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  • BMJ  (6)
  • Wang, Jie  (6)
  • 1
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    Activated intestinal muscle cells promote preadipocyte migration: a novel mechanism for creeping fat formation in Crohn’s disease
    BMJ ; 2022
    In:  Gut Vol. 71, No. 1 ( 2022-01), p. 55-67
    Details
    In: Gut, BMJ, Vol. 71, No. 1 ( 2022-01), p. 55-67
    Abstract: Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn’s disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems. Design Tissues from normal, UC, non-strictured and strictured Crohn’s disease intestinal specimens were obtained. The muscularis propria matrisome was determined via proteomics. Mesenteric fat explants, primary human preadipocytes and adipocytes were used in multiple ex vivo and in vitro cell migration systems on muscularis propria muscle cell derived or native extracellular matrix. Functional experiments included integrin characterisation via flow cytometry and their inhibition with specific blocking antibodies and chemicals. Results Crohn’s disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by transforming growth factor-β1. The muscle cell-derived matrix triggered migration of preadipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5β1 on the preadipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularised intestinal tissue extracellular matrix. Conclusion Crohn’s disease creeping fat appears to result from the migration of preadipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2020-323719
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1492637-4
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  • 2
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    Effectiveness and safety of Chinese herbal medicine xuanbi antong granules for the treatment of borderline coronary lesions: study protocol for a randomised, double-blinded, placebo-controlled, multicentre clinical trial
    BMJ ; 2019
    In:  BMJ Open Vol. 9, No. 8 ( 2019-08), p. e024968-
    Details
    In: BMJ Open, BMJ, Vol. 9, No. 8 ( 2019-08), p. e024968-
    Abstract: As the early stage of coronary heart disease (CHD), borderline coronary lesion (BCL) is defined as a 30%–70% diameter stenosis. Previous studies have demonstrated that BCL may progress to acute coronary syndrome easily. However, routine medications available for the treatments of BCL have some limitations. Xuanbi antong granule (XAG) has been used for the treatment of BCL in China for many years. Previous studies have shown that XAG has effectiveness in improving clinical symptoms and quality of life in patients with CHD. This study aims to evaluate the effectiveness and safety of XAG in patients with BCL. Methods and analysis This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 300 participants will be randomly assigned to the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with XAG and the placebo group will be treated with XAG placebo. All participants will receive a 6-month treatment and then be followed-up for another 6 months. The primary outcomes are the changes of target plaque characteristics (including target plaque volume, degree of stenosis, CT value and calcification score) measured by dual source CT angiography. The secondary outcomes include blood lipid indicators, efficacy of angina symptoms, Seattle Angina Questionnaire, high-sensitivity C-reactive protein and occurrence of major adverse cardiac events. All the data will be recorded in electronic case report forms and analysed by SPSS V.20.0. Ethics and dissemination This study has been approved by Research Ethics Committee of Guang’anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2017–083-KY-01). Written informed consent will be obtained from all participants. The results of this study will be disseminated to the public through academic conferences and peer-reviewed journals. Trial registration number ChiCTR-IOR-17013189; Pre-results.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2018-024968
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2599832-8
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  • 3
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    Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study
    BMJ ; 2020
    In:  Journal for ImmunoTherapy of Cancer Vol. 8, No. 1 ( 2020-06), p. e000437-
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 8, No. 1 ( 2020-06), p. e000437-
    Abstract: Tislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Methods The purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1. Results As of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2–21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types. Conclusions Tislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors. Trial registration number CTR20160872.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2019-000437
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2719863-7
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  • 4
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    Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer
    BMJ ; 2022
    In:  Journal of Medical Genetics Vol. 59, No. 7 ( 2022-07), p. 623-631
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 59, No. 7 ( 2022-07), p. 623-631
