°C, but not lower, 24 hours after transient transfection in HEK-293S cells will give rise to ~1.5-fold higher expression of green fluorescent protein (GFP) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. By following the time course of the GFP-expressing cells growing at 37°C and 33°C from 24 hours after transfection (including 19 hours recovery at 37°C in the normal growth medium), we found that a mild hypothermia (i.e., 33°C) reduces the growth rate of HEK-293S cells, while increasing cellular productivity of recombinant proteins. As a result, green cells remain undivided in a longer period of time. Not surprisingly, the property of a recombinant protein expressed in the cells grown at 33°C is unaffected, as shown by the use of AMPA receptors. We further demonstrate with the use of PC12 cells that this method may be especially useful when a recombinant protein is difficult to express using a chemical-based, transient transfection method.
Published: 2015
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31. Prognostic Role of Phospho-STAT3 in Patients with Cancers of the Digestive System: A Systematic Review and Meta-Analysis.

Author: Mu-xing Li, Xin-yu Bi, Zhen Huang, Jian-jun Zhao, Yue Han, Zhi-Yu Li, Ye-fan Zhang, Yuan Li, Xiao Chen, Xu-hui Hu, Hong Zhao, and Jian-qiang Cai
Subjects: Medicine, Science
Abstract: The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers.We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated.A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR = 1.809, 95% CI: 1.442-2.270, P < 0.001) and DFS (HR = 1.481, 95% CI: 1.028-2.133, P = 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) = 1.895, 95% CI: 1.364-2.632, P < 0.001) and lymph node metastases (OR = 2.108, 95% CI: 1.104-4.024, P = 0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was no significant publication bias in the meta-analysis.Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3.
Published: 2015
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32. Upregulated UHRF1 promotes bladder cancer cell invasion by epigenetic silencing of KiSS1.

Author: Yu Zhang, Zhen Huang, Zhiqiang Zhu, Xin Zheng, Jianwei Liu, Zhiyou Han, Xuetao Ma, and Yuhai Zhang
Subjects: Medicine, Science
Abstract: Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), as an epigenetic regulator, plays important roles in the tumorigenesis and cancer progression. KiSS1 functions as a metastasis suppressor in various cancers, and epigenetic silencing of KiSS1 increases the metastatic potential of cancer cells. We therefore investigated whether UHRF1 promotes bladder cancer cell invasion by inhibiting KiSS1. The expression levels of UHRF1 and KiSS1 were examined by quantitative real-time PCR assay in vitro and in vivo. The role of UHRF1 in regulating bladder cancer metastasis was evaluated in bladder cancer cell. We found that UHRF1 levels are upregulated in most clinical specimens of bladder cancer when compared with paired normal tissues, and UHRF1 expression levels are significantly increased in primary tumors that subsequently metastasized compared with non-metastatic tumors. Forced expression of UHRF1 promotes bladder cancer cell invasion, whereas UHRF1 knockdown decreases cell invasion. Overexpression of UHRF1 increases the methylation of CpG nucleotides and reduces the expression of KiSS1. UHRF1 and KiSS1 expression level is negatively correlated in vivo and in vitro. Knockdown of KiSS1 promotes bladder cancer cell invasion. Importantly, forced expression of KiSS1 partly abrogates UHRF1-induced cell invasion. These data demonstrated that upregulated UHRF1 increases bladder cancer cell invasion by epigenetic silencing of KiSS1.
Published: 2014
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33. Variants identified by hepatocellular carcinoma and chronic hepatitis B virus infection susceptibility GWAS associated with survival in HBV-related hepatocellular carcinoma.

Author: Cong Li, Xinyu Bi, Ying Huang, Jianjun Zhao, Zhiyu Li, Jianguo Zhou, Meng Zhang, Zhen Huang, Hong Zhao, and Jianqiang Cai
Subjects: Medicine, Science
Abstract: Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of hepatocellular carcinoma (HCC) or chronic hepatitis B infection (CHB). However, the relationship between these genetic variants and survival of patients with hepatitis B virus (HBV)-related HCC is still unknown. In this study, 22 single nucleotide polymorphisms (SNPs) were genotyped among 330 HBV-related HCC patients using the MassARRAY system from Sequenom. Cox proportional hazards regression was used to examine the effects of genotype on survival time under an additive model with age, sex, smoking status and clinical stage as covariates. We identified four SNPs on 6p21 (rs1419881 T>C, rs7453920 G>A,rs3997872 G>A and rs7768538 T>C), and two SNPs on 8p12 (rs2275959 C>T and rs7821974 C>T) significantly associated with survival time of HBV-related HCC patients. Our results suggest that HCC or CHB susceptibility loci might also affect the prognosis of patients with HBV-related HCC.
Published: 2014
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34. Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

