Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys.

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.

Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Mimicked Spinal Cord Fibers Trigger Axonal Regeneration and Remyelination after Injury.

Spinal cord injury (SCI) causes tissue structure damage and composition changes of the neural parenchyma, resulting in severe consequences for spinal cord function. Mimicking the components and microstructure of spinal cord tissues holds promise for restoring the regenerative microenvironment after SCI. Here, we have utilized electrospinning technology to develop aligned decellularized spinal cord fibers (A-DSCF) without requiring synthetic polymers or organic solvents. A-DSCF preserves multiple types of spinal cord extracellular matrix proteins and forms a parallel-oriented structure. Compared to aligned collagen fibers (A-CF), A-DSCF exhibits stronger mechanical properties, improved enzymatic stability, and superior functionality in the adhesion, proliferation, axonal extension, and myelination of differentiated neural progenitor cells (NPCs). Notably, axon extension or myelination has been primarily linked to Agrin (AGRN), Laminin (LN), or Collagen type IV (COL IV) proteins in A-DSCF. When transplanted into rats with complete SCI, A-DSCF loaded with NPCs improves the survival, maturation, axon regeneration, and motor function of the SCI rats. These findings highlight the potential of structurally and compositionally biomimetic scaffolds to promote axonal extension and remyelination after SCI.

Immunological effects of anti-coagulant unfractionated heparin in pregnant Chinese women with cryptic recurrent miscarriages.

Introduction: Anti-coagulant unfractionated heparin of low molecular weight (ACUHlmw) therapy is popularly practised in the therapy of recurrent miscarriages (RMC) due to its anti-coagulant properties. However, several in vitro investigations have hypothesized about the possible immunological effects of ACUHlmw. Material and methods: We examined pregnant women with cryptic RMC (cRMC) to determine whether ACUHlmw could regulate the immune reaction in vivo during their pregnancy. In this study, a total of 51 women were subjected to tinzaparin and 48 patients were considered as control women on the basis of an open single-centre randomized controlled trial. During different fertilization weeks (FW) 7, 19, 29, and 35 plasma samples were acquired for eleven chemokine and cytokine levels and then investigated by multiplex bead technology and selected to portray T-helper subset-related immunity. Results: We did not find any difference in chemokine C-C motif ligand-2, -17, -22, chemokine C-X-C motif ligand-1, -8, -12, -13 or cytokine interleukin-6 when a mixed linear model test was carried out on ACUHlmw in both the study and control women. However, differences were observed in the mixed linear model test on ACUHlmw in both the study and control women during pregnancy of the Th1/Th17 related chemokine C-X-C motif ligand-10 (p = 0.01), -11 (p < 0.001) and chemokine C-C motif ligand-20 (p = 0.04) respectively. Conclusions: A positive outcome of ACUHlmw therapy in vivo was observed, thus establishing its potential proinflammatory effect. During 2nd and 3rd trimesters, the observed harmonious enlargement in Th1/Th17 related chemokine and cytokine levels does not recommend a fruitful immunological impact of ACUHlmw therapy in vivo.

Retracted: The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome.

The authors requested retraction after reviewing the manuscript and determining that there were errors in the data. Reference: Yanli Hong, Yanyun Yin, Yong Tan, Ke Hong, Huifang Zhou. The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome. Med Sci Monit, 2019; 25: 395-401. DOI: 10.12659/MSM.912341.

