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  • 1
    Online Resource
    Online Resource
    Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner
    Springer Science and Business Media LLC ; 2022
    In:  Oncogene Vol. 41, No. 21 ( 2022-05-20), p. 3024-3036
    Details
    In: Oncogene, Springer Science and Business Media LLC, Vol. 41, No. 21 ( 2022-05-20), p. 3024-3036
    Abstract: Glioblastoma multiforme (GBM) with mesenchymal features exhibits enhanced chemotherapeutic resistance and results in reduced overall survival. Recent studies have suggested that there is a positive correlation between the GBM mesenchymal status and immune cell infiltration. However, the mechanisms by which GBM acquires its mesenchymal features in a tumor immune microenvironment-dependent manner remains unknown. Here, we uncovered a chemerin-mediated autocrine and paracrine network by which the mesenchymal phenotype of GBM cells is strengthened. We identified chemerin as a prognostic secretory protein mediating the mesenchymal phenotype-promoting network between tumor-associated macrophages (TAMs) and tumor cells in GBM. Mechanistically, chemerin promoted the mesenchymal features of GBM by suppressing the ubiquitin-proteasomal degradation of CMKLR1, a chemerin receptor predominantly expressed on TAMs and partially expressed on GBM cells, thereby enhancing NF-κB pathway activation. Moreover, chemerin was found to be involved in the recruitment of TAMs in the GBM tumor microenvironment. We revealed that chemerin also enhances the mesenchymal phenotype-promoting ability of TAMs and promotes their M2 polarization via a CMKLR1/NF-κB axis, which further exacerbates the mesenchymal features of GBM. Blocking the chemerin/CMKLR1 axis with 2-(α-naphthoyl) ethyltrimethylammonium iodide disrupted the mesenchymal network and suppressed tumor growth in GBM. These results suggest the therapeutic potential of targeting the chemerin/CMKLR1 axis to block the mesenchymal network in GBM.
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    URL: Article
    DOI: 10.1038/s41388-022-02295-w
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2008404-3
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  • 2
    Online Resource
    Online Resource
    Abstract P2086: Wirelessly Powered Miniaturized Intravascular Pacemaker Based On Inductive Coupling
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Research Vol. 131, No. Suppl_1 ( 2022-08-05)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 131, No. Suppl_1 ( 2022-08-05)
    Abstract: Introduction: Despite unparalleled advantages, clinical lead-associated complications of the conventional pacemakers remain to compromise patient safety and survival, accounting for nearly 10% of all implants. The leadless pacemakers from Medtronic or St. Jude Medical are revolutionary products, however, the integrated battery introduced new clinical constraints and health risks. Therefore, developing leadless pacemakers incorporating wireless powering owns special clinical significance to further the miniaturized integration and reduce the repetitive mechanical workload for the hearts. Methods and Results: Hereby, we achieved the leadless intravascular miniaturized pacemaker powered by electromagnetic inductive coupling. The miniaturized assembling was built up from flexible circuit boards, integrating with receiver coils and tiny electrical components for the RF-DC converting. The substrate circuit board will be bent into a cylinder with a diameter of 2.7 mm and filled with PDMS to achieve the electrical isolation and form a narrower tip for easy insertions (Figure 1a,b). The voltage of DC pulse converted at the wireless pacemaker depends on the DC voltage for the RF amplifier and the gap between the coils, ranging from 0.5V to 5V or higher (Figure 1c). After inserting the pacemaker into the anterior vein, the pacing demonstration showed the stimulation spikes and the following regular cardiac Q-R-S-T waves, indicating the pacemaker can stimulate the intrinsic cardiac rhythms (Figure 1d,e). Conclusions: The proposed medical device reveals the potentials of cardiac pacing from the anterior veins and paved the way to further device miniaturization for the intravascular deployment.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.131.suppl_1.P2086
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467838-X
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  • 3
    Online Resource
    Online Resource
    Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer : The ASTRUM-005 Randomized Clinical Trial
    American Medical Association (AMA) ; 2022
    In:  JAMA Vol. 328, No. 12 ( 2022-09-27), p. 1223-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 328, No. 12 ( 2022-09-27), p. 1223-
    Abstract: Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC. Objective To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC. Design, Setting, and Participants This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021. Interventions Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. Main Outcomes and Measures The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P   & amp;lt; .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Results Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months] ) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P   & amp;lt; .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months] ) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group. Conclusions and Relevance Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT04063163
