Surgical intervention for malignant bone tumors frequently results in bone defects located at the metaphysis of the long bones in the lower extremities.The morphological heterogeneity of the metaphysis poses significant challenges for conventional treatment methods to adequately conform to the defect area.The utilization of three-dimensional(3D)-printed titanium bone repair scaffolds has emerged as an effective reconstructive approach for metaphyseal bone defects,as these scaffolds offer precise shape conformity and provide adequate mechanical support.However,the current commonly used scaffolds do not adequately replicate the biomechanical environment of bone defects,resulting in suboptimal bone ingrowth within the scaffolds and subsequent prosthesis loosening and failure post-operation.Bone is a highly force-responsive organ,and its fate is regulated by biomechanical signals.Consequently,designing scaffolds with consideration of biomechanical principles to ensure mechanical compatibility between the scaffolds and the bone defect sites is a critical factor influencing the success of bone defects reconstruction.This review primarily introduces the biomechanical factors influencing bone defect repair and the advancements in designing 3D-printed titanium bone repair scaffolds biomechanically matched with bones,offering theoretical guidance for scaffold design and preparation.

Surgical intervention for malignant bone tumors frequently results in bone defects located at the metaphysis of the long bones in the lower extremities.The morphological heterogeneity of the metaphysis poses significant challenges for conventional treatment methods to adequately conform to the defect area.The utilization of three-dimensional(3D)-printed titanium bone repair scaffolds has emerged as an effective reconstructive approach for metaphyseal bone defects,as these scaffolds offer precise shape conformity and provide adequate mechanical support.However,the current commonly used scaffolds do not adequately replicate the biomechanical environment of bone defects,resulting in suboptimal bone ingrowth within the scaffolds and subsequent prosthesis loosening and failure post-operation.Bone is a highly force-responsive organ,and its fate is regulated by biomechanical signals.Consequently,designing scaffolds with consideration of biomechanical principles to ensure mechanical compatibility between the scaffolds and the bone defect sites is a critical factor influencing the success of bone defects reconstruction.This review primarily introduces the biomechanical factors influencing bone defect repair and the advancements in designing 3D-printed titanium bone repair scaffolds biomechanically matched with bones,offering theoretical guidance for scaffold design and preparation.

Objective:To evaluate the short-term efficacy and safety of 3D printing patient-matched artificial vertebral body in clinical research and application.Methods:A total of 12 patients with spinal tumors were enrolled 7 males (58.33%) and 5 females (41.67%), aged from 18 to 65 years old in The First Affiliated Hospital of Air Force military Medical University (hereinafter referred to as Xijing Hospital) and Peking University people's Hospital from September 2021 to July 2022. The spinal vertebra defect were restored by using 3D printing patient-matched artificial vertebral body after tumor resection. All patients who accepted TES and 3D printing patient-matched artificial vertebral body implantation were included according to the inclusion and exclusion criteria. The bone interface fusion was evaluated by the imaging fusion criteria of Brantigan and Steffee at 3 and 6 months after operation, the curative effect was evaluated by comparing Japanese Orthopaedic Association (JOA) score at 3 and 6 months after operation, visual analogue scale (VAS) 3 months after operation and intervertebral height at 3 and 6 months after operation with those before operation, and the safety was evaluated by adverse event recording.Results:All 12 patients completed the operation successfully, and the operation sites were thoracic vertebrae in 6 cases (50%), thoracolumbar in 3 cases (25%) and lumbar vertebrae in 3 cases (25%). All patients were followed up. The mean follow-up time was 23.92±3.23 months (range, 19-29 months). No tumor recurrence or metastasis was observed during this period. All patients were followed up at 15 days, 3 months and 6 months after operation. During the 6-month follow-up, X ray results showed that interface of bone and the vertebral body were fused in all of the 12 patients, and the effective rate of fusion was 100%. The 95% confidence interval is calculated to be (75.6%-100%). Six months after operation, the improvement rate of JOA score was excellent in 10 cases, good in 1 case, poor in 1 case, and the excellent and good rate was 91.66%. The preoperative VAS score was 4.08 ±2.47, and during the 3-month follow-up, the VAS score was improved to 1.83 ±1.59. Compared with the preoperative VAS score, the difference was statistically significant ( t=2.635, P=0.023). The intervertebral height before operation, 15 days after operation, 3 months after operation and 6 months after operation were 32.75 (25.94, 68.20), 41.09 (30.55, 70.20), 40.70 (30.23, 67.83) and 40.74 (30.23, 67.08), respectively, and there was no statistically significant difference (χ 2=0.768, P=0.857). No implant-related adverse events occurred after operation. Conclusion:The 3D printing patient-matched artificial vertebral body used in this study has satisfactory short-term efficacy and safety in the reconstruction of spinal stability after spinal tumor resection.

