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Bone is the most common metastatic site of advanced breast cancer. Bone related events caused by bone metastasis seriously affect the quality of life and survival time of patients. Therefore, in order to improve the quality of life and prolong the survival time of breast cancer patients with bone metastases, it is of great clinical value to investigate the occurrence and development mechanism of bone metastases, explore early diagnosis methods, and pursue abundant and effective treatment methods and drugs for bone metastases. This article mainly reviews the new research progress of bone metastasis of breast cancer from the aspects of molecular mechanism, imaging and biological diagnosis methods, systematic treatment, in order to provide more reference for clinical diagnosis and treatment.

The accuracy of traditional milling force prediction model is low, and it is difficult to provide effective support for the reasonable selection of process parameters in practical production, by synthetically considering the equivalent turning force model of working angle, cutting edge arc and radius of tool tip arc, in this model, the actual turning tool is equivalent to the ideal turning tool model to identify the material constant, the chip flow angle and the average friction angle in the material constitutive equation, according to the oblique cutting model, the shear stress on the main shear plane and the F0 vector of the unit cutting force at different cutting speeds are calculated, thus the instantaneous cutting force on the front face of the end mill can be calculated, the three-dimensional cutting force of end mill in X-Y-Z coordinate system is obtained by coordinate transformation. The prediction of the cutting force model is verified by simulation and experiment.

This study investigates the AD574, a 12-bit analog/digital converter (ADC) produced by American Analog Devices, Inc. (ADI) using bipolar/I2L technology. The test samples are subjected to a total ionizing dose (TID) of 400 Gy(Si) under 60Co γ irradiation. The samples with and without the TID are then subjected to a single-event upset (SEU) test, and the upset times of the output codes under the input signal conditions of 0 V, 1 V, and 2.5 V are obtained. The test results indicate that, after accumulating a total dose of 400 Gy(Si), the upset of the AD574 output code shifts toward the right of the center code value, resulting in a change in the upset times. Furthermore, the mechanism of the TID-SEU synergistic effect for the AD574 is preliminarily analyzed; it is believed that this phenomenon is related to the sensitivity of the ADC internal comparator single-event transient (SET). The amplitude and width of the SET pulse of the comparator with the TID increase significantly; this causes a change in the AD574 output code value upset distribution and the number of upset times. This study on the TID-SEU synergistic effect serves as a useful reference for aerospace components with radiation hardness.

BackgroundBipolar devices used in space radiation environment for a long time are simultaneously threatened by the total ionization dose (TID) effect and single event transient (SET), and there is a synergistic effect between TID and SET. The enhanced low dose rate sensitivity (ELDRS) effect unique to bipolar devices may affect the synergistic effect.PurposeThis study aims to investigate the physical mechanism of TID's impact on the SET in bipolar operational amplifier LM158.MethodsFirst of all, the LM158 samples were irradiated by 60Co γ-ray of a high dose rate of 0.1 Gy·s-1(Si) and a low dose rate of 1×10-4 Gy·s-1(Si). Then, the heavy ion (Tantalum) irradiation test was performed after the total dose was accumulated to 1 000 Gy(Si). The output single event transients of irradiated LM158 were observed by oscilloscope, and all the collected SETs were saved in computer and processed by MATLAB programming.ResultsThe experimental results show that the TID of bipolar operational amplifier LM158 causes the SET pulse amplitude to decrease and pulse width to expand. At the same time, compared with the high dose rate irradiation condition, the SET pulse width of LM158 is expanded by 50% under the low dose rate irradiation condition.ConclusionsThe study indicates that the interface trap charge accumulated in the bipolar transistor is the fundamental reason for the synergistic effect of TID and SET.

