The clinicopathological features of lung metastases of parathyroid cancinoma.

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.

lncRNA DARS-AS1 Promoted Osteosarcoma Progression through Regulating miR-532-3p/CCR7.

Background: lncRNAs have been indicated to involve in cell invasion, proliferation, and metastasis. However, function of DARS-AS1 in osteosarcoma remains poorly explored. Methods: DARS-AS1 and miR-532-3p level were measured using qRT-PCR. CCK-8 assay and cell invasion assay were done to study cell functions. Luciferase reporter assay was performed to study the mechanism about DARS-AS1 and miR-532-3p. Results: We firstly showed that DARS-AS1 expression is upregulated in 73.5% (25/34) of cases with osteosarcoma. Moreover, DARS-AS1 expression is overexpressed in osteosarcoma specimens than in nontumor samples. The DARS-AS1 is overexpressed in the osteosarcoma cell lines (Saos-2, SOSP-9607, U2OS, and MG-63) compared to hFOB. Overexpression of DARS-AS1 promotes cell growth and invasion in MG-63 osteosarcoma cell. DARS-AS1 plays as one sponge for miR-532-3p in osteosarcoma cell, and miR-532-3p overexpression inhibits luciferase activity of DARS-AS1-WT, not DARS-AS1-MUT in MG-63 cell. Ectopic expression of DARS-AS1 inhibits miR-532-3p expression in MG-63 cell. Furthermore, miR-532-3p expression is downregulated in osteosarcoma specimens compared to in paired nontumor samples. MiR-532-3p expression is downregulated in osteosarcoma cell lines compared to hFOB. MiR-532-3p expression is negatively associated with DARS-AS1 expression in osteosarcoma specimens. miR-532-3p directly regulates CCR7 expression in osteosarcoma cell. Elevated DARS-AS1 expression enhances cell growth and invasion via regulating CCR7. Conclusions: These data firstly suggested that DARS-AS1 exerted as one oncogene in osteosarcoma partly via regulating miR-532-3p/CCR7.

Transplantation of a vascularized pedicle of hemisected spinal cord to establish spinal cord continuity after removal of a segment of the thoracic spinal cord: A proof-of-principle study in dogs.

INTRODUCTION: Glial scar formation impedes nerve regeneration/reinnervation after spinal cord injury (SCI); therefore, removal of scar tissue is essential for SCI treatment. AIMS: To investigate whether removing a spinal cord and transplanting a vascularized pedicle of hemisected spinal cord from the spinal cord caudal to the transection can restore motor function, to aid in the treatment of future clinical spinal cord injuries. We developed a canine model. After removal of a 1-cm segment of the thoracic (T10-T11) spinal cord in eight beagles, a vascularized pedicle of hemisected spinal cord from the first 1.5 cm of the spinal cord caudal to the transection (cut along the posterior median sulcus of the spinal cord) was transplanted to bridge the transected spinal cord in the presence of a fusogen (polyethylene glycol, PEG) in four of the eight dogs. We used various forms of imaging, electron microscopy, and histologic data to determine that after our transplantation of a vascular pedicled hemisection to bridge the transected spinal cord, electrical continuity across the spinal bridge was restored. RESULTS: Motor function was restored following our transplantation, as confirmed by the re-establishment of anatomic continuity along with interfacial axonal sprouting. CONCLUSION: Taken together, our findings suggest that SCI patients-who have previously been thought to have irreversible damage and/or paralysis-may be treated effectively with similar operative techniques to re-establish electrical and functional continuity following SCI.

Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection.

Zika virus (ZIKV) infection is a global public health problem due to its rapid spread and the possibility of causing microcephaly. Currently, no specific antivirals against ZIKV are available for treatment. In the present study, several flavonoids (galangin, kaempferide, quercetin, myricetin and EGCG) were found to reduce ZIKV induced plaques and viral RNA copies with negligible cytotoxic effects on host cells. In addition, inhibition of ZIKV propagation by flavonoids showed structure-activity relationship. Our results demonstrate flavonoids as inhibitors of ZIKV entry and NS2B-NS3 protease. Hence, these flavonoids could be used as potential bifunctional drugs for treating ZIKV infections.

[A non-coated enzyme-linked immunosorbent assay for screening zika virus envelope protein].

