Summary: Insulin resistance is an essential characteristic of type 2 diabetes mellitus (T2DM), which can be induced by glucotoxicity and adipose chronic inflammation. Mesenchymal stem cells (MSCs) and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities. Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs. But the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in insulin resistance of human adipocytes is unclear. In this study, exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes. Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay. The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting. The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells (hAMSCs). The results showed that hAMSCs had better adipogenic ability than hUC-MSCs. After induction of mature adipocytes by adipogenesis of hAMSC, the model of insulin-resistant adipocytes was successfully established by TNF-α and high glucose intervention. After exosome treatment, the insulin-stimulated glucose uptake was significantly increased. In addition, the effect of exosomes could be stabilized for at least 48 h. Furthermore, the level of leptin was significantly decreased, and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment. In conclusion, exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes, and the mechanism involves the regulation of adipokines.

Carnivore protoparvovirus 1 (CPPV-1) is widespread among free-living carnivores, and CPPV-1 infection may directly or indirectly impact on the population of endangered carnivore species. In this study, we used molecular screening of viral capsid protein 2 (VP2) from 2015 to 2017, to assess the prevalence of CPPV-1 infection in 9 live-trapped (LT) and 17 vehicle collision (VC)-affected free-living leopard cats (Prionailurus bengalensis chinensis). In addition, we conducted the phylogenetic analysis to evaluate the possible transmission of CPPV-1 between domestic carnivores and leopard cats. We identified the circulation of feline parvovirus and variants of canine parvovirus (CPV), including CPV-2a, CPV-2b, and CPV-2c, in the free-living leopard cat population. The partial sequences of different variants of VP2 obtained from the leopard cats were identical with those obtained from the domestic dogs and cats in Taiwan. Our result suggested that CPPV-1 was currently transmitted between domestic carnivores and leopard cats in Taiwan. A plan of conservation measures based on vaccination program for domestic carnivores, strict controls on populations of free-living dogs and cats and limiting road development only to low-risk areas for leopard cats should be encouraged.

Background: Studies on various thrombopoietic agents for cancer treatment–induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens.Methods: In this retrospective, cross‐sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL‐11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO‐RA). The outcomes, compliance, and safety of different treatments were analyzed.Results: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL‐11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL‐11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy‐induced thrombocytopenia (CIT) than rhIL‐11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 10⁹/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO‐RA alone than with rhTPO and rhIL‐11.Conclusions: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL‐11, rhTPO, and TPO‐RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding.Plain Language Summary: To provide an overview of the outcome of cancer treatment–induced thrombocytopenia in China, our cross‐sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL‐11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL‐11.

Background: Optimal first-line therapy for metastatic triple-negative breast cancer (mTNBC) varied in different situations. This phase II trial explores the efficacy and safety of combination regimens with be vacizumab, ti slelizumab and na b-paclitaxel (BETINA) in first-line setting for mTNBC. Methods: Patients with previously untreated advanced TNBC received tislelizumab 200 mg and bevacizumab on day 1 and nab-paclitaxel 125 mg/m ² on day 1, day 8 in 3-week cycles. Patients were randomized to bevacizumab 7.5 mg/kg or 15 mg/kg. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR2200058567). Results: 30 female patients were enrolled from March 11, 2021 to February 5, 2024. Nine patients receiving bevacizumab 15 mg/kg experienced significantly higher hypertension rates versus 7.5 mg/kg (55.5% vs 0%), prompting subsequent enrollment of 12 additional patients at 7.5 mg/kg. By November 30, 2024, the ORR was 73.3% and the disease control rate was 90.0%, while the median PFS was 6.0 months and the median OS was 19.8 months. No new safety signal was reported. Common treatment-related adverse events (AEs) included peripheral sensory neuropathy (83.3%), dyspepsia (70.0%), anemia (70.0%), leukocytopenia (66.7%), and pruritus (53.3%). Hypothyroidism (30.0%) was the most frequent immune-related AE. Biomarker analysis indicated that lower baseline interleukin (IL)-1α was associated with poor survival, while IL-2, vascular endothelial growth factor-A and insulin-like growth factor binding protein-7 levels significantly decreased at progression. RNA sequencing highlighted the enrichment of the fatty acid metabolism pathway in poor responders. Conclusions: BETINA study demonstrated promising efficacy and favorable tolerance in treating patients with mTNBC with bevacizumab with tislelizumab and nab-paclitaxel.