Author: Manoj Bhasin, Zhen Huang, Leena Pradhan-Nabzdyk, Junaid Y Malek, Philip J LoGerfo, Mauricio Contreras, Patrick Guthrie, Eva Csizmadia, Nicholas Andersen, Olivier Kocher, Christiane Ferran, and Frank W LoGerfo
Subjects: Medicine, Science
Abstract: Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC) and medial smooth muscle cells (SMC) from canine vein grafts, 2 hours (H) to 30 days (D) following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1) signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR) as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1), a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.
Published: 2012
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35. A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain.

Author: Shang Ma, Hyo Jun Kwon, and Zhen Huang
Subjects: Medicine, Science
Abstract: Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development.
Published: 2012
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36. Correction: Prolonged Mechanical Ventilation Induces Cell Cycle Arrest in Newborn Rat Lung.

Author: Andreas A. Kroon, Jinxia Wang, Brian Kavanagh, Zhen Huang, Maciej Kuliszewski, Johannes B. van Goudoever, and Martin Post
Subjects: Medicine, Science
Published: 2011
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37. Prolonged mechanical ventilation induces cell cycle arrest in newborn rat lung.

Author: Andreas A Kroon, Jinxia Wang, Brian P Kavanagh, Zhen Huang, Maciej Kuliszewski, Johannes B van Goudoever, and Martin Post
Subjects: Medicine, Science
Abstract: RATIONALE: The molecular mechanism(s) by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. OBJECTIVE: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. METHODS: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg⁻¹). MEASUREMENT AND MAIN RESULTS: Ventilation for 24 h (h) decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation) was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27(Kip1) was significantly increased. Mechanical ventilation for 24 h also increased levels of p57(Kip2), decreased that of p16(INK4a), while the levels of p21(Waf/Cip1) and p15(INK4b) were unchanged. Increased p27(Kip1) expression coincided with reduced phosphorylation of p27(Kip1) at Thr¹⁵⁷, Thr¹⁸⁷ and Thr¹⁹⁸ (p
Published: 2011
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38. Comparable survival benefit of local excision versus radical resection for 10- to 20-mm rectal neuroendocrine tumors

Author: Zhen Huang, Jinghua Chen, Hong Zhao, Qichen Chen, and Jianqiang Cai
Subjects: Male, Local excision, medicine.medical_specialty, Urology, Neuroendocrine tumors, Epidemiology, medicine, Humans, Stage (cooking), Propensity Score, Neoplasm Staging, Proportional Hazards Models, Rectal Neoplasms, business.industry, General Medicine, Middle Aged, medicine.disease, Predictive factor, Neuroendocrine Tumors, Survival benefit, Oncology, Propensity score matching, Surgery, Radical resection, business, SEER Program
Abstract: The optimal surgical management for 10- to 20-mm rectal neuroendocrine tumors (RNET) is still a matter of debate. This study aimed to explore the optimal surgical approach for 10- to 20-mm RNET by comparing the outcomes between local excision and radical resection.We extracted clinicopathological information of 10- to 20-mm RNET from the Surveillance, Epidemiology, and End Results (SEER) database. The 1:2 propensity score matching (PSM) method was used to balance the imbalanced baseline covariates (P 0.05) between the local excision group and radical resection group. A Cox proportional hazards model was used to identify the risk factors associated with cancer-specific survival (CSS) and overall survival (OS).A total of 531 RNET patients 10-20 mm in size were included. Patients receiving radical resection had larger tumor sizes (P 0.001), higher T stages (P 0.001), higher N stages (P 0.001), higher M stages (P = 0.002) and higher grades (P = 0.041). For 10-20 mm RNET patients, radical resection had no survival benefit compared with local excision (CSS: HR = 2.048, 95% CI 0.553-7.576, P = 0.283; OS: HR = 1.090, 95% CI 0.535-2.219, P = 0.813). After 1:2 PSM, there was no significant difference between local excision and radical resection. Radical resection still had no survival benefit over local excision (CSS: HR = 0.449, 95% CI 0.050-4.022, P = 0.474; OS: HR = 1.408, 95% CI 0.488-4.061, P = 0.527). In a multivariate analysis of CSS, age60 years old (P = 0.005), tumour size 14-20 mm (P = 0.011) and M1 stage (P 0.001) were identified as independent prognostic factors for worse CSS. In multivariate analysis of OS, age60 years (P＜0.001), male sex (P = 0.007), black race (P = 0.016), and T2/T3/T4 stage (P = 0.007) were significantly associated with worse OS. N stage was not an independent predictive factor for CSS and OS.This study revealed that for 10- to 20-mm RNET patients, there was no survival benefit for radical resection compared with local excision, which suggested that local excision may be an adequate treatment for these patients.
Published: 2022

