NobleBlocks

Xian Yang Central Hospital

Hospital / health systemXianyang, China

Research output, citation impact, and the most-cited recent papers from Xian Yang Central Hospital (China). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
9.8K
Citations
136.4K
h-index
103
i10-index
3.7K
Also known as
Second People's HospitalXian Yang Central Hospital咸阳市中心医院

Top-cited papers from Xian Yang Central Hospital

Chest CT for Typical Coronavirus Disease 2019 (COVID-19) Pneumonia: Relationship to Negative RT-PCR Testing
Xingzhi Xie, Zheng Zhong, Wei Zhao, Chao Zheng +2 more
2020· Radiology2.1Kdoi:10.1148/radiol.2020200343

Some patients with positive chest CT findings may present with negative results of real-time reverse-transcription polymerase chain reaction (RT-PCR) tests for coronavirus disease 2019 (COVID-19). In this study, the authors present chest CT findings from five patients with COVID-19 infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (five patients) and/or mixed ground-glass opacity and mixed consolidation (two patients). After isolation for presumed COVID-19 pneumonia, all patients were eventually confirmed to have COVID-19 infection by means of repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful for individuals with a high clinical suspicion of COVID-19 infection but negative findings at RT-PCR screening.

Performance of Radiologists in Differentiating COVID-19 from Non-COVID-19 Viral Pneumonia at Chest CT
Harrison X. Bai, B. R. Hsieh, Zeng Xiong, Kasey Halsey +4 more
2020· Radiology1.3Kdoi:10.1148/radiol.2020200823

ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.

Brief introduction of medical database and data mining technology in big data era
Jin Yang, Yuanjie Li, Qingqing Liu, Li Li +4 more
2020· Journal of Evidence-Based Medicine593doi:10.1111/jebm.12373

Data mining technology can search for potentially valuable knowledge from a large amount of data, mainly divided into data preparation and data mining, and expression and analysis of results. It is a mature information processing technology and applies database technology. Database technology is a software science that researches manages, and applies databases. The data in the database are processed and analyzed by studying the underlying theory and implementation methods of the structure, storage, design, management, and application of the database. We have introduced several databases and data mining techniques to help a wide range of clinical researchers better understand and apply database technology.

Artificial Intelligence Augmentation of Radiologist Performance in Distinguishing COVID-19 from Pneumonia of Other Origin at Chest CT
Harrison X. Bai, Robin Wang, Zeng Xiong, B. R. Hsieh +4 more
2020· Radiology400doi:10.1148/radiol.2020201491

= .001). Conclusion Artificial intelligence assistance improved radiologists' performance in distinguishing coronavirus disease 2019 pneumonia from non-coronavirus disease 2019 pneumonia at chest CT. © RSNA, 2020

Gut microbiota and aging
Zongxin Ling, Xia Liu, Yiwen Cheng, Xiumei Yan +1 more
2020· Critical Reviews in Food Science and Nutrition322doi:10.1080/10408398.2020.1867054

Aging is characterized by the functional decline of tissues and organs and increased risk of aging-associated disorders, which pose major societal challenges and are a public health priority. Despite extensive human genetics studies, limited progress has been made linking genetics with aging. There is a growing realization that the altered assembly, structure and dynamics of the gut microbiota actively participate in the aging process. Age-related microbial dysbiosis is involved in reshaping immune responses during aging, which manifest as immunosenescence (insufficiency) and inflammaging (over-reaction) that accompany many age-associated enteric and extraenteric diseases. The gut microbiota can be regulated, suggesting a potential target for aging interventions. This review summarizes recent findings on the physiological succession of gut microbiota across the life-cycle, the roles and mechanisms of gut microbiota in healthy aging, alterations of gut microbiota and aging-associated diseases, and the gut microbiota-targeted anti-aging strategies.

