Correlations between posterior longitudinal injury and parameters of vertebral body damage.

BACKGROUND: The posterior longitudinal ligament (PLL) is an important structure of spinal stability. The loss of vertebral body height, local kyphosis (LK), and canal compromise may lead to spinal instability. This study determined the correlations between injury of the PLL and the loss of vertebrae height, kyphosis, and canal compromise. MATERIALS AND METHODS: A retrospective review of a thoracolumbar burst fracture database was conducted from January 2009 to December 2011. Patients were divided into an intact group and a disrupted group according to the status of the PLL. The loss of vertebral height, mid-sagittal canal diameter, and LK was measured. The anterior, middle, and posterior vertebral compression ratios (AVBCR, MVBCR, and PVBCR) and mid-sagittal diameter compression ratio (MSDCR) were calculated. RESULTS: Forty-seven patients were included in the study, including 25 patients in the intact group and 22 patients in the disrupted group. There were significant differences in the AVBCR (t = -3.048, P = 0.004), MVBCR (t = -2.301, P = 0.048), PVBCR (t = -2.116, P = 0.040), and MSDCR (t = -4.095, P = 0.000) but no difference in the LK (t = 0.408, P = 0.686) between the two groups. There was a positive correlation between the injury of the PLL and the MSDCR (r = 0.428, P < 0.01), AVBCR (r = 0.372, P < 0.01), and PVBCR (r = 0.271, P < 0.05). There was no correlation between the injury of the PLL and the LK and MVBCR. CONCLUSIONS: The MVBCR and LK are not predictive of a PLL injury. The MSDCR, AVBCR, and PVBCR were associated with a PLL injury.

Identification of disease-related miRNAs based on co-expression network in spinal cord injury.

OBJECTIVE: This study aimed to construct miRNA co-expression network by using miRNA microarray data and screen the miRNAs associated with spinal cord injury (SCI) by comparative analysis, which might be considered as molecule labels for future forecasts or therapies. METHODS: We first downloaded SCI gene expression data GSE19890 from GEO (Gene Expression Omnibus), then constructed the miRNA co-expression network under three different states and analyzed the topologic attributes of network. After that, miRNAs associated with SCI were screened and subjected to function analysis by DAVID (Database for Annotation, Visualization and Integrated Discovery). RESULTS: In the co-expression network, miR-520a and miR-193b had the largest degree in the SCI and sham groups, respectively. A total of 22 differentially expressed miRNAs were identified. MiR-32 and miR-471 were the most significantly expressed in the SCI group compared with control and sham groups, respectively, which were newly reported to be related to SCI in this study. Function enrichment analysis of the target genes indicated that the screened miRNA were associated with cell adhesion, cytoplasmic vesicle and so on. CONCLUSIONS: MiRNAs identified in this study could be considered targets for SCI diagnosis and therapy.

Laggeric acid, a novel seco-eudesmane sesquiterpenoid from Laggera crispata.

Laggeric acid (1), a novel 4,5-seco-eudesmane sesquiterpene acid, along with 19 known compounds, was isolated from the MeOH extract of the whole plant of Laggera crispata. The structure of 1 was elucidated to be (4S,5S*,7R*,10R*)-4,5-seco-4,5-dihydroxy-11(13)-eudesmen-12-oic acid on the basis of spectroscopic analysis and a convenient Mosher's method.

Cryo-EM structures of Candida albicans Cdr1 reveal azole-substrate recognition and inhibitor blocking mechanisms.

In Candida albicans, Cdr1 pumps azole drugs out of the cells to reduce intracellular accumulation at detrimental concentrations, leading to azole-drug resistance. Milbemycin oxime, a veterinary anti-parasitic drug, strongly and specifically inhibits Cdr1. However, how Cdr1 recognizes and exports azole drugs, and how milbemycin oxime inhibits Cdr1 remain unclear. Here, we report three cryo-EM structures of Cdr1 in distinct states: the apo state (Cdr1Apo), fluconazole-bound state (Cdr1Flu), and milbemycin oxime-inhibited state (Cdr1Mil). Both the fluconazole substrate and the milbemycin oxime inhibitor are primarily recognized within the central cavity of Cdr1 through hydrophobic interactions. The fluconazole is suggested to be exported from the binding site into the environment through a lateral pathway driven by TM2, TM5, TM8 and TM11. Our findings uncover the inhibitory mechanism of milbemycin oxime, which inhibits Cdr1 through competition, hindering export, and obstructing substrate entry. These discoveries advance our understanding of Cdr1-mediated azole resistance in C. albicans and provide the foundation for the development of innovative antifungal drugs targeting Cdr1 to combat azole-drug resistance.

Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

PCAF acetylates Runx2 and promotes osteoblast differentiation.

