Anatomical characteristics and potential gene mutation sites of a familial recurrent patellar dislocation.

BACKGROUND: Recurrent patellar dislocation is the result of anatomical alignment and imbalance of restraint of bone and soft tissue. We investigate the anatomical characteristics of the knee joint in a family of patients with recurrent patella dislocation, and to screen the possible pathogenic genes in this family by whole exome sequencing in 4 patients and 4 healthy subjects, so as to provide theoretical basis for the pathogenesis of this disease. METHODS: The data related to patella dislocation were measured by imaging data. The peripheral blood DNA of related family members was extracted for the whole exome sequencing, and then the sequencing results were compared with the human database. By filtering out synonymous variants and high-frequency variants in population databases, and then integrating single nucleotide non-synonymous variants of family members, disease-causing genes were found. RESULTS: All patients in this family have different degrees of abnormal knee anatomy, which is closely related to patella dislocation. The sequencing results of patients and normal persons in this patella dislocation family were compared and analyzed, and the data were filtered through multiple biological databases. Find HOXB9 (NM_024017.4:c.404A>G:p.Glu135Gly),COL1A1(NM_000088.3:c.3766G>A:p.Ala1256Thr),GNPAT(NM_014236.3:c1556A>G:p.Asp519Gly),NANS(NM_018946.3:c.204G>C:p.Glu68Asp),SLC26A2(NM_000112.3:c.2065A>T:p.Thr689Ser) are nonsynonymous variants (MISSENSE). Through Sanger sequencing, the identified mutations in HOXB9 and SLC26A2 genes were only present in samples from patients with recurrent patellar dislocation. CONCLUSIONS: The patients with recurrent patellar dislocation had markedly abnormal knee anatomy in this family. HOXB9 gene and SLC26A2 gene were found to be the possible pathogenic genes or related genes for patella dislocation.

GZMB gene silencing confers protection against synovial tissue hyperplasia and articular cartilage tissue injury in rheumatoid arthritis through the MAPK signaling pathway.

INTRODUCTION: Rheumatoid arthritis (RA) represents the most commonly occurring inflammatory type of arthritis and is a major cause of disability. Reports have placed emphasis on the potential of, granzyme B (GZMB) as a potentially valuable prognostic marker in early RA, the mechanism of which still remains largely unclear. Thus, the aim of the current study was to investigate the effects GZMB gene silencing influences synovial tissue hyperplasia and articular cartilage tissue injury of RA through the regulation of the MAPK signaling pathway. METHODS: Following the successful establishment of the collagen-induced animal model of RA in rats, a five-grade scoring method was applied to evaluate the swelling degree measurement of the rats for model identification. The various rat responses to GZMB shRNA and U-46619 (activator of the MAPK signaling pathway) were subsequently detected. The general status of rats was observed and recorded, with their weight and ankle diameter kept accurate record of. ELISA was employed to detect the levels of inflammatory cytokines, while RT-qPCR and Western blotting techniques were applied to determine the expressions of GZMB and pathway-related genes and proteins. RESULTS: GZMB gene silencing was observed to aid in the maintenance of rat weight increases, while acting to reduce the degree of ankle swelling, while hypertrophy of the synovial tissue and the injury of the articular cartilage tissue were not obvious. GZMB gene silencing was shown to decrease inflammatory cytokine levels, as well as decreased bcl-2, Cyclin D1, VEGF and bFGF while increasing caspase 3. Notably, GZMB gene silencing suppressed the activation of the MAPK signaling pathway by reducing the phosphorylation extent of ERK and MEK. CONCLUSION: Taken together, the key findings of the present study ultimately suggest that GZMB gene silencing acts to inhibit MAPK signaling pathway through regulating the expressions of inflammatory factors, factors correlated with apoptosis (bcl-2 and caspase), as well as factors associated with angiogenesis (VEGF and bFGF), thus relieving synovial tissue hyperplasia and articular cartilage tissue injury brought about by RA. The GZMB gene could well be a new therapeutic target for RA treatment.

Development of pulsed neutron uranium logging instrument.

This article introduces a development of pulsed neutron uranium logging instrument. By analyzing the temporal distribution of epithermal neutrons generated from the thermal fission of (235)U, we propose a new method with a uranium-bearing index to calculate the uranium content in the formation. An instrument employing a D-T neutron generator and two epithermal neutron detectors has been developed. The logging response is studied using Monte Carlo simulation and experiments in calibration wells. The simulation and experimental results show that the uranium-bearing index is linearly correlated with the uranium content, and the porosity and thermal neutron lifetime of the formation can be acquired simultaneously.

[Morphology-based criteria for ultrasonic assessment of axillary lymph node status in primary breast cancer].

OBJECTIVE: To evaluate the morphology-based criteria for the ultrasonic assessment of axillary lymph node in primary breast cancer. METHODS: A total of 2256 T0-2N0 patients underwent axillary ultrasound preoperatively. Lymph nodes were classified as normal if no node was found or cortex thickness was even and < 3 mm; abnormal, (1) if cortex thickness was even but ≥ 3 mm or (2) focally thickened cortex ≥ 3 mm or (3) fatty hilum was absent. The patients in the abnormal group underwent ultrasound guided fine-needle aspiration (US-FNA). Except for positive lymph nodes, all the others underwent sentinel lymph node biopsy (SLNB). RESULTS: In this series, 692 (30.7%) were pathologically confirmed positive LNs. Among them, 214 (9.5%) were identified by US-FNA. And 361 were abnormal according to the above mentioned criteria. The proportions were 11.6%, 54.8% and 33.5% in Group 1-3 respectively. The sensitivity, specificity, positive and negative predictive values of these criteria alone were 35.8%, 92.8%, 68.7% and 76.6% respectively. CONCLUSION: The present morphology-based criteria for the ultrasonic assessment of lymph node status is both effective and practical in primary breast cancer.

[Association of single nucleotide polymorphisms of IL-1b with lumbar disc disease].

This study was to explore the relationships between (-511)T>C and (+3954)C>T single nucleotide polymorphisms(SNP) in IL-1beta gene with lumbar intervertebral disc disease. We analyzed (-511)T>C and (+3954)C>T SNP in IL-1beta gene by the polymerase chain reaction-restriction fragment length polymorphism and electrophoresis methods respectively in 81 cases with lumbar disc disease and 101 healthy controls. The relationship between (-511)T>C and (+3954)C>T SNP in IL-1beta gene and lumbar disc disease in two groups was measured, so does the relationship between (-511)T>C and (+3954)C>T SNP in IL-1beta gene and intervertebral disc degeneration in those younger than 45-year-old. The results showed there were (-511)T>C and (+3954)C>T SNP in IL-1beta gene. There was a significant difference in the distribution of TT, TC and CC genotype or T, C genotype of (-511)T>C of IL-1beta in two groups. And there was no significant difference in the distribution of (+3954)C>T SNP in IL-1beta gene in two groups. There was no significant difference between the distribution of (-511)T>C and (+3954)C>T SNP in IL-1beta gene and intervertebral disc degeneration in those younger than 45-year-old. It suggested (-511)T>C SNP in IL-1beta gene be one of the susceptible alleles for Lumbar disc disease.