39. Mutation of a prenyltransferase results in accumulation of subglutinols and destruxins and enhanced virulence in the insect pathogen, Metarhizium anisopliae

Author: Chengzhou Li, Shuaishuai Huang, Song Huang, Qian Zhao, Ping Qi, Nemat O. Keyhani, Zhen Huang, Tingting Zhou, Peiquan Huang, and Wenyou Huang
Subjects: Metarhizium, Insecta, Virulence, biology, fungi, Prenyltransferase, Mutant, Wild type, Metarhizium anisopliae, Secondary metabolite, Dimethylallyltranstransferase, biology.organism_classification, Microbiology, Insect toxin, Mutation, medicine, Animals, Pathogen, Ecology, Evolution, Behavior and Systematics, medicine.drug
Abstract: The insect pathogenic fungus, Metarhizium anisopliae is a commercialized microbial agent used in biological control efforts targeting a diverse range of agricultural and other insect pests. The second step in the synthesis of a group of M. anisopliae α-pyrone diterpenoids (termed subglutinols) involves the activity of a prenyltransferase family geranylgeranyl diphosphate synthase (product of the subD/MaGGPPS5 gene). Here, we show that targeted gene disruption of MaGGPPS5 results in earlier conidial germination and faster greater vegetative growth as compared to the wild type parent and complemented strains. In addition, insect bioassays revealed that the ΔMaGGPPS5 mutant strain displayed significantly increased virulence, with a ~ 50% decrease in the mean lethal time (LT50 , from 6 to 3 d) to kill (50% of) target insects, and an ~15-40-fold decrease in the mean lethal dose (LC50 ). Metabolite profiling indicated increased accumulation in the ΔMaGGPPS5 mutant of select subglutinols (A, B, and C) and destruxins (A, A2, B, and B2), the latter a set of fungal secondary metabolites that act as insect toxins, with a concomitant loss of production of subglutinol 'analog 45'. These data suggest that the increased virulence phenotype seen for the ΔMaGGPPS5 strain can, at least in part, be attributed to a combination of faster growth and increased insect toxin production, linking the production of two different secondary metabolite pathways, and represents a novel approach for the screening of isolates with enhanced virulence via modulation of terpenoid secondary metabolite biosynthesis. This article is protected by copyright. All rights reserved.
Published: 2021

40. Astragalus polysaccharide ameliorates steroid‐induced osteonecrosis of femoral head through miR‐206/HIF‐1α/BNIP3 axis

Author: Shen-Yao Zhang, Zhen Huang, Ke-Fang Dong, Fan Wang, and Xiang-Jing Zeng
Subjects: Medicine (General), BNIP3, Cell, steroid‐induced osteonecrosis of the femoral head, Apoptosis, Flow cytometry, Mice, R5-920, Western blot, Downregulation and upregulation, Femur Head Necrosis, Polysaccharides, Proto-Oncogene Proteins, microRNA, Autophagy, medicine, Animals, Humans, astragalus polysaccharide, Glucocorticoids, Cells, Cultured, Gene knockdown, medicine.diagnostic_test, business.industry, HIF‐1α, Membrane Proteins, miR‐206, Astragalus Plant, General Medicine, Hypoxia-Inducible Factor 1, alpha Subunit, Cell biology, MicroRNAs, medicine.anatomical_structure, business
Abstract: Declining autophagy and rising apoptosis are the main factors driving the development of steroid‐induced osteonecrosis of the femoral head (SONFH). Here, we showed that astragalus polysaccharide (APS) improved femoral head necrosis via regulation of cell autophagy and apoptosis through microRNA (miR)‐206/hypoxia inducible factor‐1 (HIF‐1α)/BCL2 interacting protein 3 (BNIP3) axis. The expression of miR‐206, HIF‐1α, and BNIP3 in SONFH specimens and cell model were measured using qPCR. SONFH cell model was treated with APS. Cell autophagy was evaluated using LC3‐immunofluorescence assays. Flow cytometry was conducted to assess cell apoptosis. Apoptosis‐related proteins and autophagy‐related proteins were determined using western blot. Besides, dual‐luciferase reporter assay was employed to investigate the relationship between miR‐206 and HIF‐1α. Here we showed that miR‐206 expression was upregulated in SONFH tissues and cell model. APS promoted autophagy and inhibited apoptosis in SONFH cell model via downregulating miR‐206. What is more, HIF‐1α was the target of miR‐206. Knockdown of HIF‐1α reversed the recovery effect of miR‐206 inhibitor on SONFH cell model. Furthermore, BNIP3 was the target of HIF‐1α. HIF‐1α overexpression promoted autophagy and inhibited apoptosis, and knockdown of BNIP3 abolished the recovery effect of HIF‐1α overexpression in SONFH cell model. These results provided evidence that APS reduced miR‐206 expression, and the downregulated miR‐206 increased BNIP3 expression by targeting HIF‐1α to promote autophagy and inhibit bone cell apoptosis. Our research proved that APS effectively improved SONFH by regulating cell autophagy and apoptosis.
Published: 2021

