Hypoxia preconditioning of adipose stem cell-derived exosomes loaded in gelatin methacryloyl (GelMA) promote type H angiogenesis and osteoporotic fracture repair.

The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment.

Initial Development of an Immediate Implantation Model in Rats and Assessing the Prognostic Impact of Periodontitis on Immediate Implantation.

BACKGROUND: To establish an immediate implantation rat model and to evaluate the effects of pre-existing periodontitis and two different socket rinse solutions on immediate implantation prognosis. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups before immediate implantation, including the control group, the group with experimentally induced periodontitis (EP), in which rats have been experimentally induced periodontitis before implantation, and the group with induced periodontitis and with extraction sockets rinsed with three percent H2O2 (EP-H2O2), in which rats have been induced periodontitis before implantation, and extraction sockets were rinsed with three percent H2O2. Periodontitis was induced by ligating the thread around the molars for four weeks. Six weeks after titanium alloy implants were self-tapped and left to heal transmucosally, maxillae were dissected after the clinical examination to perform micro-CT and histological analysis. RESULTS: An immediate implantation model was successfully built in rats. There was no significant difference in implant survival rates between the EP and control groups. However, the clinical examination results, micro-CT analysis, and histological analysis in EP and EP-H2O2 groups showed a significantly worse prognosis than in the control group. Three percent H2O2 showed a similar effect with saline. CONCLUSION: This study presented a protocol for establishing a rat immediate implantation model and showed that periodontitis history might negatively affect the prognosis of immediate implantation. These findings urge caution and alternative strategies for patients with periodontal disease history, enhancing the long-term success of immediate implantation in dental practice. Additionally, the comparable outcomes between 3% H2O2 and saline suggest the use of saline as a cost-effective and safer alternative for implant site preparation in dental practice.

Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation.

Fangji Huangqi Tang (FHT) is a well-known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT-herb-active compound-target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein-protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS-like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt-qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti-SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS-related autoantibodies (anti-SSA and anti-SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt-qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.

Finite element analysis of maxillary first molar with mesial-occlusal-distal-palatal defect restored with different post-and-core strategies.

Purpose: To explore which restoration strategy generates the most favorable stress distribution in an endodontically-treated maxillary first molar with mesial-occlusal-distal-palatal defect. Methods: Models with one post in palatal canal (PP), each post in palatal and distobuccal canals (PDP), each post in palatal and mesiobuccal canals (PMP), and each post in all canals (PDMP) were established for an endodontically-treated maxillary first molar with mesial-occlusal-distal-palatal defect either with fiber-reinforced composite (FRC) post or gold alloy cast (GAC) post. A 400-N vertical force and a 225-N lateral force were respectively applied. The Mohr-Coulomb stress ratio (σMC ratio) in the residual tooth structure (RTS), the resin cement, and the crowns, the tensile stress (σt) and compressive stress (σc) in the FRC posts, the von-Mises stress ratio (σvM ratio) in the GAC post-and-cores, and the σt and shear stress (σs) at the adhesive interfaces were calculated using finite element analysis. Results: FRC posts generated lower σMC ratio than GAC posts in the RTS (0.3274-0.3643 vs. 0.3399-0.4118). Among the FRC post groups, the PDMP group got the lowest σs at the dentin-post interface (14.92 MPa) and the abutment-crown interface (8.242 MPa) under vertical loading, as well as the lowest σMC ratio in the RTS (0.3381) and the lowest σs at the dentin-post interface (38.00 MPa) under lateral loading. Conclusions: From the point of stress distribution, placing FRC posts in the palatal, distobuccal, and mesiobuccal canals is the optimal strategy in restoring a severely damaged maxillary first molar, provided that lateral occlusal force is reduced.

EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A.

OBJECTIVE: Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis. METHODS: In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified. RESULTS: EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance. CONCLUSION: Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

Sex-specific gene expression patterns in head and neck squamous cell carcinomas.

