A study on factors related to sleep disorders and serum BDNF expression levels in patients with primary SjÓ§gren's syndrome.

OBJECTIVES: We aimed to assess the sleep quality of patients with primary Sjögren's syndrome (pSS) and the associated factors. Moreover, Preliminary exploration of the clinical significance of serum brain-derived neurotrophic factor (BDNF) in pSS patients with sleep disorders. METHODS: A self-report survey was administered to 111 pSS patients and 40 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. General clinical information,the sleep quality and mental conditions were collected using on-site questionnaires and various scales. 40 healthy controls from the health examination center of the same hospital, who were age and sex matched. Detection of serum BDNF levels by ELISA method . Independent samples t tests, Chi-square analysis, logistic regression were used to analyze these data. RESULTS: Patients with pSS had higher scores on the PSQI than the healthy individuals. Abnormal sweating, high PHQ-9 and ESSPRI scores were independent risk factors for sleep disorders. pSS patients had lower serum BDNF than the healthy individuals, The area under the curve (AUC) of predicting sleep disorder in pSS patients using detection of serum BDNF level was 0.8470, and the sensitivity and specificity were 0.951 and 0.727, which were superior to PHQ-9 and GAD-7. CONCLUSION: Compared with the healthy individuals, pSS patients had a higher prevalence of sleep disorders and lower serum BNDF. Serum BDNF level demonstrated greater predictive advantage for sleep disorder in pSS patients.

Dimeric Tetracenomycin Derivatives from a Taklamakan Desert-Derived Streptomyces sp. HDN154193.

Bitetracenomycin A (1) and its diastereomers [(±)-bitetracenomycin B, (±)-2] were discovered from the cultures of Streptomyces sp. HDN154193. Compounds 1 and (±)-2 were the first tetracenomycin dimers obtained from a natural source with sp3 methine protons at the bridge positions (C-12/12'), which also exhibited broad-spectrum antibacterial activity. The racemate (±)-2 was semisynthesized and separated into enantiomers (+)-2 and (-)-2, and the absolute configurations were determined by specific rotation and ECD data. These metabolites exhibited potent antibacterial activity especially against drug-resistant strains (MRSA and MRCNS) with MIC values ranging from 1.0 to 1.9 µg/mL.

Antibacterial p-Terphenyl with a Rare 2,2'-Bithiazole Substructure and Related Compounds Isolated from the Marine-Derived Actinomycete Nocardiopsis sp. HDN154086.

Assisted by MS/MS-based molecular networking and X-ray diffraction analysis, five new p-terphenyl derivatives, namely, nocarterphenyls D-H (1-5), were obtained and characterized from the cultures of the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The skeleton of nocarterphenyl D (1) was defined to possess a rare 2,2'-bithiazole scaffold, naturally occurring for the first time, and nocarterphenyls E-H (2-5) are p-terphenylquinones with unusual thioether linked fatty acid methyl ester substitutions. Compound 1 showed promising activity against multiple bacteria with MIC values ranging from 1.5 to 6.2 µM, and 2 exhibited notable antibacterial activity against MRSA which surpassed the positive control ciprofloxacin.

[Analysis of PKD2 gene variant and protein localization in a pedigree affected with polycystic kidney disease].

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION: The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.

[Analysis of gene variant in a Chinese pedigree with preaxial polydactyly].

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION: The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.

[Identification of a novel SOD1 variant in a Chinese patient with amyotrophic lateral sclerosis].

OBJECTIVE: To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS). METHODS: Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls. RESULTS: The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases. CONCLUSION: The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.

Open Curettage With Bone Augmentation for Symptomatic Tumors and Tumor-like Lesions of Calcaneus: A Comparison of Bioactive Glass Versus Allogeneic Bone.

