Mendelian randomization studies of depression: evidence, opportunities, and challenges.

BACKGROUND: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. METHODS: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. RESULTS: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. CONCLUSIONS: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis.

BACKGROUND: Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. METHODS: Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. RESULTS: Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a "ceRNA" for miR-4659a/b-3p to increase HBEGF and TGF-ß/Smad expression, then promoted the development of GC. CONCLUSIONS: Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-ß/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Research Progress of Forensic Diagnosis Approaches of Early Acute Myocardial Infarction.

The postmortem diagnosis of acute myocardial infarction (AMI), especially the postmortem diagnosis of early AMI that died immediately after onset or within 1 hour, has always been a difficulty in forensic identification. This article reviews the forensic application of diagnosis and analysis methods for AMI postmortem diagnosis including autopsy imaging, histomorphology, immunohisto-chemistry, biochemical marker and molecular biology diagnosis, and explores the feasible scheme of early postmortem diagnosis in AMI.

CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R2 (R2 = 0.635, P < 0.001). The Cox proportional hazards regression model was used to estimate the effect of circSCAF8 on progression-free survival. The in vitro and in vivo functional experiments were implemented to investigate the effects of circSCAF8 on the phenotype of PCa. We found that the knockdown of circSCAF8 in PCa cells suppressed the proliferation, migration, and invasion ability, while overexpression of circSCAF8 had the opposite effects. Similar results were observed in vivo. In a cohort of 85 patients who had undergone radical prostatectomy, circSCAF8 expression in PCa tissues was a powerful predictor of progression-free survival (HR = 2.14, P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Change Rule of Diatom in Zhangweixin River in Dezhou.

OBJECTIVES: To study the annual variation of diatoms in Zhangweixin River, to provide theoretical support by using diatom examination to estimate the time and place of the corpse entering water, and to establish a diatom database. METHODS: Samples were taken from 4 sampling sites in Decheng section of Zhangweixin River for 12 consecutive months. Non-metric multi-dimensional scaling (NMDS) analysis was performed on the species and content of diatom samples. Based on the sampling site of Tianqu Road, Sprensen similarity coefficient analysis was conducted with the data of other 3 sites in Decheng section and Leling section of Zhangweixin River and Ningjin section in previous studies. RESULTS: The number of diatom species was positively correlated with diatom content. The average diatom content in different months ranged from 1 054 to 13 041/10 mL, and the species composition ranged from 8 to 16, with differences in dominant species. The similarity coefficient of diatom species within 2 km were all higher than 0.956 52, which could not be distinguished effectively. The similarity coefficients of Leling section and Ningjin section were 0.736 84 and 0.588 24 respectively, which could be effectively distinguished. CONCLUSIONS: The species and content of diatom vary in different months in Zhangweixin River, and the composition of diatom species is different in different basins, which can provide reference for estimating the time and place of the corpse entering water in the river.

Prediction of potential prognostic biomarkers in metastatic prostate cancer based on a circular RNA-mediated competing endogenous RNA regulatory network.

Recently, studies on competing endogenous RNA (ceRNA) networks have become prevalent, and circular RNAs (circRNAs) have crucial implications for the development and progression of carcinoma. However, studies relevant to metastatic prostate cancer (mPCa) are scant. This study aims to discover potential ceRNAs that may be related to the prognosis of mPCa. RNA-Seq data were obtained from the MiOncoCirc database and Gene Expression Omnibus (GEO). Differential expression patterns of RNAs were examined using R packages. Circular RNA Interactome, miRTarBase, miRDB and TargetScan were applied to predict the corresponding relation between circRNAs, miRNAs and mRNAs. The Gene Ontology (GO) annotations were performed to present related GO terms, and Gene Set Enrichment Analysis (GSEA) tools were applied for pathway annotations. Moreover, survival analysis was conducted for the hub genes. We found 820 circRNAs, 81 miRNAs and 179 mRNAs that were distinguishingly expressed between primary prostate cancer (PCa) and mPCa samples. A ceRNA network including 45 circRNAs, 24 miRNAs and 56 mRNAs was constructed. In addition, the protein-protein interaction (PPI) network was built, and 10 hub genes were selected by using the CytoHubba application. Among the 10 hub genes, survival analysis showed that ITGA1, LMOD1, MYH11, MYLK, SORBS1 and TGFBR3 were significantly connected with disease-free survival (DFS). The circRNA-mediated ceRNA network provides potential prognostic biomarkers for metastatic prostate cancer.

[Electronic focusing high-nergy extracorporeal shockwave combined with conventional oral medicine for the treatment of ankylosing spondylitis].