Objective: The head and neck squamous cell carcinomas (HNSCCs) have higher incidence rates in men, but the reasons are still obscure. This study aimed to investigate the sex-specific gene expression patterns and predict the regulatory mechanisms. Design: Data including clinical, survival, RNA-seq, miRNA, and methylation information were derived from The Cancer Genome Atlas (TCGA). A total of 131 paired male and female cases were included based on propensity score matching. We concentrated on the prognostic values of the sex-specific pathways enriched by differentially expressed genes (DEGs) and predicted the potential regulatory mechanisms from immune cell infiltration, ceRNA regulatory network, methylation, and differential coexpression analysis. Results: Compared with females, males exhibited a lower activity of immune-related functions and higher activities of mitochondrial and ubiquitination functions. The pathway activities were associated with the prognosis of males but less relevant to females. We extracted eight pathways with sex-biased survival patterns, of which five were about down-regulated immune functions, and three were up-regulated pathways (GTP biosynthetic, DNA polymerase, and spliceosomal complex assembly). The five immune pathways were moderately or strongly correlated with the proportion of macrophages. We identified six over-expressed lncRNAs that might be involved in the regulation of the three up-regulated pathways. These lncRNAs exhibited a lower methylation density in males, which might account for their over-expression. Conclusions: For HNSCCs, males were characterized by immunosuppression. It was a sign of unfavorable prognosis and might be associated the proportion of macrophages. LncRNAs and methylation might be involved in the regulation of these pathways.

Need for dental care among medical staff working in the China Antarctic stations.

Even though China Antarctic medical care has made huge progress, dental care has always been a neglected area. Dental health is well-known to be closely related with life quality and work efficiency. Hence, knowing the dental care situation there and providing ways to improve are urgently needed. We choose doctors who worked in China Antarctic station as a window to see the whole picture by sending questionnaire. The results showed dental visits ranked second high, the ratio of doctors who got pre-departure dental knowledge education and screen is low. What is worse, none of them got any after-departure dental check. Their dental knowledge is not as good as we expect, and they were troubled by dental problems in Antarctic. Interestingly, most dental problems were treated by non-dentist with no essential equipment, but 2/3 of them were satisfied with the outcome. As for the dental-related diet and behaviour, snacks eating and alcohol drinking are the strongest predictors of dental pain and gum problem. Those findings are crucial to Antarctic dental care and research.

Removal of heavy metals from fly ash using electrodialysis driven by a bioelectrochemical system: a case study of Pb, Mn, Cu and Cd.

Municipal solid waste incineration (MSWI) fly ash is classified as hazardous waste due to high leachable heavy metals, and incineration leachate belongs to organic wastewater with high biodegradability. Electrodialysis (ED) has shown potential for the removal of heavy metals from fly ash, and bioelectrochemical system (BES) employs biological and electrochemical reactions to generate electricity and remove contaminants from a wide range of substrates. In this study, the ED-BES coupled system was constructed for the co-treatment of fly ash and incineration leachate, where the ED was driven by BES. The treatment effect of fly ash by varying additional voltage, initial pH and liquid-to-solid (L/S) ratio was evaluated. Results showed that the highest removal rates of Pb, Mn, Cu and Cd were 25.43%, 20.13%, 32.14% and 18.87% after 14 days treatment of the coupled system, respectively. These values were obtained under 300 mV of additional voltage, L/S 20 and initial pH3. After the treatment of the coupled system, the fly ash leaching toxicity was lower than the threshold of GB5085.3-2007. The highest energy saving for removed Pb, Mn, Cu and Cd were 6.72, 15.61, 8.99 and 17.46 kWh/kg, respectively. The ED-BES can be considered a cleanliness approach to treating fly ash and incineration leachate simultaneously.

Primary maxillary sinus carcinosarcoma with multidisciplinary management: a case report with 4 years follow-up and literature review.

