TYRO protein tyrosine kinase-binding protein predicts favorable overall survival in osteosarcoma and correlates with antitumor immunity.

To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Firstly, the expression of TYROBP was analyzed using the t test. The Kaplan-Meier plotter analysis and a receiver operating characteristic curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, the ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. TYROBP was significantly increased in osteosarcoma (all P < .001). However, the high expression of TYROBP was related to better OS in osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P = .005), especially in patients of the male sex, age <18 years, metastasis, and tumor site leg/foot (all P < .05). Besides, TYROBP mRNA expression was significantly associated with the tumor site (P < .01) but had no remarkable relationship with age, gender, and metastasis status (all P > .05). Functional annotation and gene set enrichment analysis (GSEA) revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P < .001, R = .87). TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.

Role of anti-Müllerian hormone and testosterone in follicular growth: a cross-sectional study.

BACKGROUND: Anti-Müllerian hormone (AMH) is now considered the best serum biomarker of ovarian reserve, while basal sex hormones are classic markers used for assessing ovarian reserve. The interaction between AMH and sex hormones are complicated and not sufficiently addressed. In this study, we took diminished ovarian reserve (DOR) and polycystic ovarian syndrome (PCOS) as two extremes of ovarian reserve (deficient and excessive respectively) to investigate the role of AMH and sex hormones in follicular growth. METHODS: A retrospective cross-sectional survey was performed. The patients assessed AMH and basal sex hormones in the Second Hospital of Zhejiang University from April 2016 to March 2019 were involved in this study. Serum AMH and sex hormone concentrations were tested with electrochemiluminescence method. Stepwise linear regression and binary logistic regression was used to determine the predictors of AMH level and to explore the involved factors determining DOR and PCOS. RESULTS: In the present study, we found that age and follicle-stimulating hormone (FSH) were main negative correlation factors, and luteinizing hormone (LH) and testosterone (T) were main positive factors of AMH. In DOR group, age, FSH and estradiol (E2) increased and T decreased, while in PCOS group, LH and T increased. Binary logistic regression found that age, weight, FSH, E2, and T were the significant factors which independently predicted the likelihood of DOR, and that age, body mass index (BMI), AMH, LH, and T predicted the likelihood of PCOS. CONCLUSIONS: Our study demonstrated that age, FSH, and T were factors that most closely correlated with AMH level, and T was involved in both DOR and PCOS. Since DOR and PCOS are manifested with insufficient AMH and excessive AMH respectively, it is suggested that total testosterone correlated with AMH closely and plays an important role in follicular growth. More attention should be given to testosterone level during controlled ovarian hyperstimulation (COH) process.

A Modified 2-Stage Treatment for AO/OTA 43-C1 Pilon Fractures Accompanied by Distal Fibular and Posterior Lip of the Distal Tibia Fracture.

The management of pilon fractures remains challenging owing to the high-energy axial loading mechanism that produces comminution of the articular surface, displacement of tibia metaphysis, and severe soft tissue injury. How to preserve the vitality of soft tissue and achieve anatomic reduction has become a timely issue. We report and evaluate the effect of a modified staging treatment for AO Foundation/Orthopaedic Trauma Association (AO/OTA) 43C1 pilon fracture accompanied by distal fibular and posterior lip of the distal tibia fracture. We performed a modified 2-stage treatment of type C1 pilon fracture with distal fibular and posterior malleolar fractures. In the first stage, the posterolateral incision was used for simultaneous reduction of fibula and posterior malleolus, and the tibia was fixed with an external fixator. In the second stage, the external fixator was removed, and the medial malleolus and tibia were fixed after the edema of soft tissue had subsided. The following data were collected: Foot and Ankle Outcome Score (FAOS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Short Form 36 (SF-36) score, Burwell-Charnley fracture reduction score, and postoperative complications. Twenty-seven patients were monitored for an average of 31.70 ± 7.38 months. The Burwell-Charnley fracture reduction scores had anatomic and fair ratings of 92.59%. SF-36 physical component score was 42.94 ± 12.47 and mental component score was 48.73 ± 9.79. Score data from the multiple scales of FAOS included pain, 88.79 ± 8.59; activities of daily living, 91.89 ± 7.50; quality of life, 90.26 ± 10.52; sports, 87.93 ± 11.64; and symptoms, 85.32 ± 8.65. The AOFAS ankle-hindfoot scores were 87.30 ± 13.45. Complications were reported in 5 patients (18.52%). Our study provides a good alternative to the existing protocol for type C1 pilon fractures with distal fibular and posterior lip of the distal tibia fracture and effectively reduces soft tissue complications.

Construction of implantation failure related lncRNA-mRNA network and identification of lncRNA biomarkers for predicting endometrial receptivity.

Insufficient endometrial receptivity is a major factor leading to implantation failure (IF), and the traditional way of morphological observation of endometrium cannot determine the condition of receptivity sufficiently. Considering that long-noncoding RNAs (lncRNAs) regulate endometrial receptivity and competing endogenous RNA (ceRNA) mechanism works in plenty of biological processes, ceRNA is likely to function in the pathology of IF. In the present study, we aim to construct an implantation failure related lncRNA-mRNA network (IFLMN), and to identify the key lncRNAs as the candidates for predicting endometrial receptivity. The global background network was constructed based on the presumed lncRNA-miRNA and miRNA-mRNA pairs obtained from lncRNASNP and miRTarBase. Differentially expressed genes (DEGs) of IF were calculated using the data of GSE26787, and then re-annotated as differentially expressed mRNAs (DEMs) and lncRNAs (DELs). IFLMN was constructed by hypergeometric test, including 255 lncRNA-mRNA pairs, 10 lncRNAs, and 212 mRNAs. Topological analysis determined the key lncRNAs with the highest centroid. Functional enrichment analyses were performed by unsupervised clustering, GO classification, KEGG pathway, and co-expression module analyses, achieving six key lncRNAs and their ceRNA sub-networks, which were involved in immunological activity, growth factor binding, vascular proliferation, apoptosis, and steroid biosynthesis in uterus and prepared endometrium for embryo implantation. Sixteen endometrial samples were collected during mid-luteal phase, including 8 recurrent implantation failure (RIF) or recurrent miscarriage (RM) women and 8 controls who conceived successfully. Quantitative real-time PCR was performed to compare the expression of the above six lncRNAs, which validated that the expression of all these lncRNAs was significantly elevated in endometrium of RIF/RM patients. Further studies are needed to investigate the underlying mechanism, and the lncRNAs may be developed into predictive biomarkers for endometrial receptivity.

