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Osteoarthritis (OA) is the most common type of arthritis with no effective therapy. Subchondral bone and overlying articular cartilage are closely associated and function as "osteo-chondral unit" in the joint. Abnormal mechanical load leads to activated osteoclast activity and increased bone resorption in the subchondral bone, which is implicated in the onset of OA pathogenesis. Thus, inhibiting subchondral bone osteoclast activation could prevent OA onset. Betaine, isolated from the Lycii Radicis Cortex (LRC), has been demonstrated to exert anti-inflammatory, antifibrotic and antiangiogenic properties. Here, we evaluated the effects of betaine on anterior cruciate ligament transection (ACLT)-induced OA mice. We observed that betaine decreased the number of matrix metalloproteinase 13 (MMP-13)-positive and collagen X (Col X)-positive cells, prevented articular cartilage proteoglycan loss and lowered the OARSI score. Betaine decreased the thickness of calcified cartilage and increased the expression level of lubricin. Moreover, betaine normalized uncoupled subchondral bone remodeling as defined by lowered trabecular pattern factor (Tb.pf) and increased subchondral bone plate thickness (SBP). Additionally, aberrant angiogenesis in subchondral bone was blunted by betaine treatment. Mechanistically, we demonstrated that betaine suppressed osteoclastogenesis in vitro by inhibiting reactive oxygen species (ROS) production and subsequent mitogen-activated protein kinase (MAPK) signaling. These data demonstrated that betaine attenuated OA progression by inhibiting hyperactivated osteoclastogenesis and maintaining microarchitecture in subchondral bone.
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Objective:To design and construct a bone nonunion organoid on chip and explore the mechanism of aseptic bone nonunion.Methods:First a semi-open microfluidic chip was designed, on which human bone marrow mesenchymal stromal cells (BMSC), human fetal lung fibroblast 1, (HFL1) and human umbilical vein endothelial cells (HUVEC) were co-cultured, and a three-dimensional organ on chip system was established. Different proportions of HFL1 and HUVEC were co-cultured with BMSC, which were divided into the control group (HFL1∶HUVEC=1∶1), the fibrosis group (HFL1∶HUVEC=3∶1) and the vascularization group (HFL1∶HUVEC=1∶3). The osteogenic differentiation of BMSC was observed by alkaline phosphatase (ALP) and Alizarin red staining. The transcription level of osteogenic marker genes SP7, RUNX2, ALPL, and BGLAP, and vascularization related genes KDR and VWF were analyzed by qPCR. The expression levels of RUNX2 and ALP were determined by Western Blot. Results:In the co-culture system of BMSCs, HFL1, and HUVECs, BMSCs exhibited normal growth and apparent biomineralization behavior. Endothelial cells were capable of forming structured vascular networks, confirming the successful establishment of the system. Compared to the baseline group, the fibrotic group showed no significant decrease in BMSC osteogenic differentiation. The relative expression levels of the mineralization marker genes ALPL and BGLAP were 0.55±0.19 ( P<0.001) and 0.42±0.27 ( P<0.001), respectively. Vascularization genes KDR and VWF were downregulated, with relative expression levels of 0.49±0.17 ( P<0.001) and 0.49±0.21 ( P<0.001). In contrast, in the vascularized group, BMSC osteogenic differentiation genes SP7, RUNX2, ALPL, and BGLAP were upregulated, with relative expression levels of 2.91±0.52 ( P<0.001), 3.83±1.87 ( P<0.001), 3.22±1.29 ( P<0.001), and 5.21±1.46 ( P<0.001), respectively. Vascularization genes KDR and VWF were also upregulated, with relative expressions of 8.24±2.84 ( P<0.001) and 5.32±1.67 ( P<0.001). Western blot results indicated increased expression of RUNX2 and ALP in the vascularized group and decreased expression in the fibrotic group. Conclusion:The bone nonunion organoid on chip could partially simulate the local microenvironment of bone nonunion. Fibrosis may lead to a significant decrease in bone formation ability and vascularization level, which might be an important reason for the occurrence of aseptic bone nonunion.
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BACKGROUND: The balance of bone homeostasis is mediated by the osteoclast-related bone resorption and osteoblast-related bone formation. Over-activation of osteoclasts results in a series of bone metabolic diseases including rheumatoid arthritis and osteoporosis. The activation of nuclear factor-κB pathway induced by receptor activator of nuclear factor-κB ligand (RANKL) plays an important role in osteoclastogenesis. OBJECTIVE: To explore the effect of corylin on RANKL-mediated osteoclastogenesis. METHODS: RAW264.7 cells were incubated with 0, 1, 2, 4, 8, 16, 32, 64, 128 μmol/L corylin. The cytotoxicity of corylin was detected by cell counting kit-8 assay. RANKL induced the differentiation of RAW264.7 cells into osteoclasts, during which 2, 5, 10 μmol/L corylin was given. The number of osteoclasts was analyzed by TRAP staining after 5 days of intervention and the morphology and function of osteoclasts were analyzed by F-actin staining. Bone resorption assay was conducted after 2 days of intervention. The activation of nuclear factor-κB pathway was detected by western blot at 0, 15, 30, and 60 minutes of intervention. Then in vivo experiments were carried out, and the ovariectomized mice were intraperitoneally given 10 mg/kg twice a week. After 6 weeks of intervention, mouse femurs were taken for morphological analysis. RESULTS AND CONCLUSION: There was no cytotoxicity of corylin below the concentration of 16 μmol/L. Corylin inhibited osteoclastogenesis in a dose-dependent manner. Corylin inhibited the formation of F-actin and resorption activity of osteoclasts. Corylin inhibited RANKL-mediated nuclear factor-κB pathway. Corylin treatment reduced the bone loss in postmenopausal osteoporosis mice. Overall, corylin inhibits osteoclastogenesis via blocking nuclear factor-κB pathway and attenuates postmenopausal osteoporosis.
