Objective:To explore the clinical pathological characteristics and initial 131I curative responses of familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC). Methods:A total of 66 FDTC patients (19 males, 47 females, age (39.8±11.7) years) and 1 701 SDTC patients (442 males, 1 259 females, age (40.9±11.3) years) who underwent 131I therapy in Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2010 and August 2018 were retrospectively enrolled. The clinical pathological characteristics, preablative stimulated thyroglobulin (ps-Tg), preablative stimulated thyroglobulin antibody (ps-TgAb) and response to initial therapy (excellent response, indeterminate response, biochemical incomplete response, structural incomplete response) of two groups were analyzed and compared. The clinical pathological parameters included age, gender, pathological type, tumour maximum diameter, bilateral, multifoci, nodules goiter, thyroiditis, thyroid membrane invasion, lymph node metastasis (LNM), invasion of the surrounding soft tissues, distant metastasis, TNM staging and American Thyroid Association (ATA) risk stratification (low-risk, intermediate-risk, high-risk). χ2 test or Fisher exact test and independent-sample t test were used to compare the data between two groups. Results:Comparing with SDTC group, FDTC group showed higher proportion of bilateral foci (45.5%(30/66) vs 31.2%(530/1 701); χ2=5.999, P=0.010), thyroid membrane invasion (43.9%(29/66) vs 26.6%(452/1 701); χ2=9.672, P=0.002) and distant metastasis (15.2%(10/66) vs 6.2%(105/1 701); χ2=8.418, P=0.004). There was a statistical difference in risk stratification between two groups (high-risk: 18.2%(12/66) vs 9.2%(156/1 701); intermediate-risk: 68.2%(45/66) vs 72.7%(1 237/1 701); low-risk: 13.6%(9/66) vs 18.1%(308/1 701); χ2=6.898, P=0.030). But the tumor maximum diameter of FDTC group was smaller than that of SDTC group ((1.24±0.74) vs (1.50±0.92) cm; t=-2.275, P=0.020). There were no significant differences in other clinical pathological parameters between FDTC group and SDTC group ( t=-0.804, χ2 values: 0.101-5.359, all P>0.05). There were no significant differences between two groups in the postoperation ps-Tg, ps-TgAb levels and the response to initial therapy after 131I treatment ( χ2 values: 0.059-1.915, all P>0.05). Conclusions:The FDTC group displays distinct characteristics as increased aggressiveness at diagnosis. But after accurately treatment, there is no significant difference in the response to therapy between two groups.

Objective To explore the role of miR-137 in the proliferation and migration of hepatocellular carcinoma (HCC) cells by regulating Notch1 and mediating autophagy.Methods The human SMMC7721 hepatoma cell line was transfected with miR-137 mimics,miR-137 inhibitor and Notch1 interfering RNA (siRNA),and divided into normal control group (NC group),miR-137 mimics group,miR-137 inhibitor group,Notch1 siRNA group.The expression levels of miR-137 and Notch1 mRNA after the transfection were detected by RT-PCR in SMMC7721 cells.Transwell experiments were performed to analyze the effect of miR-137 and Notch1 on the migration and invasion of SMMC7721 cells.The expression levels of β-catenin and vimentin in SMMC7721 cells were detected by immunohistochemistry.The number of autophagosomes was detected by double labeled adenovirus.Western blot was utilized to detect the expression of Notch1,E-Cadherin,N-Cadherin,vimentin,P62,and LC3.Results The results of RT-PCR showed that the relative expression level of Notch1 in miR-137 inhibitor group (5.71 ± 0.45) was significantly higher than that in miR-137 mimics group (0.21 ± 0.06) with statistical significance (P ＜ 0.05).The Transwell experiments showed that there were fewer invasive metastatic hepatoma cells in miR-137 mimics group (66.00 ± 4.55) and Notch1 siRNA group (88.00 ± 6.78) than that in the miR-137 inhibitor group (515.00 ±35.12) (P ＜0.05).The expression levels of β-catenin in miR-137 mimics group and Notch1 siRNA group were significantly increased and the expression level of vimentin was decreased (P ＜ 0.05).The results of autophagy double labeled adenovirus test showed that the number of autophagosomes in miR-137 mimics group (5.50 ± 3.70) was significantly fewer than that in miR-137 inhibitor group (32.75 ± 4.11),and the difference was statistically significant (P ＜ 0.05).The expression levels of Notch1,N-cadherin,vimentin,and LC3 protein in miR-137 mimics group were much lower than that in miR-137 inhibitor group and NC group,and the expression levels of E-Cadherin and P62 protein were greatly increased.The expression level of Notch1,N-cadherin,and LC3 protein in Notch1 siRNA group were significantly lower than that in NC group,and the expression levels of E-cadherin and P62 protein were much higher than that in NC group.Conclusion MiR-137 can inhibit the proliferation,migration and invasion of HCC cells by inhibiting the expression of Notch1 and autophagy,which may become a new target for the treatment of HCC.