OBJECTIVE: To observe the progress of disease activity and sacroiliac joint imaging in patients with ankylosing spondylitis treated by extracorporeal shockwave combined with conventional oral medicine, and find a new safe and effective therapeutic method. METHODS: The clinical data of 30 patients with ankylosing spondylitis treated from January 2018 to December 2018 were retrospectively analyzed. Including 20 males and 10 females, aged from 18 to 50 years with an average of (34.50±9.60) years. All 30 patients had different degrees of sacroiliac joint bone marrow edema on MRI before treatment. Thirty patients were divided into treatment group and control group according to different treatment methods. Among them, 15 cases in control group were treated with non-steroidal anti-inflammatory drugs and sulfasalazine enteric-coated tablets, for the 15 cases in treatment group, in addition to oral medicine in line with control group, electronic focusing high-energy extracorporeal shockwave therapy was added. The course of disease, age, pre- and post-treatment erythrocyte sedimentation rate, C-reactive protein in the two groups were analyzed; and visual analogue scale (VAS) and spondyloarthritis research consortium Canada (SPARCC) scoring system were used to evaluate the pain of the sacroiliac joint and the structural damage of the sacroiliac joint;Bath ankylosing spondylitis disease activity index (BASDAI) was calculated. RESULTS: All patients were followed up for at least 3 months. One month after treatment, VAS, and SPARCC scores in treatment group were significantly better than in control group (P<0.05). After 1 month of treatment, there was no significant difference in BASDAI, erythrocyte sedimentation rate and C-reactive protein between two groups(P>0.05). VAS, BASDAI, SPARCC, erythrocyte sedimentation rate, and C-reactive protein of all patients after treatment were significantly improved compared with those before treatment (P< 0.01). CONCLUSION: Electronic focusing high-energy extracorporeal shockwave combined with conventional oral medicine in the treatment of ankylosing spondylitis has a good clinical effect in rapidly relieving pain, improving disease activity, and preventing imaging progress. In addition, it is safe and non-invasive, which is worthy of clinical application.

The nucleolus functions as the compartment for histone H2B protein degradation.

Histones are main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. However, how histone protein levels are regulated, especially whether and how histones are degraded, is largely unclear. Here, we found that histone H2B is mainly degraded through the proteasome-mediated pathway, and the lysine-120 site of H2B is essential for its K48-linked polyubiquitination and degradation. Moreover, the degradation-impaired H2BK120R mutant shows an increased nucleolus localization, and inhibition of the proteasome results in an elevated nucleolus distribution of wild-type H2B, which is similar to that of H2BK120R mutants. More importantly, the nucleolus fractions can ubiquitinate and degrade the purified H2B in vitro, suggesting that the nucleolus, in addition to its canonical roles regulating ribosome genesis and protein translation, likely associates with H2B degradation. Therefore, these findings revealed a novel mechanism for the regulation of H2B degradation in which a nucleolus-associated proteasome pathway is involved.

Attenuated P. falciparum Parasite Shows Cytokine Variations in Humanized Mice.

A recently developed humanized mouse has been used to assess the immune response evoked against the isolated attenuated C9 parasite clone (C9-M; carrying a single insertion disrupting the open reading frame (ORF) of PF3D7_1305500) of Plasmodium falciparum. Significant human RBC engraftment was achieved by ameliorating the residual non-adaptive immune response using clodronate-loaded liposome treatment. Controlled reactive professional phagocytic leukocytes in immunodeficient mice allowed for sizeable human blood chimerism and injected huRBCs acted as bona fide host cells for P. falciparum. huRBC-reconstituted immunodeficient mice received infectious challenge with attenuated P. falciparum C9 parasite mutants (C9-M), complemented (C9-C), and wild type (NF54) progenitors to study the role of immune effectors in the clearance of the parasite from mouse circulation. C9-M and NF54 parasites grew and developed in the huRBC-reconstituted humanized NSG mice. Further, the presence of mutant parasites in deep-seated tissues suggests the escape of parasites from the host's immune responses and thus extended the survival of the parasite. Our results suggest an evasion mechanism that may have been employed by the parasite to survive the mouse's residual non-adaptive immune responses. Collectively, our data suggest that huRBCs reconstituted NSG mice infected with attenuated P. falciparum is a valuable tool to explore the role of C9 mutation in the growth and survival of parasite mutants and their response to the host's immune responses. This mouse might help in identifying novel chemotherapeutic targets to develop new anti-malarial drugs.

"Sclerotic Band" type of classification system and measurement of necrotic area for osteonecrosis of the femoral head.

