Résumé
Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Sujets)
Humains , Anticorps monoclonaux humanisés/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/anatomopathologie , Résultat thérapeutiqueRésumé
OBJECTIVE@#To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics.@*METHODS@#Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis.@*RESULTS@#Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway.@*CONCLUSION@#Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.
Sujets)
Femelle , Rats , Animaux , Glucocorticoïdes/effets indésirables , AMP-Activated Protein Kinases , Protéomique , Rat Sprague-Dawley , Ostéoporose/génétique , Protéines nucléaires/effets indésirablesRésumé
Objective:To explore the effect of iodophor wet compress on delivery outcomes and postpartum perineum edema during the second stage of labor, and to provide reference for clinical improvement of postpartum perineal edema.Methods:This was a randomized cotrolled study. The convenient sampling method was adopted. From January 2022 to March 2022,150 pregnant women with single full-term and cephalic presentation who delivery in Wuxi Maternal and Child Health Hospital were selected as the research object. They were divided into observation group and control group according to the random number table method, each group contained 75 cases. In the second stage of labor, both groups were given routine care, based on this, the observation group received iodophor wet compress on perineum, and then the degree of perineal edema on the 1st, 2nd and 3rd day after delivery, perineotomy, intervention and treatment of perineal edema after delivery, the length of the second stage of labor, newborn 1-minute Apgar score were all observed.Results:Observation group was 72 cases and control group was 70 cases finally. The perineal edema rates of grade Ⅰ, Ⅱ and Ⅲ on postpartum day 1 in the observation group were 75.00% (54/72), 20.83% (15/72) and 4.17% (3/72), while those in the control group were 57.14% (40/70), 34.29%(24/70) and 8.57% (6/70). The perineal edema rates of grade Ⅰ, Ⅱ and Ⅲ on postpartum day 2 in the observation group were 88.89% (64/72), 8.33% (6/72) and 2.78% (2/72), and 75.71% (53/70), 15.71% (11/70) and 8.57% (6/70) in the control group. The perineal edema rates on the first and second day after delivery between the two groups was statistically significant ( Z=- 2.26,-2.09, both P<0.05); but there was no significant difference in the degree of perineal edema on the third day after delivery ( Z=-1.77, P>0.05); in the observation group, the rate of perineotomy was 34.72% (25/72) while the rate was 51.43% (36/70) in the control group, the difference was significant ( χ 2=4.04, P<0.05) ; the treatment rate of postpartum perineal edema was 29.17% (21/72) in the observation group and 50.00% (35/70) in the control group, there was significant difference ( χ 2=6.45, P<0.05); the length of the second stage of labor and newborn 1-minute Apgar score in the observation group were (51.65 ± 35.69) min, (9.92 ±0.44) points, the control group were (52.91 ± 38.61) min, (9.93 ± 0.43) points, there was no significant difference between two groups ( t=0.20, 0.16, both P>0.05) . Conclusions:The application of iodophor wet compress to perineum in the second stage of labor can effectively reduce the rate of perineotomy and postpartum perineum edema, reduce the severity of edema, it also promote postpartum rehabilitation.
Résumé
Natural killer(NK)cells as intrinsic immune cells kill tumor cells without the need for pre-stimulation by tumor antigens.Therefore,NK cell based immunotherapy has unique advantages and has made significant progress in tumor treatment.In this article,we review the development,classification,and mechanism of NK cells as well as the applications of NK cell based immunotherapies,including immune checkpoint inhibitors,adoptive cell therapy,and NK cell adapters in tumor immunity.Thus,we elucidate the principle,current status,and developmental trend of NK cell-based anti-tumor immunotherapies to provide ideas for their development and application in the field of tumor immunotherapy.
Résumé
Cholangiocarcinoma originates from bile duct epithelial cells and is a highly heterogeneous and aggressive malignant tumour. A deep understanding of the biological characteristics of the tumor can help to make progress in the treatment of cholangiocarcinoma. There are many types of animal models of cholangiocarcinoma, and different models can be induced according to different research purposes, including chemotoxic agent models, cholestatic models, implantation models, genetically engineered models, etc. This paper summarises the existing animal models of cholangiocarcinoma, compares their advantages and disadvantages as well as the application scenarios, and provides a reference for subsequent studies.
Résumé
Objective: To investigate the effect of Xuanfu Daizhe decoction on the stemness of esophageal cancer cells. Methods: The BALB/c nude mice were randomly divided into the control group and experimental group, 5 mice in each group, which were continuously administered with normal saline and Xuanfu Daizhe decoction (9.89 g/kg) by gastrogavage, respectively. Human esophageal carcinoma cells ECA-109 (5×106) were subcutaneously injected into the mice on the 8th day. Tumor volume was measured twice a week. The mice were sacrificed 4 weeks after injection, and the tumor tissue and mouse serum were collected. The expressions of the major stemness-regulating transcription factors, i.e., NANOG, OCT4 and SOX2, were detected by RT-qPCR, Western Blot and immunohistochemistry. ECA-109 cells were treated with 10% fetal bovine serum and serum from the above two groups of mice for 48 hours respectively, and three replicate wells were set in each group, and the expressions of NANOG, OCT4, SOX2 and the levels of AKT and p-AKT were detected by RT-qPCR and Western Blot, respectively. ALDH activity in tumor cells was detected by flow cytometry; the number of spheroids of tumor cells was detected by the spheroidization experiment. Results: Compared with the control group, the growth and size of esophageal cancer tumors were significantly inhibited by Xuanfu Daizhe Decoction; the expressions of NANOG, OCT4, SOX2, the ALDH activity, the number of spheroids, and the levels of AKT and phosphorylated AKT (p-AKT) in esophageal cancer cells were significantly reduced by Xuanfu Daizhe Decoction both in vivo and in vitro. Conclusion: Xuanfu Daizhe Decoction inhibits the stemness of esophageal cancer cells, it may be a potentially effective drug for the treatment of esophageal cancer and provides a theoretical basis for the exploration of new effective drugs for the treatment of esophageal cancer.