Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let-7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let-7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let-7e may regulate apoptosis and autophagy of articular chondrocytes. A total of 10 patients with KOA and 10 patients with trauma without KOA were recruited to examine the levels of let-7e in peripheral blood. Subsequently, KOA rat models were established, and the levels of let-7e in the cartilage and serum were examined, the expression of apoptotic proteins and autophagy-related proteins in the cartilage were investigated, and apoptotic and autophagic activities of primary cultured chondrocytes were also detected. In patients with KOA, let-7e levels in the peripheral serum were significantly decreased compared with the control group, and this result was confirmed in the peripheral serum and cartilage of KOA rats. In addition, the expression levels of proteins involved in the apoptotic pathway were increased in the cartilage of KOA rats, and apoptotic activity was increased. The expression of autophagy-related proteins beclin 1 and microtubule associated protein 1 light chain 3 β (Lc3B) II/Lc3BI in the articular cartilage of KOA rats was lower compared with the controls, and autophagy was decreased. Si-Miao-San (SMS) treatment restored the expression of let-7e and reversed the changes in apoptosis and autophagy. Therefore, the present study provided additional evidence that circulating let-7e may be a potential serum biomarker for the diagnosis and treatment of KOA. Elevated apoptosis levels and decreased autophagy levels of cartilage tissue are involved in KOA, and treatment with SMS may reverse these effects.

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.

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 (E 2) increased and T decreased, while in PCOS group, LH and T increased. Binary logistic regression found that age, weight, FSH, E 2 , 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.

BackgroundPercutaneous kyphoplasty (PKP) is the first-line treatment for osteoporotic vertebral compression fractures (OVCFs) that can immediately relieve pain and allow the quick recovery of lost mobility. However, some studies reported that after PKP, the incidence of vertebral refracture, particularly adjacent vertebral fracture (AVF), was high. Our previous meta-analysis suggested that the risks for vertebral refracture and AVF did not increase after percutaneous vertebral augmentation in OVCF patients. Despite the negative results of our meta-analysis, there is still significant evidence regarding the relationship between kyphoplasty and AVF, so a new prospective cohort study is warranted. In addition, in our previous retrospective study, we found that advanced age, female sex and low oestradiol (E2) concentrations might be related to the occurrence of postoperative vertebral refracture after PKP. To sufficiently evaluate the probable factors involved in the occurrence of postoperative vertebral refracture, we designed this prospective study.MethodsThis is a prospective cohort study of patients admitted for PKP to treat painful OVCFs. The baseline data, including demographic information, lifestyle, bone metabolic status, sex hormone and sex hormone-binding globulin (SHBG) levels, and clinical characteristics will be collected at the time of enrolment. Surgical features of PKP will be recorded on the operation day. Lifestyle, bone metabolic status, sex hormone levels, and SHBG levels will be assessed during the follow-up period at 1 m, 3 m, 12 m, and 24 m postoperatively. Patients suffering from acutely aggravated back pain will be referred to an orthopaedist, and refractured vertebrae will be confirmed by magnetic resonance imaging and computed tomography. The primary outcome will be the incidence of vertebral refracture. Multivariate analyses will be carried out to evaluate the variables that are independently correlated with vertebral refracture.DiscussionTo evaluate the risk of postoperative refracture preoperatively and to identify the surgical points related to postoperative refracture, this study will explore the risk factors related to vertebral refracture after PKP. The results may provide new information about defining OVCF patients suitable for PKP treatment.Trial registrationChiCTR-ROC-17011562. Registered on July 4th, 2017.

Osteoarthritis (OA) is the most common degenerative disease affecting articular cartilage. Some studies indicate that tumor necrosis factor alpha (TNF-α) gene rs1800629 polymorphism was associated with OA risk among Caucasian populations. To examine the role of this candidate gene in Asian populations, we conducted a hospital-based case-control study involving 257 knee OA patients and 305 controls in a Chinese population. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism (SNP) Scan™ kit. Our study indicated that the AA genotype of TNF-α rs1800629 polymorphism was associated with increased risk of OA. Subsequently, we conducted a meta-analysis and found that rs1800629 polymorphism increased the risk of OA in the recessive and homozygous models. Stratification analysis of ethnicity also obtained a significant association among Asian populations. In conclusion, TNF-α rs1800629 polymorphism confers susceptibility to OA, especially among Asians. Larger studies with more diverse ethnic populations are needed to confirm these results.