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The incidence of osteoporotic distal humeral fracture in the elderly is progressing in recent decade. Difficulty of reduction and poor internal fixation stability make osteoporotic distal humerus fractures become a challenging fracture type. Therefore, it is necessary to develop an individualized treatment plan based on the patient's condition and functional requirements. The authors discuss key questions in the treatment of osteoporotic distal humerus fracture in combination with current literatures and researches, so as to provide a reference for clinical diagnosis and treatment.
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Objective To discuss the clinical application of C-arm CT in guiding Hook-wire localization of solitary pulmonary nodule (SPN) before video-assisted thoracoscopic surgery (VATS).Methods The clinical data of 51 patients with SPN (51 lesions in total),who received C-arm CT-guided Hook-wire localization before VATS during the period from January 2011 to December 2015 at authors' hospital,were retrospectively analyzed.The technical success rate,the time spent for localization,the incidence of complications,the rate of VATS conversion to thoracotomy,the average size of SPN,the distance between SPN and visceral pleura,and the pathological findings were documented.Results The technical success rate of preoperative C-arm CT-guided Hook-wire localization was 100％.The mean time spent for localization was 16 minutes.Asymptomatic pneumothorax occurred in 4 patients (7.8％) and asymptomatic hemorrhage in 11 patients (21.6％).Intraoperative dislodgement of the hook-wire was seen in one patient (2.0％).The average size of SPN was 10.7 mm.The mean distance between SPN and visceral pleura was 25.3 mm,and the puncturing depth (the length from skin to pulmonary nodule) was 66.7 mm.Pathological examination revealed that 60.8％ of the 51 SPNs were malignant.Conclusion Preoperative C-arm CT-guided Hook-wire localization of SPN before VATS is an accurate,safe and fast technique.This technique is an efficient means to guide the puncturing,and it has high application value in clinical practice.
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Objective To investigate the feasibility, safety and clinical effect of percutaneous transhepatic bipolar radiofrequency catheter ablation in treating malignant obstructive jaundice. Methods Twenty patients with inoperable malignant biliary obstruction were enrolled in this study. Of the 20 cases , 2 had biliary stent re-occlusion. Percutaneous transhepatic bipolar radiofrequency catheter ablation was carried out in all patients. The ablation power was 5 - 12 W, single ablation time was 60 - 120 s, the average duration of ablation was 4.66 min (1.5 - 8.5 min), and the mean effective ablation extent was 5.76 cm (4 -10 cm). After ablation, balloon catheter was inserted to dilate the occluded segment, which was followed by implantation of biliary metal stent. The clinical efficacy , safety and complications were recorded. Results Percutaneous transhepatic bipolar radiofrequency catheter ablation was successfully completed in all the 20 patients. Implantation of biliary metal stent was performed in 17 patients , among them balloon dilatation was employed in 11 patients before stent implantation , simple balloon dilatation with no stent implantation was employed in one patient, and ablation was adopted after biliary stent re-occlusion occurred in two patients. After the ablation, no complications such as biliary fistula, biliary tract infections, liver penetrating injuries, peritonitis, etc. occurred. Biliary drainage was successfully completed in all patients. The median follow-up period was three months(0.5-10 months); the stent patency rate at the end of one and three months was 100% (19/19) and 79% (11/14) respectively. The one-month and 3-month survival rate was 95% (19/20) and 93% (14/15) respectively. During the follow-up period, 8 of the 20 patients were alive and 12 died. The median survival time was 144 days (13 - 330 days) and the median time of stent patency was 60 days (30-210 days). Of the 12 fatal patients, 8 died of cachexia with multi- system failure although their total bilirubin level was not elevated during the follow- up period. Conclusion For the treatment of malignant obstructive jaundice, percutaneous transhepatic bipolar radiofrequency catheter ablation is a newly-developed, safe and feasible means. Clinically, this technique has already achieved some certain effect although its long-term results need to be further evaluated.
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Objective To evaluate the potential of interventional regional arterial infusion for severe acute pancreatitis (SAP). Methods Regional arterial infusion with somatostatin and antibiotic was performed in 20 cases of SAP within 4 hours after diagnosis confirmed,and pressurized infusion lasted for 5 days. Another 28 cases of SAP as control group received drug treatment all over the body. The SAP clinical data such as symptom,mortality,complication rate and stay time in hospital were analysed in two groups. Results There were significant differences in remission,serum amylase,urine amylase and lipase between the regional and total infusion groups. The stay time in hospital,mortality,complication and operation rate were lower in regional infusion group than those of control group(P
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Objective To evaluate the effect of endovascular graft exclusion (EVGE) for aorta aneurysm(AA). Methods From October,2000 to August 2002,5 cases of AA were treated by EVGE, 4 of which were thoracic and abdominal aortic dissecting aneurysm and the another one was abdominal AA. Results All the operations were successfully performed. The pseudo cavity in the 4 cases of aortic dissection disappeared after the operation,and the another aortic aneurysm was successfully isolated. Conclusions EVGE is an effective ,less trauma and safe, when the indications are carefully selected.