The progress of research on the the anterior cruciate ligament (ACL) wound healing demonstrates that the synovial tissue in the knee joint plays a very important role in the healing process of injured ACL. Therefore, the molecular response mechanisms of lysyl oxidase (LOX) and matrix metalloproteina (MMP) in normal/injured ACL fibroblast cells could be considered to perform the major analysis function of injured ACL healing mechanism. The mRNA expressions of LOXs and MMPs and the activity expressions of MMP-2 in ACL fibroblasts co-cultured with synovial cells were analyzed by quantitative real-time PCR and zymography. The results showed that co-culture could regulate the mRNA expressions of LOXs and MMPs in the ACL fibroblasts cells. These results suggest that the differential expressions of LOXs and MMP-1, 2, 3 in co-cultured ACL indicate that interaction crosstalk do exist between ACL cells and synovial cells and provide a theoretical basis for subsequent exploration of the mechanisms and treatment of ACL injury and repair.
Anterior Cruciate Ligament ; cytology ; Anterior Cruciate Ligament Injuries ; Coculture Techniques ; Fibroblasts ; cytology ; metabolism ; Humans ; Knee Injuries ; physiopathology ; Knee Joint ; cytology ; Matrix Metalloproteinases ; genetics ; metabolism ; Protein-Lysine 6-Oxidase ; genetics ; metabolism ; Synovial Membrane ; cytology ; Wound Healing ; physiology

BACKGROUNDCerebral venous thrombosis (CVT) may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT.

METHODSThis retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, including plasma fibrinogen and HDL-C. Patients with CVT were followed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis.

RESULTSAt the end of the follow-up, 95 patients were eligible for the study. Twelve of 95 patients (12.6%) had recurred CVT. The median time of recurrence was 7 months (range: 1-39 months). Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio: 4.69; 95% confidence interval: 1.10-20.11; P < 0.05). Of the twelve patients with recurrent CVT in our study, 7 (58.3%) had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment.

CONCLUSIONSConcomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

Adolescent ; Adult ; Aged ; Cholesterol, HDL ; metabolism ; Cohort Studies ; Female ; Fibrinogen ; metabolism ; Humans ; Intracranial Thrombosis ; metabolism ; pathology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Young Adult

BACKGROUNDImage-guided neurosurgery, endoscopic-assisted neurosurgery and the keyhole approach are three important parts of minimally invasive neurosurgery and have played a significant role in treating skull base lesions. This study aimed to investigate the potential usefulness of coupling of the endoscope with the far lateral keyhole approach and image guidance at the ventral craniocervical junction in a cadaver model.

METHODSWe simulated far lateral keyhole approach bilaterally in five cadaveric head specimens (10 cranial hemispheres). Computed tomography-based image guidance was used for intraoperative navigation and for quantitative measurements. Skull base structures were observed using both an operating microscope and a rigid endoscope. The jugular tubercle and one-third of the occipital condyle were then drilled, and all specimens were observed under the microscope again. We measured and compared the exposure of the petroclivus area provided by the endoscope and by the operating microscope. Statistical analysis was performed by analysis of variance followed by the Student-Newman-Keuls test.

RESULTSWith endoscope assistance and image guidance, it was possible to observe the deep ventral craniocervical junction structures through three nerve gaps (among facial-acoustical nerves and the lower cranial nerves) and structures normally obstructed by the jugular tubercle and occipital condyle in the far lateral keyhole approach. The surgical area exposed in the petroclival region was significantly improved using the 0° endoscope (1147.80 mm(2)) compared with the operating microscope ((756.28 ± 50.73) mm(2)). The far lateral retrocondylar keyhole approach, using both 0° and 30° endoscopes, provided an exposure area ((1147.80 ± 159.57) mm(2) and (1409.94 ± 155.18) mm(2), respectively) greater than that of the far lateral transcondylar transtubercular keyhole approach ((1066.26 ± 165.06) mm(2)) (P < 0.05).

CONCLUSIONSWith the aid of the endoscope and image guidance, it is possible to approach the ventral craniocervical junction with the far lateral keyhole approach. The use of an angled-lens endoscope can significantly improve the exposure of the petroclival region without drilling the jugular tubercle and occipital condyle.