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2022.16464
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 4
    Online Resource
    Online Resource
    Novel Covert-Inferior Pelvic Approach with a Subpubic Plate for Anterior Pelvic Ring Fractures : Preliminary Results
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of Bone and Joint Surgery Vol. 104, No. 23 ( 2022-12-7), p. 2074-2082
    Details
    In: Journal of Bone and Joint Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 104, No. 23 ( 2022-12-7), p. 2074-2082
    Abstract: Anterior pelvic ring injuries can be treated via Pfannenstiel, modified Stoppa, or ilioinguinal approaches, but these require exposing the abdominal soft tissues and may damage pelvic organs. The scar on the abdominal wall is also unacceptable for some patients. The minimally invasive anterior pelvic ring internal fixator (INFIX) is not ideal for thin patients with easily irritated skin, and it is associated with complications such as femoral nerve palsy, vascular occlusion, and lateral femoral cutaneous nerve injury. In this study, we designed a new external pelvic approach for the treatment of an anterior pelvic ring fracture. Methods: We retrospectively reviewed 28 patients with 36 pubic ramus fractures that had been treated via the covert-inferior pelvic approach. All patients underwent a surgical procedure between August 2019 and January 2021. According to the Nakatani classification, there were 6 cases of type-I fracture, 25 cases of type-II fracture, and 5 cases of type-III fracture. Operative time, blood loss, and postoperative radiographic and computed tomographic (CT) findings were recorded. Patients were followed for fracture healing time, functional status, esthetic satisfaction, and complications. Results: A total of 27 patients had follow-up for at least 12 months (range, 12 to 29 months). Postoperative radiographs and CT scans showed well-positioned plates and screws. The mean preoperative time was 9.4 ± 3.8 days, the mean operative time was 61.3 ± 22.67 minutes, the mean intraoperative blood loss was 63.6 ± 42.62 mL, the mean fracture healing time was 4.1 ± 1.6 months, and the mean Majeed score was 89.74 ± 8.07. There were no complications of nonunion, internal fixation failure, vascular injury, nerve palsy, or hernia. All of the patients were esthetically satisfied with the scar. Conclusions: The covert-inferior pelvic approach combined with a subpubic plate effectively fixed Nakatani type-I, II, and III fractures. The advantages of this method include rapid recovery after the surgical procedure, safety, simplicity, a short learning curve, no damage to abdominal soft tissue, no effect on pubic symphysis micromotion, and esthetic benefits. It may be another option for anterior pelvic ring fractures and can supplement other approaches. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
    Type of Medium: Online Resource
    ISSN: 0021-9355 , 1535-1386
    URL: Article
    DOI: 10.2106/JBJS.22.00371
    RVK:
    XA 52200.A
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis
    Elsevier BV ; 2020
    In:  Nutrition Vol. 79-80 ( 2020-11), p. 110941-
    Details
    In: Nutrition, Elsevier BV, Vol. 79-80 ( 2020-11), p. 110941-
    Type of Medium: Online Resource
    ISSN: 0899-9007
    URL: Article
    DOI: 10.1016/j.nut.2020.110941
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2010168-5
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  • 6
    Online Resource
    Online Resource
    The IGF2BP3-COPS7B axis facilitates mRNA translation to drive colorectal cancer progression
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research ( 2023-08-10)
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), ( 2023-08-10)
    Abstract: Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer (CRC). However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to post-transcriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of CRC by evaluating the transcriptomic and proteomic features of CRC patients, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COPS7B was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in CRC. IGF2BP3 enhanced the TE of COPS7B mRNA to promote CRC growth and metastasis. COPS7B was found to be a component of the ribo-interactome that interacted with ribosomes to facilitate ribosome biogenesis and mRNA translation initiation. Collectively, this study revealed the proteomic features of CRC and highlighted elevated mRNA translation as a hallmark of CRC. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in CRC provided a promising therapeutic target to treat this aggressive disease.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-23-0557
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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