Coronary heart disease (CHD) is a kind of cardiovascular diseases originated from atherosclerosis (AS), and chronic inflammation is one of the pathological characteristics. The peripheral blood leukocytes, especially mononuclear cells, play an important role in the AS processes. Recently, in a series of Epigenome-Wide Association Studies (EWAS), multiple DNA differential methylation sites in peripheral blood cells were found to be statistically associated with CHD, which suggested that these DNA differential methylation sites might serve as new risk factors for CHD. The recognition of the variant of DNA methylation as a common epigenetic nucleic acid modification in the occurrence and development of CHD, is ongoing. DNA methylation has the potential to become warning biomarkers, which might provide new ideas and evidences for mechanistic studies of CHD.

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.

Objective: To compare instrumentation with 3D-printed patient-specific guides versus conventional techniques in supramalleolar osteotomy for varus ankle osteoarthritis. Methods: A retrospective analysis was done of the 21 patients with varus ankle osteoarthritis who had been treated at Department of Orthopaedics, Shanghai JiaoTong University Affiliated Sixth People's Hospital from January 2017 to December 2018. They were divided into 2 groups by their treatment methods. In the 9 patients treated by instrumentation with 3D-printed patient-specific guides, there were 6 males and 3 females with an age of 54.6±8.6 years, 4 left and 5 right sides involved, and one case of Takakura stage 1, 3 cases of Takakura stage 2 and 5 cases of Takakura stage 3a. In the 12 patients treated by conventional techniques, there were 7 males and 5 females with an age of 53.0±6.5 years, 7 left and 5 right sides involved, and one case of Takakura stage 1, 5 cases of Takakura stage 2 and 6 cases of Takakura stage 3a. The 3D printed guide group and the conventional group were compared in terms of operation time, intraoperative blood loss and frequency of intraoperative fluoroscopy, tibial anterior surface angle (TAS), talar tilt angle (TT), and tibial lateral surface angle (TLS). The differences in TAS, TT and TLS between pre- and post-operation in the 3D printed guide group were also evaluated. Results: There were no significant differences in the preoperative general data between the 2 groups (P>0.05), indicating they were comparable. All the patients were available for follow-up for an average of 7.8 months (from 3 to 15 months). The 3D printed guide group incurred significantly shorter operation time (106.2±10.6 min), less intraoperative blood loss (207.2±16.0 mL) and lower fluoroscopy frequency (2±0) than the conventional osteotomy group (all P<0.01). The post-operative TAS (94.3°±3.2°) and TT (3.8°±0.8°) angles in the 3D guide group were significantly different from their preoperative values (84.6°±3.5° and 7.6°±1.6°) (P<0.01). The 3D printed guide group was not significantly different from the conventional group in postoperative TAS (94.3°±3.2° versus 92.4°±5.9°), TT (3.8°±0.8° versus 4.2°±1.1°) or TLS (83.7°±3.4° versus 84.2°±2.2°) angles (P>0.05). Conclusions Compared with conventional techniques, instrumentation with 3D-printed patient-specific guides can shorten operation time and reduce intraoperative blood loss and fluoroscopy frequency. The 3D printed patient-specific guides in osteotomy can facilitate accurate correction of varus deformity, leading to similar efficacy compared with conventional osteotomy.

Objective To compare the effects between the dual-cycle intensive training mode (DCITM) of "teaching-in vitro-in vivo-summary-in vitro-in vivo-assessment" and the single-cycle basic training mode (BTM) of "teaching-in vitro-tn vivo-assessment" on training graduate students majoring in cardiovascular surgery.Methods Eight graduate students majoring in cardiovascular surgery received the basic training of coronary artery bypass vascular anastomosis under the mode of BTM or DCITM.Then the training effects were evaluated by scoring of experts.Besides,SPSS 17.0 statistical software was used to analyze the evaluation results.Results Compared with students who received BTM,the postgraduates trained by DCITM became more skilled in vascular anastomosis.In vitro,the average number of anastomosis completed by trainee increased significantly [(2.0 ± 1.0) vs.(5.0 ± 1.5),P＜0.05] over a specified period of time,the vascular leakage rate was significantly reduced [(92 ± 5)％ vs.(30 ± 2)％,P＜0.05],and the average time per anastomosis was significantly shorter [in vitro:(20.1 ± 2.5) min vs.(12.6 ± 3.3) min,P＜0.05].There was also a statistically significant difference in the average time of each anastomosis in miniature pigs with coronary vascular anastomosis [in vivo:(30 ± 2) min vs.(21 ± 3) min,P＜0.05].Conclusion Taken into together,DCITM is a highly efficient mode for promoting the quality of cardiovascular-surgery-teaching and enhancing the effectiveness of training in clinical surgical skills.

