Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study.

BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

miR-223 induces retinal ganglion cells apoptosis and inflammation via decreasing HSP-70 in vitro and in vivo.

PURPOSE: Glaucoma is an eye disease characterized by the loss of peripheral vision, high pressure in the eye, optic nerve damage, and the loss of peripheral vision due to loss of retinal ganglion cells (RGCs). A number of miRNA have been detected in the pathogenesis of glaucoma. The paper was to focus on the miR-223 in RGCs apoptosis and inflammation, and investigated the possible mechanisms in vitro and in vivo. MATERIALS AND METHODS: After miR-223 inhibitor and mimics transfected into RGCs, the expression of miR-223 was detected by QRT-PCR, cell proliferation were performed by CCK-8 and EdU assays, cell apoptosis were measured by flow cytometer and TUNEL assays, apoptosis and inflammation -related proteins were detected by western blot, and whether miR-223 target to HSP-70 was detected by Luciferease reporter assay. Moreover, the effects si-HSP-70 on RGCs or RGCs transfected with miR-223 inhibitor were detected. In vivo study. New Zealand White rabbits (20 females) were used to detect the effect of miR-223 on the rabbit glaucoma model induced by injection of carbomer. RESULTS: CCK-8 and EdU assays demonstrated that miR-223 mimics decreased RGCs proliferation. FITC-Annexin V/PI Apoptosis and TUNEL assays showed that miR-223 mimics induced RGCs apoptosis. Western blot revealed that miR-223 mimics enhanced the expression of relative apoptosis and inflammation factors. Further, we demonstrated that miR-223 could inhibit cell proliferation, induce cell apoptosis as well as inflammation by targeting HSP-70 in RGCs. Moreover, the results were confirmed in rabbit glaucoma model. CONCLUSIONS: In summary, miR-223 plays a vital role in RGCs by regulating HSP-70 expression, and the new therapeutic strategy might potentially contribute to benefit glaucoma treatment.

Identification of driver genes and somatic mutations in cell-free DNA of patients with pulmonary lymphangioleiomyomatosis.

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.

[Correlation analysis between quality and habitat phenotype of Hovenia acerba].

The contents of dihydromyricetin and total flavonoids of Hovenia acerba seeds were detected by HPLC-DAD and UV spectrophotometer. And then the correlation between the habitat, phenotype and quality of H. acerba seeds were deeply studied. There were big differences in both appearance and quality among the H. acerba seeds from different places. It showed that the content of dihydromyricetin in H. acerba seeds was 0.41-9.81 mg•g⁻¹, and the content of total flavonoids was 5.52-21.98 mg•g⁻¹. The cluster analysis showed that the quality of H. acerba seeds was related to the habitat. The samples from Jianghan Plain Area showed relatively stable and excellent quality. According to the correlation analysis, there was a significant positive correlation between 1 000-seeds weight, red-black seeds ratio and the content of dihydromyricetin, while the content of total flavonoids was not related to the 1 000-seeds weight and red-black seeds ratio. So the 1 000-seeds weight and red-black seeds ratio could be used as an initial judgment of the quality of H. acerba seeds. As dihydromyricetin and total flavonoids content was not related, both dihydromyricetin and total flavonoids should be taken into account when the quality of H. acerba seeds was studied.