HOXA-AS2 may be a potential prognostic biomarker in human cancers: A meta-analysis and bioinformatics analysis.

Background: Dysregulation of long non-coding (lncRNA) has been reported in various solid tumors. HOXA cluster antisense RNA 2 (HOXA-AS2) is a newly identified lncRNA with abnormal expression in several human malignancies. However, its prognostic value remains controversial. This meta-analysis synthesized available data to clarify the association between HOXA-AS2 expression levels and clinical prognosis in multiple cancers. Methods: Four public databases (Embase, PubMed, Web of Science, The Cochrane Library) were used to identify eligible studies. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined to assess the correlation of HOXA-AS2 expression with survival outcomes and clinicopathological features of cancer patients. Publication bias was measured using Begg's funnel plot and Egger's regression test, and the stability of the combined results was measured using sensitivity analysis. Additionally, multiple public databases were screened and extracted to validate the results of this meta-analysis. Results: The study included 20 studies, containing 1331 patients. The meta-analysis showed that the overexpression of HOXA-AS2 was associated with poor overall survival (HR = 2.06, 95% CI 1.58-2.69, p < 0.001). In addition, the high expression of HOXA-AS2 could forecast advanced tumor stage (OR = 3.89, 95% CI 2.90-5.21, p < 0.001), earlier lymph node metastasis (OR = 3.48, 95% CI 2.29-5.29, p < 0.001), larger tumor size (OR = 2.36, 95% CI 1.52-3.66, p < 0.001) and earlier distant metastasis (OR = 3.54, 95% CI 2.00-6.28, p < 0.001). However, other clinicopathological features, including age (OR = 1.09, 95% CI 0.86-1.38, p = 0.467), gender (OR = 0.92, 95% CI 0.72-1.18, p = 0.496), depth of invasion (OR = 2.13, 95% CI 0.77-5.90, p = 0.146) and differentiation (OR = 1.02, 95% CI 0.65-1.59, p = 0.945) were not significantly different from HOXA-AS2 expression. Conclusion: Our study showed that the overexpression of HOXA-AS2 was related to poor overall survival and clinicopathological features. HOXA-AS2 may serve as a potential prognostic indicator and therapeutic target for tumor treatment.

[Two different techniques combined with MIS-TLIF in the treatment of degenerative lumbar spondylolisthesis:a case-control study].

OBJECTIVE: To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis. METHODS: A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation. RESULTS: ①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(P<0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation (P<0.05), but there was no significant difference between the three group(P>0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation (P<0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation(P<0.05), and the intervertebral heigh was increased compared with that before operation(P<0.05), however, there was no significant difference among three groups at 12 months afrer operation(P>0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation(P>0.05). CONCLUSION: The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.

Upregulated mGluR5 induces ER stress and DNA damage by regulating the NMDA receptor subunit NR2B.

Dysfunction caused by mGluR5 expression or activation is an important mechanism in the development of Parkinson's disease (PD). Early clinical studies on mGluR5 negative allosteric modulators have shown some limitations. It is therefore necessary to find a more specific approach to block mGluR5-mediated neurotoxicity. Here, we determined the role of N-methyl-D-aspartate (NMDA) receptor subunit NR2B in mGluR5-mediated ER stress and DNA damage. In vitro study, rotenone-induced ER stress and DNA damage were accompanied by an increase in mGluR5 expression and overexpressed or activated mGluR5 with agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) induced ER stress and DNA damage, while blocking mGluR5 with antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) alleviated the effect. Furthermore, the damage caused by CHPG was blocked by NMDA receptor antagonist MK-801. Additionally, rotenone or CHPG increased the p-Src and p-NR2B, which was inhibited by MPEP. Blocking p-Src or NR2B with PP2 or CP101,606 alleviated CHPG-induced ER stress and DNA damage. Overactivation of mGluR5 accompanied with the increase of p-Src and p-NR2B in the ER stress and DNA damage was found in rotenone-induced PD rat model. These findings suggest a new mechanism wherein mGluR5 induces ER stress and DNA damage through the NMDA receptor and propose NR2B as the molecular target for therapeutic strategy for PD.

