Efficacy and Safety of Recombinant Human p53 Adenovirus Injection Combined with Radiotherapy or Concurrent Chemoradiotherapy in the Treatment of Cervical Cancer: A Systematic Review and Meta-analysis.

Objective: Cervical cancer remains a major health concern globally, and combined modality treatment often includes radiotherapy or concurrent chemoradiotherapy. Recently, recombinant human adenovirus-p53 (rAd-p53) has been introduced as a promising agent in treatment of cervical cancer. Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines. RCTs were identified through electronic databases without limitations on time or language. The studies should include patients diagnosed with cervical cancer receiving either rAd-p53 combined with radiotherapy or concurrent chemoradiotherapy (RT/CRT) or RT/CRT alone. Primary outcome measures were complete response rate (CRR) and objective response rate (ORR), as defined by WHO's criteria for solid tumor therapeutic evaluation. Secondary outcome measures included adverse reaction incidence. Results: We included 9 RCTs in the analysis. Meta-analysis revealed that rAd-p53 combined with radiotherapy or concurrent chemoradiotherapy significantly improved the CRR [OR = 1.67, 95%CI (1.29, 2.16), P < .0001] and ORR [OR = 1.26, 95%CI (1.15,1.37), P < .001] compared to radiotherapy or concurrent chemoradiotherapy alone. The incidence of fever was higher in the combination therapy group [OR = 2.80, 95%CI (1.40, 5.62), P < .001], but no significant differences were observed in the incidence of other adverse reactions. Conclusions: The combination of rAd-p53 with radiotherapy or concurrent chemoradiotherapy exhibits enhanced therapeutic efficacy in the treatment of cervical cancer without a significant increase in severe adverse reactions. However, multicenter, large-scale, randomized clinical trials are warranted for further validation.

Caspase-1 inhibition ameliorates murine acute graft versus host disease by modulating the Th1/Th17/Treg balance.

Our previous studies have implicated Caspase-1 signaling in driving the proinflammatory state of acute graft versus host disease (aGVHD). Therefore, we aimed to elucidate the mechanism of Caspase-1 in in murine models of aGVHD through specific inhibition of its activity with the decoy peptide Ac-YVAD-CMK. We transplanted bone marrow from donor C57BL/6 (H-2b) mice into recipient BALB/c (H-2Kd) mice and randomized the recipients into the following treatment cohorts: (1) allogeneic hematopoietic stem cell transplantation and splenic cell infusion control (PBS group); (2) low dose Ac-YVAD-CMK (AC low group); (3) and high dose Ac-YVAD-CMK (AC high group). Indeed, we observed that Caspase-1 inhibition by Ac-YVAD-CMK ameliorated pathological damage and inflammation in the liver, lungs, and colon elicited by aGVHD. This was associated with reduced mortality secondary to aGVHD. Mechanistically, we found that Caspase-1 inhibition modulated donor T cell expansion, restored the balance of Th1/Th17/Treg subsets, and markedly decreased serum levels and aGVHD target organ mRNA expression of IL-1ß, IL-18, and HMGB1. Thus, we demonstrate that inhibition of Caspase-1 by Ac-YVAD-CMK mitigates murine aGVHD by regulating Th1/Th17/Treg balance and attenuating its characteristic proinflammatory state.

A collaborative approach to reduce healthcare-associated infections.

Healthcare-associated infections (HAIs) continue to be an ongoing issue for patients in acute hospital settings. Effectively preventing and controlling HAIs requires a collaborative approach compelling all healthcare staff to take up responsibilities and be involved. A surgical ward in an acute hospital aimed to implement comprehensive HAI prevention strategies by applying both Kotter's eight-step change model and the practice development principles into its current system. The project motivated staff to be involved and engaged in the assessment, implementation and evaluation of the project processes, and take ownership of the practice change. It focused on ensuring a clean environment, improving hand hygiene compliance, increasing staff's knowledge base regarding HAIs and enhancing active surveillance. The project achieved success in the reduction and prevention of HAIs as well as the development of a sustainable workplace culture.

Co-transplantation of Hematopoietic Stem Cells and Cxcr4 Gene-Transduced Mesenchymal Stem Cells Promotes Hematopoiesis.

Mesenchymal stem cells (MSCs) are a promising candidate for cellular therapies. Co-transplantation of MSCs and hematopoietic stem cells (HSCs) promotes successful engraftment and improves hematopoietic recovery. In this study, the effects of co-transplantation of HSCs and mouse bone marrow (BM)-derived MSCs overexpressing CXCR4 (CXCR4-MSC) on CXCR4-MSC homing capacity and the reconstitution potential in lethally irradiated mice were evaluated. Recovery of donor-derived peripheral blood leukocytes and platelets was accelerated when CXCR4-MSCs were co-transplanted with BM cells. The frequency of c-kit(+)Sca(+)Lin(-) HSCs was higher in recipient BM following co-transplantation of CXCR4-MSCs compared with the EGFP-MSC control and the BMT only groups. Surprisingly, the rate of early engraftment of donor-derived BM cells in recipients co-transplanted with CXCR4-MSCs was slightly lower than in the absence of MSCs on day 7. Moreover, co-transplantation of CXCR4-MSCs regulated the balance of T helper cells subsets. Hematopoietic tissue reconstitution was evaluated by histopathological analysis of BM and spleen. Co-transplantation of CXCR4-MSCs was shown to promote the recovery of hematopoietic organs. These findings indicate that co-transplantation of CXCR4-MSCs promotes the early phase of hematopoietic recovery and sustained hematopoiesis.

[Establishment of mouse mesenchymal stem cells overexpressing CXCR4 gene and evaluation of their functions].

This study was purposed to establish the mesenchymal stem cells (MSCs) stably overexpressing mouse CXC chemokine receptor type 4 (CXCR4) gene and to explore their function. The recombinant lentiviral vector LV-CXCR4-IRES-EGFP with packaging plasmid pSPAX2 and envelope plasmid pMD.2G were co-transfected into 293FT packaging cell line using lipofectamine 2000 to produce the recombinant lentiviral vectors. The recombinant viruses were harvested and concentrated by using ultracentrifugation. Mouse bone marrow MSC were infected with the viral supernatants. Variable methods were used to optimize the transduction condition. EGFP expression was visualized using fluorescence microscope and efficiency of infection was determined by flow cytometry (FCM). Proliferation and apoptosis were detected by proliferation curve and FCM, respectively. Migration capacity was assessed by a chemotaxis assay using transwell. Expression of EGFP were detected by fluorescence microscopy in MSCs after infection. The results showed that through optimization of infection condition, the recombination lentiviral vectors had higher infection efficacy; after infection for 72 h, the higher expression of EGFP could be observed under fluorescence microscope; the expression of CXCR4 protein on MSC surface in CXCR4-MSC group significantly increased compared with those in the control group. Meanwhile, over-expression of CXCR4 had no effect on their capacity of proliferation and did not induce apoptosis. Moreover, CXCR4 enhanced the migration of cells in the transwell induced by SDF-1 gradient compared with the EGFP control group. It is concluded that the lentiviral vector can not only infect mouse MSCs efficiently, but also can make CXCR4 express stably in MSC.