41. Medical-Level Suicide Risk Analysis: A Novel Standard and Evaluation Model

Author: Qiao Yu, Long Hu, Zhongchun Liu, Bing Xiang Yang, Kai Hwang, Yujun Ma, Simeng Ma, Xiaofen Zong, Zhen Huang, Peilin Wang, and Rui Wang
Subjects: medicine.medical_specialty, Warning system, Computer Networks and Communications, Computer science, Public health, media_common.quotation_subject, Feature extraction, Applied psychology, Timeline, Computer Science Applications, Identification (information), Hardware and Architecture, Perception, Signal Processing, medicine, Baseline (configuration management), Information Systems, Medical literature, media_common
Abstract: The frequent occurrence of suicides in modern society constitutes a serious public health issue. While the motives, methods, and consequences of suicide are quite complicated, if people at risk of suicide can be identified and intervened in time, the loss of life can be reduced. Through analyses based on combining a large number of suicide texts and professional medical literature, a dictionary of potential suicide risk impact factors has been established in this article. Based on this dictionary, a novel medical-level suicide risk standard is proposed to monitor suicide risk from point-to-surface under the timeline baseline. In order to solve the problem of insufficient Chinese suicide data sets, the manually assisted method based on knowledge perception is adopted to annotate the data set with corresponding to risk level. At the same time, a Bert evaluation model based on knowledge perception was established for the classification of risk level. The experimental results showed that proposed method has a 56% recognition accuracy in the prediction of 10-Label suicide risk level proposed in this article, and the classification performance is better than traditional machine learning algorithms. Therefore, the results showed that the classification standard and evaluation model can be effectively used for the identification and early warning of suicide risk, which can discover high suicide risk groups to reduce the occurrence of suicide. It is of great significance to people’s emotion care monitoring.
Published: 2021

42. Prognostic role of the recepteur d'origine nantais (RON) expression in primary high-grade osteosarcoma

Author: Renqin Lin, Kai Shi, Zhen Huang, Jianhua Lin, Hongxiang Wei, Shenglin Wang, and Dan-Feng Weng
Subjects: musculoskeletal diseases, Oncology, Malignant bone tumor, medicine.medical_specialty, medicine.medical_treatment, Proto-Oncogene Mas, Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, Glucans, Osteosarcoma, Chemotherapy, business.industry, Proportional hazards model, Receptor Protein-Tyrosine Kinases, Distant metastasis, Bone metastasis, Prognosis, medicine.disease, Immunohistochemistry, Exact test, Surgery, business
Abstract: Background Osteosarcoma is a common primary malignant bone tumor susceptible to distant metastasis. The clinical outcome for patients remains poor due to the resistance to chemotherapy and lacking effective therapeutic targets. Recepteur d'origine nantais (RON), a transmembrane protein of the c-MET proto-oncogene family, has been reported to contribute to the malignant progression and bone metastasis in several tumors. The present study aimed to explore the prognostic significance of RON in primary high-grade osteosarcoma. Methods Immunohistochemistry (IHC) and western blotting (WB) were used to investigate the protein expression of RON in 80 surgically resected specimens (50 high-grade osteosarcoma specimens and 30 non-neoplastic bone tissues) and 6 cell lines. The χ2 test or independent-sample Student's t-test was used to assess the significance of RON difference between osteosarcoma and non-neoplastic bone tissues. The χ2 test and Fisher's exact test were used to analyze the association of RON with the clinicopathological features of osteosarcoma patients. Kaplan–Meier method and Cox proportional hazards model were used to assess the significance of RON for the survival of osteosarcoma patients. Results The results of IHC and WB observed significant overexpression of RON in osteosarcoma specimens (P Conclusions The present study demonstrated that high expression of RON held independent value for unfavorable survival in primary high-grade osteosarcoma. Its potential role as a therapeutic target for osteosarcoma treatment deserves further research.
Published: 2021

