| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Du, SH, et al.
(författare)
-
Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia
- 2021
-
Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 11, s. 603278-
-
Tidskriftsartikel (refereegranskat)abstract
- The immunoproteasome, a special isoform of the 20S proteasome, is expressed when the cells receive an inflammatory signal. Immunoproteasome inhibition proved efficacy in the treatment of autoimmune diseases. However, the role of the immunoproteasome in the pathogenesis of immune thrombocytopenia (ITP) remains unknown. We found that the expression of the immunoproteasome catalytic subunit, large multifunctional protease 2 (LMP2), was significantly upregulated in peripheral blood mononuclear cells of active ITP patients compared to those of healthy controls. No significant differences in LMP7 expression were observed between patients and controls. ML604440, an specific LMP2 inhibitor, had no significant impact on the platelet count of ITP mice, while ONX-0914 (an inhibitor of both LMP2 and LMP7) increased the number of platelets. In vitro assays revealed that ONX-0914 decreased the expression of FcγRI in ITP mice and decreased that of FcγRIII in ITP patients, inhibited the activation of CD4+ T cells, and affected the differentiation of Th1 cells in patients with ITP. These results suggest that the inhibition of immunoproteasome is a potential therapeutic approach for ITP patients.
|
|
| 5. |
- Gao, X, et al.
(författare)
-
Longitudinal patient-reported outcomes 1 year after thoracoscopic segmentectomy versus lobectomy for early-stage lung cancer: a multicentre, prospective cohort study protocol
- 2023
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:1, s. e067841-
-
Tidskriftsartikel (refereegranskat)abstract
- Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes—such as symptoms, daily functioning and quality of life—between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery.Methods and analysisOverall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery—a validated lung cancer surgery-specific scale—will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients’ quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student’s t-test, non-parametric test or Χ2test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups.Ethics and disseminationThe Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals.Trial registration numberChiCTR2200060753.
|
|
| 6. |
- Ma, Q, et al.
(författare)
-
ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4142-
-
Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-β cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-β cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-β cells that are useful as a potential source for cell replacement therapies.
|
|
| 7. |
- Ma, YF, et al.
(författare)
-
Endothelial Cells Potentially Participate in the Metastasis of Triple-Negative Breast Cancer
- 2022
-
Ingår i: Journal of immunology research. - : Hindawi Limited. - 2314-7156 .- 2314-8861. ; 2022, s. 5412007-
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibition of triple-negative breast cancer metastasis has long been a challenge, mainly due to the difficulty in identifying factors that contribute to this process. In this study, freshly isolated triple-negative breast cancer biopsied cells obtained from consenting patients were subjected to flow cytometry and bioinformatic analysis to identify three endothelial cell subclusters: EC (ATP1B3), EC (HSPA1B), and EC (KRT7) in the tumor microenvironment. These endothelial cell subclusters exhibited distinguishing biological features. Based on differentially expressed genes derived from the subclusters, gene set enrichment analysis showed that EC (ATP1B3) and EC (HSPA1B) contribute to the process of metastasis, for example, in fibrosarcoma and anaplastic carcinoma. In this study, we identified the heterogeneity of endothelial cells in the human breast cancer and have provided insights into its role in metastasis.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Wei, X, et al.
(författare)
-
Protocol of an iterative qualitative study to develop a molecular testing decision aid for shared decision-making in patients with lung cancer after surgery
- 2022
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e061367-
-
Tidskriftsartikel (refereegranskat)abstract
- Although molecular testing is crucial for many patients with lung cancer, the decision to carry out molecular testing is not easy to make in actual clinical scenarios. Using a specific decision aid (DA) to conduct shared decision-making (SDM) may help ameliorate this problem. However, no DA currently exists for lung cancer molecular testing (DA_LCMT). We aim to develop an evidence-based, iteratively refined DA, which may facilitate SDM and improve the quality of SDM.Methods and analysisAfter considering the Ottawa Decision Support Framework, International Patient Decision Aid Standards and Food and Drug Administration guidance about methods to identify what is important to patients, semistructured interviews with qualitative research methods will be used to generate the decision-making needs of patients with lung cancer diagnosed with lung adenocarcinoma by intraoperative frozen pathological sections. Input will be provided by patients and other stakeholders, including thoracic surgeons, nurses, hospital administrators, molecular testing company staff and insurance company staff. Then, a modified Delphi method will be used to develop the DA_LCMT V.1.0 (DA_LCMT 1.0). Structured interviews with qualitative research methods will be used in the cognitive debriefing (alpha tests) and field testing (beta tests) to revise and improve the DA_LCMT from version 1.0 to the final version, version 3.0. Descriptive statistics will be used to summarise the baseline characteristics of the patients and other stakeholders. Qualitative data will be analysed using the three steps of grounded theory: generate a codebook, update the codebook and create a comprehensive list of related items.Ethics and disseminationEthics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study. This protocol is based on the latest version 1.0, dated 31 October 2021. The study was also approved by the Ethics Committees of The Third People’s Hospital of Chengdu, Zigong First People’s Hospital and Jiangyou People’s Hospital. The results of this study will be presented at medical conferences and published in peer-reviewed journals.Trial registration numberNCT05191485.
|
|
| 11. |
|
|
