Health-related quality of life of men with primary osteoporosis and its changes after bisphosphonates treatment.

INTRODUCTION: Osteoporosis leads to more serious consequences in men than in women, but less is known about its impacts on health-related quality of life (HRQoL) of men, and whether the anti-osteoporosis treatment can improve HRQoL of men with osteopenia/osteoprosis. METHODS: We enrolled men with primary osteoporosis and age-matched healthy controls. We collected medical history, serum levels of carboxyl-terminal type I collagen telopeptide, procollagen type I propeptides, and bone mineral density of patients. All patients and controls completed the short-form 36 (SF-36) questionnaires. Changes in HRQoL of osteopenia/osteoporosis men were prospectively evaluated after alendronate or zoledronic acid treatment. RESULTS: A total of 100 men with primary osteoporosis or osteopenia and 100 healthy men were included. The patients were divided into three subgroups: osteopenia (n = 35), osteoporosis (n = 39) and severe osteoporosis (n = 26). Men with osteoporosis or severe osteoporosis had impaired HRQoL in domains of physical health compared to healthy controls. HRQoL scores in physical health related domains of patients with severe osteoporosis were significantly lower compared to healthy controls, and were the poorest among the three subgroups of patients. Fragility fracture history was correlated with lower SF-36 scores about physical health. In 34 men with newly diagnosed osteoporosis receiving bisphosphonates treatment, HRQoL scores were significantly improved in domains of physical health after treatments. CONCLUSIONS: The HRQoL is significantly impaired in men with osteoporosis, and the more severe the osteoporosis, the poorer the HRQoL. Fragility fracture is an important influencing factor of deteriorated HRQoL. Bisphosphonates treatment is beneficial to improve HRQoL of osteopenia/osteoporosis men.

Enhancer variants on chromosome 2p14 regulating SPRED2 and ACTR2 act as a signal amplifier to protect against rheumatoid arthritis.

Genome-wide association studies (GWASs) have repeatedly reported multiple non-coding single-nucleotide polymorphisms (SNPs) at 2p14 associated with rheumatoid arthritis (RA), but their functional roles in the pathological mechanisms of RA remain to be explored. In this study, we integrated a series of bioinformatics and functional experiments and identified three intronic RA SNPs (rs1876518, rs268131, and rs2576923) within active enhancers that can regulate the expression of SPRED2 directly. At the same time, SPRED2 and ACTR2 influence each other as a positive feedback signal amplifier to strengthen the protective role in RA by inhibiting the migration and invasion of rheumatoid fibroblast-like synoviocytes (FLSs). In particular, the transcription factor CEBPB preferentially binds to the rs1876518-T allele to increase the expression of SPRED2 in FLSs. Our findings decipher the molecular mechanisms behind the GWAS signals at 2p14 for RA and emphasize SPRED2 as a potential candidate gene for RA, providing a potential target and direction for precise treatment of RA.

AMPK activator decelerates osteoarthritis development by inhibition of ß-catenin signaling in chondrocytes.

Background: Osteoarthritis (OA) is a common degenerative joint disease with significant negative impact on the quality of life. It has been reported that abnormal upregulation of ß-catenin signaling could lead to OA development; however, the upstream regulatory mechanisms of ß-catenin signaling have not been determined. Methods: Primary rat chondrocytes and ATDC5 chondrocyte cell line were stimulated with AKT2 and treated with or without metformin, an adenosine 5'-monophosphate-activated protein kinase (AMPK) activator. Westerrn blot analysis, luciferase reporter assay and immunofluorescent (IF) staining were performed to examine changes in ß-cateninS552 phosphorylation and ß-catenin nuclear translocation in ATDC5 cells and in primary chondrocytes. Results: We found that metformin inhibited ß-cateninS552 phosphorylation in ATDC5 cells and in primary chondrocytes in a time-dependent manner. Metformin inhibited ß-catenin nuclear translocation and ß-catenin reporter activity. In addition, metformin also attenuated the expression of ß-catenin downstream target genes. We also demonstrated that metformin inhibited ß-cateninS552 phosphorylation in articular cartilage in mice. Conclusion: These findings suggest that metformin may exert its chondro-protective effect at least in part through the inhibition of ß-catenin signaling in chondrocytes. The translational potential of this article: This study demonstrated the interaction between AMPK and ß-catenin signaling in chondrocytes and defined novel molecular targets for the treatment of OA disease.