Single-cell sequencing provides insights into the landscape of ovary in PCOS and alterations induced by CUMS.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder related to psychological distress. However, the mechanism underlying increased prevalence of depression in PCOS remained unclear. This study aimed to explore the unique transcriptional landscape of ovary and offered a platform to explore the mechanism of PCOS, as well as the influences caused by depression. The PCOS rat model was established by letrozole whereas PCOS rat model with depression was established by letrozole combined with chronic unpredicted mild stress (CUMS). Then single-cell RNA sequencing (scRNA-Seq) was applied to analyze the transcriptional features of rat ovaries. Granulosa cells (GCs) and fibroblasts (Fibros) accounted for the top two clusters of total 12 cell types. There were nine clusters in GCs, related to inflammatory response, endoplasmic reticulum (ER) stress, and steroidogenesis. The expression of differentially expressed genes (DEG) Hes1 was higher in PCOS and PCOS + CUMS groups, exhibiting enhanced expression by pseudotime and positively related to inflammation. Pseudotemporal analysis revealed that inflammation contributed to the different GCs distributions. Moreover, analysis of DEGs and gene ontology (GO) function enrichment revealed CUMS aggravated inflammation in PCOS GCs possibly via interferon signaling pathway. In theca cells (TCs), nine clusters were observed and some of them were relevant to inflammation, ER stress, and lipid metabolism. DEGs Ass1, Insl3, and Ifi27 were positively related to Cyp17a1, and Ces1d might contribute to the different trajectory of TCs. Subsequent scRNA-seq revealed a signature profile of endothelial cells (ECs) and Fibros, which suggest that inflammation-induced damage of ECs and Fibro, further exacerbated by CUMS. Finally, analysis of T cells and mononuclear phagocytes (MPs) revealed the existence of immune dysfunction, among which interferon signaling played a critical role. These findings provided more knowledge for a better understanding PCOS from the view of inflammation and identified new biomarkers and targets for the treatment of PCOS with psychological diseases.NEW & NOTEWORTHY In this study, we mapped the landscape of polycystic ovary syndrome (PCOS) ovary with rat model induced by letrozole and provided a novel insight into the molecular mechanism of PCOS accompanied by chronic unpredicted mild stress (CUMS) at single-cell transcriptomic level. These observations highlight the importance of inflammation in the pathogenesis of PCOS, which might also be the bridge between PCOS and psychological diseases.

Protocatechuic acid alleviates polycystic ovary syndrome symptoms in mice by PI3K signaling in granulosa cells to relieve ROS pressure and apoptosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complicated gynecological endocrine disease that occurs in women of childbearing age. Protocatechuic acid is a phenol-rich compound derived from herbs and owns vital functions in numerous diseases. Howbeit, protocatechuic acid's impact on PCOS is unknown. METHODS: A combination of in vivo and in vitro models was examined in this study. C57BL/6 mice were injected subcutaneously daily with dehydroepiandrosterone to establish a PCOS mouse model, and protocatechuic acid was intraperitoneally injected into PCOS mice. Granulosa cells of PCOS ovaries were also isolated. The function of protocatechuic acid was appraised using enzyme-linked immunosorbent assay, hematoxylin-eosin staining, reactive oxygen species (ROS) and LC3 levels analysis, flow cytometry, quantitative real-time PCR, and western blot. Meanwhile, the mechanism of protocatechuic acid was assessed with a series of molecular experiments. RESULTS: Protocatechuic acid owned no apparent toxic effect on mice. Functionally, protocatechuic acid owned a function of mitigating PCOS in vivo. Meanwhile, protocatechuic acid repressed ROS, autophagy, and apoptosis of PCOS ovarian granulosa cells in vitro. Mechanistically, rescue assays elucidated that the protective function of protocatechuic acid against PCOS was interrelated to the activation of the PI3K/AKT/mTOR axis. CONCLUSION: Protocatechuic acid alleviated PCOS symptoms in mice through PI3K signaling in granulosa cells to reduce ROS levels and apoptosis.

Spinal cord tissue engineering via covalent interaction between biomaterials and cells.

Noncovalent interactions between cells and environmental cues have been recognized as fundamental physiological interactions that regulate cell behavior. However, the effects of the covalent interactions between cells and biomaterials on cell behavior have not been examined. Here, we demonstrate a combined strategy based on covalent conjugation between biomaterials (collagen fibers/lipid nanoparticles) and various cells (exogenous neural progenitor cells/astrocytes/endogenous tissue-resident cells) to promote neural regeneration after spinal cord injury (SCI). We found that metabolic azido-labeled human neural progenitor cells conjugated on dibenzocyclooctyne-modified collagen fibers significantly promoted cell adhesion, spreading, and differentiation compared with noncovalent adhesion. In addition, dibenzocyclooctyne-modified lipid nanoparticles containing edaravone, a well-known ROS scavenger, could target azide-labeled spinal cord tissues or transplanted azide-modified astrocytes to improve the SCI microenvironment. The combined application of these covalent conjugation strategies in a rat SCI model boosted neural regeneration, suggesting that the covalent interactions between cells and biomaterials have great potential for tissue regeneration.

Diagnostic values of MRI indexes for polycystic ovary syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) is a useful non-invasive modality for observation of ovarian morphologic characteristics. Few studies have focused on the value of MRI-derived indexes in reproductive-aged women with polycystic ovary syndrome (PCOS). PURPOSE: To assess the diagnostic value of MRI in women with PCOS. MATERIAL AND METHODS: This prospective case-control study included 85 women with PCOS and 50 controls who underwent pelvic MRI during 2017-2019. Ovarian volume (OV), follicle count (FC; counts of follicles sizing 2-3, 4-6, 7-9, 2-9 mm, respectively), follicular peripheral distribution, absence of a dominant follicle and stromal to total area ratio (S:A) were determined with MRI. The diagnostic value (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]) of OV, FC2-9, and follicular peripheral distribution for PCOS were assessed. RESULTS: The AUCs were 0.94 for OV, 0.96 for FC2-9, and 0.78 for follicular peripheral distribution. The optimal threshold to detect PCOS was 8.5 mL for OV (sensitivity 78%; specificity 96%) and 26 for FC2-9 (sensitivity 85%; specificity 98%). Sensitivity and specificity were 73% and 82% for follicular peripheral distribution, respectively. Reproducibility was perfect for OV (ICC = 0.96) and absence of a dominant follicle (k = 0.85), substantial for FC2-9 (ICC = 0.79) and S:A (ICC = 0.69), and moderate for follicular peripheral distribution (k = 0.56). CONCLUSION: Detected by MRI, OV >8.5 mL or FC2-9 >26 are accurate for diagnosing PCOS.

Single-cell chromatin accessibility identifies enhancer networks driving gene expression during spinal cord development in mouse.

Spinal cord development is precisely orchestrated by spatiotemporal gene regulatory programs. However, the underlying epigenetic mechanisms remain largely elusive. Here, we profiled single-cell chromatin accessibility landscapes in mouse neural tubes spanning embryonic days 9.5-13.5. We identified neuronal-cell-cluster-specific cis-regulatory elements in neural progenitors and neurons. Furthermore, we applied a novel computational method, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression data and identify the hub enhancers within enhancer networks. It was experimentally validated in vivo for Atoh1 that knockout of the hub enhancers, but not the non-hub enhancers, markedly decreased Atoh1 expression and reduced dp1/dI1 cells. Together, our work provides insights into the epigenetic regulation of spinal cord development and a proof-of-concept demonstration of enhancer networks as a general mechanism in transcriptional regulation.

[Regulation of vascular endothelial cell activator expression by tanshinone â ¡_A based on PI3K/Akt signaling pathway].

The present study investigated the regulatory effect of tanshinone Ⅱ_A(TAⅡ_A) on activator expression in human umbilical vein endothelial cells(HUVECs) and the effect on the phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt) signaling pathway in patients with antiphospholipid syndrome(APS). HUVECs cultured in vitro were divided into a medium group, a blank control group, an APS model group, an APS+LY5 group, an APS+LY10 group, an APS+LY20 group, an APS+TAⅡ_A5 group, an APS+TAⅡ_A10 group, an APS+TAⅡ_A20 group, and an APS+TAⅡ_A10+LY10 group. The effects of LY294002 and TAⅡ_A at different concentrations on the secretion of interleukin-6(IL-6), interleukin-8(IL-8), and monocyte chemoattractant protein-1(MCP-1) by HUVECs were investigated. The effects on the mRNA expression of annexin A2(ANXA2), PI3 K, Akt, and E-cadherin(E-cad) were detected by quantitative polymerase chain reaction(qPCR), and Western blot was used to determine the effects on the protein expression of ANXA2, p-PI3 K/PI3 K, p-Akt/Akt, and E-cad. The results revealed that compared with the APS model group, the APS+TAⅡ_A10 group showed statistically reduced IL-6 and MCP-1 and increased IL-8 in a concentration-dependent manner with the increase in TAⅡ_A dose, while the APS+TAⅡ_A10 group showed increased mRNA and protein expression of ANXA2, PI3 K, Akt, and E-cad(P<0.05 or P<0.01) in a concentration-dependent manner with the increase in TAⅡ_A dose. The findings indicated that the serum of APS patients could lead to the decreased mRNA and protein expression levels of ANXA2, PI3 K, Akt, and E-cad in HUVECs, increased secretion of IL-6 and MCP-1, and reduced secretion of IL-8, and activate vascular endothelial cells. In contrast, once the PI3 K/Akt signaling pathway was blocked, the mRNA and protein expression of ANXA2 and E-cad significantly decreased, IL-6 and MCP-1 secretion significantly increased, and IL-8 secretion was significantly reduced. It suggests that TAⅡ_A regulates the activation of vascular endothelial cells in APS patients by activating the PI3 K/Akt signaling pathway.

Correction: Transplantation of collagen sponge-based three-dimensional neural stem cells cultured in a RCCS facilitates locomotor functional recovery in spinal cord injury animals.

Correction for 'Transplantation of collagen sponge-based three-dimensional neural stem cells cultured in a RCCS facilitates locomotor functional recovery in spinal cord injury animals' by Yunlong Zou et al., Biomater. Sci., 2022, 10, 915-924. DOI: 10.1039/D1BM01744F.

Transplantation of collagen sponge-based three-dimensional neural stem cells cultured in a RCCS facilitates locomotor functional recovery in spinal cord injury animals.

Numerous studies have indicated that microgravity induces various changes in the cellular functions of neural stem cells (NSCs), and the use of microgravity to culture tissue engineered seed cells for the treatment of nervous system diseases has drawn increasing attention. The goal of this study was to verify the efficacy of collagen sponge-based 3-dimensional (3D) NSCs cultured in a rotary cell culture system (RCCS) in treating spinal cord injury (SCI). The Basso-Beattie-Bresnahan score, inclined plane test, and electrophysiology results all indicated that 3D cultured NSCs cultured in a RCCS had better therapeutic effects than those cultured in a traditional cell culture environment, suggesting that the microgravity provided by the RCCS could enhance the therapeutic effect of 3D cultured NSCs. Our study indicates the feasibility of combining the RCCS with collagen sponge-based 3D cell culture for producing tissue engineered seed cells for the treatment of SCI. This novel and effective method shows promise for application in cell-based therapy for SCI in the future.

Contralateral Axon Sprouting but Not Ipsilateral Regeneration Is Responsible for Spontaneous Locomotor Recovery Post Spinal Cord Hemisection.

Spinal cord injury (SCI) usually results in permanent functional impairment and is considered a worldwide medical problem. However, both motor and sensory functions can spontaneously recover to varying extents in humans and animals with incomplete SCI. This study observed a significant spontaneous hindlimb locomotor recovery in Sprague-Dawley rats at four weeks after post-right-side spinal cord hemisection at thoracic 8 (T8). To verify whether the above spontaneous recovery derives from the ipsilateral axonal or neuronal regeneration to reconnect the lesion site, we resected either the scar tissue or right side T7 spinal cord at five weeks post-T8 hemisected injury. The results showed that the spontaneously achieved right hindlimb locomotor function had little change after resection. Furthermore, when T7 left hemisection was performed five weeks after the initial injury, the spontaneously achieved right hindlimb locomotor function was dramatically abolished. A similar result could also be observed when T7 transection was performed after the initial hemisection. The results indicated that it might be the contralateral axonal remolding rather than the ipsilateral axonal or neuronal regeneration beyond the lesion site responsible for the spontaneous hindlimb locomotor recovery. The immunostaining analyses and corticospinal tracts (CSTs) tracing results confirmed this hypothesis. We detected no substantial neuronal and CST regeneration throughout the lesion site; however, significantly more CST fibers were observed to sprout from the contralateral side at the lumbar 4 (L4) spinal cord in the hemisection model rats than in intact ones. In conclusion, this study verified that contralateral CST sprouting, but not ipsilateral CST or neuronal regeneration, is primarily responsible for the spontaneous locomotor recovery in hemisection SCI rats.

Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury.

BACKGROUND: Microtubule-stabilizing agents have been demonstrated to modulate axonal sprouting during neuronal disease. One such agent, Epothilone D, has been used to treat spinal cord injury (SCI) by promoting axonal sprouting at the lesion site after SCI. However, the role of Epothilone D in the differentiation of neural stem cells (NSCs) in SCI repair is unknown. In the present study, we mainly explored the effects and mechanisms of Epothilone D on the neuronal differentiation of NSCs and revealed a potential new SCI treatment. METHODS: In vitro differentiation assays, western blotting, and quantitative real-time polymerase chain reaction were used to detect the effects of Epothilone D on NSC differentiation. Retrograde tracing using a pseudotyped rabies virus was then used to detect neuronal circuit construction. RNA sequencing (RNA-Seq) was valuable for exploring the target gene involved in the neuronal differentiation stimulated by Epothilone D. In addition, lentivirus-induced overexpression and RNA interference technology were applied to demonstrate the function of the target gene. Last, an Apol8-NSC-linear ordered collagen scaffold (LOCS) graft was prepared to treat a mouse model of SCI, and functional and electrophysiological evaluations were performed. RESULTS: We first revealed that Epothilone D promoted the neuronal differentiation of cultured NSCs and facilitated neuronal relay formation in the injured site after SCI. Furthermore, the RNA-Seq results demonstrated that Apol8 was upregulated during Epothilone D-induced neuronal relay formation. Lentivirus-mediated Apol8 overexpression in NSCs (Apol8-NSCs) promoted NSC differentiation toward neurons, and an Apol8 interference assay showed that Apol8 had a role in promoting neuronal differentiation under the induction of Epothilone D. Last, Apol8-NSC transplantation with LOCS promoted the neuronal differentiation of transplanted NSCs in the lesion site as well as synapse formation, thus improving the motor function of mice with complete spinal cord transection. CONCLUSIONS: Epothilone D can promote the neuronal differentiation of NSCs by upregulating Apol8, which may provide a promising therapeutic target for SCI repair.

