Objective:To analyze the expression and clinical significance of lymphoid enhancer factor-1 (LEF-1) and P53 protein in hilar cholangiocarcinoma.Methods:A total of 50 cases with hilarcholangiocarcinoma in the Tangshan People′s Hospital from March 2010 to December 2017 were retrospectively analyzed.P53 protein mutation was detected by immunohistochemistry.At the same time, the expression of LEF1 protein in cholangiocarcinoma and adjacent normal tissues was detected.The expression of LEF1 and its correlation with clinicopathological parameters were analyzed.At the same time, the relationship between p53 protein mutation and LEF1 protein expression and the prognosis of patients were discussed.Results:The positive expression rate of LEF1 in tumor tissues were 62.00%(31/50), which was higher than in adjacent tissues 36.00% (18/50). The difference was statistically significant (χ 2=6.763, P=0.016). There were 28 patients with TP53 protein mutation and 22 patients with wild type.The positive rate of LEF1 in TP53 mutant group was 75.00% (21/28), which was significantly higher than that in TP53 wild type group(45.45%, 10/22), and the difference was statistically significant(χ 2=4.565, P=0.03). The LEF1 expression was associated with tumor differentiation, TNM stage, lymph node metastasis and TP53 protein mutation (all P<0.05). LEF-1 expression was positively correlated with TP53 protein mutation ( r=0.294, P=0.04). The 1-year cumulative survival rate of patients with TP53 protein mutation was significantly lower than that of patients with TP53 protein wild type (60% vs.81%, P=0.0416). The 1-year cumulative survival rate of patients with LEF1 positive expression was also significantly lower than that of patients with negative expression (53% vs.82%, P=0.0180). Conclusion:LEF-1 is highly expressed in hilar cholangiocarcinoma, and patients with high expression have poor prognosis.The positive expression of LEF-1 in hilar cholangiocarcinoma patients with TP53 protein mutation was increased, and the prognosis of patients with TP53 protein mutation was poor.

Objective To observe glucose metabolism in C57 mice treated with different doses of fluoride.Methods Forty male C57 mice (body weight 20-24 g) were divided into four groups which were exposed to 0,50,100 and 150 mg/L sodium fluoride (NaF) by random number table according to body weight,each group had 10 mice.At 2,4,6,8,10 and 12 weeks after fluoride exposure,body weight was measured,blood glucose and glycosylated hemoglobin were detected by blood glucose meter and glycosylated hemoglobin meter,serum insulin and glucagon were detected by enzyme-linked immunosorbent assay (ELISA).Results At 10 and 12 weeks after fluoride exposure,the differences of fasting glucose between groups of C57 mice were statistically significant (F =35.12,21.92,all P ＜ 0.05),the fasting glucose of 100,150 mg/L fluoride groups [(7.7 ± 0.2),(7.3 ± 0.3),(8.6 ± 0.5),(9.1 ± 0.7)mmol/L] were higher than those of the control group [(5.4 ± 0.3),(5.0 ± 0.3)mmol/L,all P ＜ 0.01].The differences of glycosylated hemoglobin,glucagons between groups were statistically significant (F =3.85,8.74,all P ＜ 0.05).The glycosylated hemoglobin of 100,150 mg/L fluoride groups [(7.73 ± 0.76),(7.80 ± 1.15) mmo]/L] were higher than those of the control group [(5.43 ± 1.27) mmol/L,all P ＜ 0.05]; serum glucagon levels of 50,100,150 mg/L fluoride groups [(19.15 ± 11.84),(26.55 ± 15.97),(20.05 ± 7.29)ng/L] were lower than that of the control group [(48.35 ± 2.79)ng/L,all P ＜ 0.01].Conclusion Long term excess fluoride intake can reduce the function of sugar metabolism in C57 mice.

Objective To observe gene different expression of unfolded protein response signaling pathway in human osteoblasts under the excessive fluoride ,and explore the role of endoplasmic reticulum stress in fluorosis .Methods Human osteoblasts were cultured with fluoride ,intervening for 24 h .Cell viability and apoptosis were inspected by MTS assay and flow cytometer respective‐ly .The UPR signaling pathway was examined by real time PCR array ,and protein expressions were detected by Western blot .Re‐sults T he cell survival rates w ere (100 .678 5 ± 2 .830 3 )% ,(105 .393 4 ± 2 .538 4 )% ,(106 .125 7 ± 2 .048 3 )% ,(77 .977 3 ± 2 .544 3)% (P<0 .05) ,(30 .237 7 ± 0 .632 73)% (P<0 .05) treated with sodium fluoride at the concentration 0 ,5 ,10 ,20 ,40 ,80 mg/L respectively .Apoptosis rate inspected by flow cytometer was 4 .8% in 5 mg/L group ,13 .8% in 10 mg/L group ,37 .0% in 20 mg/L group ,58 .9% in 40 mg/L group ,63 .2% in 80 mg/L group (P<0 .05) .Only 1 gene was down regulated and 14 genes were up regulated .Western blot analysis showed BIP ,ATF4 ,CHOP and IRE1 both showed their protein expression gradually up regula‐ted with fluorine dose .XBP1 expression gradually increased in NaF 5-20 mg/L ,and its expression decreased at 40 and 80 mg/L . Conclusion Sodium fluoride can cause osteoblasts endoplasmic reticulum stress pathway through PTEN and IRE1 pathway ,and at high concentrations can cause apoptosis of osteoblast .