The roles of sclerostin and irisin on bone and muscle of orchiectomized rats.

BACKGROUND: The reduction in androgen level gives rise to a decrease in bone mineral density (BMD) and muscle strength, but the exact mechanisms are unclear. We investigated the roles of novel cytokines of sclerostin and irisin on bone and muscle of orchiectomized rats. METHODS: Twenty 3-month-old male rats were randomized to receive sham or orchiectomy (ORX) operation. Rats were euthanized after 8 weeks of surgery, and serum levels of sclerostin and irisin were measured by enzyme-linked immunosorbent assay at baseline and execution. Grip strength was measured by a grip strength tester at baseline and before execution. BMD and bone microarchitecture were measured by microcomputed tomography. The samples of bone and muscle were harvested at execution. Bone biomechanics were measured by three-point bending tests and vertebral body indentation tests. Bone and muscle histological features were analyzed by hematoxylin and eosin stain, Von Kossa's stain and tartrate resistant acid phosphatase stain. Simple linear regression analyses were used to analyze the relationships between serum levels of sclerostin, irisin and grip strength and BMD of ORX rats. RESULTS: Serum sclerostin level increased from 279 ± 44 pg/mL to 586 ± 57 pg/mL since baseline to 8 weeks after ORX (P = 0.002), which was significantly higher than that in sham rats (406 ± 20 pg/mL at execution) (P = 0.012). Serum irisin level decreased from 4.12 ± 0.20 ng/mL to 3.55 ± 0.29 ng/mL since baseline to 8 weeks of ORX (P = 0.048), which was significantly lower than sham rats (4.84 ± 0.37 pg/mL at execution) (P = 0.013). Trabecular BMD, parameters of bone microarchitecture, bone strength, grip strength and the myofibers size of soleus muscles were significantly lower in ORX rats than in sham group. Grip strength was positively correlated with femoral trabecular BMD (r = 0.713, P < 0.001) and bone volume/total volume (r = 0.712, P < 0.001) in all rats. The serum sclerostin level was negatively correlated to femoral trabecular BMD (r = -0.508, P = 0.022) and grip strength (r = -0.492, P = 0.028). Serum irisin level was positively correlated with femoral trabecular BMD (r = 0.597, P = 0.005), but no obvious correlation was found between irisin level and muscle strength in all rats. CONCLUSIONS: Reduced BMD, impaired bone microarchitecture, weak strength of bone and muscle, and thin myofibers were induced by androgen deficiency of ORX rats. Serum sclerostin and irisin levels were significantly changed after ORX, which might be closely correlated with the occurrence of osteoporosis and sarcopenia in ORX rats.

Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) can be differentiated into osteoblasts and adipocytes. During these processes, super enhancers (SEs) play important roles. Here, we performed comprehensive characterization of the SEs changes associated with adipogenic and osteogenic differentiation of hMSCs, and revealed that SEs changed more dramatically compared with typical enhancers. We identified a set of lineage-selective SEs, whose target genes were enriched with cell type-specific functions. Functional experiments in lineage-selective SEs demonstrated their specific roles in directed differentiation of hMSCs. We also found that some key transcription factors regulated by lineage-selective SEs could form core regulatory circuitry (CRC) to regulate each other's expression and control the hMSCs fate determination. In addition, we found that GWAS SNPs of osteoporosis and obesity were significantly enriched in osteoblasts-selective SEs or adipocytes-selective SEs, respectively. Taken together, our studies unveiled important roles of lineage-selective SEs in hMSCs differentiation into osteoblasts and adipocytes.

The role of osteocalcin in regulation of glycolipid metabolism and muscle function in children with osteogenesis imperfecta.