The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge.

BACKGROUND: Recently, neural stem cell (NSC) therapy has shown promise for the treatment of many neurological diseases. Enhancing the quality of implanted cells and improving therapeutic efficacy are currently research hotspots. It has been reported that collagen sponge material provided sufficient room for cell growth in all directions and promoted the absorption of nutrients and removal of wastes. And also, the Rotary Cell Culture System (RCCS), which mimics the microgravity environment, can be used to culture cells for tissue engineering. MATERIALS AND METHODS: We performed the mRNA and miRNA sequencing to elucidate the regulatory mechanism of NSCs cultured on the collagen sponge in the RCCS system. The luciferase assay and Western blot revealed a direct regulatory role between let-7i-5p and neurotrophic receptor tyrosine kinase 3 (NTRK3; also called TrkC). And then, the neural differentiation markers Tuj1 and Map2 were detected by immunofluorescence staining. In the meantime, the migratory ability of NSCs was detected both in vitro and in spinal cord injury animals. RESULTS: In this study, we demonstrated that the expression of NTRK3 was elevated in NSCs cultured on collagen sponge in the RCCS system. Furthermore, increased NTRK3 expression was regulated by the downregulation of let-7i-5p. Compared to traditionally cultured NSCs, the NSCs cultured on collagen sponge in the RCCS system exhibited better neuronal differentiation and migratory ability, especially in the presence of NT-3. CONCLUSIONS: As the biological properties and quality of transplanted cells are critical for therapeutic success, the RCCS system combined with the collagen sponge culture system shows promise for applications in clinical practice in the future.

Spatiotemporal dynamic changes, proliferation, and differentiation characteristics of Sox9-positive cells after severe complete transection spinal cord injury.

Studying the spatiotemporal dynamic changes of various cells following spinal cord injury (SCI) is of great significance for understanding the pathological processes of SCI. Changes in the characteristics of Sox9-positive cells, which are widely present in the spinal cord, have rarely been studied following SCI. We found that Sox9-positive cells were widely distributed in the central canal and parenchyma of the uninjured adult spinal cord, with the greatest distribution in the central spinal cord and relatively few cells in the dorsal and ventral sides. Ranging between 14.20% ± 1.61% and 15.60% ± 0.36% of total cells in the spinal cord, almost all Sox9-positive cells were in a quiescent state. However, Sox9-positive cells activated following SCI exhibited different characteristics according to their distance from the lesion area. In the reactive region, Sox9-positive cells highly expressed nestin and exhibited a single-branching structure, whereas in the non-reactive region, cells showed low nestin expression and a multi-branching structure. In response to SCI, a large number of Sox9-positive cells in the spinal cord parenchyma proliferated to participate in the formation of glial scars, whereas Sox9-positive cells in the central canal located near the lesion site accumulated at its broken ends through proliferation. Finally, we found that approximately 6.30% ± 0.35% of Sox9-positive cells differentiated into oligodendrocytes within two weeks after SCI. By examining the spatiotemporal dynamic changes, proliferation and differentiation characteristics of Sox9-positive cells after SCI, our findings provide a theoretical basis for understanding the pathological process of SCI.

Collagen particles with collagen-binding bone morphogenetic protein-2 promote vertebral laminar regeneration in infant rabbits.