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease
Yumin Zhou, Nanshan Zhong, Xiaochen Li, Shuyun Chen +4 more
2017· New England Journal of Medicine290doi:10.1056/nejmoa1700228

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: before and after bronchodilator use from day 30 to month 24. RESULTS: after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics
Zhichao Feng, Qizhi Yu, Shanhu Yao, Lei Luo +4 more
2020· Nature Communications273doi:10.1038/s41467-020-18786-x

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.

Wnt/β-catenin-driven EMT regulation in human cancers
Wenhua Xue, Lin Yang, Chengxin Chen, Milad Ashrafizadeh +2 more
2024· Cellular and Molecular Life Sciences272doi:10.1007/s00018-023-05099-7

Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial-mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/β-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3β that destructs β-catenin, while ligand-receptor interaction impairs GSK-3β function to increase β-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/β-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance β-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/β-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/β-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression.

Traditional Chinese Medicine for Neck Pain and Low Back Pain: A Systematic Review and Meta-Analysis
Qiling Yuan, Tuanmao Guo, Liang Liu, Fu Sun +1 more
2015· PLoS ONE267doi:10.1371/journal.pone.0117146

BACKGROUND: Neck pain (NP) and low back pain (LBP) are common symptoms bothering people in daily life. Traditional Chinese medicine (TCM) has been used to treat various symptoms and diseases in China and has been demonstrated to be effective. The objective of the present study was to review and analyze the existing data about pain and disability in TCM treatments for NP and LBP. METHODS: Studies were identified by a comprehensive search of databases, such as MEDLINE, EMBASE, and Cochrane Library, up to September 1, 2013. A meta-analysis was performed to evaluate the efficacy and safety of TCM in managing NP and LBP. RESULTS: Seventy five randomized controlled trials (n = 11077) were included. Almost all of the studies investigated individuals experiencing chronic NP (CNP) or chronic LBP (CLBP). We found moderate evidence that acupuncture was more effective than sham-acupuncture in reducing pain immediately post-treatment for CNP (visual analogue scale (VAS) 10 cm, mean difference (MD) = -0.58 (-0.94, -0.22), 95% confidence interval, p = 0.01), CLBP (standardized mean difference = -0.47 (-0.77, -0.17), p = 0.003), and acute LBP (VAS 10 cm, MD = -0.99 (-1.24, -0.73), p< 0.001). Cupping could be more effective than waitlist in VAS (100 mm) (MD = -19.10 (-27.61, -10.58), p < 0. 001) for CNP or medications (e.g. NSAID) for CLBP (MD = -5.4 (-8.9, -0.19), p = 0.003). No serious or life-threatening adverse effects were found. CONCLUSIONS: Acupuncture, acupressure, and cupping could be efficacious in treating the pain and disability associated with CNP or CLBP in the immediate term. Gua sha, tai chi, qigong, and Chinese manipulation showed fair effects, but we were unable to draw any definite conclusions, and further research is still needed. The efficacy of tuina and moxibustion is unknown because no direct evidence was obtained. These TCM modalities are relatively safe.

Posttraumatic stress symptoms of health care workers during the corona virus disease 2019
Qianlan Yin, Zhuoer Sun, Tuanjie Liu, Xiong Ni +4 more
2020· Clinical Psychology & Psychotherapy247doi:10.1002/cpp.2477