Objective: Osteoblasts are discovered to secrete hormones with endocrine effects on metabolism, and osteocalcin (OC) is the most abundant non-collagenous protein in bone. We investigate the relationship between serum OC levels and glycolipid metabolism and muscle function in children with osteogenesis imperfecta (OI). Methods: A total of 225 children with OI and 80 healthy controls matched in age and gender were included in this single center study. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated analyzers. Serum levels of fasting insulin (FINS) were measured using an automated electrochemiluminescence system. Serum levels of OC and undercarboxylated osteocalcin (ucOC) were measured by enzyme-linked immunosorbent assay. Grip strength and timed-up-and-go (TUG) test were measured. Bone mineral density (BMD) and body composition were measured using dual-energy X-ray absorptiometry. Results: OI patients had significantly higher body mass index (BMI), FBG, and HOMA-IR, but lower HDL-C levels, lower grip strength and longer TUG than control group (all P<0.05). Serum OC, ucOC levels, and ucOC/OC in OI type III patients were significantly lower than those in OI patients with type I and IV. Serum levels of OC, ucOC, and ucOC/OC were negatively correlated to BMI, FBG, insulin levels, and HOMA-IR (all P<0.05). The ratio of ucOC/OC was positively correlated to grip strength (r=0.512, P=0.036), lean mass percentage (%LM) of the total body and limbs, and negatively correlated to fat mass percentage (%FM) of the total body, %FM and fat mass index (FMI) of the trunk (all P<0.05). Conclusions: Obesity, glucolipid metabolic abnormalities, and reduced grip strength were common in children with OI. Circulating osteocalcin and ucOC may play an important role in the regulation of glucose metabolism, as well as the muscle function of children with OI.

Lineage-specific rearrangement of chromatin loops and epigenomic features during adipocytes and osteoblasts commitment.

Human mesenchymal stem cells (hMSCs) can be differentiated into adipocytes and osteoblasts. The processes are driven by the rewiring of chromatin architectures and transcriptomic/epigenomic changes. Here, we induced hMSCs to adipogenic and osteogenic differentiation, and performed 2 kb resolution Hi-C experiments for chromatin loops detection. We also generated matched RNA-seq, ChIP-seq and ATAC-seq data for integrative analysis. After comprehensively comparing adipogenesis and osteogenesis, we quantitatively identified lineage-specific loops and screened out lineage-specific enhancers and open chromatin. We reveal that lineage-specific loops can activate gene expression and facilitate cell commitment through combining enhancers and accessible chromatin in a lineage-specific manner. We finally proposed loop-mediated regulatory networks and identified the controlling factors for adipocytes and osteoblasts determination. Functional experiments validated the lineage-specific regulation networks towards IRS2 and RUNX2 that are associated with adipogenesis and osteogenesis, respectively. These results are expected to help better understand the chromatin conformation determinants of hMSCs fate commitment.

Thickness dependent thermal performance of a poly(3,4-ethylenedioxythiophene) thin film synthesized via an electrochemical approach.

Polymer-based thermal interface materials (TIMs) have attracted wide attention in the field of thermal management because of their outstanding properties including light weight, low cost, corrosion resistance and easy processing. However, the low thermal conductivity (∼0.2 W m-1 K-1) of the intrinsic polymer matrix largely degrades the overall thermal performance of polymer-based TIMs even those containing highly thermal conductive fillers. Hence, enhancing the intrinsic thermal conductivity of the polymer matrix is one of the most critical problems needed to be solved. This paper studies the thermal conductivity of poly(3,4-ethylenedioxythiophene) (PEDOT) films fabricated via cyclic voltammetry. By controlling the number of cycles in the electrochemical synthesis, different thickness of PEDOT films could be obtained. A time-domain thermoreflectance (TDTR) system was employed to evaluate the thermal performance of such as-prepared PEDOT films. We have demonstrated that a PEDOT film with thickness of 40 nm achieves the highest out-of-plane thermal conductivity of ∼0.60 W m-1 K-1, which is almost three folds the thermal conductivity of commercially available pristine PEDOT:PSS film with similar thickness. The X-ray diffraction spectrum reveals that the PEDOT thin film with high crystallinity at the initial stage of electrochemical synthesis leads to enhanced thermal transportation. The findings in this work not only offer an opportunity to fabricate polymer materials exhibiting enhanced thermal conductivity, but also allow one to adjust the thermal performance of conducting polymers in practical applications.

Giant Thermal Transport Tuning at a Metal/Ferroelectric Interface.