Few studies have characterized the clinical outcomes of 45S5 Bioglass® applied as a bone graft to that of allogeneic bone applied in calcaneal open curettage. Therefore, the purpose of the present investigation was to compare the outcomes of patients with calcaneal tumors and tumor-like lesions treated by open curettage with 45S5 Bioglass® or allogeneic bone. Of the 31 patients who underwent open curettage (18 cases of unicameral bone cysts, 7 cases of aneurysmal bone cysts, and 6 cases of intraosseous lipoma), 16 (52%) received grafts with 45S5 Bioglass® and 15 (48%) with allogeneic bone. All the feet achieved bone fusion according to the modified Neer radiographic classification system at the last follow-up examination. The mean bone ingrowth time for the grafts with 45S5 Bioglass® versus allogeneic bone was 3.71 ± 0.86 versus 4.46 ± 1.04 months (p = .038), the mean bone healing time was 4.86 ± 0.93 versus 5.73 ± 1.07 months (p = .021), and the mean incision drying time was 7.2 ± 1.8 versus 8.2 ± 1.5 days (p = .047), respectively. No differences were found in the postoperative American Orthopaedic Foot and Ankle Society ankle-hindfoot scale scores between the 2 groups (p = .213). These results show that 45S5 Bioglass® can better facilitate the formation of new bone with a faster drying time of the incision than allogeneic bone. Although both materials can benefit the clinical outcomes of calcaneal tumors and tumor-like lesions, further studies are needed to observe the long-term complications and lesion recurrence rates.

Antibacterial Cyclic Tripeptides from Antarctica-Sponge-Derived Fungus Aspergillus insulicola HDN151418.

Three new aspochracin-type cyclic tripeptides, sclerotiotides M-O (1-3), together with three known analogues, sclerotiotide L (4), sclerotiotide F (5), and sclerotiotide B (6), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus, Proteus species, Mycobacterium phlei, Bacillus subtilis, Vibrio parahemolyticus, Edwardsiella tarda, MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM.

Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration.

C-C chemokine receptor 7 (CCR7) and its ligands CCL19 contributes to the directional migration of certain cancer cell lines, but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible interaction between CCL19-induced conditions and matrix metalloproteinases-9 (MMP9) expression in BMSCs. Cell migration using Transwell assay indicated that activation of CCR7 by its specific ligand, exogenous chemokine ligand 19 (CCL19), was associated with a significant linear increase. Western blot and real-time PCR indicated that CCL19/CCR7 significantly upregulated expression of MMP9, which is related to metastasis-associated genes. The CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, as measured by Western blot. P-Akt and MMP9 protein expression exhibited a time-dependent pattern, and the peak was at 48h. LY294002 significantly abolished the effects of exogenous CCL19. These results suggest that CCL19/CCR7 contributes to the migration of BMSCs by upregulating MMP9 potentially via the PI3K/Akt pathway.

CIP2A is overexpressed in osteosarcoma and regulates cell proliferation and invasion.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a newly characterized oncoprotein involved in a variety of malignant tumors. However, its expression pattern and biological functions in osteosarcoma remain unclear. In the present study, CIP2A expression was analyzed in 51 human osteosarcoma specimens using immunohistochemistry. CIP2A siRNA was used in the MG-63 cell line, and the effect of CIP2A depletion on cell proliferation and invasion was evaluated. We found that CIP2A was overexpressed in 76.5 % (39/51) of osteosarcoma tissues, while normal bone tissues showed negative CIP2A expression. In addition, the positive rate of CIP2A expression was higher in stage IIB osteosarcoma than stage IIA cases. Knockdown of the CIP2A expression significantly reduced osteosarcoma cell proliferation and invasion, with decreased c-Myc expression and p-AKT expression. CIP2A depletion also facilitated apoptosis and inhibited MMP9 mRNA expression. Taken together, our data identified CIP2A as a critical oncoprotein involved in cell proliferation and invasion, which could serve as a therapeutic target in osteosarcoma.

Specific rules for time and space of multisensory plasticity in the superior colliculus.

Cat superior colliculus (SC) neurons commonly combine information from different senses, which facilitates event detection and localization. Integration in SC multisensory neurons depends on the spatial and temporal relationships between cross-modal cues. Here, we revealed the parallel process of short-term plasticity in the temporal/spatial integration process during adulthood that adapts multisensory integration to reliable changes in environmental conditions. Short-term experience alters the temporal preferences of SC multisensory neurons, and this short-term plasticity in the temporal/spatial integration process is limited to changes in cross-modal timing (a factor commonly induced by events at different distances from the receiver). However, this plasticity was not evident in response to changes in the cross-modal spatial configuration.

Degraded iota-carrageenan can induce apoptosis in human osteosarcoma cells via the Wnt/ß-catenin signaling pathway.