Osteonecrosis of the femoral head is a common orthopedic disease. Based on years of clinical experience and significant imaging data, this study aimed to elucidate a new type of it, to help improve prognosis in young adults and provide a basis for hip preservation treatment.From January 2014 to December 2016, a total of 211 patients undergoing hip preservation surgery for femoral head necrosis at our hospital were enrolled in this study. Coronal plane classification and cross-sectional area analysis were performed by nuclear magnetic resonance imaging (computed tomography optional) in cases meeting the inclusion criteria. Meanwhile, a new method of classification and calculating the necrotic area was proposed. The application simulation was conducted using sample cases. Additionally, treatment methods were recommended. We used our method to compare the outcome of the selected patients with the JIC classification so as to judge the advantages and disadvantages.The " pressure bone trabecular angle " of the femoral head was measured, and the "sclerotic band" (Zhang Ying) type of classification system and the "quartile" (Zhang Ying) method of measurement were used in 2 sample cases. After analysis, it is more accurate than JIC.The "Sclerotic band" type of classification system and 'quartile' methods are new methods to evaluate the stability of femoral head necrosis. They are convenient for clinical application and easily adopted.

lncRNA Signature for Predicting Cerebral Vasospasm in Patients with SAH: Implications for Precision Neurosurgery.

Subarachnoid hemorrhage (SAH) patients' surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients.

Anesthetic propofol epigenetically regulates breast cancer trastuzumab resistance through IL-6/miR-149-5p axis.

Propofol, a common intravenous anesthetic, has been found to exert anti-cancer effects with inhibition of cancer cell proliferation, migration and invasion. We tested its possible action against HER2-overexpressing breast cancer cells that developed resistance against trastuzumab. Cell viability assay, ELISA for cytokines, mammosphere formation, quantitative RT-PCR for EMT/IL-6-targeting miRNAs and the in vivo experimental pulmonary metastasis model were performed to understand the epigenetic action of propofol. Propofol sensitized HER2 overexpressing cells to trastuzumab but such action was even more pronounced in resistant cells. Increased cytokines IL-6 as well as IL-8 were released by resistant cells, along with increased mammospheres and induction of EMT, all of which was inhibited by propofol. IL-6 targeting tumor suppressor miR-149-5p was found to be the novel miRNA that was up-regulated by propofol, resulting in the observed effects on cell viability, IL-6 production, mammospheres generation as well as EMT induction. Further, antagonizing miR-149-5p attenuated the propofol effects confirming the epigenetic activity of propofol through miR-149-5p regulation. Finally, in vivo validation in an experimental metastasis model conformed an inhibitory action of propofol against experimental lung metastasis and the essential mechanistic role of miR-149-5p/IL-6 loop. These results present a novel role of general anesthetic propofol against resistant breast cancer cells and the underlying epigenetic regulation of a tumor suppressor miRNA.

The Role of Mitochondrial Dynamics and Mitophagy in Carcinogenesis, Metastasis and Therapy.

Mitochondria are key cellular organelles and play vital roles in energy metabolism, apoptosis regulation and cellular homeostasis. Mitochondrial dynamics refers to the varying balance between mitochondrial fission and mitochondrial fusion that plays an important part in maintaining mitochondrial homeostasis and quality. Mitochondrial malfunction is involved in aging, metabolic disease, neurodegenerative disorders, and cancers. Mitophagy, a selective autophagy of mitochondria, can efficiently degrade, remove and recycle the malfunctioning or damaged mitochondria, and is crucial for quality control. In past decades, numerous studies have identified a series of factors that regulate mitophagy and are also involved in carcinogenesis, cancer cell migration and death. Therefore, it has become critically important to analyze signal pathways that regulate mitophagy to identify potential therapeutic targets. Here, we review recent progresses in mitochondrial dynamics, the mechanisms of mitophagy regulation, and the implications for understanding carcinogenesis, metastasis, treatment, and drug resistance.

[Intervention effect of Youguiwan on rats with knee osteoarthritis and its mechanism].