Objective To investigate the role of miRNA-30a-3p on inhibiting the proliferation,invasion and metastasis of HCC cells by targeting Caspase 1 involved in pyroptosis.Methods The qRT-PCR and immunohistochemical staining were used to detect the expressions of miRNA-30a-3p and Caspase 1 in HCC cells.SMMC-7721 cells were transfected with miR-30a-3p agonists,inhibitors and Caspase 1-specific inhibitors.Western blot was obtained to detect the expression of EMT-related proteins (N-cadherin,vimentin,snail,MMP-2) and Caspase 1,IL-18 and IL-1β.Plate clone assay,CCK-8 kit and Transwell were carried out to detect the proliferation and immigration of HCC cells.Results Caspase 1 was highly expressed (t =17.54,P ＜ 0.05) in HCC tissues.Overexpression of miR-30a-3p inhibited HCC cells proliferation and metastasis,while miR-30a-3p inhibition increased the proliferation and metastasis of HCC cells.Overexpression of miR-30a-3p decreased the expression of Caspase 1 (t =12.73,P ＜ 0.05) and inhibited the induction of pyroptosis,inhibiting the expression of IL-18 (t =7.32,P ＜ 0.05) and IL-1 β (t =7.32,P ＜0.05).When miRNA-30a-3p was inhibited,the cell viability of HCC was increased (F1 =9.57,P ＜0.05).When miRNA-30a-3p and Caspase 1 were inhibited together,the cell viability of HCC decreased (F2 =10.66,P ＜ 0.05).Conclusion MiRNA-30a-3p regulate cell pyroptosis through Caspase 1 pathway,inhibiting the proliferation,invasion and metastasis of HCC cells.

Objective:To explore the effect of miR-223-3p regulating FOXO3a-mediated autophagy in hepatic injury-reperfusion injury (LIRI).Methods:The model of hepatic ischemia-reperfusion injury (IR) was established in C57BL6 mice. According to different reperfusion timepoints, mice were randomly divided into 2 h, 6 h, 12 h and 24 h group. For sham group, there was no intraoperative clamping of hepatic pedicle. Murine hepatic AML12 cells were treated with miR-223-3p mimics, miR-223-3p inhibitor and FOXO3a interfering RNA. A hypoxic 1 h reoxygenation 6 h model was established. And miRNA-NC, miR-223-3p mimics, miR-223-3p inhibitor and siRNA-NC and FOXO3a siRNA groups were assigned. Hepatic injury and apoptosis were detected by hematoxylin eosin or TdT-mediated nick end labeling (HE/TUNEL) at different timepoints. The changes of proliferating cell nuclear antigen (PCNA) and Caspase-3 in hepatocytes were detected by immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed for detecting the expressions of miR-223-3p, FOXO3a, LC3, p62 and Caspase-3 in hepatocytes.Results:The results of HE/TUNEL indicated that reperfusion injury and apoptosis of hepatic tissue were most severe in 12 h group. In hepatic ischemia-reperfusion model, RT-PCR results showed that the expressions of miR-223-3p and FOXO3a were higher in IR group than those in sham group (1.00±0), the expression level of miR-223-3p mRNA peaked at 12 h (9.13±2.12) after reperfusion and FOXO3a was the highest at 6 h (5.23±0.90, P<0.05). Western blot showed that the expression of FOXO3a peaked at 6 h post-reperfusion and the expressions of LC3 and caspase-3 were the highest at 12 h. ( P<0.05). In the model of cell hypoxia and reoxygenation, RT-PCR indicated that the expression of FOXO3a mRNA decreased in miR-223-3p mimics group (0.45±0.21) as compared with miRNA-NC group (1.00±0). In contrast, miR-223-3p inhibitor group increased (2.73±0.53, P<0.05). Western blot indicated that FOXO3a protein expression was highest in miR-223-3p inhibitor and miR-223-3p mimics groups whereas LC3 and Caspase-3 were the highest in miR-223-3p mimics group ( P<0.05). The expression of FOXO3a was higher in siRNA-NC group than that in FOXO3a siRNA group while the expressions of Caspase-3 and LC3 were the higher in FOXO3a siRNA group. Conclusions:FOXO3a has protective effect on hepatic ischemia-reperfusion injury. It may be related to its inhibition of autophagy and apoptosis and miR-223-3p promotes injury through a down-regulation of FOXO3a-mediated autophagy. It suggests that miR-223-3p and FOXO3a are negatively correlated and may be potential gene therapeutic targets for hepatic injury.

