Rosuvastatin: A Potential Therapeutic Agent for Inhibition of Mechanical Pressure-Induced Intervertebral Disc Degeneration.

Background: Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear. Purpose: To explore the molecular mechanism of mechanical pressure (MP)-induced IDD and to assess the role and mechanism of Rosuvastatin (RSV) inhibits MP-induced IDD. Methods: SD rat nucleus pulposus cells (NPCs) were cultured in vitro and an apoptosis model of NPCs was constructed using MP. Proliferative activity, reactive oxygen species content, apoptosis, and wound healing were detected in each group of NPCs, respectively. The expression of relevant proteins was detected by qPCR and Western Blot techniques. 18 SD rats were randomly divided into control, pressure and RSV groups. Elisa, qPCR, Western Blot and immunohistochemical staining techniques were used to detect changes in the content of related proteins in the intervertebral discs of each group. HE staining and Modified Saffron-O and Fast Green Stain Kit were used to assess IDD in each group. Results: MP treatment at 1.0 MPa could significantly induce apoptosis of NPCs after 24 h. MP could significantly inhibit the proliferative activity and wound healing ability of NPCs, and increase the intracellular reactive oxygen species content and apoptosis rate; pretreatment with RSV could significantly activate the Nrf2/HO-1 signaling pathway and reverse the cellular damage caused by MP; when inhibit the Nrf2/HO-1 signaling pathway activation, the protective effect of RSV was reversed. In vivo MP could significantly increase the content of inflammatory factors within the IVD and promote the degradation of extracellular matrix, leading to IDD. When the intervention of RSV was employed, it could significantly activate the Nrf2/HO-1 signaling pathway and improve the above results. Conclusion: RSV may inhibit MP-induced NPCs damage and IDD by activating the Nrf2/HO-1 signaling pathway.

Sinomenine Ameliorates IL-1ß-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways.

Purpose: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1ß (IL-1ß)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD). Methods: The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1ß to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL-1ß. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1ß. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques. Results: IL-1ß significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-κB signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1ß injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes. Conclusion: SN can prevent IL-1ß-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB signaling pathway.

An anatomical study of the origins courses and distributions of the transverse branches of lumbar arteries at the L1-L4 levels.

Pseudoaneurysms of the lumbar arteries following transforaminal lumbar interbody fusion (TLIF) are rare postoperative complications that usually occur around the transverse process. However, there are few detailed descriptions of the transverse branch and other branches of the dorsal branches at the L1-L4 disks. STUDY DESIGN: Ten adult embalmed cadavers were anatomically studied. OBJECTIVES: The purposes of the study were to describe the vascular distribution of the dorsal branches, especially the transverse branches, at the L1-L4 levels and provide information useful for TLIF. METHODS: Ten embalmed cadavers studied after their arterial systems were injected with red latex. The quantity, origin, pathway, distribution range and diameter of the branches were recorded and photographed. RESULTS: The transverse branch appeared in all 80 intervertebral foramina. The transverse branch was divided into 2 types: In type 1, the arteries divided into superior branches and inferior branches; the arteries in type 2 divided into 3 branches (superior, intermedius and inferior branches). CONCLUSIONS: The transverse branches of the dorsal arteries are common structures from L1 to L4, and 2 types of transverse branches were found. A thorough understanding of the dorsal branches, especially the transverse branches of the lumbar artery, may be very important for reducing both intraoperative bleeding during the surgery and the occurrence of pseudoaneurysms after transforaminal lumbar interbody fusion.

Variation in spatial distance between the lumbar interlaminar window and intervertebral disc space during flexion-extension.

PURPOSE: Knowledge of interlaminar space is important for undertaking percutaneous endoscopic discectomy via an interlaminar approach (PED-IL). However, dynamic changes in the lumbar interlaminar space and the spatial relationship between the interlaminar space and intervertebral disc space (IDS) are not clear. The aim of this study was to anatomically clarify the changes in interlaminar space height (ILH) and variation in distance between the two spaces during flexion-extension of the lumbar spine in vitro. METHODS: First, we used a validated custom-made loading equipment to obtain neutral, flexion, and extension 3D models of eight lumbar specimens through 3D reconstruction software. Changes in ILH (ILH, IL-yH, IL-zH) and distances between the horizontal plane passing through the lowest edge of the lamina of the superior lumbar vertebrae and the horizontal plane passing through the lowest position of the trailing edge of the same-level IDS (DpLID) at L3/4, L4/5 and L5/S1 were examined on 3D lumbar models. RESULTS: We found that ILH was greater at L4/5 than at L3/4 and L5/S1 in the neutral position, but the difference was not significant. In the flexion position, ILH was significantly more than that in neutral and extension positions at L3/4, L4/5, and L5/S1. There were significantly more DpLID changes from neutral to flexion than that from neutral to extension at all levels (L3/4, L4/5, L5/S1). CONCLUSION: These findings demonstrated level-specific changes in ILH and DpLID during flexion-extension. The data may provide a better understanding of the spatial relationship between lumbar interlaminar space and IDS, and aid the development of segment-specific treatment for PED-IL.