BACKGROUND: Primary maxillary sinus carcinosarcoma (CS) is an extremely rare malignant tumor characterized by biphasic histologic components, lack of standardized treatment, high recurrence rate, and poor prognosis. This paper presents a case of primary maxillary sinus CS and its treatment. CASE PRESENTATION: A 39-year-old female patient complained of right facial pain and maxillary teeth numbness on March 21, 2018. Computed tomography examination revealed a malignant mass with osteolytic destruction. Preoperative biopsy suggested sarcomatoid carcinoma or CS. A total right maxillectomy under general anesthesia was performed on April 12, 2018. The final staging was T3N0M0 (ACJJ 2019). Postoperative radiotherapy and chemotherapy were performed. On May 26, 2018, the patient received the first cycle of doxorubicin plus ifosfamide. Two days before radiotherapy, the patient received an intra-oral prosthesis. From June 20, 2018, to August 22, 2018, the patient received concurrent chemoradiotherapy: radiotherapy (60 Gy in 30 fractions) and the second cycle of doxorubicin. Then, the patient received four cycles of doxorubicin plus ifosfamide. The patient was followed for 39 months with no evidence of disease. CONCLUSION: Using multidisciplinary therapy, clinical-stage T3N0M0 (ACJJ 2019) maxillary sinus CS may achieve a good prognosis.

Prognostic value of the nodal yield in oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: To systematically evaluate the prognostic value of the nodal yield in oral squamous cell carcinoma by meta-analysis. METHODS: The meta-analysis was adherence to PRISMA. We searched MEDLINE, Embase, and Cochrane for studies published up to 20 April 2022. We collected evidences from observational studies regarding nodal yield in oral squamous cell carcinoma, and investigated its prognostic value by the routine methods of meta-analysis. RESULTS: From seven studies, there was no significant impact of the lymph node yield on overall survival among patients with oral squamous cell carcinoma cases and <18 lymph nodes (hazard ratio (HR) = 1.019, 95% confidence interval (CI) = 0.786-1.320, p = 0.887), with significant heterogeneity (I2 = 80%). The pooled result indicated that a > 18-lymph node yield was a favorable prognostic factor (HR = 0.786, 95%CI = 0.646-0.956, p = 0.016; I2 = 39%). The lymph node yield was not associated with disease-specific survival (HR = 1.594, 95%CI = 0.996-2.552, p = 0.052; I2 = 81%) or disease-free survival (HR = 1.508, 95%CI = 0.924-2.460, p = 0.100; I2 = 41%). CONCLUSION: A lymph node yield of ≥18 lymph nodes might be a favorable prognostic factor for the overall survival of patients with oral squamous cell carcinoma.

Survival after laparoscopic radical surgery for stage IA-IIB cervical cancer: 1316 consecutive cases from a national laparoscopic training center in China.

BACKGROUND: To investigate the survival of cervical cancer patients undergoing laparoscopic radical hysterectomy (LRH) in a minimally invasive gynecology center. METHODS: A consecutive series of patients undergoing first LRH for cervical cancer from May 2008 to December 2017 at a national laparoscopic training center was retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were compared between groups. RESULTS: In total, 1316 women with FIGO (2009) stage IA-IIB cervical cancer received LRH. Among them, 1114 (84.7%) were followed up for 3 months or longer; the median follow-up period was 48 months (range 3-144 months). In patients with stage IA, IB1 (≤ 2 cm), IB1 (> 2 cm), IB2, IIA1 and IIA2-IIB tumors, the 4-year PFS rates were 98.6, 94.5, 87.4, 65.6, 80.0 and 67.4%, respectively, and the 4-year OS rates were 98.6, 96.8, 91.1, 77.4, 85.6 and 76.2%, respectively. The 4-year PFS and OS were as high as 96.2 and 97.5%, respectively, in patients with squamous cell carcinoma of 2 cm or smaller in diameter. A stable high 4-year OS and PFS was achieved after completing 100 LRHs. In patients operated on by the same surgeon, an improvement in survival was observed after 40 LRHs. CONCLUSION: Favorable oncologic outcomes can be achieved in patients with IA-IB1 cervical cancer after LRH in a center with a high surgery volume.