Objective: To explore the genetic basis for a couple with recurrent conceptions of fetus with abnormal longbones, and another couple with a history of omphalocele., Methods: Genomic DNA was extracted from the peripheral blood samples from both couples. All exons and flanking regions were analyzed with next generation sequencing. Candidate variants were verified by Sanger sequencing., Results: Couple one was found to be heterozygous for, a c.997+1G>T splice-site variant and a missence c.871G>A(p.Glu291Lys) variant of the ALPL gene. Both variants were predicted to be pathogenic and may result in reduced function or loss of alkaline phosphatase. For couple two, the wife was found to harbor a novel c.637_652 delins CCC variant of the CDKN1C gene. This deletion-insertion variant resulted in frame-shift and loss of function (p.Ala213Profs*55) of the CDKN1C protein. Maternally inherited CDKN1C LOF variant has been found to underlie Beckwith-Wiedemann syndrome (BWS), which may manifest as omphalocele., Conclusion: Dispite the lack the direct proof from the lost fetuses, the variants of ALPL and CDKN1C genes can explain the recurrence of fetal malformations for both couples.

Objective: To explore the genetic basis for a consanguineous pedigree affected with inherited coagulation factor V deficiency., Methods: Genomic DNA was extracted from peripheral blood samples from the pedigree and subjected to next generation sequencing for screening variants of the F5 gene. Suspected pathogenic variant was verified by using Sanger sequencing. Pathogenicity of the variant was evaluated according to ACMG guidelines., Results: A homozygous frameshifting variant, c.4096delC (p.Leu1366Phefs*3), was identified in the F5 gene in the proband, which was confirmed to be derived from her consanguineous parents. This variant was absent in all databases including 10 000 in-house Chinese exome sequences. Based on the ACMG guidelines, the c.4096delC was predicted to be a pathogenic variant., Conclusion: A novel pathogenic variant has been identified in the F5 gene in a consanguineous pedigree with inherited coagulation factor V deficiency, which has enriched the spectrum of F5 gene variants.

Objective: To emphasize the clinical significance of copy number variations (CNVs) detection by describing a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis., Methods: A girl with obesity and short stature was diagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis. Considering the discrepancy of her karyotype with her phenotype, genomic CNVs was detected by next-generation sequencing and the result was verified by quantitative PCR (qPCR)., Results: A microduplication of 16p11.2: 29 642 339-29 775 631 (133.292 kb) was detected. qPCR assay for QPRT and SPN located in the duplicated region confirmed the finding of CNVs assay. Meanwhile, her parents did not present similar duplication in 16p11.2., Conclusion: The 16p11.2 microduplication was a novel genomic structural variation in the girl, though it may not be associated with her clinical manifestations. Chromosomal microarray or next-generation sequencing-based CNVs detection can accurately determine the origin of small supernumerary marker chromosome and reduce the chance of misdiagnosis.

In present work the p-hydroxy-phenylacetic acid (PHPA) and m-hydroxy-phenylacetic acid(MHPA) in rhizospheric soil solutions and decomposed root residues were detected by High Performance Liquid Chromatography (HPLC), and their effects on soybean germination at the level of 0, 30, 60, 150, 300 and 600 mg.kg-1, on melting temperature of DNA at the level of 600 mg.kg-1 and on cytoplasm protein patterns at the level of 0, 30, 150, 300 mg.kg-1 were also studied. PHPA and MHPA were detected in decomposed products of root residue and soil solutions collected from rhizosphere in which soil sickness was occurred, but not detected in soil on which soybean rotated with wheat. The standard samples of PHPA and MHPA were used for bioassay in Petri dish. The main root length and lateral root number of soybean were seriously reduced, even at the level of 30 mg.L-1. Soybean germination and root growth were retarded seriously by MHPA, in contrast with PHPA. At the level of 600 mg.kg-1, the melting temperature (Tm) of soybean DNA was increased sharply from 77 degrees C to 84.5 degrees C with PHPA, and from 77 degrees C to 88.5 degrees C with MHPA. Tm was affected markedly by MHPA, compared to PHPA, and the result was consistent with that of bioassay. The cytoplasm protein patterns of soybean leaves were obtained from SDS-PAGE, showing several low weight molecular proteins were affected, especially on 16. 1 kD and 20.2 kD. The results implied that PHPA and MHPA had allelopathic effect on soybean, and might have a role in soil-sickness of soybean.