Strain distribution of the anterolateral ligament during internal rotation at different knee flexion angles: A biomechanical study on human cadavers.

BACKGROUND: Injuries of the anterolateral ligament (ALL) are fairly common in patients with ruptures of the anterior cruciate ligament (ACL). Before considering repair or reconstruction of the ALL, the lack of knowledge with regard to the biomechanical behavior of this ligament must be considered. The purpose of this study was to analyze the strain of the ALL induced by tibial internal rotation at different flexion angles and find out the strain distribution features. METHODS: The ALLs of ten fresh-frozen cadaver knees were dissected. All specimens underwent tibial internal rotation from 0° to 25° at 30°, 60°, 90°, and 120° of knee flexion. Strain distribution of the ALL during internal rotation was recorded by digital image correlation (DIC). The overall strain and sub-regional strain were measured. RESULTS: The strain of the ALL increased with increasing tibial internal rotation. With 25° of internal rotation, the overall strain at each flexion angle was 12.89 ±â€¯2.73% (30°), 15.32 ±â€¯2.50% (60°), 18.94 ±â€¯2.34% (90°), and 20.10 ±â€¯3.27% (120°). The sub-regional strain was significantly different at all flexion angles. The strain of the distal 1/3 of the ALL was the greatest, followed by the middle 1/3, while the proximal 1/3 was the smallest (all P < 0.001). CONCLUSION: The ALL resisted internal rotation of the tibia by becoming more tense with increasing rotation. A significantly high strain was observed in the distal portion near the tibial insertion site of the ALL, which may suggest that this region is prone to injury with excessive internal rotation.

Strain Distribution in the Anterior Inferior Tibiofibular Ligament, Posterior Inferior Tibiofibular Ligament, and Interosseous Membrane Using Digital Image Correlation.

BACKGROUND: Ligament repair and augmentation techniques can stabilize syndesmosis injuries. However, little is known about the mechanical behavior of syndesmotic ligaments. The aim of this study was to analyze full-field strain, strain trend under foot rotation, and subregional strain differences of the anterior inferior tibiofibular ligament (AITFL), posterior inferior tibiofibular ligament (PITFL), and interosseous membrane (IOM). METHODS: Eleven fresh-frozen lower limbs were dissected to expose the AITFL, PITFL, and IOM. The foot underwent rotation from 0° to 25° internal and 35° external, with 3 ankle positions (neutral, 15° dorsiflexion, and 25° plantarflexion) and a vertical load of 430 N. Ligament strain was recorded using digital image correlation. RESULTS: The mean strain on the AITFL with 35° external rotation was greater in the proximal portion compared with distal portion in the neutral position ( P = .009) and dorsiflexion ( P = .003). The mean strain in the tibial insertion and midsubstance near tibial insertion were greater when compared with other regions ( P = .018 and P = .009). The subregions of mean strain in the PITFL and IOM groups were not significantly different. The strain trend of AITFL, PITFL, and IOM showed common transformation, just when the foot was externally rotated. CONCLUSION: The findings of this study show that a significantly high strain was observed on the proximal part and the midsubstance near the Chaput tubercle of the AITFL when the ankle was externally rotated. All 3 ligaments resisted the torque in the syndesmosis by external rotation of the foot. CLINICAL RELEVANCE: This study allows for better understanding of the mechanical behavior of the syndesmosis ligaments, which could influence the repair technique and AITFL augmentation techniques.

An ex vivo liver training model continuously perfused to simulate bleeding for suture skills involved in laparoscopic liver resection: development and validity.