Osteosarcoma (OS) is a high-grade malignant bone tumor. Therefore, using both in vitro and in vivo assays, the effects of degraded iota-Carrageenan (ι-CGN) on a human osteosarcoma cell line, HOS, were examined. Degraded ι-CGN was observed to induce apoptosis and G(1) phase arrest in HOS cells. Moreover, degraded ι-CGN suppressed tumor growth in established xenograft tumor models. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors treated with native ι-CGN or PBS. In addition, the formation of intratumoral microvessels was inhibited following treatment with degraded ι-CGN. In Western blot assays, degraded ι-CGN was found to inhibit the Wnt/ß-catenin signaling pathway. Overall, these studies demonstrate the antitumor activity of degraded ι-CGN toward the OS cell line, HOS. Moreover, valuable insight into the mechanisms mediated by degraded ι-CGN was obtained, potentially leading to the identification of novel treatments for OS. However, additional studies are needed to confirm these results in other cell types, particularly in human umbilical vein endothelial cells.

Intraoperative electrical stimulation promotes the short-term recovery of patients with cubital tunnel syndrome after surgery.

BACKGROUND: This study was designed to investigate whether intraoperative electrical nerve stimulation has effects on the short-term recovery of cubital tunnel syndrome patients after ulnar nerve release. METHODS: Patients diagnosed as cubital tunnel syndrome were selected. At the same time, they received conventional surgery treatment. The patients were divided by a randomized digits table into two groups. The control group underwent conventional surgery, and the electrical stimulation (ES) group underwent intraoperative electrical stimulation. All the patients were tested for sensory and motor functions, grip strength, key pinch strength, motor conductivity velocity (MCV), and maximum compound muscle action potential (CMAP) before operation and 1 month and 6 months after operation. RESULTS: In patients treated with intraoperative ES, the sensory and motor functions and the strength of muscle were significantly improved after 1-month and 6-month follow-up than the control group. After the follow-up, the patients in the ES group had significantly higher grip strength and key pinch strength than the control group. After the follow-up, the patients in the ES group had significantly higher MCV and CMAP than the control group. CONCLUSION: Intraoperative electrical stimulation of nerve muscle can significantly promote the short-term recovery of nerve and muscle functions after the surgery in cubital tunnel syndrome patients.

Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression.

BACKGROUND: As one of the malignant tumors most often affecting children and young adults, Ewing sarcoma (ES) is characterized by early metastasis contributing to unfavorable prognosis. However, the molecular mechanisms responsible for ES metastasis remain poorly understood. In this study, we aimed to explore whether Wnt5a, a putative pro-metastatic factor, plays a role in ES metastasis. METHODS: Expression of Wnt5a and CXCR4 was determined by real-time PCR or Western blot in 15 ES specimens and 4 ES cell lines, A-673, RD-ES, SK-N-MC and SK-ES-1. Expression of Wnt antagonists, SFRP1, SFRP2 and SFRP5, and some components in noncanonical Wnt pathway (p-JNK, p-cJUN and p-PKC) was also analyzed in this study. Methylation status of SFRP1, SFRP2 and SFRP5 was detected by Methylation-specific PCR (MSP). Wnt5a shRNA and pcDNA3.1 SFRP5 vector were used to abrogate Wnt5a expression and overexpress SFRP5 in ES cells, respectively. RESULTS: Wnt5a expression was positively correlated with CXCR4 expression in ES specimens. Levels of both Wnt5a mRNA and CXCR4 mRNA were significantly higher in specimens from ES patients with metastasis at diagnosis compared with specimens from those without metastasis. Recombinant Wnt5a enhanced CXCR4 expression in ES cells, which was accompanied by increased ES cell migration, whereas Wnt5a shRNA has opposite effects. SFRP5 was methylated and silenced in ES cells, and both recombinant SFRP5 and pcDNA3.1 SFRP5 vector suppressed CXCR4 expression as well as ES cell migration. Wnt5a shRNA and recombinant SFRP5 inhibited phosphorylation of JNK and cJUN, and JNK inhibitor also reduced CXCR4 expression and cell migration in ES cells. CONCLUSIONS: Wnt5a increases ES cell migration via upregulating CXCR4 expression in the absence of Wnt antagonist SFRP5, suggesting that Wnt5a overexpression and SFRP5 deficiency may jointly promote ES metastasis.

Applicability of the Padua scale for Chinese rheumatic in-patients with venous thromboembolism.