Objective To investigate the efficacy and safety of salvage radical prostatectomy for men with recurrent prostate cancer (PCa) after radiotherapy.Method Ten pathologically confirmed PCa patients who relapsed after radiotherapy from Jan.2008 to Dec.2013 were retrospectively reviewed.The mean age was (64.7 ±3.7) years,with range from 56 to 72 year.Local recurrence was confirmed by retransrectal biopsy.All patients had increased PSA and/or lower urinary tract symptoms.Pelvis MRI and bone scan were performed to detect lymph node involvement and bone metastasis.All patients received radical prostatectomy with standard pelvic lymphadenectomy.Seven received open surgery (open group),three patients underwent laparoscopic surgery (laparoscopic group).Postoperative complication and PSA level were compared.Results Salvage radical prostatectomies with lymph node dissection were performed in all patients without major complications.The mean operation time of open group versus laparoscopic group were (225 ± 57)min vs.(210 ± 80)min and the mean blood loss was (275 ± 49)ml vs.(260 ± 93) ml,both of which were with no significant difference (P ＞ 0.05).The average length of stay was (14 ± 4) vs.(8 ± 2) day with significant difference (P ＜ 0.05).No rectal injury was observed.Two (20％) patients were with positive margin,and three (30％) patients had postoperative complications,including one case of deep vein thrombosis,one case of incision infection and and one case of anastomotic leakage.After a mean of 20.6 months'follow-up,two patients (25％) reached biochemical recurrence.Conclusion Both open and laparoscopic salvage radical prostatectomies after radiotherapy failure were feasible.Largescaled prospective studies were needed to verify the long-term effectiveness.

Objective To explore the safty and feasibility of transrectal ultrasound guided transperineal seminal vesicle biopsy in the evaluation of clinical staging of prostate cancer.Methods Retrospectively study 57 suspected prostate cancer patients with seminal abnormality during 2010.7-2015.1,age ranged from 50 to 78 years,average 65 ±7 years,serum total prostate specific antigen (tPSA) 3.2-131.1 μg/L, average (23.7 ± 11.3) μg/L.Twenty-two cases had palpable prostate nodules through rectal examination.All the 57 patients underwent ultrasound and template guided transperineal prostate and seminal vesicle puncture biopsies.Results Forty-four cases out of 57 found prostate cancer cells in biopsies, and 32 cases had seminal vesicle invasion (positive group) while the other 12 were negative.Twenty cases had been performed prostatectomy in the positive group and their post-operative pathological examination all showed prostate cancer with seminal vesicle invasion.Eleven cases in the negative group had been performed prostatectomy ,and 2 cases showed seminal vesicle invasion.The clinical stages of all cases in the positive group were considered as T3b both pre-operatively and post-operatively.In the negative group however, 11 cases were considered as T2 stage pre-operatively,while 2 cases were increased to T3b stage post-operatively.The sensitivity of puncturing seminal vesicle was 91％ (20/22) ,specificity was 100.0％ (9/9).Positive predictive value was 100.0％ (20/20),while negative predictive value was 82％ (9/11).All the 57 cases did not present fever after puncture biopsies, while 23 cases presented hematuria (40％) ,20 cases presented hemospermia (35％) and 1 case presented urinary retention (2％).Conclusions Transrectal ultrasound-guided transperinealseminal vesicle puncture is safe and reliable, it helps to improve the accuracy of pre-operative staging.

The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.
Adipose Tissue ; cytology ; Animals ; Cell Communication ; Cell Differentiation ; Cell Movement ; Cell Survival ; Coculture Techniques ; Fibrosis ; Male ; Mesenchymal Stem Cells ; cytology ; Myocardium ; pathology ; Myofibroblasts ; cytology ; Phenotype ; Rats ; Rats, Sprague-Dawley