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.

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.

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.

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.

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.

Influence of impaired right ventricular contractile reserve on exercise capacity in patients with precapillary pulmonary hypertension: A study with exercise stress echocardiography.

OBJECTIVES: Right ventricular (RV) contractile reserve reflects the ability of RV to accommodate the increased afterload and may play an essential role in the evaluation of precapillary pulmonary hypertension (PH). This study aimed to assess RV contractile reserve based on exercise stress echocardiography (ESE) and to determine the echocardiographic determinants of exercise capacity in patients with precapillary PH. METHODS: A total of 31 patients with precapillary PH and 15 age- and sex-matched healthy control subjects were prospectively recruited. All subjects underwent ESE to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. Patients with precapillary PH also underwent cardiopulmonary exercise test (CPET), and data pertaining to peak oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) were collected. RESULTS: Right ventricular contractile reserve including change in tricuspid annular plane systolic excursion (∆TAPSE), change in RV fractional area change (∆RVFAC), and change in Doppler-derived tricuspid lateral annular peak systolic velocity (∆S') was significantly depressed in precapillary PH patients compared with control subjects (P < 0.05). Parameters of RV function and RV contractile reserve were markedly associated with maximal exercise capacity (P < 0.05). ∆RVFAC was an independent predictor of peak VO2 (r2  = 0.601, P < 0.05). CONCLUSIONS: Assessment of RV contractile reserve facilitates identification of subclinical dysfunction and evaluation of clinical status and severity of precapillary PH. ESE as a noninvasive method may provide a comprehensive clinical assessment and facilitate therapeutic decision-making for these patients.

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.

Association of urinary sodium and potassium excretion with blood pressure.

BACKGROUND: Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different populations is unknown. METHODS: We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device. RESULTS: Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of association was steeper for persons with hypertension (2.49 mm Hg per gram) than for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age; P<0.001 for interaction). Potassium excretion was inversely associated with systolic blood pressure, with a steeper slope of association for persons with hypertension than for those without it (P<0.001) and a steeper slope with increased age (P<0.001). CONCLUSIONS: In this study, the association of estimated intake of sodium and potassium, as determined from measurements of excretion of these cations, with blood pressure was nonlinear and was most pronounced in persons consuming high-sodium diets, persons with hypertension, and older persons. (Funded by the Heart and Stroke Foundation of Ontario and others.).

[Decomposition of X-Ray Fluorescence Overlapping Peaks Based on Statistical and Genetic Algorithms].

In fluorescence analysis, the phenomenon of overlapping often occurs among adjacent peaks. In the view of the random physical properties of formation process of X fluorescence spectra, Gaussian Mixture Statistics Model (GMSM) and Genetic Algorithms were used for the decomposition of overlapping peaks. First, the GMSM was proposed to describe the overlapping peaks, and the local convergence problem of expectation maximization (EM) was analyzed. Secondly, the GMSM parameters were regarded as individual genes, and the log-likelihood function of overlapping peaks random data was set as fitness function. A fast algorithm for the objective function value was proposed. Finally, the population search technology of Genetic Algorithm was used to find the global optimal solution, and to realize the decomposition of overlapping peaks. All measured data were regarded as "useful" data. The "useful" degree was reflected by their probability. The GMSM method can achieve the "best match" effect in the maximum global probability with zero loss of original data, which can fit the random of radiation measurement process. The decomposition experiments of four serious overlapping peaks show high precision of the peak position, peak area and standard deviation. The maximum error was 0.7 channel, 2.3% and 2.17%, respectively, which is especially suitable for the condition of serious overlap and can be widely used for the decomposition of other energy spectrum.

A broadband and omnidirectional electromagnetic wave concentrator with gradient woodpile structure.

We present the first realized three-dimensional (3D) practical implementation of the so called "optical black hole" in microwave frequencies, an electromagnetic (EM) concentrator. The 3D EM wave concentrator was designed with non-resonant gradient index (GRIN) 3D woodpile photonic crystals (PCs) structure in metamaterial regime, and fabricated by Stereolithography (SL) process. Omnidirectional EM wave capture and absorbing ability of the device in a broad bandwidth (12GHz-15GHz) were validated by full-wave simulation and experiments. Such devices may have applications in microwave energy harvesting and radiation detector.

[Three-dimensional flow perfusion culture enhances proliferation of human fetal osteoblasts in large scaffold with controlled architecture].

OBJECTIVE: To demonstrate the feasibility and benefits of custom designed perfusion bioreactor in conjunction with well-defined three-dimensional (3D) environment for enhanced proliferation and homogeneous distribution of human fetal osteoblasts in large scaffold in vitro. METHODS: Large-scale ß-tricalcium phosphate (ß-TCP) scaffolds with tightly controlled architectures were fabricated. And a custom designed perfusion bioreactor was developed. Human fetal osteoblasts were seeded onto the scaffolds, cultured for up to 16 days in static or flow perfusion conditions. At Days 4, 8 & 16 post-incubation, the proliferation and distribution of osteoblasts were determined by daily D-glucose consumption, cell viability (methyl thiazolyl tetrazolium (MTT) assay), histological evaluation and scanning electron microcopy (SEM). Sphere like structures observed in the SEM images were assessed by energy dispersive X-ray (EDX) analysis. RESULTS: In both static and perfusion cultures, the daily D-glucose consumption increased with prolonged time. The daily D-glucose consumption was significantly higher in the perfusion culture than that in static culture (P < 0.05). The increased cell viability with time during the culture was similar to the daily D-glucose consumption under both conditions. There was much greater cell viability under flow perfusion culture compared to static culture (P < 0.05). Flow perfused constructs demonstrated improved cell proliferation and a homogeneous layer composed of cells and extracellular matrix in channels throughout the whole scaffold. However, the cells were biased to periphery in scaffolds culture statically. Sphere like structures present in the matrix were identified as calcium phosphate nodules via EDX analysis. CONCLUSIONS: Flow perfusion culture plus well-defined 3D interconnected channel environments enhances the proliferation and improve the distribution of human fetal osteoblasts in large scaffolds. Scaffolds with controlled architecture may be a potential tool of studying the fluid flow configuration and cell behavior inside scaffold in details. And human fetal osteoblasts can be used as a cell source in large bone graft research.

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.

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.

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.

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-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.

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.

[Measurement of the irregular retinal lesion area based on the back propagation neural network method].

In this study, the automatic segmentation of the irregular lesion region in the image of fundus fluorescence angiography was actualized by means of the modified Back Propagation (BP) neural network method. Combining the transfer scaling coefficient between pixel of the image and the actual size, the area of the irregular lesion region was measured. The results may provide valuable data for the clinical diagnosis, treatment and prognostic evaluation.

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.

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.