Corona virus disease 2019 (COVID-19) outbreak has attracted worldwide attention. The COVID-19 outbreak is unique in its rapid transmission and results in heavy stress for the front-line health care workers (HCWs). The current study aimed to exam posttraumatic stress symptoms (PTSSs) of HCWs fighting for the COVID-19 and to evaluate their sleep quality after 1-month stressful suffering. Three hundred seventy-seven HCWs working in different provinces of China participated in the survey between February 1 and 5. The demographic information was collected first. Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) and the Pittsburgh Sleep Quality Index (PSQI) were selected to measure PTSSs and sleep quality. Results showed that 1 month after the outbreak, the prevalence of PTSSs was 3.8% in HCWs. Female HCWs were more vulnerable to PTSSs with hazard ratio of 2.136 (95% CI = 1.388-3.286). HCWs with higher exposure level also significantly rated more hyperarousal symptoms (hazard ratio = 4.026, 95% CI = 1.233-13.140). There was a significant difference of sleep quality between participants with and without PTSSs (z value = 6.014, p < .001) and among different groups with various contact frequencies (chi-square = 7.307, p = .026). Path analysis showed that there was a significant indirect effect from exposure level to PTSSs through sleep quality (coefficient = 1.750, 95% CI of Boostroop test = 0.543-2.998). In summary, targeted interventions on sleep contribute to the mental recovery during the outbreak of COVID-19. Understanding the mental health response after a public health emergency might help HCWs and communities prepare for a population's response to disaster.

[Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China].
Duan Wang, Xiuli Ju, Feng Xie, Yan Lu +4 more
2020· PubMed241doi:10.3760/cma.j.cn112140-20200225-00138

In this case series, 2019-nCoV infection in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis of 2019-nCoV infection. After general treatment, the short-term prognosis is good.

Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer's Disease
Zongxin Ling, Manlian Zhu, Xiumei Yan, Yiwen Cheng +4 more
2021· Frontiers in Cell and Developmental Biology232doi:10.3389/fcell.2020.634069

Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut–brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium , increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.

Chinese experts’ consensus on the Internet of Things-aided diagnosis and treatment of coronavirus disease 2019 (COVID-19)
Li Bai, Dawei Yang, Xun Wang, Tong Lin +4 more
2020· Clinical eHealth224doi:10.1016/j.ceh.2020.03.001

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study
Yu Yuan, Dan Xu, Shouzhi Fu, Jun Zhang +4 more
2020· Critical Care218doi:10.1186/s13054-020-02939-x

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.

Silver Nanoparticles and Growth Factors Incorporated Hydroxyapatite Coatings on Metallic Implant Surfaces for Enhancement of Osteoinductivity and Antibacterial Properties
Chaoming Xie, Xiong Lu, Kefeng Wang, Fanzhi Meng +4 more
2014· ACS Applied Materials & Interfaces204doi:10.1021/am501428e

Research on incorporation of both growth factors and silver (Ag) into hydroxyapatite (HA) coatings on metallic implant surfaces for enhancing osteoinductivity and antibacterial properties is a challenging work. Generally, Ag nanoparticles are easy to agglomerate and lead to a large increase in local Ag concentration, which could potentially affect cell activity. On the other hand, growth factors immobilization requires mild processing conditions so as to maintain their activities. In this study, bone morphology protein-2 (BMP-2) and Ag nanoparticle contained HA coatings were prepared on Ti surfaces by combining electrochemical deposition (ED) of Ag and electrostatic immobilization of BMP-2. During the ED process, chitosan (CS) was selected as the stabilizing agent to chelate Ag ions and generate Ag nanoparticles that are uniformly distributed in the coatings. CS also reduces Ag toxicity while retaining its antibacterial activity. Afterwards, a BMP/heparin solution was absorbed on the CS/Ag/HA coatings. Consequently, BMP-2 was immobilized on the coatings by the electrostatic attraction between CS, heparin, and BMP-2. Sustained release of BMP-2 and Ag ions from HA coatings was successfully demonstrated for a long period. Results of antibacterial tests indicate that the CS/Ag/HA coatings have high antibacterial properties against both Staphylococcus epidermidis and Escherichia coli. Osteoblasts (OB) culture reveals that the CS/Ag/HA coatings exhibit good biocompatibility. Bone marrow stromal cells (BMSCs) culture indicates that the BMP/CS/Ag/HA coatings have good osteoinductivity and promote the differentiation of BMSCs. Ti bars with BMP/CS/Ag/HA coatings were implanted into the femur of rabbits to evaluate the osteoinductivity of the coatings. Results indicate that BMP/CS/Ag/HA coatings favor bone formation in vivo. In summary, this study presents a convenient and effective method for the incorporation of growth factors and antibacterial agents into HA coatings. This method can be utilized to modify a variety of metallic implant surfaces.

NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages
Yangang Liu, Ji‐Kuai Chen, Zi-Teng Zhang, Xiu‐Juan Ma +4 more
2017· Cell Death and Disease196doi:10.1038/cddis.2016.460

A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation.

Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke
Dawei Chen, Yu Cui, Zhonghe Zhou, Hong Zhang +4 more
2023· JAMA191doi:10.1001/jama.2023.7827

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.

GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment
Pu Dai, Fei Yu, Bing Han, Xuezhong Liu +4 more
2009· Journal of Translational Medicine191doi:10.1186/1479-5876-7-26

BACKGROUND: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. METHODS: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. RESULTS: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. CONCLUSION: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary.

SIRT1 Regulates N6‐Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2‐Dependent FTO SUMOylation
Xiaoming Liu, Jianye Liu, Wen Xiao, Qinghai Zeng +4 more
2020· Hepatology176doi:10.1002/hep.31222

Background and Aims Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N 6 ‐methyladenosine (m 6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m 6 A modification to induce hepatocarcinogenesis remain unclear. Approach and Results Here we demonstrate that SIRT1 exerts an oncogenic role by down‐regulating fat mass and obesity‐associated protein (FTO), which is an m 6 A demethylase. A crucial component of small ubiquitin‐related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)‐216 site that promotes FTO degradation. Moreover, Guanine nucleotide‐binding protein G (o) subunit alpha (GNAO1) is identified as m 6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m 6 A + GNAO1 and down‐regulates its mRNA expression. Conclusions We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m 6 A + of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.

Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial
Hanren Dai, Chuan Tong, Daiwei Shi, Meixia Chen +4 more
2020· OncoImmunology173doi:10.1080/2162402x.2020.1846926

Expressed by cancer stem cells of various epithelial cell origins and hepatocellular carcinoma (HCC), CD133 is an attractive therapeutic target for HCC. The marker CD133 is highly expressed in endothelial progenitor cells (EPC). EPCs circulate in increased numbers in the peripheral blood of patients with highly vascularized HCC and contribute to angiogenesis and neovascularization. This phase II study investigated CD133-directed chimeric antigen receptor (CAR) T (CART-133) cells in adults with HCC. Patients with histologically confirmed and measurable advanced HCC and adequate hematologic, hepatic, and renal functions received CART-133 cell infusions. The primary endpoints were safety in phase I and progression-free survival (PFS) and overall survival (OS) in phase II. Other endpoints included biomarkers for CART-133 T cell therapy. Between June 1, 2015, and September 1, 2017, this study enrolled 21 patients who subsequently received CART-133 T cells across phases I and II. The median OS was 12 months (95% CI, 9.3-15.3 months) and the median PFS was 6.8 months (95% CI, 4.3-8.4 months). Of 21 evaluable patients, 1 had a partial response, 14 had stable disease for 2 to 16.3 months, and 6 progressed after T-cell infusion. The most common high-grade adverse event was hyperbilirubinemia. Outcome was correlated with the baseline levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR2), stromal cell-derived factor (SDF)-1, and EPC counts. Changes in EPC counts, VEGF, SDF-1, sVEGFR2, and interferon (IFN)-γ after cell infusion were associated with survival. In patients with previously treated advanced HCC, CART-133 cell therapy demonstrates promising antitumor activity and a manageable safety profile. We identified early changes in circulating molecules as potential biomarkers of response to CART-133 cells. The predictive value of these proangiogenic and inflammatory factors as potential biomarkers of CART-133 cell therapy in HCC will be explored in prospective trials. This study is registered at ClinicalTrials.gov (NCT02541370).