GCNT3 regulated MUC13 to promote the development of hepatocellular carcinoma through the GSK3ß/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Extensive research is currently directed at identifying novel targets for its diagnosis and treatment. AIMS: We investigated the biological functions and clinical significance of mucin-type N-acetylglucosaminyltransferase 3 (GCNT3) in HCC. METHODS: Variations in the mRNA expression of GCNT3 were examined in normal and HCC tissues. Cell function assays and animal models characterized the effects of GCNT3 on the proliferation, invasion, and migration abilities of HCC cells. Western blot and immunofluorescence analyses were performed to explore further the specific mechanisms whereby GCNT3 affects HCC progression. RESULTS: There is a strong correlation between GCNT3 overexpression and tumor formation and metastasis in vivo and in vitro. GCNT3 acted as a regulator of the synthesis of mucin-type O-glycans by interacting with mucin 13 (MUC13) to regulate its expression levels, activating the GSK3ß/ß-catenin signaling pathway. The activation of GSK3ß/ß-catenin signaling by GCNT3 was mitigated by MUC13 knockdown. In clinical HCC specimens, GCNT3 expression was upregulated in HCC tissues compared to non-tumor tissues. Further, there was a significant correlation between high GCNT3 expression and poor patient survival. CONCLUSIONS: GCNT3 regulated tumor progression in HCC through the MUC13/GSK3-ß/ß-catenin signaling pathway.

FEN1 promotes cancer progression of cholangiocarcinoma by regulating the Wnt/ß-catenin signaling pathway.

PURPOSE: Cholangiocarcinoma (CHOL) comprises a cluster of highly heterogeneous malignant biliary tumors. Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. This study aimed to explore the biological functions and mechanisms of FEN1 in CHOL. METHODS: FEN1 expression was analyzed in tissues of patients with CHOL and FEN1 mutations. We observe the influence of FEN1 on cellular proliferation, migration, and invasion, as well as on DNA damage repair and glycolysis. Western blotting was performed to determine the regulatory mechanism of FEN1 in CHOL progression. RESULTS: FEN1 was highly expressed in the cancer tissues of CHOL patients. The high mutation rate of FEN1 in CHOL tissues was mainly due to the amplified repeats. FEN1 promotes the proliferation, migration, and invasion of HUCCT1 and QBC939 cells. In addition, FEN1 induced DNA damage repair and aerobic glycolysis in CHOL cells. FEN1 also promoted xenograft tumor growth in vivo. Moreover, we showed that FEN1 mediated the epithelial-mesenchymal transition (EMT) of CHOL. FEN1-mediated EMT was found to be transduced by the Wnt/ß-catenin signaling pathway. CONCLUSION: FEN1 was significantly overexpressed in CHOL tissues, and FEN1 regulates the progression of CHOL through the Wnt/ß-catenin signaling pathway.

Emergence and Spread of SARS-CoV-2 Variants of Concern in Canada: a Retrospective Analysis from Clinical and Wastewater Data

The spread of SARS-CoV-2 has been studied at unprecedented levels worldwide. In jurisdictions where molecular analysis was performed on large scales, the emergence and competition of numerous SARS-CoV-2 lineages has been observed in near real-time. Lineage identification, traditionally performed from clinical samples, can also be determined by sampling wastewater from sewersheds serving populations of interest. Of particular interest are variants of concern (VOCs), SARS-CoV-2 lineages that are associated with increased transmissibility and/or severity. Here, we consider clinical and wastewater data sources to retrospectively assess the emergence and spread of different VOCs in Canada. We show that, overall, wastewater-based VOC identification provides similar in-sights to the surveillance based on clinical samples. Based on clinical data, we observed a synchrony in VOC introduction as well as similar emergence speeds across most Canadian provinces despite the large geographical size of the country and differences in provincial public health measures. In particular, it took approximately four months for VOC Alpha and Delta to contribute to half of the incidence, whereas VOC Omicron achieved the same contribution in less than one month. By quantifying the timing and rapidity of SARS-CoV-2 VOCs invasion in Canada, this study provides important benchmarks to support preparedness for future VOCs, and to some extent, for future pandemics caused by other pathogens.