Adult ; Endoscopes ; Humans ; Neuronavigation ; methods ; Skull Base ; anatomy & histology ; surgery ; Surgery, Computer-Assisted

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate and regulate cardiac rhythm and rate. It has been suggested that, unlike the HCN1 and HCN2 channels, the slower HCN4 channel may not exhibit voltage-dependent hysteresis. We studied the electrophysiological properties of human HCN4 (hHCN4) channels and its modulation by cAMP to determine whether hHCN4 exhibits hysteresis, by using single-cell patch-clamp in HEK293 cells stably transfected with hHCN4. Quantitative real-time RT-PCR was also used to determine levels of expression of HCNs in human cardiac tissue. Voltage-clamp analysis revealed that hHCN4 current (I(h)) activation shifted in the depolarizing direction with more hyperpolarized holding potentials. Triangular ramp and action potential clamp protocols also revealed hHCN4 hysteresis. cAMP enhanced I(h) and shifted activation in the depolarizing direction, thus modifying the intrinsic hHCN4 hysteresis behavior. Quantitative PCR analysis of human sinoatrial node (SAN) tissue showed that HCN4 accounts for 75% of the HCNs in human SAN while HCN1 (21%), HCN2 (3%), and HCN3 (0.7%) constitute the remainder. Our data suggest that HCN4 is the predominant HCN subtype in the human SAN and that I(h) exhibits voltage-dependent hysteresis behavior that can be modified by cAMP. Therefore, hHCN4 hysteresis potentially plays a crucial role in human SAN pacemaking activity.
Biological Clocks ; physiology ; Cyclic AMP ; physiology ; Cyclic Nucleotide-Gated Cation Channels ; physiology ; Electrophysiological Phenomena ; HEK293 Cells ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Muscle Proteins ; physiology ; Patch-Clamp Techniques ; Potassium Channels ; Sinoatrial Node ; physiology ; Transfection

BACKGROUNDA practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts. Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds, enhanced production of bone marrow cells, and improved tissue-engineered bone formation. The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells (BMSCs).

METHODSBMSCs/β-tricalcium phosphate (β-TCP) composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound (LIPUS) treatment group and a control group. These implants were harvested at 5, 10, 25, and 50 days after implantation. The samples were then biomechanically tested and analyzed for alkaline phosphate (ALP) activity and osteocalcin (OCN) content and were also observed by light microscopy.

RESULTSThe levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group. Histomorphometric analysis revealed a greater degree of soft tissue repair, increased blood flow, better angiogenesis, and more extensive bone formation in the LIPUS groups than in the controls. No significant difference in the compressive strength was found between the two groups.

CONCLUSIONLIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β-TCP composites.

Animals ; Bone Marrow Cells ; physiology ; Bone Transplantation ; Calcium Phosphates ; pharmacology ; Male ; Osteogenesis ; physiology ; Rats ; Stromal Cells ; Tissue Engineering ; methods ; Transplantation, Isogeneic ; Ultrasonics ; methods

This paper is aimed to investigate the effect of titanium (Ti) particles and tumor necrosis factor alpha (TNF-alpha) on the expressions of MMP-1, 2, 3 in human synovial cells, so as to explore the possible mechanism of osteolysis post-operation of metal-on-metal total joint arthroplasty in human synovial cells induced by Ti particles. In vitro cell cultures, human synovial cells were treated by Ti particles and/or TNF-alpha. The total RNA was isolated at 2 hours after the treatment. The gene expression of MMP-1, 2, 3 was analyzed by Semi-quantitative Reverse-transcriptional PCR and quantitative real-time PCR. Cell supernatant was collected at 12, 24, 48 hours after the treatment and Gelatin zymography was performed to detect the activity of MMP-2. Compared to those in the control group (untreated), Ti particles and TNF-alpha increased the gene expression of MMP-1, 2, 3 respectively (P < 0.05), and the effect of combination of the two was even more significant (P < 0.01). The trend of activities of MMP-2 is similar with gene expression. Ti particles and TNF-alpha increased MMP-2 activities by 1.3 times and 1.5 times respectively (P < 0.05), and the combination of the two increased by 1.7 times (P < 0.01). Ti particles and TNF-alpha-induced the stimulation of MMP-1, 2, 3 expressions and MMP-2 activities in human knee joint synovial cells may be involved in aseptic loosening after metal-on-metal arthroplasty through increasing the degradation of bone matrix and declining of osseous support structure mechanics.
Cells, Cultured ; Humans ; Joint Prosthesis ; Knee Joint ; cytology ; Matrix Metalloproteinase 1 ; genetics ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 3 ; genetics ; metabolism ; Matrix Metalloproteinases ; genetics ; metabolism ; Particle Size ; Prosthesis Failure ; adverse effects ; RNA ; genetics ; metabolism ; Synovial Membrane ; cytology ; enzymology ; Titanium ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology