Potential effect on molecular pathways in different targeted genes in the VEGF family in retina - From the genomic point of view.

This study's goal is to determine similarities and differences in the molecular pathways or potential functions of the various targeted regions or genes of the Vegf family-VegfA, VegfB, VegfC, and Pgf-using the BXD genetic reference panel. Data from whole genome expression profiles of retinas from the well-characterized mouse recombinant inbred (RI) strain population derived from C57BL/6J X DBA/2J (BXD) were analyzed. Multiple analytical tools and statistical strategies were used to investigate the expression level. The expression Quantitative Trait Loci (QTLs) of these probes were mapped and compared. Our data showed that VegfA2 has the highest expression levels among all probes of Vegf genes. The expression levels of Vegf family genes are not significantly correlated. In the overall comparison, expression levels of VegfA1 and VegfA2 are positively correlated (R = 0.540). The expression levels of VegfB and VegfC are weakly correlated (R = 0.360). VegfC is also weakly correlated with the expression levels of Pgf (R = 0.324). The interaction of VegfB- and VegfA2-associated 50a2 genes was very weak (R50 ab = 0.3129). The interaction of top VegfB-associated 50b genes with VegfA2 has a reciprocal negative impact (R50ba = -0.42758). The VegfC-associated top 50c genes are strongly correlated with VegfB (R50 cb = 0.8159), while they are negatively correlated with VegfA2 (R50ca = -0.1450). Expression quantitative trait loci (eQTL) analysis suggested that the regulatory mechanisms for the expression levels of these genes in the Vegf family are different from each other. The expression level of VegfA associates with a group of genes that are not associated with other genes in the Vegf family.

Tertiary syphilis in the lumbar spine: a case report.

BACKGROUND: The incidence of tertiary syphilis involvement in the spinal column with destructive bone lesions is very rare. It is difficult to establish the correct diagnosis from radiographs and histological examination alone. Limited data are available on surgical treatment to tertiary syphilitic spinal lesions. In this article, we report a case of tertiary syphilis in the lumbar spine with osteolytic lesions causing cauda equina compression. CASE PRESENTATION: A 44-year-old man who suffered with low back pain for 6 months and progressive radiating pain at lower extremity for 1 week. Radiologic findings showed osteolytic lesion and new bone formation in the parts of the bodies of L4 and L5. Serum treponema pallidum hemagglutination (TPHA) test was positive. A surgery of posterior debridement, interbody and posterolateral allograft bone fusion with instrumentation from L3 to S1 was performed. The low back pain and numbness abated after operation. But the follow-up radiographs showed absorption of the bone grafts and failure of instrumentation. A Charcot's arthropathy was formed between L4 and L5. CONCLUSION: It is challenging to diagnose the tertiary syphilis in the spine. Surgery is a reasonable auxiliary method to antibiotic therapy for patients who suffered with neuropathy. Charcot's arthropathy should be considered as an operative complication.

Cervical intervertebral disc calcification with extreme lateral herniation in a child: T2-weighted signal intensity of the involved disc can be restored to normal.

PURPOSE: The purpose of this case report is to present a very atypical case of cervical intervertebral disc calcification (IDC) with extreme lateral herniated calcification in a child. This is the first ever reported case in which T2-weighted signal intensity of the involved disc was restored to normal after a 2-year follow-up. METHODS: A 10-year-old girl presented with neck pain and right upper limb numbness for 2 months. The initial computed tomography (CT) images on admission showed calcified nucleus pulposus with extreme lateral herniated calcification at the C6-C7 level. Meanwhile, T2-weighted magnetic resonance imaging (MRI) revealed decreased signal intensity of the involved disc. The patient was treated conservatively with nonsteroidal anti-inflammatory drugs and jaw-occipital belt traction for 2 weeks. The cervical CT and MRI scans were repeated at 2-year follow-up. RESULTS: Her clinical symptoms were completely resolved after 2 weeks. At 2-year follow-up, CT and MRI images demonstrated that calcification was completely absorbed and T2-weighted signal intensity of the C6-C7 disc was restored back to normal. CONCLUSION: Cervical IDC combined with extreme lateral herniated calcification is extremely rare in children. The recovery of signal intensity of intervertebral disc on MRI may provide further support to the feasibility of conservative treatment of IDC.

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling.

Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA) disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark), orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling.

Lipase member H is a novel secreted protein associated with a poor prognosis for breast cancer patients.

The objective of this study is to identify the expression status and clinical implications of lipase member H (LIPH) in breast cancer in order to develop strategies for breast cancer management. LIPH expression status was detected in 346 breast cancer specimens by immunohistochemistry. The relationship between LIPH expression, clinico-pathological parameters, and prognosis of breast cancer was determined. LIPH expression was higher in breast cancer specimens than in paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer samples had high expression of the LIPH protein. LIPH was related to tumor size, histological grade, lymph node metastasis, and distant metastasis (P=0.073, 0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH expression had a significantly higher rate of distant metastasis and poorer disease-specific survival than those with no or low LIPH expression (P=0.01). A Cox regression test indicated that the LIPH protein was an independent prognostic factor (P=0.001). LIPH was differentially expressed in breast cancer individuals and is an independent prognostic factor for breast cancer as well as a potential target for its management.

TIKI2 suppresses growth of osteosarcoma by targeting Wnt/ß-catenin pathway.

Osteosarcoma is the most bone-associated malignancy with high lethality. The current therapeutic strategy benefits little on the survival of patients. Studies have shown that aberrant activation of Wnt/ß-catenin pathway is essential for the progression of osteosarcoma, implying that targeting this signaling may be an effective way of therapeutics. Recently, TIKI family has been identified as a new class of negative regulators for Wnt/ß-catenin pathway. However, the implication of TIKIs with osteosarcoma has not been explored. Here, we constructed an adenoviral vector that expresses TIKI2 in osteosarcoma cells (Ad-TIKI2). TIKI2 expression was found to be reduced in osteosarcoma specimens and cell lines. In tested osteosarcoma cells, the activation of Wnt/ß-catenin pathway was found to be inhibited by TIKI2 expression. Furthermore, the proliferation, colony formation ability, and invasion were all significantly suppressed in osteosarcoma cells infected with Ad-TIKI2. Finally, animal experiments further confirmed that TIKI2 restoration was able to inhibit the growth of osteosarcoma in vivo. Taken together, we provided evidence that reduced expression of TIKI family protein in osteosarcoma may participate in the progression of osteosarcoma and restoring its expression was able to impair the growth of osteosarcoma.

Copublication promotes dissemination hypertension guidelines: a retrospective cohort study.

To evaluate the impact of copublication on hypertension-related clinical practice guidelines' citation, we searched the Web of Science Core Collection and guide.medlive.cn until 31 December 2017 using the terms "hypertension" and "guideline". The copublished group was matched with the noncopublished group at a 1:2 ratio. Primary outcomes were total citations and citations within the first five years after publication. Secondary outcomes included the adjusted impact factor ratio (excluding copublished guidelines) to the actual impact factor of the journal. Altmetric scores were compared using Altmetric explorer data. 21 copublished and 42 noncopublished guidelines were included. The copublished group had higher median current total citations [387.0 (90.0, 1806.0) vs 70.5 (23.25, 158.25)], and higher median citations at one, two, three, four, and five years [7.0 (0.5, 58.5) vs 1.0 (0.0, 5.5), 33.0 (14.0, 142.0) vs 5.5 (1.75, 26.25), 46.0 (24.5, 216.0) vs 10.5 (3, 25.75), 50.0 (19.0, 229.0) vs 9.0 (3.0, 19.0), 52.0 (13.5, 147.0) vs 7.0 (2.0, 20.0), all p < 0.05]. The adjusted IF analysis showed that if they had not copublished the guidelines, 10 of 24 and 11 of 24 journals would have had a lower IF in the first and second years. Median altmetric scores were significantly higher for copublished guidelines [38.5 (9.5, 90.5) vs 3.5 (1.0, 9.0)] (p < 0.05). Copublication is associated with a higher citation frequency of hypertension guidelines and may increase the journal IF. Positive impacts extend beyond academia, benefiting society through broader guideline application and dissemination. This facilitates broader application of guidelines and promotes their dissemination. We conducted a retrospective cohort study to demonstrate how copublication promotes the dissemination of hypertension guidelines.

Recent advances in nanomaterials for the treatment of spinal cord injury.