The screening of patients with hepatocellular carcinoma suitable for TACE after radical resection based on microvascular invasion and Ki-67 expression / 中华肝胆外科杂志

Objective:To investigate the patients with hepatocellular carcinoma suitable for transcatheter arterial chemoembolization (TACE) after radical resection who were screened based on microvascular invasion (MVI) and Ki-67 expression.Methods:Of 400 patients with hepatocellular carcinoma who underwent radical resection in the Affiliated Hospital of Qingdao University from January 2013 to December 2019 were included and analyzed retrospectively, including 324 males and 76 females, aged (59.7±9.8) years, ranging from 32 to 87 years. According to whether they received adjuvant TACE treatment after operation, they were divided into simple operation group ( n=210) and TACE + operation group ( n=190). The recurrence in the first year after operation was followed up by outpatient reexamination. Univariate and multivariate Cox regression analysis were used to analyze the influencing factors of recurrence free survival after surgical resection. Subgroup analysis was performed according to Ki-67 and MVI to compare the recurrence free survival. Results:Multivariate Cox regression analysis showed that patients with proportion of Ki-67 positive cells ≥27.5% ( HR=2.073, 95% CI: 1.433-3.000, P<0.001) and MVI positive ( HR=2.339, 95% CI: 1.584-3.456, P<0.001) had increased risk of recurrence after radical resection. The 1-year cumulative recurrence free survival rate in the simple operation group was 70.0%, and there was no significant difference compared with 67.9% in the operation + TACE group( χ 2=0.08, P=0.774). Subgroup analysis: in the low expression of Ki-67 combined with negative MVI group ( n=128), the cumulative recurrence free survival rate of one year after operation in the simple operation group ( n=84) was 91.7%, which was significantly higher than 72.7% in the operation + TACE group ( n=44)( χ 2=8.22, P=0.004). There was no significant difference in the 1-year cumulative recurrence free survival rate between the simple operation group and the operation + TACE group (both P>0.05) in patients of Ki-67 high expression combined with MVI negative or Ki-67 low expression combined with MVI positive. In the Ki-67 high expression combined with MVI positive group ( n=107), the cumulative one-year recurrence free survival rate in the simple operation group ( n=62) was 40.3%, which was significantly lower than 60.0% in the operation + TACE group ( n=45)(χ 2=4.22, P=0.040). Conclusion:High expression of Ki-67 (≥27.5%) combined with positive MVI are the prediction factors for postoperative TACE treatment. Low expression Ki-67 (<27.5%) combined with negative MVI was contraindicated for postoperative TACE treatment.

Impact of adjuvant transcatheter arterial chemoembolization with anti-tumor drug for prevention early recurrence of hepatocellular carcinoma patients with microvascular invasion after radical hepatectomy / 中华肝胆外科杂志