Carcinoma ; pathology ; Carcinoma, Papillary ; Histiocytosis, Langerhans-Cell ; pathology ; Humans ; Thyroid Neoplasms ; pathology

Ex-RAD (ON01210) is a novel and efficient anti-radiation drug with low toxicity developed by US army and Onconova Pharmaceuticals in recent years. The significant survival advantage and low toxicity of Ex-RAD have contributed to the approval by the FDA as an investigational new drug in December 2008. Meanwhile, the drug is currently in phase I clinical trials in humans. In this paper, the chemical structure, synthesis route, detection method and pharmacological action of Ex-RAD were reviewed, and the appli-cation prospect of Ex-RAD was also explored.

The pathogenesis of diabetic cystopathy(DCP)is complex and early diagnosis is hindered by a lack of specific and sensitive criteria and more research is needed to establish guidelines for its clinical diagnosis and treatment.Exosomes are membrane vesicles carrying various biological information such as proteins and nucleic acids, which are critical for communication between different tissues and organs.This review discusses the potential role of exosome miRNA in the pathogenesis of DCP and its application in therapy, aiming to provide new insight into the diagnosis and treatment of DCP.

Objective To screen out the biomarkers with diagnostic value in lung cancer by biochip technology. Methods We screened four pairs of differentially-expressed circRNAs in lung cancer by circRNA expression profiling chip, and then verified the screened differential circRNA hsa_circ_0044569 by qRT-PCR, and collected clinical case information of patients at the same time. The independent sample t test and ROC curve were used to analyze the relation between the clinical data of lung cancer patients and the expression of circRNA hsa_circ_0044569 on clinical samples. Results The expression level of hsa_circ_0044569 in lung cancer tissues was higher than that of its paired adjacent tissues. The cutoff value of hsa_circ_0044569 for the diagnosis of lung cancer was 9.62, AUC was 0.758, P < 0.05, sensitivity was 0.712, and specificity was 0.712. The expression of hsa_circ_0044569 was significantly related with the pathological type of lung cancer patients (P < 0.05). Conclusion hsa_circ_0044569 is highly expressed in lung cancer and related to the pathological type, suggesting that it may become a potential biomarker in the early diagnosis of lung cancer.

This paper first summarizes the cognition and understanding of online teaching, then introduces the active design and practice of online teaching in Harbin Medical University, and fully comprehends the quality of online teaching through the feedback to teachers and students. Through the investigation, the research group found that there are problems in online teaching, including teachers' difficulty in applying the teaching platform efficiently, limited Internet speed and hardware equipment, insufficient understanding and attention of individual teachers to online teaching, insufficient interaction between teachers and students, and difficulty in carrying out experiments and practical teaching. In this regard, the research group proposed countermeasures to change online teaching concept, reform online teaching methods, improve the function of online teaching platform, and optimize online course resources in order to timely summarize the online teaching situation, improve the shortcomings and promote advanced experience, and ensure the quality of follow-up online teaching.

Objective To investigate the expression of hsa_circ_0018574 in colorectal cancer tissues and human colon cancer HT29 cell line, as well as its effect on the proliferation and apoptosis of colorectal cancer cells. Methods The circPrimer 1.2 software was used to draw the circRNA sequence structure. Meanwhile, the circRNA microarray was used to screen differentially-expressed circRNA in colorectal cancer tissues and adjacent tissues, and RNA was extracted from tissue samples. The expression of hsa_circ_0018574 in human colorectal tumors was detected by RT-qPCR. The si-circ_0018574 was transfected into HT29 cells, and the expression of CDK2, CDK4, CDK6, cyclinD1, and cyclinE cyclins were detected by colony formation assay, flow cytometry, and Western blot, respectively. Results The expression of hsa_circ_0018574 in human colorectal tumor tissues was significantly higher than that in adjacent tissues (P < 0.01). Meanwhile, the si-circ_0018574 in HT29 cells could significantly inhibit the proliferation of cancer cells, reduce clone formation and colony formation ability (P < 0.01), and induce tumor cell apoptosis (P < 0.01). The expressions of CDK2, CDK4, CDK6, cyclinD1 and cyclinE cyclins were decreased. Conclusion The hsa_circ_0018574 is highly expressed in colorectal tumors, and si-circ_0018574 could significantly inhibit the proliferation of HT29 cells, reduce cell division, and induce apoptosis.

Objective:To investigate the expression of hsa_circ_0019413 in the peripheral blood of patients with primary Sj?gren's syndrome (pSS) and its role in the development of pSS disease.Methods:Microarray screening of circ ribonucleic acid (circRNA) changes was first performed in the peripheral blood of 4 pSS patients and 4 healthy controls. Real-time quantitative reverse transcription polymerase chain reaction (qPCR) was used to verify the difference in the expression of hsa_circ_0019413 in the peripheral blood of 30 pSS patients and 30 controls. By establishing the receiver operating characteristic (ROC) curve, the potential diagnostic value of hsa_circ_0019413 in peripheral blood was analyzed, and the expression level of hsa_circ_0019413 was correlated with the clinical presentations of patients with pSS.Results:① By microarray analysis, 437 circRNAs were differentially expressed between the two groups (FC≥2.0, P<0.05), of which 365 were up-regulated and 72 were down-regulated. ② The expression level of hsa_circ_0019413 in pSS patients was significantly higher than that in healthy controls by qPCR. The difference between the two groups was statistically significant ( P<0.05). It showed that hsa_circ_0019413 in peripheral blood of pSS patients had potential diagnostic value by ROC curve analysis [area under the curve (AUC)=0.883, 95% CI (0.782, 0.984), P<0.01]. ③ The expression level of hsa_circ_0019413 was positively correlated with the ESSDAI, ANA, titer of the pSS patients by correlation analysis ( r=0.721, P=0.012; r=0.625, P=0.040), but not with (immunoglobulin (Ig)G or erythrocyte sedimentation rate (ESR). Conclusion:Hsa_circ_0019413 in the peripheral blood may be involved in the development of pSS and may be a biomarker for the diagnosis of pSS.