Predicting anti-tumor efficacy of multi-functional nanomedicine on decellularized hepatocellular carcinoma-on-a-chip.

Traditional hepatocellular carcinoma-chip models lack the cell structure and microenvironments necessary for high pathophysiological correlation, leading to low accuracy in predicting drug efficacy and high production costs. This study proposed a decellularized hepatocellular carcinoma-on-a-chip model to screen anti-tumor nanomedicine. In this model, human hepatocellular carcinoma (HepG2) and human normal liver cells (L02) were co-cultured on a three-dimensional (3D) decellularized extracellular matrix (dECM) in vitro to mimic the tumor microenvironments of human hepatocellular carcinoma in vivo. Additionally, a smart nanomedicine was developed by encapsulating doxorubicin (DOX) into the ferric oxide (Fe3O4)-incorporated liposome nanovesicle (NLV/Fe+DOX). NLV/Fe+DOX selectively killed 78.59% ± 6.78% of HepG2 cells through targeted delivery and synergistic chemo-chemodynamic-photothermal therapies, while the viability of surrounding L02 cells on the chip model retained high, at over 90.0%. The drug efficacy tested using this unique chip model correlated well with the results of cellular and animal experiments. In summary, our proposed hepatocellular carcinoma-chip model is a low-cost yet accurate drug-testing platform with significant potential for drug screening.

Negative-pressure wound therapy (NPWT) for the treatment of pacemaker pocket infection in patients unable or unwilling to undergo CIED extraction.

PURPOSE: The occurrence of cardiac pacemaker pocket infection has markedly increased and has become a new problem facing cardiovascular internists. The aim of our study was to investigate the effectiveness and safety of treating cardiac pacemaker pocket infection using negative-pressure wound therapy (NPWT) in patients who are unwilling or unable to have their cardiac implantable electronic devices (CIEDs) removed. METHODS: From March 2013 to April 2019, NPWT was applied to 26 patients with cardiac pacemaker pocket infection who were unwilling or unable to have their CIEDs removed. In the first stage, a negative-pressure drainage system was placed in the pacemaker pocket after debridement. Then, NPWT was used to seal the wound, and the negative pressure (300-400 mmHg) was sustained for 5-7 days. In the second stage, the pacemaker was relocated to the subpectoral layer, and the wound was closed. RESULTS: In all but three of our 26 patients, the wound healed completely without complications and without evidence of residual infection. The average follow-up period was 26.92 ± 9.46 months. Only 3 diabetic patients whose tissue bacterial cultures revealed that methicillin-resistant Staphylococcus epidermidis developed uncontrolled infections. Eventually, the entire original pacemaker systems were removed, and new pacemakers were implanted in the contralateral chest wall. CONCLUSIONS: When warranted by strictly selected indications, the method of NPWT without CIED extraction can be considered as a new and effective treatment for patients with pacemaker pocket infection who are unwilling or unable to have the device removed.

[Experimental study on the effect of desferrioxamine on targeted homing and angiogenesis of bone marrow mesenchymal stem cells].

Objective: To investigate whether desferrioxamine (DFO) can enhance the homing of bone marrow mesenchymal stem cells (BMSCs) and improve neovascularization in random flaps of rats. Methods: BMSCs and fibroblasts (FB) of luciferase transgenic Lewis rats were isolated and cultured. Forty 4-week-old Lewis male rats were used to form a 10 cm×3 cm rectangular flap on their back. The experimental animals were randomly divided into 4 groups with 10 rats in each group: in group A, 200 µL PBS were injected through retrobulbar venous plexus; in group B, 200 µL FB with a concentration of 1×10 6 cells/mL were injected; in group C, 200 µL BMSCs with a concentration of 1×10 6 cells/mL were injected; in group D, cells transplantation was the same as that in group C, after cells transplantation, DFO [100 mg/(kg·d)] were injected intraperitoneally for 7 days. On the 7th day after operation, the survival rate of flaps in each group was observed and calculated; the blood perfusion was observed by laser speckle imaging. Bioluminescence imaging was used to detect the distribution of transplanted cells in rats at 30 minutes and 1, 4, 7, and 14 days after operation. Immunofluorescence staining was performed at 7 days after operation to observe CD31 staining and count capillary density under 200-fold visual field and to detect the expressions of stromal cell derived factor 1 (SDF-1), epidermal growth factor (EGF), fibroblast growth factor (FGF), and Ki67. Transplanted BMSCs were labeled with luciferase antibody and observed by immunofluorescence staining whether they participated in the repair of injured tissues. Results: The necrosis boundary of ischemic flaps in each group was clear at 7 days after operation. The survival rate of flaps in groups C and D was significantly higher than that in groups A and B, and in group D than in group C ( P<0.05). Laser speckle imaging showed that the blood perfusion units of flaps in groups C and D was significantly higher than that in groups A and B, and in group D than in group C ( P<0.05). Bioluminescence imaging showed that BMSCs gradually migrated to the ischemia and hypoxia area and eventually distributed to the ischemic tissues. The photon signal of group D was significantly stronger than that of other groups at 14 days after operation ( P<0.05). CD31 immunofluorescence staining showed that capillary density in groups C and D was significantly higher than that in groups A and B, and in group D than in group C ( P<0.05). The expressions of SDF-1, EGF, FGF, and Ki67 in groups C and D were significantly stronger than those in groups A and B, and in group D than in group C. Luciferase-labeled BMSCs were expressed in the elastic layer of arteries, capillaries, and hair follicles at 7 days after transplantation. Conclusion: DFO can enhance the migration and homing of BMSCs to the hypoxic area of random flap, accelerate the differentiation of BMSCs in ischemic tissue, and improve the neovascularization of ischemic tissue.

Genetic analysis of a congenital split­hand/split­foot malformation 4 pedigree.

In the present study whole-exome sequencing using the Complete Genomics platform was employed to scan a proband from a split­hand/split­foot malformation (SHFM) 4 family. The missense mutation c.728G>A (p.Arg243Gln) in the TP63 gene was revealed to be associated with SHFM. Sanger sequencing confirmed the sequences of the proband and his father. The father was diagnosed with SHFM and harbored a CGG­to­CAG mutation in exon 5, which produced a R243Q substitution in the zinc binding site and dimerization site of TP63. The R243Q mutation was predicted to be pathogenic by PolyPhen­2. The proband, who was diagnosed with four digit SHFM, exhibited a more severe phenotype. X­ray analysis returned the following results: Absence of third phalange bilaterally and third metacarpus of the left hand; absence of the second toes bilaterally and partial third toes; and partial fusion of the second, third and metatarsal bones of the right side with deformity of the second metatarsal of the right side. Osteochondroma was present in the fourth proximal radial metacarpal of the left hand and the basal and proximal parts of the second metatarsal of the right side. The proband's father had five digits in both feet. These results indicate that the R243Q mutation produces a novel phenotype named SHFM4. The present study revealed that the R243Q mutation in the TP63 gene produced a novel phenotype named SHFM4, thereby demonstrating the mutational overlap between ectrodactyly­ectodermal dysplasia­cleft syndrome and SHFM4.