Objective:To compare the differences in distribution and prognosis of cervical cancer patients in the 2009 and 2018 editions of International Federation of Gynecology and Obstetrics (FIGO) staging, and to analyze the prognostic factors of cervical cancer patients.Methods:The clinical data of 524 cervical cancer patients admitted to the First Affiliated Hospital of Soochow University from January 2010 to December 2018 were retrospectively analyzed. The cases were staged according to the 2009 and 2018 FIGO staging, and the Kendall τb coefficient was calculated to compare the consistency of the distribution of the two stages. Kaplan-Meier was used for survival analysis, and log-rank test was used to test the difference of prognosis in each stage. Cox-regression was used to analyze the prognostic factors of cervical cancer patients.Results:In the 2009 FIGO edition of staging, 1 case of stage ⅠB1 was reduced to stage ⅠA1 due to the microscopic infiltration depth <5 mm, 51 cases of stage ⅠB1 were raised to stage ⅠB2 due to 2 cm4 cm. A total of 119 cases raised to stage ⅢC1 due to pelvic lymph node metastasis, and 11 cases raised to stage ⅢC2 due to para-aortic lymph node metastasis. The distribution of cases in the two stages was consistent (τb=0.61, P<0.001). There were statistically significant differences in overall survival (OS) ( χ2=107.13, P<0.001; χ2=93.02, P<0.001; χ2=92.74, P<0.001) and progression-free survival (PFS) ( χ2=91.95, P<0.001; χ2=77.69, P<0.001; χ2=73.27, P<0.001) among patients with different stages of FIGO in 2018 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, ⅢC1, ⅢC2, Ⅳ) and 2009 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, Ⅳ) and patients with different T stages (T 1, T 2, T 3, T 4). There were statistically significant differences in OS ( χ2=20.71, P<0.001) and PFS ( χ2=24.25, P<0.001) in 2018 FIGOⅠB and ⅢC stages, and there was a statistically significant difference in OS between stage ⅢC1 and stage ⅠB2 ( χ2=6.18, P=0.013). Multivariate analysis showed that age ( HR=1.88, 95% CI: 1.08-3.28, P=0.026), pathological type ( HR=2.11, 95% CI: 1.04-4.27, P=0.038), lymph node metastasis ( HR=2.18, 95% CI: 1.34-3.56, P=0.002), parametrial spread ( HR=2.56, 95% CI: 1.52-4.29, P<0.001), maximum tumor diameter ( HR=1.98, 95% CI: 1.18-3.30, P=0.009), squamous cell carcinoma antigen (SCCA) positive after treatment ( HR=4.49, 95% CI: 2.09-9.68, P<0.001) and Hemoglobin (HB) level before treatment ( HR=0.58, 95% CI: 0.35-0.96, P=0.035) were independent risk factors for OS in patients with cervical cancer. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅠB1, ⅠB2, ⅠB3 were 100%, 97.1% and 87.9% respectively, with a statistically significant difference ( χ2=7.79, P=0.020), and there was a statistically significant difference between stage ⅠB1 and ⅠB3 ( χ2=5.55, P=0.019). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅠB1 and ⅠB2 were 95.7% and 84.3% respectively, with a statistically significant difference ( χ2=9.08, P=0.003). For patients with 2018 FIGO stage ⅠB, SCCA positive after treatment ( HR=1 172.50, 95% CI: 10.37-132 554.51, P=0.003) was an independent risk factor for OS, and differentiation degree ( HR=0.09, 95% CI: 0.01-0.81, P=0.032), treatment method ( HR=0.17, 95% CI: 0.04-0.71, P=0.015) and SCCA positive after treatment ( HR=190.68, 95% CI: 14.27-2 547.67, P<0.001) were independent risk factors for PFS. For patients with 2018 FIGO stage ⅠB, stage ( HR=9.56, 95% CI: 2.38-38.32, P=0.001), SCCA positive after treatment ( HR=126.32, 95% CI: 12.36-1 290.60, P<0.001) and lymph node metastasis ( HR=20.07, 95% CI: 3.63-111.11, P=0.001) were independent risk factors for OS, and differentiation degree ( HR=0.11, 95% CI: 0.02-0.63, P=0.013), treatment method ( HR=0.22, 95% CI: 0.06-0.75, P=0.015) and SCCA positive after treatment ( HR=43.83, 95% CI: 7.94-241.84, P<0.001) were independent risk factors for PFS. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 95.7% and 75.6% respectively, with a statistically significant difference ( χ2=13.96, P<0.001). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 83.1% and 67.1% respectively, with a statistically significant difference ( χ2=7.61, P=0.006). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 90.9% and 75.0% respectively, with a statistically significant difference ( χ2=8.85, P=0.003). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 75.7% and 66.7% respectively, with a statistically significant difference ( χ2=4.07, P=0.044). For patients with 2018 FIGO stage Ⅱ, pathological type ( HR=20.28, 95% CI: 2.93-140.32, P=0.002) and stage ( HR=4.35, 95% CI: 1.02-18.55, P=0.047) were independent risks factors for OS. For patients with 2009 FIGO stage Ⅱ, pathological type ( HR=5.82, 95% CI: 1.62-20.94, P=0.007) was an independent risk factor for OS, and pathological type ( HR=3.09, 95% CI: 1.22-7.85, P=0.017) and lymph node metastasis ( HR=2.07, 95% CI: 1.22-3.51, P=0.007) were independent risk factors for PFS. For patients with 2018 FIGO stage Ⅲ, maximum tumor diameter ( HR=3.31, 95% CI: 1.45-7.56, P=0.005) and SCCA positive after treatment ( HR=4.67, 95% CI: 1.22-17.86, P=0.024) were independent risk factors for OS, and pathological type ( HR=4.15, 95% CI: 1.47-11.77, P=0.007) and SCCA positive after treatment ( HR=3.96, 95% CI: 1.45-10.86, P=0.007) were independent risk factors for PFS. Conclusion:The 2018 and 2009 FIGO staging have a good distribution consistency in the cervical cancer patients, and the 2018 FIGO stage ⅠB has more advantages in judging the prognosis, but stage ⅢC cannot accurately judge the prognosis. Lymph node metastasis and maximum tumor diameter are more important prognostic factors.

Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.

Objective To investigate the changes and related factors of maternal thyroid autoantibodies during early pregnancy. Methods Urinary iodine concentration( UIC) , serum thyroid stimulating hormone( TSH) , free thyroxine ( FT4 ) , thyroid-peroxidase antibody ( TPOAb ) , thyroglobulin antibody ( TgAb ) concentrations were determined in 7 190 women during early pregnancy in an iodine-sufficient region of China. Results The prevalence of TPOAb positivity and TgAb positivity were 8. 7% and 12. 0% respectively. The prevalence of overt hypothyroidism and subclinical hypothyroidism increased significantly in group of thyroid antibody positivity. The prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess, especially increased significantly in the group with UIC<100 μg/L. Conclusion Prevalence of thyroid antibodies positivity became higher during early pregnancy. The positive thyroid autoantibodies during pregnancy were significantly associated with maternal hypothyroidism. Both iodine excess and iodine deficiency are risk factors of positive thyroid antibodies.

Objective To investigate the effect of miRNA-30a-3p on the proliferation,invasion and metastasis of liver cancer cells by targeting Atg3-mediated autophagy pathway.Methods The immunohistochemical staining was used to detect content of miRNA-30a-3p and Atg3 and their correlation in human hepatocellular carcinoma.Liver cancer cells were cultured in vitro and hunger environment was used to induce autophagy.RFP-GFP-LC3 double-labeled adenovirus infected hepatoma cells were used to detect autophagosomes in hepatoma cells.The expressions of autophagy-related proteins (autophagocytosis associated protein (Atg3),polyubiquitin-binding protein p62,autophagy microtubule-associated protein light chain 3 (LC3)) and EMT-related proteins (N-cadherin,vimentin,snail,ZO-1) were detected by Western blot.Platelet cloning assay and transwell assay were carried out to detect the proliferation,invasion and metastasis of carcinoma cell.CCK-8 kit was used to detect hepatocarcinoma cells' viability.Results The expression of miRNA-30a-3p was down-regulated.The expression of Atg3,E-cadherin and N-cadherin in miRNA-30a-3p high-expressed hepatocellular carcinoma was lower than that in miRNA-30a-3p low-expressed hepatocellular carcinoma.Increasing the expression of miRNA-30a-3p in hepatocellular carcinoma cells can decrease the expression of Atg3 and LC3,increase the expression of p62 and inhibit the formation of autophagosomes;otherwise,Atg3 and LC3 were increased,p62 was decreased and the formation of autophagosomes was promoted.Inhibition of Atg3 expression could decrease the expression of EMT-related proteins.When miRNA-30a-3p was inhibited,the cell viability of HCC was increased at each time point (F1 =10.314,P ＜0.05).When miRNA-30a-3p and Atg3 were inhibitor together,the cell viability of HCC was decreased at each time point(F2 =6.599,P ＜ 0.05).Conclusion miRNA-30a-3p can inhibit Atg3-mediated autophagy pathway and reduce cell autophagy activity,thus inhibiting the proliferation,invasion and metastasis of hepatocarcinoma cells.

Objective:To establish a standard colorectal neoplasm tissue biobank with complete clinical information to provide high quality samples for fundamental and clinical research of colorectal neoplasm.Methods:Based on Affiliated Jinhua Hospital, Zhejiang University School of Medicine, to conduct structural design of colorectal neoplasm tissues, normal tissues and related information. Establish standard operating procedures from the collection and storage of tissue samples, standardize the entry of basic information, medical history, pathology and other relevant clinical information of the patients, and conduct random quality inspections on the pathological morphology and molecular level on a regular basis.Results:A tissue biobank of colorectal neoplasm was successfully constructed. During the establishment and improvement of this tissue biobank, standardized quality control was implemented during the whole-process including sample collection, warehousing, storage and delivery. According to the random sampling quality inspection, the RNA preservation effect was good, the rates of neoplasms in cancer tissue was >80%, and the clinical data of samples were complete.Conclusions:The preliminary construction of colorectal neoplasm tissue biobank not only improves the utilization value of tissue samples, but also provides a guarantee for realizing the bidirectional transformation of fundamental research and clinical application.

Objective To explore the application of MRI in the differential diagnosis of high-and low-risk thymoma.Methods The data of patients with pathologically confirmed thymoma were collected bidirectionally,and the differences in clinical data,MRI image characteristics of lesions,signal characteristics and apparent diffusion coefficient(ADC)values were compared and analyzed between high-and low-risk thymoma according to the pathological subtype.The receiver operating characteristic(ROC)curve analysis was used to screen out meaningful features,then the diagnostic efficacy and combined prediction probability of indicators were evaluated.Results There was no significant difference in clinical data(P＞0.001).The morphology of high-risk lesions was mainly irregular,while that of low-risk lesions was mainly regular.The edges of high-risk lesions were mostly not smooth,and the edges of low-risk lesions were mostly smooth.The enhancement degree of high-risk lesions was higher than that of low-risk lesions,and the ADC value was lower than that of low-risk lesions,with statistical significance(P＜0.001),in which the ADC value area under the curve(AUC)was higher than other indicators(AUC=0.968),and the combined prediction probability of indicators was the highest(AUC=0.981).Conclusion MRI shows great potential application value in preoperative differential diagnosis of high-and low-risk thymoma.