Objective:To evaluate the effect of botulinum toxin type A (BTXA) on flap surgery in animal models.Methods:Nine databases (PubMed, Cochrane Library, Ovid, Web of Science, Embase, Scopus, CBM, CNKI, and WANFANG database) were searched for published literature comparing the effects of BTXA (BTXA group) versus saline or no treatment (control group) on flap operation in animal models from January 1979 to March 2022. The literature was screened according to inclusion and exclusion criteria. Indicators included flap survival rate, blood flow and vascular endothelial growth factor (VEGF) expression level after surgery. The subjects were divided into pre-operation injection group and intraoperation injection group according to the intervention timing, and were divided into random flap group and axial flap group according to the type of flaps, and subgroup analysis was conducted respectively. Review Manager (RevMan) 5.3 software and Stata 15.1 software were used for all statistical analysis.Results:A total of 603 animals from 19 studies were included after rigorous inclusion and exclusion screening. Compared with control group, BTXA group revealed a significantly higher flap survival rate [mean difference ( MD)=15.65%, 95% CI: 13.11%-18.19%, Z=12.08, P<0.001], blood flow [standardized mean difference ( SMD)=1.96, 95% CI: 1.39-2.54, Z=6.71, P<0.001] and VEGF expression (at mRNA level: SMD=6.01, 95% CI: 0.89-11.13, Z=2.30, P=0.020; at protein level: SMD=3.44, 95% CI: 2.44-4.43, Z=6.73, P<0.001). Subgroup analysis showed that the flap survival rate of the pre-operation injection group ( MD=21.54%, 95% CI: 16.07%-27.01%, Z=7.71, P<0.001) was significantly higher than that of the intraoperative injection group ( MD=9.40%, 95% CI: 6.79%-12.00%, Z=7.07, P<0.001). The flap survival rate of the random flap group ( MD=20.87%, 95% CI: 16.67%-25.07%, Z=9.73, P<0.001) was significantly higher than that of the axial flap group ( MD=13.11%, 95% CI: 8.91%-17.31%, Z=6.12, P<0.001). Conclusion:BTXA assisted flap surgery may have positive effects on the survival rate, blood flow and VEGF expression in animal models. In addition, injection timing and flap type may also be important factors in the effect of BTXA on flap surgery.

Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.

Objective:To evaluate the effect of botulinum toxin type A (BTXA) on flap surgery in animal models.Methods:Nine databases (PubMed, Cochrane Library, Ovid, Web of Science, Embase, Scopus, CBM, CNKI, and WANFANG database) were searched for published literature comparing the effects of BTXA (BTXA group) versus saline or no treatment (control group) on flap operation in animal models from January 1979 to March 2022. The literature was screened according to inclusion and exclusion criteria. Indicators included flap survival rate, blood flow and vascular endothelial growth factor (VEGF) expression level after surgery. The subjects were divided into pre-operation injection group and intraoperation injection group according to the intervention timing, and were divided into random flap group and axial flap group according to the type of flaps, and subgroup analysis was conducted respectively. Review Manager (RevMan) 5.3 software and Stata 15.1 software were used for all statistical analysis.Results:A total of 603 animals from 19 studies were included after rigorous inclusion and exclusion screening. Compared with control group, BTXA group revealed a significantly higher flap survival rate [mean difference ( MD)=15.65%, 95% CI: 13.11%-18.19%, Z=12.08, P<0.001], blood flow [standardized mean difference ( SMD)=1.96, 95% CI: 1.39-2.54, Z=6.71, P<0.001] and VEGF expression (at mRNA level: SMD=6.01, 95% CI: 0.89-11.13, Z=2.30, P=0.020; at protein level: SMD=3.44, 95% CI: 2.44-4.43, Z=6.73, P<0.001). Subgroup analysis showed that the flap survival rate of the pre-operation injection group ( MD=21.54%, 95% CI: 16.07%-27.01%, Z=7.71, P<0.001) was significantly higher than that of the intraoperative injection group ( MD=9.40%, 95% CI: 6.79%-12.00%, Z=7.07, P<0.001). The flap survival rate of the random flap group ( MD=20.87%, 95% CI: 16.67%-25.07%, Z=9.73, P<0.001) was significantly higher than that of the axial flap group ( MD=13.11%, 95% CI: 8.91%-17.31%, Z=6.12, P<0.001). Conclusion:BTXA assisted flap surgery may have positive effects on the survival rate, blood flow and VEGF expression in animal models. In addition, injection timing and flap type may also be important factors in the effect of BTXA on flap surgery.