Comparison of radiofrequency kyphoplasty (RFK) and balloon kyphoplasty (BKP) in the treatment of vertebral compression fractures: A meta-analysis.

BACKGROUND: Balloon kyphoplasty (BKP) is a widely adopted minimally invasive treatment for vertebral compression fractures (VCFs), but leakage of cement is a main complication of BKP. A novel vertebral augmentation technique radiofrequency kyphoplasty (RFK) with high viscosity cement was developed in 2009. Here, we aim to evaluate whether RFK can relieve symptoms efficiently and reduce cement leakage. METHODS: A literature search was performed using Pubmed, Embase, and Cochrane CENTRAL until September 30, 2016. Both randomized controlled trial (RCT) and non-RCT studies comparing RFK and BKP were included. The main outcomes included pain relief (VAS), functionality improvement (ODI), operation time, reduction of deformity (vertebral height and kyphosis angle), and incidence of cement leakage. The origin of heterogeneity was further explored by subgroup stratification. RESULTS: A total of 6 studies involving 833 patients with VCFs were included. The reduction of VAS score in the RFK group was 3.96 points more than that in the BKP group (P  =  .0007) postoperatively, and the improvement persisted until 12 months after the surgery (P < .00001). The operation time was shorter in RFK group than that in BKP group (P  =  .01). The increase of anterior vertebral height shortly after the operation was 0.53 mm greater in RFK group (P  =  .01). The decrease of kyphotic angle after RFK was 0.63° and 0.92° greater than that after BKP, both immediately and 6 months after operation (P  =  .002 and P < .00001, respectively). There was no significant difference between the incidence of cement leakage after RFK and BKP (P  =  .06). Further subgroup analysis stratified by study design indicated that the incidence of leakage decreased 15% in RFK than BPK (P < .00001) in non-RCT subgroup, but RFK and BKP treatments were equivalent in the RCT studies (P  =  .86). CONCLUSION: RFK appears to be more effective and safer than BKP in the present meta-analysis. The incidence of cement leakage diverges in RCT and non-RCT studies, so large-sample multicentered RCT studies are required to validate this new surgery system.

IGFBP1 Involved in the Decreased Birth Weight Due to Fetal High Estrogen Exposure in Mice.

Our previous study indicated that maternal high-estrogen environment in the first trimester is correlated with increased risks of low birth weight (LBW) and adult diseases. The present study aimed to establish an animal model to confirm such an effect in mice, and to further explore the mechanism involved. A mouse model with high estradiol (E2) exposure during early pregnancy was established, and the birth weight, growth after birth, and expression levels of insulin-like growth factor-binding protein 1 (IGFBP1) of pups were examined. Meanwhile, IGFBP1 expression after treatment of E2 was examined in a HepG2 hepatoma cell line. We found that after exposure to a high-E2 environment the weight of the pups decreased significantly, not only before but also after birth. Meanwhile, both mRNA and protein expressions of IGFBP1 were elevated in placenta and liver tissues. Furthermore, the level of IGFBP1 in the HepG2 cell line was elevated by the treatment of E2, whereas this effect was blocked by estrogen receptor antagonist ICI 182780. In summary, maternal high estrogen up-regulates expression of IGFBP1 in placenta and fetal livers, which contributes to LBW and decreases body weight in offspring.

The association between polymorphism of INSR and polycystic ovary syndrome: a meta-analysis.

Polycystic ovary syndrome (PCOS) is the most common gynecological endocrine disorder. The genetic background is believed to play a crucial role in the pathogenesis of PCOS. In recent years, the role of insulin receptor (INSR) polymorphisms in PCOS predisposition has attracted much attention. We performed a meta-analysis to investigate the association between the single nucleotide polymorphisms (SNPs) of INSR and PCOS. Published literature from Pubmed, Embase, and Cochrane CENTRAL was retrieved up until 7 August 2014. A total of 20 case-control studies including 23,845 controls and 17,460 PCOS cases with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.75 were analyzed. Ninety-eight SNPs distributed in 23 exons and the flanking regions of INSR were investigated, among which 17 SNPs were found to be associated with PCOS. Three SNPs detected in more than three studies were selected for further analyses. Twelve studies including 1158 controls and 1264 PCOS cases entered the analysis of rs1799817, but no significant association was found for every genotype (p > 0.05). Further subgroup stratification by ethnicity and weight did not lead to discovery of significant correlation (p > 0.05). For rs2059806, four studies including 442 controls and 524 PCOS cases were qualified for meta-analysis, and no significant association with PCOS was found for any genotype (p > 0.05). Four studies including 12,830 controls and 11,683 PCOS cases investigated the correlation between rs2059807 and PCOS, and five of the six cohorts indicated a significant impact. Our current meta-analysis suggests no significant correlation between rs1799817/rs2059806 SNPs and susceptibility of PCOS, while rs2059807 could be a promising candidate SNP that might be involved in the susceptibility of PCOS.