43. Deregulation of circ_003912 contributes to pathogenesis of erosive oral lichen planus by via sponging microRNA-123, -647 and -31 and upregulating FOXP3

Author: Wenjuan Wang, Ting Sang, Zikun Huang, Shaobo Ouyang, Fen Liu, Lan Liao, Jun Wu, and Zhen Huang
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, Microarray, THP-1 Cells, FOXP3, RM1-950, QD415-436, Biology, T-Lymphocytes, Regulatory, Biochemistry, Proinflammatory cytokine, Pathogenesis, Western blot, microRNA, Genetics, medicine, Humans, circRNA, RNA, Messenger, CD4+ Treg cells, Molecular Biology, Genetics (clinical), medicine.diagnostic_test, Forkhead Transcription Factors, RNA, Circular, Middle Aged, medicine.disease, Molecular medicine, Up-Regulation, miR-146a, MicroRNAs, Gene Expression Regulation, Oral lichen planus, Cancer research, Molecular Medicine, Cytokines, Female, RNA Interference, Therapeutics. Pharmacology, TRAF6, Lichen Planus, Oral, Signal Transduction, Research Article
Abstract: BackgroundThe FOXP3/miR-146a/NF-κB axis was previously reported to modulate the induction and function of CD4+ Treg cells to alleviate oral lichen planus. Also, other signaling pathways including microRNA-155-IFN-γ loop and FOXP3/miR-146a/TRAF6 pathways were reported to be involved in the pathogenesis of oral lichen planus. In this study, we aimed to investigate the molecular mechanism underlying the pathogenesis of EOLP.MethodCircRNA microarray was used to observe the expression of candidate circRNAs in CD4+ T-cells collected from different groups. Real-time PCR and Western blot were conducted to observe the changes in the expression of different miRNAs, mRNAs and proteins. Flow cytometry was performed to compare the counts of Treg cells in the HC and EOLP groups, and ELISA was performed to evaluate the changes in the expression of inflammatory cytokines.ResultNo obvious differences were seen between the HC and EOLP groups in terms of age and gender. Among all candidate circRNAs, the expression of circ_003912 was most dramatically elevated in CD4+ T-cells collected from the EOLP group. The levels of miR-1231, miR-31, miR-647, FOXP3 mRNA and miR-146a were decreased while the expression of TRAF6 mRNA was increased in CD4+ T-cells collected from the EOLP group. The count of Treg cells in the EOLP group was dramatically increased. The levels of inflammatory cytokines including IL-4 IFN-γ, IL-10 and IL-2 were influenced by the presence of circ_003912. In CD4+ T-cells in the EOLP group, the levels of IL-4 and IL-10 were decreased while the levels of IFN-γ and IL-2 were increased. The presence of miR-1231, miR-31 and miR-647 all obviously inhibited the expression of circ_003912, which was validated to sponge the expression of above miRNAs. Also, FOXP3 mRNA was proved to be targeted by miR-1231, miR-31 and miR-647. Transfection of circ_003912 up-regulated the expression of circ_003912, miR-146a and FOXP3 mRNA/protein while down-regulating the expression of miR-1231, miR-31, miR-647, and TRAF6 mRNA/protein. The levels of inflammatory cytokines including IL-4 IFN-γ, IL-10 and IL-2 as well as the speed of cell proliferation were influenced by circ_003912.ConclusionIn this study, we investigated the molecular mechanisms underlying the pathogenesis of EOLP which involved the functioning of circ_003912. We first demonstrated that circ_003912 was up-regulated in CD4+ T-cells of the EOLP group. And miRNAs including miR-1231, miR-31 and miR-647 were sponged by circ_003912 and down-regulated in CD4+ T cells of the EOLP group, which subsequently up-regulated the expression of FOXP3 and miR-146a, and resulted in the inhibition of NF-kB.
Published: 2021

