Artificial tumor microenvironment regulated by first hemorrhage for enhanced tumor targeting and then occlusion for synergistic bioactivation of hypoxia-sensitive platesomes

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.

Effect of intensive chemotherapy or hypomethylation agent treatment before allogeneic hematopoietic stem cell transplantation on myelodysplastic syndrome patients / 中华器官移植杂志

Objective:To evaluate the outcomes and prognostic factors of myelodysplasia syndrome with excess blasts (MDS-EB) patients on intensive chemotherapy or hypomethylating agent treatment prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 108 MDS-EB patients undergoing allo-HSCT from April 2015 to September 2019 were collected retrospectively, intensive chemotherapy or hypomethylating agent treatment (IC/HAM) group, n=72; support care (SC) group, n=36. Clinical outcomes and prognostic risk factors were analyzed. Results:Intensive chemotherapy or hypomethylating agent treatment pre-HSCT had no effects on overall survival (OS) ( P=0.725), relapse-free survival (RFS)( P=0.658), cumulative incidence rate (CIR) ( P=0.121) or non-relapse mortality (NRM)( P=0.236). Univariate and multivariate analysis of an entire cohort showed that poor cytogenetics was an independent risk factor for OS ( P=0.005), DFS ( P=0.001) and CIR( P=0.032); grade Ⅱ-Ⅳ acute graft venous host disease was independently correlated with unfavorable DFS( P=0.004). Conclusions:IC/HAM treatment pre-HSCT fails to yield discrepant post-HSCT outcomes in MDS-EB patients. The pooling of more patients in a well-designed multi-center clinical trial will further demonstrate the efficacy of treatment pre-HSCT in MDS-EB patients.

Quantitative power Doppler signal assessment in the subchondral bone region of the metacarpophalangeal joint is an effective predictor of radiographic progression in the hand of rheumatoid arthritis: a pilot study.

Ultrasonography is useful for assessment of synovitis in the hand of rheumatoid arthritis (RA) patients. The aim of this study was to investigate the predictive value of the quantitative power Doppler (PD) signal assessment in the subchondral bone region of the metacarpophalangeal (MCP) joint in patients with RA showing radiographic progression of the hand by comparing with those of previously reported scoring systems. Twenty-two patients (20 women) with RA who underwent power Doppler ultrasonography (PDUS) of the bilateral one to five MCP joints at baseline were included in the study. Radiography of both hands was performed at baseline and at 1 year. PDUS of the synovial space was evaluated according to semi-quantitative scoring (0-3) and quantitative measurement (0-100%). The PD signal in the subchondral bone region was qualitatively (0, 1) and quantitatively (mm2) assessed. The performance of PDUS assessment was compared using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the risk ratio (RR). As a predictor for radiographic progression, the quantitative PD signal assessment in the subchondral bone region (AUC = 0.842, p < 0.01) was equivalent to quantitative vascularity (AUC = 0.817, p < 0.05) and semi-quantitative scoring (AUC = 0.754, p < 0.05). As for the RR of the PD signal in the subchondral bone region for radiographic progression, the quantitative PD signal assessment was 5.40 (p < 0.01), whereas the qualitative PD signal assessment was 1.60 (p = 0.204). Quantitative PD signal assessment in the subchondral bone region can predict radiographic progression in the hand of RA patients.

Effects of different doses of cytarabine consolidation therapy followed by haploidentical hematopoietic stem cell transplantation on low-risk and intermediate-risk acute myeloid leukemia patients / 白血病·淋巴瘤