Osteoblasts play a crucial role in bone formation. However, the molecular mechanisms involved in osteoblast differentiation remain largely unclear. Runt-related gene 2 (Runx2) is a master transcriptional factor for osteoblast differentiation. Here we reported that p300/CBP-associated factor (PCAF) directly binds to Runx2 and acetylates Runx2, leading to an increase in its transcriptional activity. Upregulation of PCAF in MC3T3-E1 cells increases the expression of osteogenic marker genes including alkaline phosphatase (ALP), osteocalcin (Ocn), and Osteopontin (Opn), and ALP activity was stimulated as well. Consequently, the mineralization of MC3T3-E1 cells was remarkably improved by PCAF. In contrast, PCAF knockdown decreases the mRNA levels of ALP, Ocn, and Opn. ALP activity and the mineralized area were attenuated under PCAF knockdown conditions. These results indicate that PCAF is an important regulator for promoting osteoblast differentiation via acetylation modification of Runx2.

Multilevel unilateral versus bilateral pedicular percutaneous vertebroplasty for osteoporotic vertebral compression fractures.

Study design: Retrospective study. Objective: Controversy exists over the need for unilateral vs. bilateral pedicular percutaneous vertebroplasty (PVP) for patients with osteoporotic vertebral compression fractures (OVCFs). Clinical research is scarce comparing two approaches for multi-level PVP. This study aimed at evaluating the clinical and radiographic outcomes of multi-level PVP using two approaches for OVCFs. Methods: Seventy-eight patients with OVCFs undergoing multi-level PVP were enrolled including 36 patients undergoing unilateral PVP and 42 undergoing bilateral PVP. The clinical and radiological assessments including the Visual Analogue Scale (VAS), sagittal and coronal segmental Cobb, vertebral compression ratio (VCR), and vertebral sides ratio (VSR) were evaluated preoperatively and postoperatively. Results: All patients achieved a minimum 2-year follow-up. A total of 164 fractured vertebrae were enrolled. Regarding clinical efficacy, the VAS score improved in both groups after surgery, but the two groups did not differ significantly. The changes tendency in Sagittal Segmental Cobb, VSR, and VCR were similar postoperatively, and no statistically significant difference between groups. As for the Coronal Segmental Cobb angle, patients in unilateral and bilateral groups were shown to have 5.0° ± 4.0° and 2.6° ± 2.2° degrees loss of correction at a minimum 2-years follow-up duration, respectively. The loss of correction in the Coronal Segmental Cobb of unilateral group was significantly greater than that of bilateral group. Conclusion: Both multi-level unilateral and bilateral pedicular PVP achieved significant pain reduction and vertebral height restoration. Moreover, the bilateral PVP has shown advantages in stabilizing Coronal Cobb angle in patients with OVCFs.

Chemical constituents of Equisetum debile.

Three new compounds, debilitriol (1), debilignanoside (2), and equisetumine (3), along with nine known compounds, were isolated from the whole plant of Equisetum debile. Their structures were elucidated by spectral and chemical methods.

[Treatment of bilateral cervical facet dislocation by reduction through anterior distraction].

OBJECTIVE: To investigate the effect of reduction through anterior distraction in treatment of bilateral cervical facet dislocation. METHODS: Twenty-one patients with bilateral cervical facet dislocation underwent leverage reduction through anterior distraction, interbody fusion, and internal fixation. Follow-up lasted 16 months (4 months to 5 years). RESULTS: All of the 21 patients got reduction of cervical facet dislocation and bony fusion. The neurological deficiency in 4 of the 21 patients improved. CONCLUSION: Simple and safe, reduction through anterior distraction is effective in treatment of bilateral cervical facet dislocation with reliable fusion.

Study on different surgical approaches for acute Lumber disk protrusion combined with Cauda Equina Syndrome.

To compare the long and short term effectiveness and complications of different surgical approaches for Lumber disk protrusion combined with Cauda Equina Syndrome and find a better surgical method for the disease. In this study, follow up records of 144 patients received conventional laminectomy and minimally invasive decompression and fenestration 48 hours within acute injury of lumber disk protrusion combined with Cauda Equina Syndrome were analyzed. Surgical outcome immediately and 3, 6, 12, 36 months after the surgery were compared to evaluate the effectiveness two different approaches. The results indicated that there are no significant differences regarding age, sexual proportion, body mass index (BMI), visual analogue scale of pain (VAS) score as well as Frankel scores before the surgery, and significant differences VAS score as well as Frankel scores immediately after the surgery. In conclusion, minimally invasive decompression and fenestration can be of the same effectiveness and less complications comparing with the conventional laminectomy.

Association between osteoprotegerin genetic variants and bone mineral density in Chinese women.