Objective: To study the effects of Youguiwan on the osteoglycin (OGN), osteonectin (ON), fibrinogen 2 (FBN2) of articular cartilage tissue in the model of knee osteoarthritis (KOA). Methods: Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group, Youguiwan (high-dose, middle-dose and low-dose )group. The modified Hulth method was used to establish KOA models for 6 weeks. The sham control group and the model group were treated with normal saline. The rats in Youguiwan high-dose, middle-dose, low-dose groups were treated with Youguiwan at the doses of 4.8, 2.4, 1.2 g/kg by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g/kg. The rats were administrated for 8 weeks according to the dose. After intervening, articular cartilage of rats were obtained, the pathological changes were observed by using HE staining method, and Mankin score was evaluated. The expressions of OGN, ON and FBN2 in articular cartilage were detected by immunohistochemistry. The expression of GSK-3ß in articular cartilage was detected by Western blot. Results: Compared with the sham control group, the Mankin score was obviously increased in the model group, the protein expression of FBN2 was increased significantly, yet the protein expressions of OGN, ON and GSK-3ß were decreased significantly (P＜0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Mankin score was declined obviously in the high-dose Youguiwan group, the protein expression of FBN2 was significantly decreased, but the protein expression of GSK-3ß was significantly increased, the protein expressions of OGN and ON were significantly increased in the middle-dose and high-dose Youguiwan group (P＜0.05 or P＜0.01), cartilage structure was tended to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. Conclusion: Youguiwan can significantly improve the articular cartilage degeneration of KOA rats, its mechanism maybe raise OGN and ON protein expression level to promote the ossification and reconstruction of articular cartilage.

Genome profiling revealed the activation of IL2RG/JAK3/STAT5 in peripheral T­cell lymphoma expressing the ITK­SYK fusion gene.

Peripheral T­cell lymphomas (PTCLs) are heterogeneous malignancies that are types of non­Hodgkin lymphomas; patients with this disease have poor prognoses. The IL­2­inducible T­cell kinase­spleen tyrosine kinase (ITK­SYK) fusion gene, the first recurrent chromosome translocation in PTCL­not otherwise specified (NOS), can drive cellular transformation and the development of T­cell lymphoma in mouse models. The aim of the current study was to investigate the signal transduction pathways downstream of ITK­SYK. The authors constructed a lentiviral vector to overexpress the ITK­SYK fusion gene in Jurkat cells. By using Signal­Net and cluster analyses of microarray data, the authors identified the tyrosine­protein kinase JAK (JAK)3/STAT5 signalling pathway as a downstream pathway of ITK­SYK, activation of which mediates the effects of ITK­SYK on tumourigenesis. JAK3­selective inhibitor tofacitinib abrogated the phosphorylation of downstream signalling molecule STAT5, supressed cell growth, induced cell apoptosis and arrested the cell cycle at the G1/S phase in ITK­SYK+ Jurkat cells. In a xenograft mouse model, tumour growth was significantly delayed by tofacitinib. Since JAK3 associates with interleukin­2 receptor subunit γ (IL2RG) only, siRNA­specific knockdown of IL2RG showed the same effect as tofacitinib treatment in vitro. These results first demonstrated that the activation of the IL2RG/JAK3/STAT5 signalling pathway contributed greatly to the oncogenic progress regulated by ITK­SYK, supporting further investigation of JAK3 inhibitors for the treatment of PTCLs carrying the ITK­SYK fusion gene.

Metal trabecular bone reconstruction system better improves clinical efficacy and biomechanical repair of osteonecrosis of the femoral head than free vascularized fibular graft: A case-control study.

In this study, we aim to compare and analyze the biomechanical repair and clinical efficacy of osteonecrosis of the femoral head (ONFH) with the use of metal trabecular bone reconstruction system and free vascularized fibular graft. The study enrolled 66 adult patients from medical records of nontraumatic ARCO 2A-3B stage ONFH. A simple ONFH model without surgical treatment was established in 13 cases, 29 cases were treated with metal trabecular bone reconstruction system, and 24 cases were treated with free vascularized fibular graft. Computer-recognized and extracted femur outlines were imported, and three-dimensional reconstructions were performed. The stress concentration and stress peak value were analyzed, and the Harris score, visual analog scale pain score, and operation status of the above patients were compared. Finally, quality of life assessment was performed using SF-36 scale. Metal trabecular bone reconstruction system provided less operation time, blood loss, and the total length of postoperative hospital stay than free vascularized fibular graft. Metal trabecular bone reconstruction system promoted bone reconstruction, increased bone mineral density and Harris score. The total clinical effective rate of young patients (20-40 years) was higher than that of older patients (41-60 years). Metal trabecular bone reconstruction system provided higher physical component summary, mental component summary, and role/social component summary than free vascularized fibular graft. This study demonstrates that both metal trabecular bone reconstruction system and free vascularized fibular graft can prevent or delay the progression of ONFH, while metal trabecular bone reconstruction system is a better choice because of better short-term clinical efficacy.

Unusual case of extracutaneous pyoderma gangrenosum with myelodysplastic syndrome.

Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory disease characterized by neutrophilic infiltration and destruction of tissue. Extracutaneous involvement in PG is unusual. Myelodysplastic syndrome (MDS) is the most frequent hematologic disease associated with PG. We present a case diagnosed with MDS-EB-I. He had a large ulcer in his buttocks. Tissue culture and microscopy showed no evidence of fungi, bacteria, or mycobacteria. Histology showed granulation tissue, inflammatory infiltrate, abscess formation, and focal necrotizing vasculitis. Dermatology opinion confirmed PG. The skin lesions responded well to corticosteroid treatment at first, but it relapsed quickly with involvement of skin and lungs. In the meantime, MDS progressed to acute myeloid leukemia. The patient received chemotherapy and immunosuppressive therapy at the same time. After achievement of complete remission (CR), he had allogeneic hematopoietic stem cell transplantation. Two years later, the patient is still in CR status with no sign of PG relapse.

Multiple cannulated screws vs. dynamic hip screws for femoral neck fractures : A meta-analysis.

OBJECTIVE: Various fixation devices have been reported for stabilization of femoral neck fractures. Numerous studies on arthroplasty versus internal fixation devices in the treatment of femoral neck fractures have been performed, but the optimal approach for internal fixation has not been analyzed. METHODS: A meta-analysis and system evaluation were performed to compare clinical effects. We searched PubMed, Embase, Cochrane Library, and Web of ScienceTM for randomized, controlled trials (RCTs) comparing multiple cannulated screws (MCS) with dynamic hip screws (DHS) and analyzed the failure rate of operations, the reoperation rate, and postoperative complications. Risk ratios (RRs) and mean differences from each trial were pooled using random effects or fixed effects models, depending on study heterogeneity. The analysis was performed using RevMan5.2. RESULTS: In this meta-analysis, 592 femoral neck fractures from 7 studies were assessed, and the meta-analysis results indicated significant differences in reoperation (RR 1.44, 95% confidence interval [CI] 1.10-1.88, P = 0.008) and failure rate (RR 2.28, 95% CI 1.10-4.72, P = 0.03), but no significant differences in the rate of postoperative complications between the MCS group and DHS group. CONCLUSIONS: DHS fixation has a larger skin incision and more soft tissue dissection, but it is associated with lower rates of fixation failure, reoperation, and overall rate of postoperative complications, and its use in elderly patients with osteoporosis is still recommended due to simplicity, efficacy, and high overall success rate. Multicenter RCTs with large samples are needed to better understand the comparative efficacy and safety of MCS and DHS in femoral neck fractures of restricted fracture type.

Increased microRNA-93-5p inhibits osteogenic differentiation by targeting bone morphogenetic protein-2.

BACKGROUND AND PURPOSE: Trauma-induced osteonecrosis of the femoral head (TIONFH) is a major complication of femoral neck fractures. Degeneration and necrosis of subchondral bone can cause collapse, which results in hip joint dysfunction in patients. The destruction of bone metabolism homeostasis is an important factor for osteonecrosis. MicroRNAs (miRNAs) have an important role in regulating osteogenic differentiation, but the mechanisms underlying abnormal bone metabolism of TIONFH are poorly understood. In this study, we screened specific miRNAs in TIONFH by microarray and further explored the mechanism of osteogenic differentiation. DESIGN: Blood samples from patients with TIONFH and patients without necrosis after trauma were compared by microarray, and bone collapse of necrotic bone tissue was evaluated by micro-CT and immunohistochemistry. To confirm the relationship between miRNA and osteogenic differentiation, we conducted cell culture experiments. We found that many miRNAs were significantly different, including miR-93-5p; the increase in this miRNA was verified by Q-PCR. Comparison of the tissue samples showed that miR-93-5p expression increased, and alkaline phosphatase (ALP) and osteopontin (OPN) levels decreased, suggesting miR-93-5p may be involved in osteogenic differentiation. Further bioinformatics analysis indicated that miR-93-5p can target bone morphogenetic protein 2 (BMP-2). A luciferase gene reporter assay was performed to confirm these findings. By simulating and/or inhibiting miR-93-5p expression in human bone marrow mesenchymal stem cells, we confirmed that osteogenic differentiation-related indictors, including BMP-2, Osterix, Runt-related transcription factor, ALP and OPN, were decreased by miR-93-5p. CONCLUSION: Our study showed that increased miR-93-5p in TIONFH patients inhibited osteogenic differentiation, which may be associated with BMP-2 reduction. Therefore, miR-93-5p may be a potential target for prevention of TIONFH.