OBJECTIVE: To investigate the risk factors for venous thromboembolism (VTE) in hospitalized patients with rheumatic diseases in China. The efficacy of the Padua scale was evaluated and an improved model for predicting VTE in hospitalized patients with rheumatic diseases was developed. METHODS: Records of 2282 patients hospitalized in the department of rheumatology of the Sichuan Provincial People's Hospital were retrospectively reviewed. The risk factors for VTE were analyzed. The efficacy of the Padua scale was evaluated, Padua-combined prediction model and the independent risk factor-combined prediction model for predicting VTE were assessed using the receiver operating curve (ROC). RESULTS: A total of 50 patients in the VTE group and 2232 in the non-VTE group were included. Antiphospholipid syndrome (APS), VTE history, a hospital stay of over 3 days, high D-dimer (D-D), and decreased serum albumin were independent risk factors for VTE. APS was very closely associated with VTE (OR = 19.446). Padua scores in the VTE group and the non-VTE group were 3 (2, 6) and 2 (1, 2) points, respectively (p < 0.05), and the proportion of high-risk patients were 48.0% and 7.4%, respectively (p < 0.05). The incidence of VTE in the high-risk (Padua score ≥4) and low-risk (Padua score <4) groups was 12.7% and 1.2%, respectively (p < 0.05). The area under curve (AUC) of the Padua scale, Padua combined prediction model (Padua scale along with D-D and serum albumin), and the independent risk factor-combined prediction model was 0.771, 0.836, and 0.873, respectively. CONCLUSION: The Padua scale has limited predictive efficacy of VTE in hospitalized rheumatic patients. The independent risk factor-combination prediction model was superior in predicting VTE compared to Padua scale and Padua-combined prediction model.

Genetic and functional analyses detect an EXT1 splicing pathogenic variant in a Chinese hereditary multiple exostosis (HME) family.

BACKGROUND: Hereditary multiple exostosis (HME) is an autosomal dominant skeletal disorder characterized by the development of multiple cartilage-covered tumors on the external surfaces of bones (osteochondromas). Most of HME cases result from heterozygous loss-of-function mutations in EXT1 or EXT2 gene. METHODS: Clinical examination was performed to diagnose the patients: Whole exome sequencing (WES) was used to identify pathogenic mutations in the proband, which is confirmed by Sanger sequencing and co-segregation analysis: qRT-PCR was performed to identify the mRNA expression level of EXT1 in patient peripheral blood samples: minigene splicing assay was performed to mimic the splicing process of EXT1 variants in vitro. RESULTS: We evaluated the pathogenicity of EXT1 c.1056 + 1G > T in a Chinese family with HME. The clinical, phenotypic, and genetic characterization of patients in this family were described. The variant was detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. Sequencing of the RT-PCR products from the patient's blood sample identified a large deletion (94 nucleotides), which is the whole exome 2 of the EXT1 cDNA. Splicing assay indicated that the mutated minigene produced alternatively spliced transcripts, which cause a frameshift resulting in an early termination of protein expression. CONCLUSIONS: Our study establishes the pathogenesis of the splicing mutation EXT1 c.1056 + 1G > T to HME and provides scientific foundation for accurate diagnosis and precise medical intervention for HME.

Clinical characteristics and related influencing factors of common rheumatic diseases concomitant with tuberculosis.

Objective: To explore the clinical characteristics and risk factors of common systemic rheumatism concomitant with tuberculosis (TB). Methods: A total of 3,906 patients of RA, SLE, and SS diagnosed in the People's Hospital of Sichuan Province from January 2007 to January 2017 were collected. One hundred and five patients with TB were included as TB group, including 42 RA, 41 SLE, and 22 SS patients. In the non-TB group, 84 RA, 82 SLE, and 44 SS patients were randomly selected during the same period. Results: Fever was the most common symptom among RA, SLE, and SS patients with TB, accounting for 83.3%, 92.7%, and 68.2%, respectively. Cough, weight loss or fatigue were the next common. RA patients with TB were mostly pulmonary TB (PTB), accounting for 64.3%. The proportion of PTB for SLE and SS were 46.3%, 59.01%, respectively. In TB group, 59% RA, 57% SLE, and 62% SS with PTB had two or more chest CT findings. There were 48 TB cases received both Interferon Gamma Release Assay (IGRA) and Tuberculin skin test (TST) with positive rates of 91.8%, 45.8%, respectively. The daily average dose of glucocorticoids within 1 year in TB group was higher than that in non-TB group of SLE patients, lower counts of CD4+ T cell count were found in TB group (P < 0.05), while no such differences were found in RA and SS patients. Conclusion: RA patients with TB are mainly pulmonary TB. For SLE and SS patients, the chance of PTB and extrapulmonary tuberculosis is similar. Daily average dose of glucocorticoids within 1 year may be a common risk factor for RA, SLE and SS patients developing TB. Decreased CD4+ T cell count may also be a risk factor for SLE patients with TB. Symptoms of RA, SLE, SS with TB, are similar with the primary disease or other infection. It is recommended to conduct both TST and IGRA to help diagnose TB.