BACKGROUND: Suture skills are essential to laparoscopic liver resection. The current suture training models are not ideal enough. The aim of this study is to develop and verify a highly simulated-bleeding continuously perfused training model (CPTM) and to evaluate its training efficacy. METHODS: CPTM was constructed using fresh lamb liver whose portal veins were perfused with red-dyed liquid gelatin. Construct validity of CPTMs was tested in 33 participants with three levels of laparoscopic experience (experts, intermediates, and novices) who were demanded to finish one superficial stitch and one deep stitch for suture hemostasis on CPTMs. The CPTMs were also evaluated by the experts. CPTMs were compared with dry box training models (DBTMs) regarding training efficacy among the novices who were assigned to DBTM and CPTM groups to, respectively, complete a 10-day training on CPTMs or DBTMs. Before and after their assignments, their superficial stitches were assessed by completion time, suture accuracy, and suture knot performance while their deep stitches by completion time and bleeding control. RESULTS: CPTM proved to be construct valid by both superficial and deep stitches. Significant differences were found regarding completion time (763, 271, 174 s), suture accuracy (4.4, 1.8, 0.2 mm), and suturing knot performance (12.1, 21.5, 22.0) for superficial stitches (p < 0.001), as well as regarding completion time (807, 423, 277 s) for deep stitches (p < 0.001). Positive comments were given by all experts. CPTMs helped novices to acquire laparoscopic suture skills. Their training efficacy was significantly better than that of DBTMs (p < 0.05). Learning curves of CPTM group plateaued at the sixth round for superficial stitches and at the seventh round for deep stitches. CONCLUSION: CPTM offers trainees a highly simulated-bleeding means to acquire advanced laparoscopic suture skills. The suture skills learned on CPTMs may improve significantly at the seventh round.

[Construction of a three-dimensional digital model of the liver of Wuzhishan mini-pig].

OBJECTIVE: To construct a three-dimensional (3D) liver model of Wuzhishan mini-pig for virtual liver surgeries. METHODS: The biliary tree and hepatic arteries of Wuzhishan mini-pig were perfused with perchloroethylene and ethyl acetate along mixed with lead oxide, and the hepatic vein and portal vein were perfused with a mixture of dental base acrylic resin and lead oxide. The sectional images were acquired using a 64-slice spiral CT, and the 3D models of the portal vein, hepatic vein, biliary tree, hepatic arteries, and liver parenchyma were reconstructed using Mimics software; the resection image of the liver was also designed. The intrahepatic vascular cast was prepared by corroding the soft tissue with hydrochloric acid. RESULTS AND CONCLUSION: The intrahepatic vascular cast obtained fully retained the vascular architecture and displayed the fifth- and sixth-level branches of the hepatic vein and portal vein and the third- and fourth-level branches of the artery and bile duct. The 3D model of liver allowed stereoscopic and accurate display of the third- and fourth-level branches of the hepatic vein and portal vein and the second- and third-level branches of the artery and bile duct. The 3D model showed fewer branches but represented the structural distribution identical to the cast. The 3D model could clearly display the spatial relationship between the vasculature and the soft tissue in virtual resection of the liver tissues, and thus provides a useful model for training of laparoscopic liver resection.

Construction and accuracy assessment of patient-specific biocompatible drill template for cervical anterior transpedicular screw (ATPS) insertion: an in vitro study.

BACKGROUND: With the properties of three-column fixation and anterior-approach-only procedure, anterior transpedicular screw (ATPS) is ideal for severe multilevel traumatic cervical instabilities. However, the accurate insertion of ATPS remains challenging. Here we constructed a patient-specific biocompatible drill template and evaluated its accuracy in assisting ATPS insertion. METHODS: After ethical approval, 24 formalin-preserved cervical vertebrae (C2-C7) were CT scanned. 3D reconstruction models of cervical vertebra were obtained with 2-mm-diameter virtual pin tracts at the central pedicles. The 3D models were used for rapid prototyping (RP) printing. A 2-mm-diameter Kirschner wire was then inserted into the pin tract of the RP model before polymethylmethacrylate was used to construct the patient-specific biocompatible drill template. After removal of the anterior soft tissue, a 2-mm-diameter Kirschner wire was inserted into the cervical pedicle with the assistance of drill template. Cadaveric cervical spines with pin tracts were subsequently scanned using the same CT scanner. A 3D reconstruction was performed of the scanned spines to get 3D models of the vertebrae containing the actual pin tracts. The deviations were calculated between 3D models with virtual and actual pin tracts at the middle point of the cervical pedicle. 3D models of 3.5 mm-diameter screws were used in simulated insertion to grade the screw positions. FINDINGS: The patient-specific biocompatible drill template was constructed to assist ATPS insertion successfully. There were no significant differences between medial/lateral deviations (P = 0.797) or between superior/inferior deviations (P = 0.741). The absolute deviation values were 0.82±0.75 mm and 1.10±0.96 mm in axial and sagittal planes, respectively. In the simulated insertion, the screws in non-critical position were 44/48 (91.7%). CONCLUSIONS: The patient-specific drill template is biocompatible, easy-to-apply and accurate in assisting ATPS insertion. Its clinical applications should be further researched.