[HVPG minimally invasive era: exploration based on forearm venous approach].

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score (r = 0.47, P = 0.002), albumin-bilirubin score (r = 0.37, P = 0.001), Lok index (r = 0.36, P = 0.02), liver stiffness (r = 0.58, P = 0.01), and spleen stiffness (r = 0.77, P = 0.01), while negatively correlated with albumin (r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer].

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.

[Construction of prediction model combined dual-energy CT quantitative parameters and conventional CT features for assessing the Ki-67 expression levels in invasive breast cancer].

Objective: To develop a model combined with dual-energy CT quantitative parameters and conventional CT features for evaluating the expression level of Ki-67 in invasive breast cancer. Methods: A total of 191 patients with histologically confirmed invasive breast cancer in Lishui Central Hospital from March 2019 to December 2020, were retrospectively enrolled, all of them were females, aged from 25 to 77 (53.2±11.3) years. All patients underwent preoperative non-contrast chest and contrast-enhanced Dual energy CT scans, and the normalized iodine concentration (NIC) of lesions on arterial and venous phase, spectral curve slope (λHU), and normalized effective atomic number (nZeff) were measured and calculated, and their conventional CT characteristics were assessed. According to the results of immunohistochemistry (IHC), the patients were divided into Ki-67 high expression group (n=129 patients) and low expression group (n=62 patients) level. The differences in clinical data, conventional CT characteristics and dual-energy CT quantitative parameters between the two groups were analyzed. The receiver operating characteristic curve (ROC) curve was conducted to assess the efficacy of each individual model and joint model in evaluating Ki-67 expression levels, and the area under the curve (AUC), sensitivity, specificity, and accuracy were calculated, respectively. Results: In the analysis of CT features, the longest diameter, shape and enhancement pattern of the tumor were significantly difference between the two groups (all P<0.05). The NIC, nZeff on the arterial phase and NIC, nZeff and λHU [M(Q1,Q3)] on the venous phase were higher in the high Ki-67 expression group compared to the low expression group [0.13 (0.12, 0.16) vs 0.11 (0.08, 0.14), 0.71 (0.70, 0.75) vs 0.70 (0.67, 0.72), 0.40 (0.32, 0.48) vs 0.23 (0.17, 0.32), 3.10 (2.58, 3.63) vs 2.86 (2.19, 3.48), 0.88 (0.85, 0.92) vs 0.85 (0.84, 0.86), all P<0.05]. The logistic regression model, which integrated significant conventional CT features and dual-energy CT quantitative parameters, demonstrated the highest diagnostic performance for assessing Ki-67 expression levels, with an AUC of 0.924, sensitivity of 88.37%, specificity of 83.87%, and accuracy of 86.91%; the AUC of the dual-energy CT parameter model was 0.908, sensitivity of 82.17%, specificity of 88.71%, and accuracy of 84.29%. Though the diagnostic efficacy was no significant difference (P=0.238), both models showed superior to the conventional CT feature model (all P<0.001). Conclusion: A dual-energy CT quantitative parameter combined with a conventional CT feature model was successfully constructed, which has a good evaluation performance on the expression level of Ki-67 in invasive breast cancer.

[Analysis of the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 for intrahepatic parenchymal substantial lesions ≤3.0 cm].

Objective: To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm. Methods: A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results: The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively. Conclusions: LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

[Differential population screening and efficacy analysis of (125)I implantation after radiofrequency ablation of primary liver cancer].

Objective: To investigate the clinical efficacy radiofrequency ablation (RFA) combined with (125)I radioactive seed implantation in treatment of hepatocellular carcinoma HCC with the tumor diameter 3-5 cm. Methods: One hundred patients with HCC diagnosed clinically or pathologically with Barcelona staging of B or C in Lishui Central Hospital from February 2012 to September 2017 were retrospectively analyzed. Of the included 100 cases, 89 were males and 11 were females with the mean age of 18-80 (57±11) years old.According to the treatment modality, the subjects were divided into control group (RFA, n=67) and combined group (RFA+(125)I, n=33). Patients in control group were only received RFA and cases in combined group received RFA plus sequenced with (125)I implantation therapy. The prognosis of progression free survival (PFS) and overall survival (OS) between the two groups were compared through the Kaplan-Meier curve and Log-rank test. Results: The median follow-up time period was 6-55 months in the last follow-up time point of Dec 30, 2017. The median PFS were 4-55 (23.0±4.7) and 1-53 (12.0±1.6) months for combined and control groups respectively with significant statistical difference (P=0.015). The median OS were 6-55 (42.0±7.9) and 2-55 (38.0±2.8) months for combined and control groups with the trend of improvement in combined group, but without statistical difference (P=0.444). Subgroup analysis further indicated that the PFS was significant improved in patients with residual tumor lesions who received the combined treatment (PFS: 18 vs 9 months, P=0.025). However, there was no statistical difference for PFS between the control and combined treatment groups for cases without residual tumor lesions after RAF treatment(P=0.685). Conclusions: PFS was obviously increased in HCC patients(tumor diameter 3-5 cm) who received(125)I implantation after radiofrequency ablation, especially for cases with residual tumor lesions.

[Prediction of short-term prognosis of hepatocellular carcinoma after TACE surgery based on MRI texture analysis technology].

