objective: Bone morphogenetic proteins have the function of inducing and promoting bone growth and formation. However, there is controversy between the research results of the treatment of acute tibial fracture with bone morphogenetic proteins, which makes the effect of bone morphogenetic proteins unclear. Meta-analysis was used to systematically evaluate the efficacy and safety of bone morphogenetic proteins for the treatment of acute tibial fracture. METHODS: PubMed, Elsevier, Web of Science, Cochrane Library, CNKI and Wanfang databases were searched to retrieve the clinical controlled trials of bone morphogenetic proteins for acute tibial fracture published before February 2020. Quality evaluation, bias risk assessment and data extraction of the included literatures were performed. Meta-analysis of outcome indicators was performed using RevMan 5.1 software provided by Cochrane system. RESULTS: (1) Seven articles were enrolled for meta-analysis, including six randomized controlled trials and one cohort study. A total of 1 256 cases of acute tibial fracture were included, with 793 cases in bone morphogenetic protein group and 463 cases in control group. (2) Meta-analysis results showed that bone morphogenetic proteins could not significantly improve the healing rate (P=0.07), but reduce the secondary intervention rate [RR=0.64, 95%CI(0.49, 0.84), P=0.001]. The application of bone morphogenetic proteins had no significant effect on postoperative pain, infection, hardware failure, edema and swelling (P > 0.05). Bone morphogenetic proteins significantly increased the incidence of heterotopic ossification and soft tissue calcification [RR=2.89, 95%CI(1.40, 5.95), P=0.004]. As for patients with open tibial fractures, bone morphogenetic proteins significantly improved the healing rate [RR=1.16, 95%CI(1.04, 1.30), P=0.009]. CONCLUSION: On the basis of conventional treatment, the application of bone morphogenetic proteins significantly reduces the secondary intervention rate and is more suitable for the auxiliary treatment of complex open tibial fracture. In addition, the higher rate of heterotopic ossification and soft tissue calcification is related to bone morphogenetic protein.

BACKGROUND: Bone morphogenetic proteins have strong bone induction properties and have been proved to promote bone healing in fracture, bone defect and other diseases. However, few studies are reported on the use of bone morphogenetic proteins in the treatment of bone nonunion, and the results of various studies remain controversial, which makes the role of bone morphogenetic proteins in the treatment of limb long bone nonunion unclear. OBJECTIVE: Meta-analysis was used to systematically evaluate the advantages and disadvantages of bone morphogenetic protein versus autogenous bone grafting in the treatment of limb long bone nonunion. METHODS: PubMed, Elsevier, Web of Science, Cochrane Library, CNKI and WanFang databases were searched to retrieve the randomized controlled trials and non-randomized controlled trials of bone morphogenetic proteins for limb long bone nonunion published before April 2019. Quality evaluation and data extraction of the included literatures were performed. Meta-analysis of outcome indicators was performed using RevMan 5. 1 software provided by Cochrane system. RESULTS AND CONCLUSION: Eight articles were enrolled, including 4 randomized controlled trials and 4 non-randomized controlled trials, all of which were small sample-size studies involving 30-124 cases. A total of 613 cases of nonunion were included. In the study group, patients received bone morphogenetic proteins or bone morphogenetic proteins in combination with bone grafting. In the control group, patients received autologous bone grafting. Meta-analysis results showed that there were no significant differences in postoperative healing rate, infection rate, secondary operation rate, and postoperative improvement in limb function between study and control groups (P > 0. 05). The mean healing time in the study group was significantly shorter than that in the control group [WMD=-1. 24, 95%C/(-1. 70,-0. 79), P< 0. 01]. Intraoperative blood loss in patients receiving simple bone morphogenetic protein was less than that in patients receiving autologous bone grafting (P < 0. 05). The hospitalization cost of bone morphogenetic protein in combination with autologous bone grafting was significantly higher than that of autologous bone grafting (P < 0. 01). There was no significant difference in hospital stay between patients receiving simple bone morphogenetic protein and patients receiving autologous bone grafting (P > 0. 05). These results suggest that bone morphogenetic protein can provide a viable alternative to autologous bone grafting, and it is also a safe adjuvant for autologous bone grafting, which has the potential advantage of accelerating fracture healing, but the current evidence does not support bone morphogenetic protein in combination with autologous bone grafting.