Spinal cord injuries (SCIs) are devastating. In SCIs, a powerful traumatic force impacting the spinal cord results in the permanent loss of nerve function below the injury level, leaving the patient paralyzed and wheelchair-bound for the remainder of his/her life. Unfortunately, clinical treatment that depends on surgical decompression appears to be unable to handle damaged nerves, and high-dose methylprednisolone-based therapy is also associated with problems, such as infection, gastrointestinal bleeding, femoral head necrosis, obesity, and hyperglycemia. Nanomaterials have opened new avenues for SCI treatment. Among them, performance-based nanomaterials derived from a variety of materials facilitate improvements in the microenvironment of traumatic injury and, in some cases, promote neuron regeneration. Nanoparticulate drug delivery systems enable the optimization of drug effects and drug bioavailability, thus contributing to the development of novel treatments. The improved efficiency and accuracy of gene delivery will also benefit the exploration of SCI mechanisms and the understanding of key genes and signaling pathways. Herein, we reviewed different types of nanomaterials applied to the treatment of SCI and summarized their functions and advantages to provide new perspectives for future clinical therapies.

Delayed Presentation of Thoracic Aortic Pseudoaneurysm Following Pedicle Screw Implantation: A Case Report.

BACKGROUND: Pedicle screw insertion has been known to have several complications even in the most skilled surgical hands. However, injury to the thoracic aorta during pedicle screw insertion is rare, delayed presentation secondary to pseudoaneurysm is even rarer, the pseudoaneurysm formation caused by a series of malpositioned pedicle screws has perhaps not been reported so far. CASE PRESENTATION: In this paper, we report here a case in which inadvertent injury to the thoracic aorta resulted in pseudoaneurysm, its manifestation was initially vague, resulting in a delayed diagnosis. Delayed aortic pseudoaneurysm or injury can be asymptomatic for a long time. Patients with renewed or continued back pain should alert orthopaedic surgeons regarding the possibility of pseudoaneurysms, regardless of the period that has elapsed after pedicle screw implantation.

miR-140 inhibits osteosarcoma progression by impairing USP22-mediated LSD1 stabilization and promoting p21 expression.

Osteosarcoma is a bone tumor frequently diagnosed in children and young adults. Despite advances in chemotherapy and surgical resection, tumors metastasize in 30% of osteosarcoma patients. In addition, side effects caused by chemotherapeutic drugs, as well as the development of chemoresistance, highlight the need to identify the molecular mechanisms involved in the pathogenesis of osteosarcoma. We compared 65 osteosarcoma samples to their adjacent normal tissues, as well as commercially obtained osteosarcoma cell lines with normal osteoblast cell lines, and identified a role for the microRNA (miR)-140/ubiquitin-specific protease 22 (USP22)/lysine-specific demethylase 1 (LSD1)/p21 axis in the development of osteosarcoma. Osteosarcoma tissues and cells exhibited poor miR-140 and p21 expression, whereas the expression of USP22 and LSD1 was increased. Overexpression of miR-140 inhibited cell proliferation, migration, and invasion and promoted cell apoptosis by directly targeting USP22, resulting in its decreased expression. Overexpression of USP22 reversed the effects of miR-140 overexpression in osteosarcoma cells. Overexpression of miR-140 or USP22 knockdown led to the ubiquitination and degradation of LSD1. miR-140 overexpression also suppressed tumorigenesis in vivo. This study revealed a role for miR-140 in the restriction of osteosarcoma development and identified miR-140 as a potential target for therapeutic intervention.

Characterization of human induced pluripotent stem cells line JLUEYEi002-A from a 48 year old healthy male.

Peripheral blood was extracted from a 48-year old healthy male donor. Induced pluripotent stem cells (iPSC) were reprogrammed by sendai virus encoding Klf-4, c-Myc, Oct-4, and Sox-2. The iPSC line showed pluripotency, which was verified by immunofluorescence staining. The iPSC line showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This cell line can be served as healthy control for studying inherited disease.

Generation and characterization of human induced pluripotent stem cells line JLUEYEi001-A from a 45 year old female with Stickler syndrome.

Peripheral blood was extracted from a 45-year old female patient clinically diagnosed with Stickler syndrome harboring a heterozygous splicing mutation in COL2A1 (NM_033150, IVS22-1C>T). Induced pluripotent stem cells (iPSC) were reprogrammed by sendai virus encoding Klf-4, c-Myc, Oct-4, and Sox-2. The iPSC line showed pluripotency, which was verified by immunofluorescence staining. The iPSC line showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This in vitro cellular model can be used to study the pathogenesis underlying Stickler syndrome.

[Progress on clinical treatment of Kümmell's disease].