Multi-UAV simultaneous target assignment and path planning based on deep reinforcement learning in dynamic multiple obstacles environments.

Target assignment and path planning are crucial for the cooperativity of multiple unmanned aerial vehicles (UAV) systems. However, it is a challenge considering the dynamics of environments and the partial observability of UAVs. In this article, the problem of multi-UAV target assignment and path planning is formulated as a partially observable Markov decision process (POMDP), and a novel deep reinforcement learning (DRL)-based algorithm is proposed to address it. Specifically, a target assignment network is introduced into the twin-delayed deep deterministic policy gradient (TD3) algorithm to solve the target assignment problem and path planning problem simultaneously. The target assignment network executes target assignment for each step of UAVs, while the TD3 guides UAVs to plan paths for this step based on the assignment result and provides training labels for the optimization of the target assignment network. Experimental results demonstrate that the proposed approach can ensure an optimal complete target allocation and achieve a collision-free path for each UAV in three-dimensional (3D) dynamic multiple-obstacle environments, and present a superior performance in target completion and a better adaptability to complex environments compared with existing methods.

Preparation and characterization of two novel osteoinductive fishbone-derived biphasic calcium phosphate bone graft substitutes.

Many studies have reported on the conversion of natural resources into xenografts with hydroxyapatite (HA) as major component, but the extraction of biphasic calcium phosphate (HA/ß-TCP) from animal bones and transformation into bone graft substitutes are rarely reported. In this research, two kinds of fish bones were made into granular porous biphasic calcium phosphate bone graft substitutes with particle sizes between 500 to 1000 µm through a series of preparation procedures (Salmo salar calcined at 900°C named Sa900 and Anoplopoma fimbria calcined at 800°C named An800). The chemical composition was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The morphology and porous structure of the scaffolds were comparatively analyzed by scanning electron microscopy (SEM) and mercury porosimeter. The specific surface area of materials was measured by the nitrogen adsorption technique based on BET theory. Cytotoxicity and ectopic osteogenesis were also carried out to investigate the biocompatibility and osteoinductive potential of these materials. The results showed that both fishbone-derived scaffolds were composed of HA and ß-TCP with different proportions, and numerous interconnected pores with different sizes were observed at the surface of materials. An800 had higher total porosity reaching 74.8% with higher interconnectivity and micropores mostly distributed at 0.27 µm and 0.12 µm, while Sa900 had a higher specific surface area and higher intraparticle porosity with nanopores mostly distributed at 0.07 µm. CCK-8 assays and Live/dead staining demonstrated excellent biocompatibility. Material-induced osteoid formation were observed on the interface of both internal pores and periphery of materials after implantation in muscle pouch of Wistar rats for 8 weeks which indicated some extent of osteoinductive potential of materials. The possible mechanism of material-induced osteogenesis and the effects of chemical composition, surface topography, and spatial structure on osteogenesis were also discussed in this paper.

Finite element analysis of maxillary first molar with a 4-wall defect and 1.5-mm-high ferrule restored with fiber-reinforced composite resin posts and resin core: The number and placement of the posts.