The vertebral laminar defects caused by severe spina bifida occulta, spinal fracture, or bone tuberculosis require surgical treatment. The reconstruction of vertebral laminar defects remains challenging, especially in children. In this study, we created an animal model of vertebral laminar defects in newly weaned rabbits to evaluate the therapeutic effect of bovine bone collagen particle (BBCP) that combined with bone morphogenetic protein-2 with collagen binding domain (CBD-BMP-2). The tissues at the injury site which were harvested after 12 weeks indicated that newly formed bone was observed in both BBCP and BBCP/CBD-BMP-2 groups, whereas the injury site of the control group was mostly filled by fibrous tissue. The BBCP/CBD-BMP-2 group recovered better than the BBCP group. These findings indicate that a combination of BBCP with CBD-BMP-2 may be a good strategy for vertebral laminar defects in children.

Predicting necrosis in adnexal torsion in women of reproductive age using magnetic resonance imaging.

PURPOSE: To identify the diagnostic performance of magnetic resonance (MR) imaging for patients with adnexal torsion and to develop a predictive model for necrosis related to torsion. METHODS: The institutional ethics committee approved this retrospective study. A total of 56 women with a preoperative pelvic MR scan and a surgical and pathologic diagnosis of adnexal torsion were enrolled from five institutions. Three radiologists reviewed the MR images independently. The kappa value of interrater agreement was assessed. Differences between patients treated with conservative surgery and adnexectomy were evaluated by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the model to predict ovarian necrosis. RESULTS: Fifty-six patients were divided into the conservative surgery group (24/56, 42.9%) or the adnexectomy group (32/56, 57.1%) depending on the surgical outcomes. The radiographic features related to torsion were interpreted by three raters retrospectively with substantial interrater agreement (kappa > 0.60). Older reproductive age and pedicle hemorrhagic infarction were significantly associated with adnexectomy (p < 0.05). At multivariate analysis, pedicle hemorrhagic infarction (odds ratio = 10.476 [95% confidence interval 1.103, 99.504; p = 0.041]) was associated with adnexectomy. Using the predictive model (older reproductive age and pedicle hemorrhagic infarction), a receiver operating characteristic curve was generated with an area under the curve (AUC = 0.870 ± 0.049). CONCLUSION: The presence of pedicle hemorrhagic infarction and older reproductive age can predict necrosis of adnexal torsion and may be used to guide the optimal treatment strategy. KEY POINTS: • Pedicle hemorrhagic infarction and older reproductive age are predictors of necrosis in adnexal torsion in patients of reproductive age (AUC = 0.870 ± 0.049). • Cystic wall thickening, enlarged vascular pedicle, tubal thickening, and uterine deviation are associated with a high risk for adnexal torsion, occurring in more than half of the cases in this study. • MR findings are useful for the definitive diagnosis of adnexal torsion and for the prediction of adnexal necrosis.

Comparison between magnetic resonance hysterosalpingography and conventional hysterosalpingography: direct visualization of the fallopian tubes using a novel MRI contrast agent mixture.

BACKGROUND: Magnetic resonance hysterosalpingography (MR-HSG) is a promising technique in the work-up of female infertility. Few existing MR-HSG studies focus on the comparison between MR-HSG with gold standard examination. PURPOSE: To compare the diagnostic value of MR-HSG with conventional HSG in patients receiving both exams in one day. MATERIAL AND METHODS: This study included 33 infertile women who completed pelvic MR scanning, HSG, and MR-HSG in that order. A traditional HSG contrast agent (iohexol) and a magnetic resonance imaging (MRI) contrast agent (1 mL gadopentetate dimeglumine (Gd-DTPA) blended with 100 mL iohexol) were used to achieve image enhancement. Inter-observer and inter-modality agreements of HSG and MR-HSG exams were assessed. The results were calculated by using the kappa test. Three radiologists who were blinded to the clinical data independently reviewed the MR images. Extratubal abnormalities were analyzed. RESULTS: A total of 62 fallopian tubes of 33 women were included in the study. MR-HSG imaging findings to depict tubal patency were similar to these of HSG (AUC 0.911, sensitivity 0.821, specificity 1.000, positive predictive values 1.000, and negative predictive values 0.872). Pairwise inter-observer agreement among three observers and inter-modality agreement of the diagnosis were excellent (mean kappa 0.863 and 0.835, respectively). In addition, 29 extratubal abnormalities in 21 patients were found on pelvic MR scanning. CONCLUSION: MR-HSG and HSG demonstrated similar results in assessing tubal patency. Because it offers the comprehensive assessment of female pelvic structures, and avoids ionizing radiation, MR-HSG may be used as an alternative imaging technique for evaluation of female infertility.