Kümmell's disease is a delayed complication of osteoporotic vertebral compression fracture (OVCF) . The disease can occur months or even years after the initial spinal injury. Unlike the common osteoporotic compression fracture, it develops slowly and causes intractable pain or neurological dysfunction due to intraspinal instability. So far, the pathogenesis of Kümmell's disease has not been completely clear, there is no standard treatment or single effective treatment for Kümmell's disease. The effect of conservative treatment is often not good. Minimally invasive treatment has become the main treatment for patients with Kümmell's disease due to its short operation time, small trauma and exact effect. However, there are complications such as leakage of bone cement and delayed displacement of bone cement. Moreover, minimally invasive treatment is not suitable for all types of Kümmell's disease patients. Patients with posterior cortical fracture and spinal cord compression need to be opened Radiotherapy, whether anterior or posterior, has the disadvantages of long operation time, large trauma and high treatment cost. This article reviews the progress in the treatment of Kümmell's disease to provide guidance for clinical treatment.

CITED2 mediates the mechanical loading-induced suppression of adipokines in the infrapatellar fat pad.

Adipokines secreted from the infrapatellar fat pad (IPFP), such as adipsin and adiponectin, have been implicated in osteoarthritis pathogenesis. CITED2, a mechanosensitive transcriptional regulator with chondroprotective activity, may modulate their expression. Cited2 haploinsufficient mice (Cited2+/- ) on a high-fat diet (HFD) exhibited increased body weight and increased IPFP area compared to wild-type (WT) mice on an HFD. While an exercise regimen of moderate treadmill running induced the expression of CITED2, as well as PGC-1α, and reduced the expression of adipsin and adiponectin in the IPFP of WT mice on an HFD, Cited2 haploinsufficiency abolished the loading-induced expression of PGC-1α and loading-induced suppression of adipsin and adiponectin. Furthermore, knocking down or knocking out CITED2 in adipose stem cells (ASCs)/preadipocytes derived from the IPFP in vitro led to the increased expression of adipsin and adiponectin and reduced PGC-1α, and abolished the loading-induced suppression of adipsin and adiponectin and loading-induced expression of PGC-1α. Overexpression of PGC-1α in these ASC/preadipocytes reversed the effects caused by CITED2 deficiency. The current data suggest that CITED2 is a critical regulator in physiologic loading-induced chondroprotection in the context of an HFD and PGC-1α is required for the inhibitory effects of CITED2 on the expression of adipokines such as adipsin and adiponectin in the IPFP.

Giant Ganglioneuroma of Thoracic Spine: A Case Report and Review of Literature.

Ganglioneuroma (GN) is a rare benign tumor of neural crest origin usually found in the abdomen, but may occasionally present at uncommon sites including the cervical, lumbar, or sacral spine. However, GNs of thoracic spine are extremely rare. In this report, we describe a 12-year-old girl with giant GN in the thoracic spine, who underwent successful resection (T1-4 level) of the tumor. Histopathological examination confirmed the diagnosis. GN should be considered in the differential diagnosis of any paraspinal mass. A high index of suspicion and correlation of clinico-radiological findings is necessary in differentiating a large benign tumor from a malignant growth. Complete surgical excision is the treatment of choice; however tumor size and location need to be considered for the surgical approach (one-step or multiple surgeries). Close follow-up after surgery is mandatory.

MicroRNA-342-3p Inhibits the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Targeting Astrocyte-Elevated Gene-1 (AEG-1).

Recent studies suggest that microRNAs (miRNAs) are critical regulators in many types of cancer, including osteosarcoma. miR-342-3p has emerged as an important cancer-related miRNA in several types of cancers. However, the functional significance of miR-342-3p in osteosarcoma is unknown. The aims of this study were to investigate whether miR-342-3p is dysregulated in osteosarcoma and to explore the biological function of miR-342-3p in regulating cellular processes of osteosarcoma cells. We found that miR-342-3p expression was significantly decreased in osteosarcoma tissues and cell lines. Overexpression of miR-342-3p inhibits the proliferation, migration, and invasion of osteosarcoma cells. In contrast, the inhibition of miR-342-3p exhibited the opposite effect. Astrocyte-elevated gene-1 (AEG-1) was identified as one of the target genes of miR-342-3p in osteosarcoma cells by bioinformatics analysis, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Overexpression of miR-342-3p also inhibited the Wnt and nuclear factor κB signaling pathways. Moreover, overexpression of AEG-1 partially rescued the inhibitory effects of miR-342-3p mediated on the proliferation, migration, and invasion of osteosarcoma cells. Overall, our results show that miR-342-3p inhibits the proliferation, migration, and invasion of osteosarcoma cells through targeting AEG-1, suggesting a potential target for the development of miRNA-based therapy for osteosarcoma.