Interfacial thermal transport plays a prominent role in the thermal management of nanoscale objects and is of fundamental importance for basic research and nanodevices. At metal/insulator interfaces, a configuration commonly found in electronic devices, heat transport strongly depends upon the effective energy transfer from thermalized electrons in the metal to the phonons in the insulator. However, the mechanism of interfacial electron-phonon coupling and thermal transport at metal/insulator interfaces is not well understood. Here, the observation of a substantial enhancement of the interfacial thermal resistance and the important role of surface charges at the metal/ferroelectric interface in an Al/BiFeO3 membrane are reported. By applying uniaxial strain, the interfacial thermal resistance can be varied substantially (up to an order of magnitude), which is attributed to the renormalized interfacial electron-phonon coupling caused by the charge redistribution at the interface due to the polarization rotation. These results imply that surface charges at a metal/insulator interface can substantially enhance the interfacial electron-phonon-mediated thermal coupling, providing a new route to optimize the thermal transport performance in next-generation nanodevices, power electronics, and thermal logic devices.

Passive treatment test of acid mine drainage from an abandoned coal mine in Kaili Guizhou, China.

Discharge of acid mine drainage (AMD) from abandoned coal mines of the YuDong catchment in Kaili City, Guizhou Province, China, has severely damaged local ecological environments. In this study, a laboratory-scale dispersed alkaline substrate (DAS) was studied for the treatment of simulated AMD. The experimental conditions and reaction mechanisms were preliminarily explored. The treatment effect and variation law of vertical effluent water quality of the experimental conditions were thoroughly analysed. The results indicated that small-sized limestone (diameter 5-7 mm) having a 20:1 mixture ratio with shavings and minimum HRT of 20 hours result in increasing effluent pH from 3.5 to 6.6, achieving 66.2% and 99.1% removal of Fe and Al, respectively. There were obvious differences in each reaction layer for the removal of various pollutants from AMD along the depth by DAS, the main reaction zone was first 20-30 cm of the reaction column. The removal process of metal ions and sulfate was accompanied by bio-mineralization reaction. This test provided a valuable support for the local practical engineering applications, enriched the AMD processing technology experimental cases, and provided reference for the treatment technology of similar polluted areas.

A novel mutation in PLS3 causes extremely rare X-linked osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous bone disease characterized by bone fragility and recurrent fractures. X-linked inherited OI with mutation in PLS3 is so rare that its genotype-phenotype characteristics are not available. METHODS: We designed a novel targeted next-generation sequencing (NGS) panel with the candidate genes of OI to detect pathogenic mutations and confirmed them by Sanger sequencing. The phenotypes of the patients were also investigated. RESULTS: The proband, a 12-year-old boy from a nonconsanguineous family, experienced multiple fractures of long bones and vertebrae and had low bone mineral density (BMD Z-score of -3.2 to -2.0). His younger brother also had extremity fractures. A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in exon 10 of PLS3 was identified in the two patients, which was inherited from their mother who had normal BMD. Blue sclerae were the only extraskeletal symptom in all affected individuals. Zoledronic acid was beneficial for increasing BMD and reshaping the compressed vertebral bodies of the proband. CONCLUSION: We first identify a novel mutation in PLS3 that led to rare X-linked OI and provide practical information for the diagnosis and treatment of this disease.

A novel variant in AIRE causing a rare, non­classical autoimmune polyendocrine syndrome type 1.

Autoimmune polyendocrine syndrome type 1 (APS­1) is a rare inherited autoimmune disease, characterized by a classic triad, including chronic mucocutaneous candidiasis, primary adrenocortical insufficiency and hypoparathyroidism. The present study investigated phenotypes and pathogenic variants in a Chinese woman with non­classical APS­1. Disease­associated variants in a patient with APS­1 were identified via targeted next generation sequencing and the variant was confirmed via Sanger sequencing. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), follicle­stimulating hormone (FSH), luteinizing hormone (LH), estradiol and urinary levels of calcium were measured. Blood count assays and bone marrow morphology were investigated. The patient was a 32­year­old woman who had suffered from typical carpopedal spasms since she was 7 years old. She developed syncope, primary amenorrhea, intermittent diarrhea and general fatigue in subsequent years. Hypocalcemia, hyperphosphatemia, low levels of PTH and estradiol, elevated levels of FSH and LH, and absence of erythroblasts were observed, which indicated hypoparathyroidism, primary ovarian insufficiency and pure red cell aplasia. A novel heterozygous missense variant (NM_000383.2: c.623G>T, NP_000374.1: p.Gly208Val) in exon 5 of autoimmune regulator and a reported variant (NM_000383.2: c.371C>T, NP_000374.1: p.Pro124Leu) in exon 3 were detected, of which the c.623G>T variant may be a pathogenic variation that induces APS­1. Under a regular follow­up and therapeutic adjustment of calcium, calcitriol, hormone replacement therapy and methylprednisolone, the endocrine function and clinical symptoms of the patient were notably improved. The results of the present study expand the known genetic and phenotypical spectra of APS­1.