Convolutional neural network for automatically segmenting magnetic resonance images of the shoulder joint.

BACKGROUND: Magnetic resonance imaging (MRI) has been known to replace computed tomography (CT) for bone and skeletal joint examination. The accurate automatic segmentation of bone structure in shoulder MRI is important for the measurement and diagnosis of bone injury and disease. Existing bone segmentation algorithms cannot achieve automatic segmentation without any prior knowledge, and their versatility and accuracy are relatively low. Therefore, an automatic segmentation combining pulse coupled neural network (PCNN) and full convolutional neural networks (FCN) is proposed. METHODOLOGY: By constructing the block-based AlexNet segmentation model and U-Net-based bone segmentation module, we implemented the humeral segmentation model, articular bone segmentation model, humeral head and articular bone segmentation model synthesis model. We use this four kinds of segmentation models to obtain candidate bone regions, and accurately detect the positions of humerus and articular bone by voting. Finally, we perform an AlexNet segmentation model in the detected bone area in one step to segment accuracy at the pixel level. RESULTS: The experimental data came from 8 groups of patients in Shengjing Hospital affiliated to China Medical University. The scanning volume of each group is approximately 100 images. Five fold cross-validations and for training were recorded, and five sets of data were carefully separated. After using our technique in the three groups of patients tested, the positive predictive value of dice coefficient (PPV) and the average accuracy of sensitivity were very significant, which reached 0.96±0.02, 0.97±0.02 and 0.94±0.03, respectively. CONCLUSION: The method used in the experiment in this paper is based on a small amount of patient sample data. The deep learning required for the experiment needs to be performed through 2D medical images. The shoulder segmentation data obtained in this way can be very accurate.

Accurate simulation of the herniated cervical intervertebral disc using controllable expansion: a finite element study.

Expansions were carried out in finite element (FE) models of disc hernia including symmetric (median, lateral, paramedian) and asymmetric types. In all models, lubricous disk bulging that applied a linear compression to the anterior part of the cord was observed at the posterior surfaces of the expansion zone, respectively. The shape and position of protrusions varyed with the temperature, magnitude, and location of expanding elements. The geometric deformation and stress distribution of the spinal cord increased as the extent of compression grew. This method is in possession of enormous potential in promoting further individualized research of cervical spondylotic myelopathy.

Skeletal bone age prediction based on a deep residual network with spatial transformer.

OBJECTIVE: Bone age prediction can be performed by medical experts manually assessment of X-ray images of the hand bone. In practice, the workload is huge, resource consumption is large, measurement takes a long time, and it is easily influenced by human factors. As such, manual estimation of bone age takes a long time and the results fluctuate greatly depending on the proficiency of the radiologist. METHODS: The left-hand X-ray image data was identified and pre-processed. X-ray image analysis method using on deep neural network was used to automatically extract the key features of the left-hand joint bone age, and evaluation performance of the model was implemented. RESULTS: In this paper, the deep learning method can be used to obtain the X-ray bone image features, and the convolutional neural network is used to automatically assess the age of bone. The feature region extraction method based on deep learning can extract feature information with superior performance compared to the traditional image analysis technique. Based on the residual network (ResNet) model in the deep learning algorithm, the average absolute error of the age of bones detected by the bone age assessment model is 0.455 better than traditional methods and only end-to-end deep learning methods. When the learning rate is greater than 0.0005, the MAE of Inception Resnet v2 model is higher than most models. Accuracy of bone age prediction is as high as 97.6%. CONCLUSION: In comparison with the traditional machine learning feature extraction technique, the convolutional neural network based on feature extraction has better performance in the bone age regression model, and further improves the accuracy of image-based age of bone assessment.