Nonreciprocal Tamm plasmon absorber based on lossy epsilon-near-zero materials.

Contrary to conventional Tamm plasmon (TP) absorbers of which narrow absorptance peaks will shift toward short wavelengths (blueshift) as the incident angle increases for both transverse magnetic (TM) and transverse electric (TE) polarizations, here we theoretically and experimentally achieve nonreciprocal absorption in a planar photonic heterostructure composed of an isotropic epsilon-near-zero (ENZ) slab and a truncated photonic crystal for TM polarization. This exotic phenomenon results from the interplay between ENZ and material loss. And the boundary condition across the ENZ interface and the confinement effect provided by the TP can enhance the absorption in the ENZ slab greatly. As a result, a strong and nonreciprocal absorptance peak is observed experimentally with a maximum absorptance value of 93% in an angle range of 60∼70°. Moreover, this TP absorber shows strong angle-independence and polarization-dependence. As the characteristics above are not at a cost of extra nanopatterning, this structure is promising to offer a practical design in narrowband thermal emitter, highly sensitive biosensing, and nonreciprocal nonlinear optical devices.

miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma.

PURPOSE: Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown. MATERIALS AND METHODS: U2OS and SAOS-2 cells were treated with various concentrations of epirubicin. Flow cytometry was employed to evaluate cell apoptotic rate. Cell proliferation was measured by Cell Counting Kit-8 assay. Western blot and quantitative real-time polymerase chain reaction were utilized to detect the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerases (PARP1), TP53-regulated inhibitor of apoptosis 1 (TRIAP1), and microRNA-1301 (miR-1301). The relationship between miR-1301 and TRIAP1 was determined by luciferase reporter assay. RESULTS: Epirubicin inhibited proliferation in a dose-dependent manner, induced apoptosis, decreased the expression of Bcl-2, and increased the expressions of Bax, cleaved-caspase-3, and cleaved-PARP1 in osteosarcoma cells. miR-1301 was downregulated in U2OS and SAOS-2 cells. Importantly, epirubicin significantly increased the levels of miR-1301. Overexpression of miR-1301 suppressed proliferation and promoted apoptosis. Interestingly, those effects were enhanced by epirubicin. In contrast, miR-1301 depletion attenuated the epirubicin-mediated anti-osteosarcoma effect. miR-1301 negatively regulated the expression of TRIAP1 in U2OS and SAOS-2 cells. Furthermore, epirubicin inhibited the mRNA and protein levels of TRIAP1 by upregulating miR-1301 levels. Epirubicin suppressed cell proliferation by downregulating TRIAP1. CONCLUSION: miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1.

Construction of microRNA-messenger networks for human osteosarcoma.

Osteosarcoma is the most common bone tumor in children and young adults. Although the microRNAs (miRNA) expression analyses of osteosarcoma have been performed previously, the construction of miRNA-messenger RNA (mRNA) networks for osteosarcoma is needed. This study aimed to identify osteosarcoma-related miRNAs through analyzing the microarray datasets and to construct the regulatory network of miRNA-mRNA for human osteosarcoma. The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs were screened through the limma package in Bioconductor. Genes targeted by the differentially expressed miRNAs were screened out by using the Miranda, MirTarget2, PicTar, PITA, and TargetScan databases. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of differentially expressed miRNAs and their target osteosarcoma-associated genes was constructed. A total of 36 downregulated miRNAs and 182 upregulated miRNAs were identified in osteosarcoma samples compared with normal samples and 397 target genes for upregulated miRNAs and 222 target genes for downregulated miRNAs were obtained. The enriched pathways for target genes of differentially expressed miRNAs included transcriptional misregulation in cancer, the AMPK signaling pathway, and MAPK signaling pathway. In the regulatory network, has-miR-199a-5p targeted the highest number of genes and nemo-like kinase (NLK) was targeted by five miRNAs (hsa-miR-140-5p, hsa-miR-107, hsa-miR-324-5p, hsa-miR-199a-5p, and hsa-miR-28-5p). The has-miR-324-5p targets NLK, TGFB2, and PPARG. These miRNAs and their target genes may serve as potential therapeutic targets of osteosarcoma.