STATEMENT OF PROBLEM: Whether fiber-reinforced composite (FRC) posts should be inserted in root canals to restore teeth with multiple roots remains unclear. PURPOSE: The purpose of this finite element analysis (FEA) study was to determine the optimal use of FRC posts in an endodontically treated maxillary first molar with a 4-wall defect and 1.5-mm-high ferrule. MATERIAL AND METHODS: Eight different models of a maxillary first molar were established: no post (NP), post in palatal root (P), post in distobuccal root (DB), post in mesiobuccal root (MB), posts in palatal root and distobuccal root (P+DB), posts in palatal root and mesiobuccal root (P+MB), posts in 2 buccal roots (DB+MB), and posts in all roots (P+DB+MB). Two types of loading were applied: a force of 800 N parallel to the long axis of the tooth to simulate the vertical masticatory force and another force of 225 N at 45 degrees to the long axis of the tooth to simulate the lateral masticatory force. The equivalent stresses on the external surfaces of the tooth tissue, the internal surfaces of the root canals and in the posts, as well as the maximal shear stresses on the post-core interface and the core-dentin interface, were calculated with FEA. RESULTS: All the models showed similar maximal equivalent stress values on the external surfaces of the tooth tissue, and stress concentrations were found at the cervical and furcation area. On the internal surfaces of root canals, an increase of equivalent stress at the middle third of the canals with posts and a decrease at the cervical third were observed. Under vertical loading, the P+DB+MB group showed the largest equivalent stress in the post (76.45 MPa in the palatal post), the DB+MB group showed the largest shear stress on the post-core interface (19.02 MPa), and the MB group showed the largest shear stress on the core-dentin interface (12.07 MPa). Under lateral loading, the P+DB+MB group showed the largest equivalent stress in the post (60.11 MPa in the mesiobuccal post) and the largest shear stress on the post-core interface (13.48 MPa) and the DB group showed the largest shear stress on the core-dentin interface (21.03 MPa). CONCLUSIONS: One post in the palatal canal was found to be appropriate for the FRC post and resin core restoration of a maxillary first molar with a 4-wall defect and 1.5-mm-high ferrule. An additional post in the mesiobuccal canal could help disperse lateral occlusal force and improve retention of the restoration.

Region-specific Risk Factors for Pelvic Lymph Node Metastasis in Patients with Stage IB1 Cervical Cancer.

Objectives: We aimed to identify the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location in patients with stage IB1 cervical cancer. Methods: A primary cohort of 728 patients with stage IB1 cervical cancer who underwent radical hysterectomy and systematic pelvic lymphadenectomy were retrospectively studied. All removed pelvic nodes (N=20,134) were pathologically examined. The risk factors for LNM in different anatomic regions (obturator, internal iliac, external iliac, and common iliac) were evaluated by multivariate logistic regression analyses. Nomograms were generated from the primary cohort and validated in another external cohort (N=242). The performance of the nomogram was assessed by its calibration and discrimination. Overall survival and progression-free survival in patients with different LNM patterns were compared. Results: LNM was found in 266 (1.3%) removed nodes and 106 (14.6%) patients. The incidences of LNM at the obturator, internal iliac, external iliac, common iliac, and parametrial regions were 8.5%, 5.4%, 4.7%, 1.9% and 1.8%, respectively. Among others, tumour size and lymph-vascular space invasion (LVSI), which are preoperatively assessable, were identified as independent risk factors of LNM in the common iliac region and the lower pelvis, respectively, and age was an additional independent risk factor of obturator LNM. The negative predictive values of tumour size <2 cm for common iliac LNM and negative LVSI combined with older age (> 50 years) for obturator LNM were 100% and 98.7%, respectively. A nomogram of these two factors showed good calibration and discrimination (concordance index, 0.761 in the primary cohort and 0.830 in validation cohort). The patients with common iliac LNM had poorer survival than those with LNM confined to the lower pelvis, while the differences in survival between patients with LNM confined to one node, one region or single side and those with more widely spreading LNM were not statistically significant. Conclusions: Tumour size, LVSI and age are region-specific risk factors for pelvic LNM in IB1 cervical cancer, which could be used to allocate the appropriate extent of pelvic lymphadenectomy.

Diagnostic Value of Circulating PIGF in Combination with Flt-1 in Early Cervical Cancer.

The utility of placental growth factor (PlGF) and its receptor VEGFR-1 (Flt-1) as biomarkers for cervical cancer has not been clarified yet. To address this issue, we investigated the levels of soluble PlGF (sPlGF) and soluble Flt-1 (sFlt-1) in the serum from patients with early cervical cancer, cervical intraepithelial neoplasia (CIN) and controls in this study. sPlGF and sFlt-1 were detected in 44 preoperative patients with cervical cancer, 18 cases with CIN, and 20 controls by ELISA. It was found that both sPlGF and sFlt-1 were significantly increased in the cervical cancer group as compared with those in CIN and control groups. sPlGF presented a high diagnostic ability of cervical cancer, with a sensitivity of 61.36% and a specificity of 89.47%; and sFlt-1 with a sensitivity of 50.00% and a specificity of 92.11%. Importantly, the combined use of sPlGF and sFlt-1 could increase the diagnostic rate of cervical cancer, with a sensitivity of 70.45% and a specificity of 92.11%. These results indicated that both sPlGF and sFlt-1 in circulation can serve as possible valuable diagnostic biomarkers for cervical cancer, and the combined use of them can be more valuable to diagnose the patients with early cervical cancer.

Investigation of long non-coding RNA expression profiles in patients with post-menopausal osteoporosis by RNA sequencing.

The present study aimed to investigate the implication of long non-coding RNA (lncRNA) expression profiles in post-menopausal osteoporosis (PMOP). A total of 10 patients with PMOP and 10 age-matched healthy post-menopausal females as controls were consecutively enrolled. Their peripheral blood mononuclear cells were obtained and lncRNA as well as mRNA expression profiles were detected by RNA sequencing, followed by bioinformatics analyses. The lncRNA expression profiles were able to distinguish patients with PMOP from controls based on principal component analysis and heatmap analysis. In total, 254 upregulated lncRNAs and 359 downregulated lncRNAs were identified in patients with PMOP vs. controls. The top 5 upregulated lncRNAs were RP11-704M14.1, RP11-754N21.1, RP11-408E5.5, ANKRD26P3 and TPTEP1. The top 5 downregulated lncRNAs were RP11-310E22.4, RP11-326K13.4, FABP5P1, SERPINB9P1 and RPL13P2. Based on the interaction of dysregulated lncRNAs and mRNAs by RNA sequencing, functional annotations were then performed. Gene Ontology enrichment analysis revealed that the dysregulated lncRNAs were enriched in terms including apoptotic process and positive regulation of NF-κB transaction, and Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment in PMOP-associated signaling pathways, including osteoclast differentiation, tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway. In addition, the regulatory network and circos graph further indicated the implication of lncRNA expression profiles in PMOP via interactions with mRNAs. In conclusion, the present study suggested that aberrant lncRNA expression is deeply involved in the pathogenesis of PMOP by affecting osteoclast differentiation, inflammation and apoptotic processes.

HOTAIR promotes paclitaxel resistance by regulating CHEK1 in ovarian cancer.