Novel variants in COL2A1 causing rare spondyloepiphyseal dysplasia congenita.

BACKGROUND: Spondyloepiphyseal dysplasia congenita (SEDC) is an extremely rare inherited chondrodysplasia characterized by abnormal epiphyses, short stature, and flattened vertebral bodies. We investigate the phenotypes and the disease-associated variants of SEDC in two unrelated Chinese families. METHODS: We identified disease-associated variants in two nonconsanguineous families with SEDC using targeted next-generation sequencing and confirmed the variants using Sanger sequencing. We investigated the phenotypes of the patients, including clinical manifestations, bone turnover biomarkers, bone mineral density and skeletal radiographic features. RESULTS: Two probands were diagnosed as SEDC according to the phenotypes of disproportionately short-trunk stature, kyphosis, lumbar lordosis and adduction deformity of hips. Radiographs revealed kyphosis and lumbar lordosis, flattened vertebral bodies, compressed femoral heads and shortening of the femurs. Bone mineral density of the probands was lower than that of age- and gender-matched normal children, but bone turnover biomarker levels were within normal range. Two novel heterozygous missense variants (NM_001844.5: c.1654 G>A, NP_001835.3: p.Gly552Arg; NM_001844.5: c.3518G>T, NP_001835.3: p.Gly1173Val) in collagen type II alpha 1 chain (COL2A1) were detected in the two families, which would impair the formation of stable triple-helical type II collagen. CONCLUSIONS: We identified two novel disease-associated variants in COL2A1, which led to severe SEDC. Our findings expanded the gene variant spectrum and phenotypic spectrum of extremely rare type II collagenopathies.

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD. METHODS: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (ß-CTX) were evaluated. RESULTS: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum ß-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline). CONCLUSION: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol. ABBREVIATIONS: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; ß-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid.

Screening and Identification of Key Biomarkers in Pancreatic Cancer: Evidence from Bioinformatic Analysis.

Pancreatic cancer (PC) whose mortality is comparable to morbidity is a highly fatal disease. Early approaches of diagnosis and treatment for PC are quite limited, so it is of great urgency to figure out the exact tumorigenesis and development mechanism of PC. To identify the related molecular markers of pancreatic oncogenesis, we downloaded three microarray datasets (GSE63111, GSE101448, and GSE107610) from Gene Expression Omnibus (GEO) database. The common differentially expressed genes (DEGs) among them were identified, and the corresponding function enrichment analyses were accomplished. The protein-protein interaction network was conducted by Search Tool for the Retrieval of Interacting Genes (STRING), and the corresponding module analysis was accomplished by Cytoscape. There were 55 DEGs found in total. The molecular function and biological processes (BP) of these DEGs mainly include cytokinesis, mitotic nuclear division, cell division, cell proliferation, microtubule-based movement, and mineral absorption. Among the 55 DEGs, 14 hub genes were further confirmed and it was concluded that they mainly function in mitotic cytokinesis, microtubule-based movement, mitotic chromosome condensation, and mitotic spindle assembly from the BP analysis. The survival analysis showed that all the 14 hub genes, especially nucleolar and spindle associated protein 1 and abnormal spindle microtubule assembly, may involve in the tumorigenesis and development of PC. And they might be used as new biomarkers for auxiliary diagnosis and potential targets for immunotherapy of PC.

Severe and prolonged cyclophosphamide-induced hepatotoxicity in a breast cancer patient carrying a CYP2B6*7 variant.