Isoniazid-loaded chitosan/carbon nanotubes microspheres promote secondary wound healing of bone tuberculosis.

Poor blood circulation makes it difficult for antitubercular drugs to achieve effective bactericidal concentration at tuberculose focus. The residual Mycobacterium tuberculosis around surgical wound would multiply, resulting in nonunion or sinus formation. Carbon nanotubes have strong tissue penetration and can cross many kinds of physiological barriers. Here, we constructed a chitosan/carbon nanotubes nanoparticles to control slow release of isoniazid. Transmission electron microscopy and nanoparticle tracking and analysis results showed that the diameter of chitosan/carbon nanotubes nanoparticles was between 150 and 250 nm. Chitosan/carbon nanotubes nanoparticles significantly prolonged the release time of isoniazid, and the release rate was more uniform, no sudden release was observed. In vitro experiments showed that chitosan/carbon nanotubes nanoparticles did not destroy biological function of isoniazid, but could reduce its cytotoxicity and inflammation. We further constructed animal model of tuberculous ulcer. The results showed that isoniazid/chitosan/carbon nanotubes nanoparticles promoted the healing of tuberculosis ulcer. Compared with isoniazid group and isoniazid/carbon nanotubes group, the area of wounds decreased by 94.6% and 89.8%, respectively. Immunohistochemistry showed that CD3+ and CD4+ T cell number decreased significantly in isoniazid/chitosan/carbon nanotubes group. In conclusion, we constructed a kind of isoniazid/chitosan/carbon nanotubes nanoparticles, which can significantly promote the healing of tuberculosis ulcer. Our study provided an effective way for the treatment of secondary wound healing of bone tuberculosis.

[Internal fixation of lateral and medial borders for displaced scapular body fractures via minimally invasive approach:results of 23 cases].

OBJECTIVE: To evaluate the efficacy of internal fixation of lateral and medial borders for displaced scapular body fractures via the minimally invasive approach. METHODS: The internal fixation of lateral and medial borders via minimally invasive approach was applied in surgical treatment of 23 patients with scapular body comminuted fractures from January 2014 to June 2018. The lateral approach was made straightly orienting over the lateral border of scapula. The dissection was taken down to the deltoid fascia. The deltoid was retracted cephalically, revealing the external rotators. Blunt dissection was used down to the lateral border between infraspinatus and teres minor, exposing the fracture site. The medial incision was done along the medial border of the scapula over site of the fracture. Dissections were taken down to the fascia and the periosteum. A subperiosteal dissection was then performed to elevate the infraspinatus to the degree necessary to visualize the fracture. The medial and lateral borders of scapula body were fixed with plates and screws in a frame-like way. RESULTS: One patient developed the delayed healing of the incisions due to liquefactive fat necrosis. The other 22 patients showed no complications of the incisions. The glenopolar angle (GPA) of fractured scapula was increased from preoperative (25±12) degrees to postoperative (41±5) degrees (P<0.01). The healing time of fractures healed was 3-8 months, with an average time of (4.4±1.3) months. CONCLUSIONS: The lateral-medial combined fixation through minimally invasive surgical approach for the scapula body fractures allows visualization of fracture reduction without extensive muscular or subcutaneous flaps, and is associated with successful fracture healing and high functional scores of the shoulder.

A non-invasive, rapid method to genotype late-onset Alzheimer's disease-related apolipoprotein E gene polymorphisms.

The apolipoprotein E gene ε4 allele is considered a negative factor for neural regeneration in late-onset Alzheimer's disease cases. The aim of this study was to establish a non-invasive, rapid method to genotype apolipoprotein E gene polymorphisms. Genomic DNA from mouth swab specimens was extracted using magnetic nanoparticles, and genotyping was performed by real-time PCR using TaqMan-BHQ probes. Genotyping accuracy was validated by DNA sequencing. Our results demonstrate 100% correlation to DNA sequencing, indicating reliability of our protocol. Thus, the method we have developed for apolipoprotein E genotyping is accurate and reliable, and also suitable for genotyping large samples, which may help determine the role of the apolipoprotein E ε4 allele in neural regeneration in late-onset Alzheimer's disease cases.