Objective:To investigate the expression and role of DEAD-box RNA helicases 5(DDX5 helicases)in head and neck squamous carcinoma(HNSCC).Methods:Tissue microarray microarray was used to assess relevant mRNA expression profile data,and R software was used to screen differential mRNAs(DEGs).The expression level of DDX5 was predicted using GEPIA 2,TCGA databases,and detected by immunohistochemistry,western blot and RT-qPCR in the HNSCC tissue and cell lines.Based on high-throughput sequencing data of DECs,differentially expressed miRNAs(DEMIs)relevant DDX5 competitive endogenous RNA network(ceRNA)was constructed.The software cytoscape was used to visualize the ceRNA network map and further screen the regulatory ax-is.Results:The results of microarray screening revealed that DDX5 expression in HNSCC was upregulated.Immunohistochemistry ver-ified that DDX5 was stronger expressed in the nuclei of squamous carcinoma cells.qPCR results suggested that significant expression of DDX5 mRNA at the tissue and cellular levels(P＜0.05).Western blot results showed high expression of DDX5 protein in the tissues.The ceRNA network was constructed,from which the relevant HNSCC axis circRNA-039626-miR-222-5p-DDX5 was identified.Con-clusion:DDX5 is highly expressed in HNSCC,and the circRNA-039626-miR-222-5p-DDX5 axis may be a potential regulatory axis for the development of HNSCC.

OBJECTIVE: Dexmedetomidine (DEX), the most specific α ₂-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. METHODS: We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O ₂) and hypoxic (1% O ₂) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. RESULTS: The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). CONCLUSION We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α ₂-adrenergic receptor mediation might be the critical mechanisms.
Animals ; Humans ; Mice ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Carcinoma, Hepatocellular ; Cardiovascular Physiological Phenomena ; Dexmedetomidine/pharmacology* ; Hypoxia ; Liver Neoplasms/drug therapy* ; Oxygen ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/genetics* ; Receptors, Adrenergic, alpha-2/metabolism*

DDX5 helicase (DEAD box helicases 5), also known as P68, is an important member of an ATP dependent RNA helicase.Studies have shown that DDX5 is abnormally expressed in a variety of cancers, targeting a variety of tumor related signal pathways, regulating upstream and downstream factors to affect the occurrence, invasion and migration of tumor cells. This article describes the biological role of DDX5 in malignant tumors and provides prospects for targeted treatment of tumors.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

OBJECTIVEThis research aims to further explore the expression and significance of proliferating cell nuclear antigen (PCNA) and P53 in regenerating rat atrophy parotid gland from the gene and protein levels.

METHODSOne hundred and two Wistar rats were randomly divided into experimental and control groups; the former group's duct was ligated and then released respectively in 7 (Group A) and 14 days (Group B). Fresh parotid specimens were obtained at 0, 3, 5, 7, 10, 14, 21, and 28 days after being released. Hematoxylin-eosin staining method was used to observe the morphological changes of the parotid gland. The significance of P53 and PCNA in two groups was resolved by real-time fluorescence quantitative polymerase china reaction and Western blot.

RESULTSAcinar cells aoptosis and duct cells proliferation occurred when the occlusion of the parotid duct was reversed on days 7 and 14. The expression of P53 was higher than that of PCNA, and they reached the peak at the third and fifth days after groups A and B regenerated, respectively. This finding was significantly different compared with the control (P<0.01). P53 and PCNA contents decreased gradually; acinar and duct gradually returned to normal morphology; PCNA and P53 contents gradually close to the normal control group.

CONCLUSIONSAfter ligating the parotid duct, P53 was highly expressed, and induced parotid gland atrophy. Mean-while, PCNA was highly expressed, which then decreased inducing gland recovery.

A case of seminoma metastasis to neck 2 years after operation is reported and the reference for clinical diagnosis of neck masses of the tumor is provided.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Objective:To investigate the expression and correlation of Bcl-2 and Bax in the parotid gland after leading duct ligation in rats. Methods:Atrophy of the right parotid was induced by ligating the right main duct of 72 rats. Immunohistochemical labelling was performed to study the expression of Bcl-2 and Bax 1, 3, 5, 7, 14, 21, 30, 60, 90, 150 and 180 days after duct ligation. Results:7 d after duct ligation most acinar cells disappeared. The distribution of Bcl-2 and Bax protein in normal parotid was in cytoplasm with unifo-maity. Bcl-2 and bax higher expression was identified in the gland at all time points. The expression of Bcl-2 protein was significantly in-creased and reached the peak at 21 d after duct ligation. More Bax-positive acinar cells on day 3 were observed, then the expression of Bcl-2 and Bax protein was descended. Higher Bcl-2/Bax ratio was identified at 1-21 d, then descended. Conclusion:The expression of Bcl-2 and Bax is associated with the atophy of the parotid glad after rat parotid duct ligation.

Objective:To investigate the expression of Survivin and programmed cell death 5(PDCD5)protein in mucoepidermoid carcinoma(MEC).Methods:Survivin and PDCD5 were detected by immunohistochemical staining in 20 cases of normal parotid tis-sue(group A),40 cases of pleomorphic adenoma(group B)and 45 cases of MEC tissues(group C).Results:The positive expres-sion ratio of Survivin in group A,B and C was 10.0%,27.5% and 55.6% respectively(χ2 =14.556,P <0.01),while that of PD-CD5 was 85%,65% and 33.3% respectively (χ2 =17.439,P <0.01).The expression of survivin or PDCD5 was related with dif-ferentiation,lymph node metastasis and TNM staging of MEC.Survivin and PDCD5 showed a negative correlation in MEC(χ2 =4.500,P =0.034,γs =-0.316).Conclusion:Survivin over-expression and PDCD5 down-expression may play a role in the de-velopment and progress of mucoepidermoid carcinoma.

OBJECTIVETo investigate the changes on the number and distribution of myoepithelial cells (MECs) during parotid gland regeneration.

METHODSA total of 54 Wistar rats were divided into eight experimental groups and one normal control group, with six rats in each group. The right parotid ducts of the rats in the experimental groups were ligated for 14 days and then reopened. The parotid tissue specimens were harvested at days 0, 1, 3, 5, 7, 10, 14, and 21. The histological changes of the regenerating gland were examined using hematoxylin-eosin staining. Immunohistochemical labeling was also performed to investigate the changes in the number and distribution of MECs at different time points of parotid regeneration. Both the histological and immunohistochemical changes observed in the experimental groups were compared with those in the normal control group.

RESULTSThe parotid gland showed marked atrophy 14 days after ligation. Most acinar cells disap- peared, but the number of duct-like structures obviously increased. MECs apparently increased in number and were mainly located at the periphery of the duct-like structures. Three days after duct reopening, the number of acinar cells significantly increased and the duct-like structures significantly reduced. Meanwhile, MECs also decreased in number and were mainly located at the periphery of the newly formed acini and duct-like structures. The number of MECs noticeably decreased 3 and 5 days after duct reopening. At 14 days after duct reopening, the glandular structures and the number and distribution of MECs returned to normal compared with those in the normal control group.

CONCLUSIONThe number and distribution of MECs returned to normal condition after parotid gland atrophy. Parotid regeneration mainly occurred within 5 days after duct reopening.