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  • BMJ  (3)
  • Zhang, Yan  (3)
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  • BMJ  (3)
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  • 1
    Online Resource
    Online Resource
    Latent class cluster analysis of knowledge on acute myocardial infarction in community residents: a cross-sectional study in Tianjin, China
    BMJ ; 2022
    In:  BMJ Open Vol. 12, No. 6 ( 2022-06), p. e051952-
    Details
    In: BMJ Open, BMJ, Vol. 12, No. 6 ( 2022-06), p. e051952-
    Abstract: Public knowledge of early onset symptoms and risk factors (RF) of acute myocardial infarction (AMI) is very important for prevention, recurrence and guide medical seeking behaviours. This study aimed to identify clusters of knowledge on symptoms and RFs of AMI, compare characteristics and the awareness of the need for prompt treatment. Design Multistage stratified sampling was used in this cross-sectional study. Latent GOLD Statistical Package was used to identify and classify the respondent subtypes of the knowledge on AMI symptoms or modifiable RFs. Multivariable logistic regression was performed to identify factors that predicted high knowledge membership. Participants A structured questionnaire was used to interview 4200 community residents aged over 35 in China. 4122 valid questionnaires were recovered. Results For AMI symptoms and RFs, the knowledge levels were classified into two or three distinct clusters, respectively. 62.7% (Symptom High Knowledge Cluster) and 39.5% (RF High Knowledge Cluster) of the respondents were able to identify most of the symptoms and modifiable RFs. Respondents who were highly educated, had higher monthly household income, were insured, had regular physical examinations, had a disease history of AMI RFs, had AMI history in immediate family member or acquaintance or had received public education on AMI were observed to have higher probability of knowledge on symptoms and RFs. There was significant difference in awareness of the prompt treatment in case of AMI occurs among different clusters. ‘Calling an ambulance’ was the most popular option in response of seeing others presenting symptoms of AMI. Conclusions A moderate or relatively low knowledge on AMI symptoms and modifiable RFs was observed in our study. Identification of Knowledge Clusters could be a way to detect specific targeted groups with low knowledge of AMI, which may facilitate health education, further reduce the prehospital delay in China and improve patient outcomes.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2021-051952
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2599832-8
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    Online Resource
  • 2
    Online Resource
    Online Resource
    STING mediates microglial pyroptosis via interaction with NLRP3 in cerebral ischaemic stroke
    BMJ ; 2023
    In:  Stroke and Vascular Neurology
    Details
    In: Stroke and Vascular Neurology, BMJ
    Abstract: Ischaemia-evoked neuroinflammation is a critical pathogenic event following ischaemic stroke. Gasdermin D (GSDMD)-associated pyroptosis represents a type of inflammation-associated programmed cell death, which can exacerbate neuroinflammatory responses and brain damage. Stimulator of interferon genes (STING) was recently described as a vital innate immune adaptor protein associated with neuroinflammation. Nevertheless, the regulatory effects of STING on microglial pyroptosis post-stroke have not been well elaborated. Methods STING-knockout and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO). STING small interfering RNA (siRNA) was transfected into BV2 cells before oxygen-glucose deprivation/reoxygenation (OGD/R). STING-overexpressing adeno-associated virus (AAV) and NOD-like receptor family pyrin domain containing 3 (NLRP3) siRNA were administered by stereotaxic injection. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, TdT-mediated dUTP nick end labeling (TUNEL) staining, Fluoro-Jade C (FJC) staining, neurobehavioural tests, immunohistochemistry, cytokine antibody array assay, transmission electron microscopy, immunoblot, Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) were carried out. Co-immunoprecipitation assays were used to investigate the interplay between STING and NLRP3. Results STING expression was increased after MCAO and mainly detected on microglia. STING deletion alleviated brain infarction, neuronal damage and neurobehavioural impairment in mice subjected to MCAO. STING knockout suppressed microglial activation and the secretion of inflammatory chemokines, accompanied by mitigation of microglial pyroptosis. Specific upregulation of microglial STING by AAV-F4/80-STING aggravated brain injury and microglial pyroptosis. Mechanistically, co-immunoprecipitation showed that STING bound to NLRP3 in microglia. Supplementation of NLRP3 siRNA reversed AAV-F4/80-STING-induced deterioration of microglial pyroptosis. Conclusions The current findings indicate that STING modulates NLRP3-mediated microglial pyroptosis following MCAO. STING may serve as a therapeutic target in neuroinflammation induced by cerebral ischaemic/reperfusion (I/R) injury.
    Type of Medium: Online Resource
    ISSN: 2059-8688 , 2059-8696
    URL: Article
    DOI: 10.1136/svn-2023-002320
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2847692-X
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  • 3
    Online Resource
    Online Resource
    First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer
    BMJ ; 2021
    In:  Journal for ImmunoTherapy of Cancer Vol. 9, No. 7 ( 2021-07), p. e002926-
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. 7 ( 2021-07), p. e002926-
    Abstract: Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89 Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers. Methods Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18 F-FDG and 89 Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope. Results Preclinical studies showed that 89 Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89 Zr-CTB006 with a mean maximum standardized uptake value (SUV max ) of 6.63±3.29 (range 1.8–13.8). Tumor tissue was obtained from 18 patients, and 89 Zr-CTB006 uptake in patients with RNAscope scores of 3–4 was significantly higher than that in patients with scores of 0–2. An SUV max of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively. Conclusions 89 Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2021-002926
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2719863-7
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