Objective:To evaluate regulatory effects of fibroblast growth factor receptor 3 (FGFR3) and human papillomavirus type 2 (HPV2) E2 protein on the differentiation of an immortalized human keratinocyte line HaCaT and a normal human epidermal keratinocyte line NHEK.Methods:In both HaCaT and NHEK cells, HPV2 E2-stably transfected cell lines (HPV2 E2-transfected groups) were established by using the lentivirus transfection method, wide-type FGFR3-overexpressing cells (FGFR3-WT transfected groups) and FGFR3-K650E mutant-overexpressing cells (FGFR3-K650E transfected groups) were constructed by using the plasmid transfection method, and cells transfected with blank vectors served as control groups (blank vector control groups). Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of HPV2 E2, and Western blot analysis to determine the protein expression of HPV2 E2, FGFR3, and keratinocyte differentiation markers including loricrin, filaggrin, as well as involucrin. Laser scanning confocal microscopy was conducted to observe the spatial localization of HPV2 E2 and FGFR3 in HaCaT cells. Statistical analysis was carried out by using two-independent-sample t test for the comparison between two groups, one-way analysis of variance for the comparison among multiple groups, and Dunnett t-test for multiple comparisons. Results:The HPV2 E2-stably transfected cell lines were successfully constructed, and the expression of HPV2 E2 FLAG protein was significantly higher in the HPV2 E2-transfected groups than in the blank vector control groups in both HaCaT and NHEK cells ( t = 13.71, 25.91, respectively, both P < 0.001) ; both FGFR3-WT and FGFR3-K650E were successfully overexpressed in both HaCaT and NHEK cells, and the FGFR3 protein expression was significantly higher in the FGFR3-WT transfected groups and the FGFR3-K650E transfected groups than in the blank vector control groups ( F = 473.90, 579.90, respectively, both P < 0.001). In both HaCaT and NHEK cells, the expression of keratinocyte differentiation markers including loricrin, filaggrin, and involucrin was significantly upregulated in the HPV2 E2-transfected groups, the FGFR3-WT transfected groups, and the FGFR3-K650E transfected groups than in the blank vector control groups (all P < 0.05). In the HPV2 E2-stably transfected HaCaT and NHEK cells, the expression of loricrin, filaggrin, and involucrin was significantly down-regulated in the HPV2 E2 + FGFR3-WT transfected groups and the HPV2 E2 + FGFR3-K650E transfected groups than in the HPV2 E2 + blank vector groups (all P < 0.05). Laser scanning confocal microscopy showed the spatial co-localization of HPV2 E2 and FGFR3 in the nuclear membrane and cytoplasm of HaCaT cells. Conclusion:HPV2 E2 and FGFR3 could both induce the differentiation of HaCaT and NHEK cells, while FGFR3 could inhibit HPV2 E2-induced differentiation trend of HaCaT and NHEK cells, which may be related to the cellular spatial co-localization of HPV2 E2 and FGFR3.

Objective:To investigate the correlations between perfused lung volumes, visual scores (using perfusion SPECT/CT) and right-heart catheter (RHC) hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH).Methods:A total of 51 consecutive CTEPH patients (17 males, 34 females, age (59±12) years) in the First Affiliated Hospital of Guangzhou Medical University between March 2015 and July 2019 were retrospectively analyzed. All patients underwent lung perfusion SPECT/CT imaging and RHC examinations. Perfused lung volumes were determined using threshold-based (15%-85%) segmentation. Visual semiquantitative scoring in each lung segment was performed using Begic method. RHC hemodynamic parameters including pulmonary artery systolic pressure (PASP), pulmonary arterial diastolic pressure (PADP), mean pulmonary artery pressure (mPAP), pulmonary arteriolar wedge pressure (PAWP), pulmonary vessel resistance (PVR), cardiac output (CO), cardiac index (CI) were recorded. Spearman correlation analysis was used to evaluate the correlations between perfused lung volumes, visual scores and hemodynamic parameters.Results:There were significant correlations between perfused lung volumes (30%-70% threshold) and mPAP ( rs values: from -0.414 to -0.302, all P<0.05). Among them, perfused lung volumes under the threshold of 40% and 45% were moderately correlated with mPAP ( rs values: -0.414, -0.412, both P<0.05). Perfused lung volume (40% threshold) was moderately negatively correlated with PASP, PADP ( rs values: -0.402, -0.440, both P<0.05), and slightly negatively correlated with PVR ( rs=-0.352, P<0.05). Visual scores were slightly positively correlated with the PADP ( rs=0.311, P<0.05), while there was no correlation between visual scores and other RHC hemodynamic parameters ( rs values: from -0.201 to 0.275, all P>0.05). Conclusion:Perfused lung volumes based on threshold-based segmentation in lung perfusion SPECT/CT imaging can accurately reflect hemodynamic status and may provide useful information for severity assessment of CTEPH.

This article briefly describes the imaging performance standards of the kilovolt X-ray image guidance system used in radiotherapy, analyzes the main aspects that should be considered in the image quality of X-IGRT system, and focuses on parameters that should be considered in the imaging performance evaluation criteria of the CBCT X-IGRT. The purpose is to sort out the imaging performance evaluation standards of kilovolt X-IGRT system, clarify the image quality requirements of X-IGRT equipment, and reach a consensus when evaluating the imaging performance of X-IGRT system.
Radiotherapy Planning, Computer-Assisted/methods* ; Cone-Beam Computed Tomography/methods* ; Spiral Cone-Beam Computed Tomography ; Radiotherapy, Intensity-Modulated/methods* ; Radiotherapy, Image-Guided/methods*