[Effectiveness of improved elbow anteromedial approach in treatment of ulna coronoid process fracture].

Objective: To observe the effectiveness of reduction and fixation by the improved elbow anteromedial approach in treatment of ulna coronoid process fracture. Methods: Between January 2010 and December 2014, 13 patients with the ulna coronoid process fracture were treated with reduction and fixation by the improved elbow anteromedial approach. There were 10 males and 3 females with an average age of 37.2 years (range, 18-57 years). Five cases were caused by traffic accident, 7 cases by falling injury from height, and 1 case by object impact injury. Seven cases were the terrible triad of the elbow, 4 cases were the ulna coronoid process and radial head fractures, 1 case was the proximal radius and ulna fractures, and 1 case was the ulna coronoid process and distal radius fractures. According to Regan-Morrey classification criteria, the ulna coronoid process fracture was rated as type Ⅱ in 2 cases and as type Ⅲ in 11 cases. According to O'Driscoll classification criteria, 10 of the 13 cases were anterior coronoid fracture (8 cases of type Ⅱb, 2 of type Ⅱc), and 3 of basal fracture. The operation time, amount of intraoperative bleeding, postoperative complications, range of motion (ROM) of the elbow joint, Mayo elbow function index (MEPI) score and fracture healing time were recorded. Results: The average operation time was 38.7 minutes (range, 30-55 minutes), and the average amount of intraoperative bleeding was 109.3 mL (range, 90-160 mL). All incisions healed at stage Ⅰ. There was no iatrogenic vascular or nerve injury. All patients were followed up 13-24 months (mean, 16.9 months). All fractures achieved clinical healing. The average healing time was 11.2 weeks (range, 8-16 weeks). There were 2 cases of heterotopic ossification. At last follow-up, the ROM of elbow flexion was 119-145° (mean, 132.4°); the ROM of elbow extension was -8-15° (mean, 7°). The ROM of forearm pronation was 68-90° (mean, 78.6°), and the ROM of forearm supination was 76-90° (mean, 84.3°). At last follow-up, the MEPI score was 70-100; and 9 cases were excellent, 3 cases were good, and 1 case was fair. The excellent and good rate was 92.3%. Conclusion: Improved elbow anteromedial approach for the ulna coronoid process fracture can not only avoid the injuries of surrounding blood vessels and nerves, but also perform fracture reduction and fixation under direct vision. It is a safe, simple, and effective treatment method for the ulna coronoid process fracture.

Advances of stem cell based-therapeutic approaches for tendon repair.

Tendon injuries are significant clinical problems. Current treatments often result in incomplete repair or healing, which may lead to reduced function and rupture. Stem cell-based therapy is a promising intervention for tendon repair. In this article, we attempt to provide a brief overview on the recent progress in the field, current understanding of the underlying mechanisms of the approach, and the potential of stem cell-based therapies beyond cell implantation. We conclude the review by sharing our viewpoints on the challenges, opportunities, and future directions of this approach. The translational potential of this article: This paper reviews recent progress on stem cell-based therapeutic approaches for tendon repair, which highlights its translational potential and challenges.

Development of human induced pluripotent stem cell (iPSC) line from a 60year old female patient with multiple schwannoma.

Peripheral blood was collected from a clinically diagnosed 60-year old female patient with multiple schwannoma. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus reprogramming system. The transgene-free iPSC line showed pluripotency verified by immunofluorescent staining for pluripotency markers, and the iPSC line was able to differentiate into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This in vitro cellular model will be useful for further pathological studies of multiple schwannoma.

Characterization of human induced pluripotent stem cell (iPSC) line from a 72year old male patient with later onset Alzheimer's disease.

Peripheral blood was collected from a clinically diagnosed 72-year old male patient with later onset Alzheimer's disease. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus reprogramming system. The transgene-free iPSC line showed pluripotency verified by immunofluorescent staining for pluripotency markers, and the iPSC line was able to differentiate into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This in vitro cellular model will be useful for studying the pathological mechanism of Alzheimer's disease.