As a widely used alkylating agent, cyclophosphamide often leads to various toxicities. Severe hepatotoxicity has been rarely reported in breast cancer patients receiving chemotherapy containing cyclophosphamide. Differences in cyclophosphamide metabolism may contribute to variability in adverse events of patients. Here, we report on a case of a 68-year-old Chinese female with breast cancer who experienced severe and prolonged hepatotoxicity induced by cyclophosphamide. Pharmacogenetic tests showed that she was a carrier of CYP2B6*7 allele and this is the first case of a CYP2B6*7 variant in the Han Chinese population so far reported. In addition, the patient was also a carrier of an ALDH3A1*2 variant potentially contributing to the occurrence of hepatotoxicity. CYP2B6 and ALDH3A1 genotyping may play a role in guiding cyclophosphamide therapy.

TPM2 as a potential predictive biomarker for atherosclerosis.

Cardiac-cerebral vascular disease (CCVD), is primarily induced by atherosclerosis, and is a leading cause of mortality. Numerous studies have investigated and attempted to clarify the molecular mechanisms of atherosclerosis; however, its pathogenesis has yet to be completely elucidated. Two expression profiling datasets, GSE43292 and GSE57691, were obtained from the Gene Expression Omnibus (GEO) database. The present study then identified the differentially expressed genes (DEGs), and functional annotation of the DEGs was performed. Finally, an atherosclerosis animal model and neural network prediction model was constructed to verify the relationship between hub gene and atherosclerosis. The results identified a total of 234 DEGs between the normal and atherosclerosis samples. The DEGs were mainly enriched in actin filament, actin binding, smooth muscle cells, and cytokine-cytokine receptor interactions. A total of 13 genes were identified as hub genes. Following verification of animal model, the common DEG, Tropomyosin 2 (TPM2), was found, which were displayed at lower levels in the atherosclerosis models and samples. In summary, DEGs identified in the present study may assist clinicians in understanding the pathogenesis governing the occurrence and development of atherosclerosis, and TPM2 exhibits potential as a promising diagnostic and therapeutic biomarker for atherosclerosis.

Incidental finding of an asymptomatic pulmonary valve papillary fibroelastoma: A case report.

Primary cardiac tumors are rare, but papillary fibroelastoma (PFE) is reportedly the most common form, which usually occurs on the left-side valves of the heart. However, PFE involving the tricuspid and pulmonary valves has also been documented. Although PFE is benign and seldom associated with valvular dysfunction, the associated embolic complications may lead to serious consequences. Most patients with PFE lack specific clinical symptoms and the diagnosis is incidental. Surgical resection is the mainstay treatment for PFE in order to prevent the occurrence of embolic complications. In this report, we present a case of a rare asymptomatic PFE of the pulmonary valve, which was incidentally noted during a routine examination with transthoracic echocardiography (TEE). There was neither valvular dysfunction nor hemodynamic change. The PFE was surgically removed, and the diagnosis was further confirmed with histopathology.

Exploration of the Differentially Expressed Long Noncoding RNAs and Genes of Morphine Tolerance via Bioinformatic Analysis.

Morphine tolerance is one of the most common complications in patients with chronic pain. Many patients with morphine tolerance have poor efficacy in the treatment of primary pain, and are accompanied by the side effects. Previous studies have found that many mechanisms are involved in morphine tolerance, but few researches could fully explain morphine tolerance, and no effective treatment for morphine tolerance has been found. One expression profiling data set was downloaded from the Gene Expression Omnibus (GEO) database. The probes would be transformed into the homologous gene symbol by means of the platform's annotation information. GEO2R was used to search for differentially expressed long noncoding RNAs (lncRNAs) and differentially expressed genes (DEGs) that were differentially expressed between spinal cord samples. Receiver operator characteristic curve analysis was performed to determine the ability of the hub lncRNAs to predict morphine tolerance. Through the principal component analysis, the intragroup data repeatability is fine in the GSE110115. A total of 10 genes were identified as hub genes from the protein-protein interaction network with degrees ≥10. Compared with the normal saline group, the expression levels of LncRNA XR_006440, XR_009493, AF196267, MRAK150340, and MRAK037188 were more downregulated, while the expression levels of MRAK046606, XR_005988, DQ266361, uc.167-, and uc.468+ were more upregulated in the morphine tolerance group. LncRNAs and DEGs were differentially expressed between the morphine tolerance group and nonmorphine tolerance group, which may be involved in the development of morphine tolerance, especially LncRNA DQ266361, uc.167-, and Mmp9, CCL7 genes.