Osteoprotegerin gene (OPG) is one of the most important candidate genes for osteoporosis. The aim of this study was to assess the association between the single nucleotide polymorphisms (SNPs) of OPG gene and bone mineral density (BMD). A total of 706 Chinese postmenopausal women were enrolled in this study. OPG gene variants were genotyped through created restriction site-polymerase chain reaction (CRS-PCR) and verified using DNA sequencing methods. The lumbar spine (L2-4), total hip and femoral neck were evaluated for BMD. Two genetic variants (g.18910G>A and g.27406C>T) were detected in this study. Our data indicated that the significant differences of spine BMD, neck hip BMD and total hip BMD were detected among different g.27406C>T genotype, subjects with the genotype CC were significantly higher than those of genotype CT and TT. However, the g.18910G>A polymorphism was not significantly associated with spine BMD, neck hip BMD and total hip BMD in the studied subjects. Results from this study indicated that OPG gene variants were associated with BMD in Chinese postmenopausal women. These findings will be useful to analyze the role of OPG gene in osteoporosis in the further studies.

Changes in compressed neurons from dogs with acute and severe cauda equina constrictions following intrathecal injection of brain-derived neurotrophic factor-conjugated polymer nanoparticles.

This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury (48 hours) of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly(lactide-co-glycolide) nanoparticles on this injury was then analyzed. Dorsal root ganglion cells (L7) of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1, 2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion. Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.

Brain-derived neurotrophic factor is up-regulated in severe acute cauda equina syndrome dog model.

To determine the level of brain-derived neurotrophic factor (BDNF) in experimental dog model of severe acute cauda equina syndrome, which was induced by multiple cauda equina constrictions throughout the entire lumbar (L), sacral (S) and coccygeal (Co) spinal cord and their central processes of the dorsal root ganglia neurons. Adult male mongrel dogs were randomly divided into 2 groups. The experiment group (n=4) was subjected to multiple cauda equina constrictions. The control group (n=4) was subjected to cauda equina exposure without constrictions. Level of BDNF in the spinal cord and the dorsal root ganglion cells (L7, S1-S3) was assessed 48 hours after multiple constrictions by immunohistochemical and histopathological analyses. 48 hours after multiple constrictions of cauda equina, up-regulation of BDNF within lumbosacral (L7-S3) spinal cord and dorsal root ganglion was observed in experimental group as compared to control group. Our result suggests that BDNF might play a role in the inflammatory and neuropathic pain as a result of multiple cauda equina constrictions. Regulation of BDNF level could potentially provide a therapy for treating cauda equina syndrome.

Lamiolactone, a new iridoid lactone from Lamiophlomis rotata.

Lamiolactone (1), a new iridoid lactone, together with five known iridoids, were isolated from the 95% EtOH extract of the roots of Lamiophlomis rotata. The structure of 1 was elucidated to be methyl antirrhinolide-4-carboxylate on the basis of spectroscopic analysis.

[Comparing loss of anterior column height and cervical Cobb angle with three different types of anterior cervical discectomy and fusion].

OBJECTIVE: To compare the loss of anterior column height and cervical Cobb angle with three different types of anterior cervical discectomy and fusion (ACDF). METHODS: A prospective randomized study was performed on 60 patients who had undergone ACDF with the autologous iliac crest graft (group A, n=20), the autogenous bone and the anterior cervical locking plates (group B, n=20), and Syncage-C filled with the local autograft reamings (group C, n=20) from January 1998 to January 2003. The patients diagnosed as having cervical radiculopathy (RP) and cervical spondylotic myelopathy (CSM) were indicated for ACDF. Of the patients, 41 were male and 19 female with a mean age of 57 years (range, 36-68) and their average course of disease was 6.2 months (range, 1-36). There were 36 one-level and 24 two-level fusions from C(3,4) to C7, T1. Radiological measurements were performed on the cervical radiographs taken before operation, 7 days and 3 months after operation, and on the last day of the follow-up; then, the height and Cobb angle of the fused segment, functional restoration, and clinical outcome were evaluated in the three groups. RESULTS: The follow-up of more than 2 years (range, 2-7) showed that the average loss of anterior column height and Cobb angle of the fused segments in groups A and B, which had not preserved the endplate, had a greater increase than that in group C, which had preserved the endplate. Of the patients, 12 had autograft collapse, 3 autograft displacement, and 10 postural abnormality between the fused segments, most of which happened in groups A and B. The fusion rate was 93.3% (56 cases) according the strict arthrodesis criteria; their excellent and good rate in the functional assessment was 83.3% (RP 90.4%, CSM 79.5%); the overall satisfactory (excellent and good) rates in groups A, B and C were 75%, 85% and 90%, respectively. CONCLUSION: To increase the resistance to graft subsidence, which is a major reason for narrowness of the fused segments, and to maintain normal cervical curvature, we should improve our skills of bone grafting performance, preserve the endplate, carefully evaluate the degree of osteoporosis before operation, and use anterior cervical locking plate and/or fusion with Syncage-C when necessary.