PURPOSE: The HOX transcript antisense RNA (HOTAIR) has been reported to be aberrantly expressed in ovarian cancer (OC). Abnormal high expression level of HOTAIR has been found to be associated with poor overall survival of OC patients. Yet, the role of HOTAIR in paclitaxel resistance of OC is unclear. This study aims to investigate the effect, as well as the mechanism of HOTAIR in promoting paclitaxel resistance of OC. METHODS: Ovarian cancer cell lines with down-regulated and up-regulated expression of HOTAIR were, respectively, established. The expression of HOTAIR was confirmed by qRT-PCR. The sensitivity of ovarian cancer cells to paclitaxel was detected by MTT assays, colony formation, EdU assays, flow cytometry, and in vivo experiments. RESULTS: An increased expression level of HOTAIR was observed in ovarian cancer cell lines following treatment with paclitaxel. When the expression of HOTAIR was down-regulated, the proliferation of ovarian cancer cells was found to be inhibited, coupled with enhanced cell sensitivity to paclitaxel. Conversely, when the HOTAIR expression was up-regulated, an opposite effect was observed on the ovarian cancer cells. In addition, cell cycle arrest in G2/M phase was also shown to be accelerated upon HOTAIR suppression. Strikingly, our results also revealed that HOTAIR plays a regulatory role in the expression of checkpoint kinase 1 (CHEK1), and that the restored paclitaxel sensitivity through knockdown of HOTAIR can be weakened by CHEK1 up-regulation. Consistently, in vivo data confirmed that the therapeutic efficacy of paclitaxel can be enhanced through down-regulation of HOTAIR, and that CHEK1 is the down-stream target of HOTAIR in inducing paclitaxel resistance. CONCLUSION: HOTAIR confers paclitaxel resistance in epithelial ovarian cancer by increasing the protein level of CHEK1.

miR­126 regulates the progression of epithelial ovarian cancer in vitro and in vivo by targeting VEGF­A.

MicroRNA (miRNA/miR­126) has been shown to be associated with ovarian cancer in previous studies. In ovarian cancer, however, the specific status of miR­126 remains largely unknown. In the present study, to clarify its role in ovarian cancer, the levels of miR­126 were first examined using laser microdissection and RT­qPCR. It was found that the miR­126 level was decreased in ovarian tissue samples and the restoration of miR­126 inhibited cell proliferation, cell invasion and migration in vitro and suppressed tumor growth in vivo. A bioinformatics search revealed that the angiogenesis­related gene, vascular endothelial growth factor (VEGF)­A, was among the potential targets of miR­126. The suppression of invasion and proliferation induced by ectopic miR­126 expression was nullified by the ectopic expression of VEGF­A, suggesting that these suppressive effects were largely attributable to the ability of miR­126 to target VEGF­A. Moreover, the restoration of miR­126 suppressed the angiogenic potential of human umbilical vein endothelial cells (HUVECs). On the whole, these findings indicate that the loss of expression of miR­126 contributes to the abnormal VEGF­A accumulation and subsequent unchecked cell invasion and cell proliferation in epithelial ovarian cancer.

Angiopoietin-1 is associated with a decreased risk of lymph node metastasis in early stage cervical cancer.

OBJECTIVES: Lymph node metastasis (LNM) is an important determinant of prognosis in patients with cervical cancer. Members of the angiopoietin family have been demonstrated to regulate tumor-associated angiogenesis and lymphangiogenesis. This study aimed to investigate the expression levels of angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2) in clinically early stage of cervical cancer along with their correlations with LNM. METHODS: In total, 124 human cervical cancer cases classified into stage IA-IIB in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria were included. ANG1 and ANG2 expression levels in the tumor sections were assessed by immunohistochemistry (IHC). Univariate and multivariate logistic regression models, including age at diagnosis, FIGO stage, tumor size, pathological type, histological grading, depth of stromal invasion, lymph-vascular space invasion (LVSI) and the expression status of ANG1 and ANG2, were used to evaluate the odds ratios (ORs) for LNM. RESULTS: ANG1 and ANG2 were positively expressed in 75 (60.5%) and 89 (71.8%) cervical cancers respectively, with predominant staining in the cytoplasm. ANG1 expression was significantly decreased in tumors with LNM, while no correlation was observed between ANG2 expression and LNM. More importantly, the multivariate logistic regression analysis demonstrated that high ANG1 expression was an independent protective factor of LNM (OR 0.107, 95% confidential interval [CI] 0.020~0.567), while LVSI was an independent risk factor of LNM (OR 34.313, 95% CI 5.914~199.092). CONCLUSION: ANG1 is associated with a significantly decreased risk of LNM in early stage cervical cancer. The predictive value and role of ANG1 in LNM needs to be further investigated in future studies.