Objective@#To explore the impact on efficacy and prognosis of low-risk and intermediate-risk acute myeloid leukemia (AML, non-M3) patients with complete remission (CR) treated by high-dose cytarabine (HD-Ara-C) or standard-dose cytarabine(SD-Ara-C) before haploidentical hematopoietic stem cell transplantation (Haplo-HSCT).@*Methods@#A retrospective analysis was performed on 71 low-risk and intermediate-risk adult AML patients in the First Affiliated Hospital of Soochow University from March 2008 to April 2017. All the patients were treated by consolidation regimens containing cytarabine before Haplo-HSCT. According to the dosages of cytarabine, the patients were divided into HD-Ara-C group and SD-Ara-C group. Kaplan-Meier method, log-rank test and Cox regression model were used to make survival analysis, and the prognosis and efficacy between the two groups were compared.@*Results@#Of the 71 patients, 43 were male and 28 were female, and the median age was 37 years (18-56 years). The median follow-up time was 39 months (6-119 months). Sixty-four patients were in first remission, and 7 patients were in second remission. At the end of follow-up, the 2-year cumulative incidence of recurrence (CIR), overall survival (OS) rate, progression-free survival (PFS) rate, and non-recurrent death (NRM) rate in SD-Ara-C group were 19.33%, 77.44%, 80.67%, and 17.29%, respectively, the 2-year CIR, OS rate, PFS rates and NRM rate in HD-Ara-C group were 6.29%, 79.90%, 93.71%, and 17.68%, respectively. There was no significant difference in CIR (P = 0.124), OS rate (P = 0.862), PFS rate (P = 0.124) and NRM rate (P = 0.734) between the two groups. The incidence of severe infection in HD-Ara-C group was higher than that in SD-Ara-C group after consolidation therapy [62.8% (22/35) vs. 27.8% (10/36), P = 0.03].@*Conclusion@#Compared with SD-Ara-C, the consolidation therapy containing HD-Ara-C before Haplo-HSCT cannot significantly improve the prognosis of low-risk and intermediate-risk AML patients in CR, but would increase the risk of severe infection after intensive consolidation therapy.

Effects of different doses of cytarabine consolidation therapy followed by haploidentical hematopoietic stem cell transplantation on low-risk and intermediate-risk acute myeloid leukemia patients / 白血病·淋巴瘤

Objective To explore the impact on efficacy and prognosis of low-risk and intermediate-risk acute myeloid leukemia (AML, non-M3) patients with complete remission (CR) treated by high-dose cytarabine (HD-Ara-C) or standard-dose cytarabine(SD-Ara-C) before haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Methods A retrospective analysis was performed on 71 low-risk and intermediate-risk adult AML patients in the First Affiliated Hospital of Soochow University from March 2008 to April 2017. All the patients were treated by consolidation regimens containing cytarabine before Haplo-HSCT. According to the dosages of cytarabine, the patients were divided into HD-Ara-C group and SD-Ara-C group. Kaplan-Meier method, log-rank test and Cox regression model were used to make survival analysis, and the prognosis and efficacy between the two groups were compared. Results Of the 71 patients, 43 were male and 28 were female, and the median age was 37 years (18-56 years). The median follow-up time was 39 months (6-119 months). Sixty-four patients were in first remission, and 7 patients were in second remission. At the end of follow-up, the 2-year cumulative incidence of recurrence (CIR), overall survival (OS) rate, progression-free survival (PFS) rate, and non-recurrent death (NRM) rate in SD-Ara-C group were 19.33%, 77.44%, 80.67%, and 17.29%, respectively, the 2-year CIR, OS rate, PFS rates and NRM rate in HD-Ara-C group were 6.29%, 79.90%, 93.71%, and 17.68%, respectively. There was no significant difference in CIR (P＝0.124), OS rate (P＝0.862), PFS rate (P＝0.124) and NRM rate (P＝0.734) between the two groups. The incidence of severe infection in HD-Ara-C group was higher than that in SD-Ara-C group after consolidation therapy [62.8% (22/35) vs. 27.8% (10/36), P＝ 0.03]. Conclusion Compared with SD-Ara-C, the consolidation therapy containing HD-Ara-C before Haplo-HSCT cannot significantly improve the prognosis of low-risk and intermediate-risk AML patients in CR, but would increase the risk of severe infection after intensive consolidation therapy.

Explore the pathogenesis of breast cancer based on the theory of emotional pathogenic / 国际中医中药杂志

Psychogenic diseases is an important etiology thinking in traditional Chinese medicine,and it lays a solid foundation for the bio-psycho-social medical pattern to establish.Follows the principle of treatment based on syndrome differentiation,and bases on the basic pathogenesis of breast cancer stagnation of liver-qi attacking spleen,this article provides a brief overview of the relationship between emotional factors and breast cancer,and therapeutic principle of breast to enrich Chinese medicine theory of Qingzhi.