Objective:To study combined adjuvant transcatheter arterial chemoembolization (TACE) with anti-tumor drug treatment on early hepatocellular carcinoma (HCC) recurrence in patients with microvascular invasion (MVI) after partial hepatectomy with curative intent.Methods:The clinical and pathological data of 169 patients with HCC who underwent partial hepatectomy with curative intent from January 2015 to December 2018 at the Affiliated Hospital of Qingdao University were retrospectively analyzed. MVI was diagnosed by postoperative histopathology. There were 147 males and 22 females, with the median age 56 years(ranged 32-79 years). The patients were divided into surgery group ( n=62, patients who did not receive adjuvant therapy), TACE group ( n=42, patients who only received TACE) and combined group ( n=65, patients who received TACE with anti-tumor drug) according to the therapies after resection. Patients in each group were further divided into grade M1 (mild) and grade M2 (severe) subgroups according to the severity of MVI. All patients were followed-up for observing tumor recurrence. The relapse-free survival in the three groups were compared using the Kaplan-Meier method and the log-rank test was used to compare the tumor-free survival rates. Results:The tumor-free survival rates of 169 patients at 1 and 2 years after operation were 59.2% and 40.8%. The tumor-free survival rates at 1 and 2 years after operation were 45.2% and 25.8% in surgery group, 61.9% and 40.5% in TACE group, 70.8% and 52.3% in combined group respectively. The differences among the three groups were significant: TACE group was better than surgery group, and combined group was better than TACE group, combined group was better than surgery group (all P<0.05). In TACE group and combined group, tumor-free survival rates of M1patients better than M2 patients, and the difference was significant ( P<0.05). Among M1 patients and M2 patients, tumor-free survival rates of combined group patients were better than surgery group and TACE group, the difference was significant (all P<0.05). The cumulative tumor-free survival rate was not significantly affected by different antineoplastic agents. Conclusion:Adjuvant TACE reduced the early recurrence rate of HCC patients with MVI. Adjuvant TACE combined with anti-tumor drug further reduced early tumor recurrence.

A dosimetric analysis of combined intracavitary/interstitial brachytherapy for locally advanced cervical cancer / 中华放射医学与防护杂志

Objective To compare the dosimetric differences between intracavitary brachytherapy in combination with interstitial brachytherapy or not for locally advanced cervical cancer.Methods From May 2016 to March 2017,35 patients with locally advanced cervical cancer treated with combined external beams and intracavitary/interstitial brachytherapy were selected in this study.The prescription of intensity-modulated radiation therapy was:46.8-50.4 Gy/26-28 fractions,1.8 Gy/fraction.The prescription for combined intracavitary/interstitial brachytherapy was 7 Gy/fraction × 4,once per week.Each patient was first implanted with a three tube applicator for brachytherapy,and the CT images were acquired for treatment planning.The three tube applicator was removed before a uterine tube and needles were implanted,thereafter planning images were acquired again.Dose to the targets and organs at risk were evaluated respectively for the two groups.Results A total of 212 brachytherapy plans were developed,including 106 intracavitary and 106 endoluminal combined interstitial plans.The target dose in endoluminal combined interstitial brachytherapy was significantly higher than that of intracavitary treatment alone,where D90 of the high-risk clinical target volume (CTV) and moderate CTV were both significantly increased (t =-6.01,-2.73,P ＜ 0.05).The D2 cm3 of the bladder,rectum and sigmoid colon were significantly reduced (t=3.07,4.52,2.91,P＜0.05).Conclusions The application of the endoluminal combined interstitial brachytherapy for locally advanced cervical cancer can significantly increase the target dose,and reduce the dose to organs at risk such as the bladder,rectum and sigmoid colon.

An atomic force microscopy study on the images of para influenza virus under different treatment conditions / 生物医学工程学杂志

Using atomic force microscope (AFM), we investigated the images of Pars influenza virus (PIV) under different treatment conditions and observed the different appearances of the virus and its ultra-microstructure from the exterior to the interior. From the 2D images under transmission electron microscope (TEM), we could see that the surfaces of PIV particles exhibited spherical and band-shaped 'tufts'; from the 3D images under AFM, we could further observe the whole spherical virus particles and their detailed surfaces, which exhibited round and band-shaped 'tufts'. Comparing the images under TEM with those under AFM, we found that the latter could reveal the surface topograph and ultramicrostructure of viruses more truly than did the former. The samples of viruses were treated by Tritonx-100, the lipid envelopes of virions were partly or completely resolved, and then most of their capsids were exposed. We could observe the different appearances of the virions under AFM, the lipid envelopes of which were gradually removed. The samples of viruses were also treated by SDS, and the RNA was released from the virions. From the AFM images, we could see the structure of the RNA. It was thus clear that AFM could be used to investigate the different appearances and ultramicrostructure of viruses rapidly and efficiently.