    Abstract: Most small non-coding RNAs (sncRNAs) with regulatory functions are encoded by majority sequences in the human genome, and the emergence of high-throughput sequencing technology has greatly expanded our understanding of sncRNAs. sncRNAs are composed of a variety of RNAs, including tRNA-derived small RNA (tsRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), PIWI-interacting RNA (piRNA), etc. While for some, sncRNAs’ implication in several pathologies is now well established, the potential involvement of tsRNA, snoRNA, snRNA and piRNA in human diseases is only beginning to emerge. Recently, accumulating pieces of evidence demonstrate that tsRNA, snoRNA, snRNA and piRNA play an important role in many biological processes, and their dysregulation is closely related to the progression of cancer. Abnormal expression of tsRNA, snoRNA, snRNA and piRNA participates in the occurrence and development of tumours through different mechanisms, such as transcriptional inhibition and post-transcriptional regulation. In this review, we describe the research progress in the classification, biogenesis and biological function of tsRNA, snoRNA, snRNA and piRNA. Moreover, we emphasised their dysregulation and mechanism of action in cancer and discussed their potential as diagnostic and prognostic biomarkers or therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2021-108327
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2009590-9
    SSG: 12
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  • 5
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    Plasma-based microsatellite instability detection strategy to guide immune checkpoint blockade treatment
    BMJ ; 2020
    In:  Journal for ImmunoTherapy of Cancer Vol. 8, No. 2 ( 2020-11), p. e001297-
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 8, No. 2 ( 2020-11), p. e001297-
    Abstract: Microsatellite instability (MSI) represents the first pan-cancer biomarker approved to guide immune checkpoint blockade (ICB) treatment. However its widespread testing, especially outside of gastrointestinal cancer, is hampered by tissue availability. Methods An algorithm for detecting MSI from peripheral blood was established and validated using clinical plasma samples. Its value for predicting ICB efficacy was evaluated among 60 patients with advanced gastrointestinal cancer. The landscape of MSI in blood was also explored among 5138 advanced solid tumors. Results The algorithm included 100 microsatellite markers with high capture efficiency, sensitivity, and specificity. In comparison with orthogonal tissue PCR results, the method displayed a sensitivity of 82.5% (33/40) and a specificity of 96.2% (201/209), for an overall accuracy of 94.0% (234/249). When the clinical validation cohort was dichotomized by pretreatment blood MSI (bMSI), bMSI-high (bMSI-H) predicted both improved progression-free survival and overall survival than the blood microsatellite stable (bMSS) patients (HRs: 0.431 and 0.489, p=0.005 and 0.034, respectively). Four patients with bMSS were identified to have high blood tumor mutational burden (bTMB-H) and trended towards a better survival than the bMSS-bTMB-low (bTMB-L) subset (HR 0.026, 95% CI 0 to 2.635, p=0.011). These four patients with bMSS-bTMB-H plus the bMSI-H group collectively displayed significantly improved survival over the bMSS-bTMB-L patients (HR 0.317, 95% CI 0.157 to 0.640, p 〈 0.001). Pan-cancer prevalence of bMSI-H was largely consistent with that shown for tissue except for much lower rates in endometrial and gastrointestinal cancers, and a remarkably higher prevalence in prostate cancer relative to other cancer types. Conclusions We have developed a reliable and robust next generation sequencing-based bMSI detection strategy which, in combination with a panel enabling concurrent profiling of bTMB from a single blood draw, may better inform ICB treatment.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2020-001297
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2719863-7
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  • 6
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    Association between neutrophil-to-albumin ratio and mortality in patients with cardiogenic shock: a retrospective cohort study
    BMJ ; 2020
    In:  BMJ Open Vol. 10, No. 10 ( 2020-10), p. e039860-
    Details
    In: BMJ Open, BMJ, Vol. 10, No. 10 ( 2020-10), p. e039860-
    Abstract: To investigate the prognostic value of neutrophil-to-albumin ratio (NAR) in critically ill patients with cardiogenic shock (CS). Design A retrospective cohort study. Setting A single centre in Boston, USA. Participants 475 patients with CS were included, among which 272 (57.3%) were men and 328 (69.1%) were white. Primary and secondary outcome measures The primary outcome was 90-day mortality and the secondary outcomes were 30-day and 365-day mortality. Results A significant positive correlation between NAR levels and 90-day, 30-day or 365-day mortality was observed. For 90-day mortality, the adjusted HR (95% CI) values given NAR levels 23.54–27.86 and 〉 27.86 were 1.71 (1.14 to 2.55) and 1.93 (1.27 to 2.93) compared with the reference (NAR 〈 23.47). Receiver operator characteristic curve analysis showed that NAR had a certain prognostic value in predicting 90-day mortality of CS, which was more sensitive than the neutrophil percentage or the serum albumin level alone (0.651 vs 0.509, 0.584). For the secondary outcomes, the upward trend remained statistically significant. Conclusions NAR level was associated with the mortality of CS patients. The prognostic value of NAR was more sensitive than the neutrophil percentage or the serum albumin level alone, but not as good as Sequential Organ Failure Assessment or Simplified Acute Physiology Score.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-039860
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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