44. Development of a random forest model for hypotension prediction after anesthesia induction for cardiac surgery

Author: Jing-Ying Tang, Xiao-Qi Wang, Yong-Zhen Huang, Xuan-Fa Li, and Rui-Chen Li
Subjects: medicine.medical_specialty, business.industry, Hypotension prediction, General Medicine, Cardiac surgery, Random forest, Retrospective Study, Anesthesia, Machine learning, cardiovascular system, Medicine, Anesthesia induction, business
Abstract: BACKGROUND Hypotension after the induction of anesthesia is known to be associated with various adverse events. The involvement of a series of factors makes the prediction of hypotension during anesthesia quite challenging. AIM To explore the ability and effectiveness of a random forest (RF) model in the prediction of post-induction hypotension (PIH) in patients undergoing cardiac surgery. METHODS Patient information was obtained from the electronic health records of the Second Affiliated Hospital of Hainan Medical University. The study included patients, ≥ 18 years of age, who underwent cardiac surgery from December 2007 to January 2018. An RF algorithm, which is a supervised machine learning technique, was employed to predict PIH. Model performance was assessed by the area under the curve (AUC) of the receiver operating characteristic. Mean decrease in the Gini index was used to rank various features based on their importance. RESULTS Of the 3030 patients included in the study, 1578 (52.1%) experienced hypotension after the induction of anesthesia. The RF model performed effectively, with an AUC of 0.843 (0.808-0.877) and identified mean blood pressure as the most important predictor of PIH after anesthesia. Age and body mass index also had a significant impact. CONCLUSION The generated RF model had high discrimination ability for the identification of individuals at high risk for a hypotensive event during cardiac surgery. The study results highlighted that machine learning tools confer unique advantages for the prediction of adverse post-anesthesia events.
Published: 2021

45. Targeted truncated TGF-β receptor type II delivery to fibrotic liver by PDGFβ receptor-binding peptide modification for improving the anti-fibrotic activity against hepatic fibrosis in vitro and in vivo

Author: Minglu Ding, Zhen Huang, Yanhui Chu, Xudong Song, Xiaohua Wang, Yong Liu, Hua Feng, Manman Ma, Zhihan Gao, Huilin Guan, Yixin Dong, and Haifeng Liu
Subjects: Liver Cirrhosis, Recombinant Fusion Proteins, medicine.medical_treatment, Genetic Vectors, Biochemistry, Receptor, Platelet-Derived Growth Factor beta, Mice, Structural Biology, In vivo, Fibrosis, Cell Line, Tumor, medicine, Animals, Carbon Tetrachloride, Molecular Biology, Peptide modification, Chemistry, Growth factor, Receptor, Transforming Growth Factor-beta Type II, General Medicine, medicine.disease, Small Ubiquitin-Related Modifier Proteins, Cancer research, Hepatic stellate cell, Liver function, Peptides, Hepatic fibrosis, Transforming growth factor
Abstract: Truncated transforming growth factor-β receptor type II (tTβRII) is a promising anti-fibrotic candidate because it attenuates excessive transforming growth factor-β1 (TGF-β1) and then blocks TGF-β1 activity in hepatic fibrosis. However, its use has been greatly limited due to the fact that it is expensive to chemically synthesize and it does not specifically target to the lesion site. In this study, we describe that platelet-derived growth factor β receptor (PDGFβR)-binding peptide BiPPB modified tTβRII (BiPPB-tTβRII) was prepared from the cleavage of SUMO-BiPPB-tTβRII by digestion with SUMO-specific protease. Moreover, compared to the unmodified tTβRII, the target protein BiPPB-tTβRII not only highly specific targeted activated hepatic stellate cells (HSCs) and fibrotic liver tissue, but also significantly inhibited the protein levels of fibrosis-related genes in TGF-β1-induced HSC-T6 cells and CCl4-induced liver fibrosis in mice. Furthermore, BiPPB-tTβRII markedly ameliorated liver morphology, fibrotic responses and the damage of liver function in fibrosis animal. More importantly, BiPPB-tTβRII showed a much lesser extent in binding to quiescent HSCs and non-fibrotic liver tissue. Taken together, our results suggested that the target protein BiPPB-tTβRII, with its high specific fibrotic liver-targeting potential and its improved anti-fibrotic activity in liver fibrosis, may be a potential therapeutic agent for liver fibrosis.
Published: 2021