OBJECTIVE: To establish a non-coated enzyme-linked immunosorbent assay (ELISA) based on zika virus envelope (E) protein for detecting the expression of E protein in infected cells. METHODS: Adherent Vero-143 cells infected with zika virus in a 96-well plate were fixed, and the antibodies against zika virus E protein were added at an optimized concentration to establish the non-coated ELISA method for E protein. The antiviral activities of lignans compound C1 was evaluated using this method. The accuracy of this non-coated ELISA was verified by RT-PCR, and the cross reaction with dengue virus was assessed. RESULTS: After optimization, the background absorbance at 450 nm of uninfected cells was reduced to about 0.20. The antiviral activities of lignans compound C1 detected by this method were basically consistent with the results of RT-PCR. No cross reaction with dengue virus was found in this assay. CONCLUSIONS: A non- coated ELISA method based on zika virus E protein was established, which can be used for screening antiviral agents against zika virus.

Identifying the optimal target genes associated with multiple myeloma by a novel bioinformatical analysis.

Multiple myeloma (MM) is one of the most frequent malignant hematopoietic diseases, the pathogenesis of which remains unclear. It is well known that miRNAs are aberrantly expressed in many tumors, thus, investigating the target genes of miRNAs contributes to understanding the functional effect of miRNAs on MM. In this study, plasma samples of 147 patients with MM and 15 normal donors were collected. Using high-throughout microarray and limma package to screen the differentially expressed genes. Furthermore, to accurately predict the optimal target genes of MM, the logFC, targetScanCS and targetScanPCT values of known genes in four miRNAs (i.e. has-miR-21, has-miR-20a, has-miR-148a and has-miR-99b) were used to compute the targetScore values. As a result, 171 genes with larger difference were screened out using t-test, F-test and eBayes statistics analysis. Furthermore, 34 potential target genes associated with MM were selected by integrating the differentially expressed genes (DEGs) and the genes obtained by targetScore algorithm. Additionally, combining with the mutated genes in MM and the obtained DEGs, 41 consistently expressed genes were obtained. Finally, 5 optimal target genes, including SYK, LCP1, HIF1A, ALDH1A1 and MAFB, were screened out by the intersection of 34 DEGs and 41 mutated genes. In a word, this novel target gene prediction algorithm may contribute to improve our understanding on the pathogenesis of miRNAs in MM, which open up a new approach for future study.

[ADS-J1 antagonizes semen-derived enhancer of virus infection-mediated enhancement of transmitted founder HIV-1 and its matched chronic control strain infection].

OBJECTIVE: To investigate the effect of semen-derived enhancer of virus infection (SEVI) on the infection of transmitted/founder (TF) HIV-1 and its matched chronic control (CC) viruses and the antagonism of ADS-J1 on SEVI-mediated enhancement of TF and CC virus infection in vitro. METHODS: PAP248-286 self-assembling into SEVI amyloid fibrils was validated by ThT assay. We generated the virus stocks of TF and CC virus pair. TZM-bl cells were infected with the mixture of SEVI and TF or CC viruses for 72 h. Luciferase activity was used to observe the enhancement of SEVI. SEVI was treated with different concentrations of ADS-J1 and incubated with TF or CC viruses. TZM-bl cells were then infected with the mixture and luciferase activity was detected 72 h after infection to analyze the antagonism of ADS-J1 on the enhancing effect of SEVI. ADS-J1 was also incubated with TF and CC viruses directly and TZM-bl cells were infected for 72 h to evaluate the antiviral effect using luciferase assay. SEVI was treated with ADS-J1 and Zeta potential was determined to explore the antagonistic mechanism of ADS-J1. RESULTS: ThT assay showed that PAP248-286 was capable of self-assembly into SEVI amyloid fibrils. SEVI significantly accelerated TF and CC viruses infection (P<0.05), and ADS-J1 not only significantly antagonized the enhancement of SEVI (P<0.05) but also directly inhibited the infection of TF and CC viruses (P<0.05). ADS-J1 neutralized the positive charge of SEVI in a dose-dependent manner. CONCLUSIONS: SEVI promotes the infection of TF and CC strains, and ADS-J1 antagonizes SEVI-mediated enhancement of TF and CC viruses by neutralizing the positive charge of SEVI.

[Line scanning analysis of white porcelain from Gong Kiln in early Tang dynasty by energy disperse X-ray fluorescence].

Gong kiln, for its long porcelain-firing history, was one of three representative white porcelain kilns in northern China. In order to improve the quality and whiteness of white porcelain, a decorating layer or cosmetic earth was laid on the body surface in Gong kiln during early Tang dynasty, which was able to blot out rough surface and weaken the influence of fuscous body upon surface color. In this paper the main chemical composition of the white porcelain's profile was analyzed by using energy disperse X-Ray fluorescence. The result showed that different materials were used as cosmetic earth during early Tang dynasty, in accordance with the phenomenon under optical microscope. In addition, the glaze belongs to calcium glaze in which plant ash was added.