46. The Clinical Significance of the Expression of FEN1 in Primary Osteosarcoma

Author: Jianhua Lin, Hongxiang Wei, Guang-Xian Zhong, Shenglin Wang, Huangfeng Lin, Jinlong Huang, Yunqing Wang, Zhen Huang, and Meifang Chen
Subjects: Oncology, medicine.medical_specialty, Poor prognosis, Univariate analysis, Multivariate analysis, business.industry, International Journal of General Medicine, General Medicine, medicine.disease, flap endonuclease 1, Primary osteosarcoma, Exact test, osteosarcoma, Internal medicine, immunohistochemistry, medicine, Immunohistochemistry, Osteosarcoma, Clinical significance, prognosis, business, neoplasms, Original Research
Abstract: Guangxian Zhong,1,&ast; Yunqing Wang,1,&ast; Hongxiang Wei,1 Meifang Chen,2 Huangfeng Lin,1 Zhen Huang,1 Jinlong Huang,3 Shenglin Wang,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, Peopleâs Republic of China; 2The Health Management Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, Peopleâs Republic of China; 3Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, Peopleâs Republic of China&ast;These authors contributed equally to this work.Correspondence: Jianhua Lin; Shenglin Wang Tel/Fax +86 591 87981029Email jianhual@126.com; Shenglinwang0216@163.comPurpose: The aim of this research was to investigate the clinical significance of the expression of flap structure-specific endonuclease 1 (FEN1) in primary osteosarcoma.Methods: The expression of FEN1 was detected by immunohistochemistry analysis. The association of the expression of FEN1 in osteosarcoma with clinicopathological parameters was analyzed by using Ï2 test or Fisherâs exact test. Survival analyses were performed by KaplanâMeier method and Cox proportional hazards regression model.Results: Of the 40 osteosarcoma patients, 19 (47.5%) patients presented with FEN1 high expression, while in the non-neoplastic bone specimens, the FEN1 high expression was observed in 10% (3/30), the positive expression rate in osteosarcoma patients was significantly higher than that of non-neoplastic bone specimens (P< 0.01). Univariate analysis indicated that the progression-free survival (PFS) and overall survival (OS) were correlated with the expression level of FEN1 (PFS, P < 0.001; OS, P = 0.002), Enneking staging (PFS, P = 0.026; OS, P = 0.044) and chemotherapy response (PFS, P = 0.019; OS, P = 0.031). Multivariate analysis demonstrated that FEN1 expression was an independent prognostic factor for the PFS (HR = 4.73, P = 0.002) and OS (HR = 4.01, P = 0.038) of osteosarcoma patients.Conclusion: This study showed that FEN1 was overexpressed in osteosarcoma patients and positively associated with poor prognosis of osteosarcoma patients. Further studies should focus on the relative mechanisms and the targeted FEN1 therapies for osteosarcoma.Keywords: osteosarcoma, flap endonuclease 1, immunohistochemistry, prognosis
Published: 2021

47. Differences of intraoperative outcomes and postoperative complications between intrahepatic cholangiocarcinoma and colorectal liver metastasis in different surgical methods

Author: Xinyu Bi, Jianguo Zhou, Jianjun Zhao, Jianqiang Cai, Jinghua Chen, Jianxiong Wu, Yiling Zheng, Liming Wang, Zhen Huang, Zhiyu Li, Yefan Zhang, Qichen Chen, and Hong Zhao
Subjects: Intrahepatic cholangiocarcinoma (IHCC), Cancer Research, medicine.medical_specialty, business.industry, medicine.disease, Surgical methods, Metastasis, hepatectomy, Oncology, Medicine, Original Article, postoperative complication, Radiology, Nuclear Medicine and imaging, Radiology, business, colorectal liver metastasis (CRLM), Intrahepatic Cholangiocarcinoma
Abstract: Background Hepatectomy is the only potentially curable treatment for intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastasis (CRLM). This study aimed to explore the difference in intraoperative outcomes and postoperative complications between IHCC and CRLM in different surgical methods including major hepatectomy and minor hepatectomy. Methods We included 319 patients with IHCC or CRLM who underwent hepatectomy at our hospital. According to major hepatectomy and minor hepatectomy, eligible patients were divided into two groups. In each group, the clinicopathological characteristics of IHCC and CRLM patients were compared, then propensity score matching (PSM) was performed based on the results. Intraoperative outcomes and postoperative complications were compared between IHCC and CRLM before and after PSM. Intraoperative variables, including intraoperative blood transfusion, duration of operation, and intraoperative blood loss, were used to evaluate the intraoperative conditions of patients. The postoperative complications were measured according to the Clavien-Dindo classification. Grade III to V complications were defined as major complications. Results The major hepatectomy group included 118 patients with IHCC and 93 patients with CRLM. IHCC patients presented a longer operation time and a higher postoperative complication rate than CRLM patients. The infection-related complication rate of the CRLM patients was significantly higher than the IHCC patients. In multivariate analysis, major hepatectomy for IHCC was independently associated with the presence of postoperative complications. The minor hepatectomy group included 146 IHCC patients and 62 CRLM patients. Compared with CRLM patients, IHCC patients presented a longer operation time. There was no significant difference in the intra-operative blood loss, postoperative complication rate, the major complications rate, and the minor complications rate between the IHCC patients and CRLM patients. Conclusions This study revealed major hepatectomy for IHCC led to significantly higher morbidity of postoperative complications than CRLM patients. For minor hepatectomy, there was no difference in postoperative complications between IHCC and CRLM. More attention should be paid to improving the preoperative planning and surgical management of hepatic malignancies especially in the setting of IHCC.
Published: 2021

48. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine 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Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020

49. Analysis of sleep characteristics and clinical outcomes of 139 adult patients with infective endocarditis after surgery

Author: Xiang-Ming Hu, Xiao-Ming Li, Fen Lu, Fu-Jun Jia, De-Yi Huang, Xue-Zhen Huang, Zhi-Hong Yu, Cai-Di Lin, Huo-Sheng Liao, Fang Huang, and W W Wei
Subjects: medicine.medical_specialty, Sleep quality, Adult patients, business.industry, Epworth Sleepiness Scale, Pittsburgh sleep quality index, Observational Study, Epworth sleepiness scale, General Medicine, medicine.disease, Sleep in non-human animals, Surgery, Pittsburgh Sleep Quality Index, Infective endocarditis, medicine, business
Abstract: BACKGROUND Little is known about the postoperative sleep quality of infective endocarditis patients during hospitalization and after discharge. AIM To investigate the sleep characteristics of infective endocarditis patients and to identify potential risk factors for disturbed sleep quality after surgery. METHODS The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale were used to assess patient sleep quality. Logistic regression was used to explore the potential risk factors. RESULTS The study population (n = 139) had an average age of 43.40 ± 14.56 years, and 67.6% were men (n = 94). Disturbed sleep quality was observed in 86 patients (61.9%) during hospitalization and remained in 46 patients (33.1%) at 6 mo after surgery. However, both PSQI and Epworth Sleepiness Scale scores showed significant improvements at 6 mo (P < 0.001 and P = 0.001, respectively). Multivariable logistic regression analysis showed that the potential risk factors were age (odds ratio = 1.125, 95% confidence interval: 1.068-1.186) and PSQI assessed during hospitalization (odds ratio = 1.759, 95% confidence interval: 1.436-2.155). The same analysis in patients with PSQI ≥ 8 during hospitalization suggested that not using sleep medication (odds ratio = 15.893, 95% confidence interval: 2.385-105.889) may be another risk factor. CONCLUSION The incidence of disturbed sleep after infective endocarditis surgery is high. However, the situation improves significantly over time. Age and early postoperative high PSQI score are risk factors for disturbed sleep quality at 6 mo after surgery.
Published: 2021

50. Whole-exome sequencing in osteosarcoma with distinct prognosis reveals disparate genetic heterogeneity

Author: Shanbo Cao, Renxian Wang, Huina Wang, Yongkun Yang, Yang Sun, Yanrui Zhang, Weifeng Liu, Xiaohui Niu, Zhen Huang, and Tao Jin
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Adolescent, Somatic cell, Biology, medicine.disease_cause, Germline, Genetic Heterogeneity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Exome Sequencing, Genetics, medicine, Humans, Mutation frequency, Child, Molecular Biology, Exome sequencing, Osteosarcoma, Mutation, Genome, Human, Genetic heterogeneity, Prognosis, medicine.disease, Primary tumor, Clone Cells, Child, Preschool, 030220 oncology & carcinogenesis, Female, Genes, Neoplasm, Signal Transduction
Abstract: The genomic profiles of osteosarcoma (OS) patients have been extensively investigated; however, the genetic prognostic biomarkers still remain unclear. In the present study, we analyzed the mutational profiles of pre-treatment primary tumor samples from 33 OS patients using whole exome sequencing (WES). These 33 OS patients were divided into two groups according to clinical outcomes: a good prognosis group involving 21 patients with tumor free survival, and a poor prognosis group involving the remaining12 patients who had lung metastases at initial diagnosis. Overall we found that the MAPK signaling pathway may play an important role in determining a good prognosis, while the PI3K-Akt signaling pathway may be an important factor leading to a poor prognosis. Significant differences were observed in the number of somatic copy number alterations, including del (3p), amp (4q), del (7p) and amp (8q), between the two groups. Moreover, significant differences were observed in mutation sites and frequencies between these two groups. The good prognosis group exhibited a significantly higher mutation frequency in somatic JAK-STAT and germline base excision repair pathways than the poor prognosis group. Furthermore, significant difference was also observed in the frequency of potentially actionable alterations between the two groups, suggesting that patients with a poor prognosis potentially have access to a larger number of treatment options. These findings highlight the importance of evaluating genomic disparities in OS, and provide a novel insight into the potential prognostic biomarkers.
Published: 2021

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