Objective: To explore the feasibility of short-term efficacy prognosis prediction model for HCC patients undergoing transcatheter arterial chemoembolization (TACE) based on MRI-based radiomics technique. Methods: A total of 123 patients with liver cancer who received TACE treatment in Lishui Central Hospital from June 2016 to July 2018 were retrospectively collected, including 90 males and 33 females, with an average age of 24-83 (58±10) years. All the patients were pathologically confirmed as hepatocellular carcinoma and underwent MRI scan before surgery.All patients were followed up 3-4 months after TACE, and further divided into training group (n=85, 42 of which were effective and 43 cases were ineffective) and the validation group (n=38, 19 of which were effective and 19 were ineffective) according to the modified response evaluation criteria in solid tumors (mRECIST). There was no statistical difference in the general information between the two groups of patients, which was comparable. Then, preoperative T(2)WI images were used for radiomics analysis, texture parameters were screened based on R language, and short-term efficacy prediction model of TACE for training group and verification group was constructed. Results: T(2)WI image analysis of each patient received 396 different texture parameters, and further used Lasso dimensionality reduction and 10 times cross-validation screening to obtain 5 characteristic texture parameters, specifically stdDeviation, ClusterProminence_angle135_offset4, Correlation_angle135_offset4, Inertia_angle135_offset4, InverseDifferenceMoment_angle45_offset4. According to the above five texture parameters and their corresponding coefficient values, the corresponding radiomics scores (Radscore) were calculated, and the prediction models of the training group and the verification group were further constructed.It was found that the area under the ROC curve of the training group was 0.812 (95%CI: 0.722-0.901), the sensitivity and specificity were 83.7% and 69.0%, respectively. The area under the ROC curve of the validation group was 0.801 (95%CI:0.654-0.947), and the sensitivity and specificity were 89.5% and 63.2%, respectively. Conclusion: The constructed TACE prediction model in the present study has high prediction accuracy, sensitivity and specificity.The short-term efficacy prognosis prediction model for HCC based on MRI is constructed, stable and reliable.

[The correlation between functional magnetic resonance imaging features and expression of Her-2 in breast cancer].

Objective: To explore the correlation between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance diffusion-weighted imaging (DWI) images of breast cancer and human epidermal growth factor receptor-2 (Her-2) expression. Methods: A retrospective analysis of 84 patients with breast cancer confirmed by biopsy from January 2012 to December 2016 in Zhejiang University Lishui Hospital was conducted. The data of DCE-MRI, DWI scanning were collected before surgery and Her-2 was detected by immunohistochemistry (IHC). Then, all the patients were divided into Her-2 positive group and Her-2 negative group according to Her-2 expression. There were 44 cases in the Her-2 positive group and 40 cases in the Her-2 negative group. The differences in the characteristics of the lesion morphology, time-signal intensity curve (TIC), early enhancement rate and apparent diffusion coefficient (ADC) were compared, and their correlation with Her-2 expression was analyzed. Results: Of the 84 lesions, 12 were orthotopic ductal carcinoma, 6 were lobular carcinoma, and 66 were invasive ductal carcinoma. There were significant differences in lesion morphology (P=0.012) and TIC curve morphology (P=0.038) between Her-2 positive group and negative group. At the same time, the early enhancement rate (P=0.012) and ADC value (P=0.038) of Her-2 positive group were significantly higher than those of negative group. Except morphology of segmental lesions and TIC curve morphology, other characteristic parameters were correlated to Her-2 (all P<0.05). The correlation coefficients between early enhancement rate, ADC value and Her-2 expression were as high as 0.758 and 0.809 (all P<0.05). Conclusions: The morphology of breast cancer lesions, time-signal intensity curve, early enhancement rate and ADC value are all correlated with Her-2 expression.The early enhancement rate and ADC value are significantly positively correlated with Her-2 expression.

[Clinical value of (125)I radioactive seed implantation plus transcatheter arterial chemoembolization combined with radiofrequency ablation in treating patient with sub-capsular hepatocellular carcinoma].

Objective: To analyze the clinical efficacy and safety of (125)I radioactive seed implantation in the treatment of sub-capsular hepatocellular carcinoma (sub-HCC) with sequential radiofrequency ablation and transcatheter arterial chemoembolization (TACE). Methods: The clinical data of 76 cases with advanced HCC with sub-capsular nodules including 68 males and 8 females, with an average age of (58±9) years, ranging from 33 to 78 years, enrolled in Lishui Central Hospital from January 2010 to December 2016 were collected.The average maximum diameter of tumor is (5.7±2.3) cm, ranging from 3.1 cm to 12.0 cm.The patients were divided into TACE+ RFA group and (125)I + TACE+ RFA group with 38 cases in each group.The overall survival (OS) and progression free survival(PFS) were calculated.The clinical efficiency and adverse events were evaluated. Results: The disease control rate were 84.2%(32/38) in (125)I + TACE+ RFA group and 63.2% (24/38) in TACE+ RFA group, χ(2)=4.34, P= 0.04.The median PFS were 18 months in (125)I + TACE+ RFA group and 11 months in TACE+ RFA group, χ(2)=4.84, P=0.03.The FPS cumulative rate in (125)I + TACE+ RFA group were higher than that in TACE+ RFA group at 6 months (94.7%±3.6% vs 81.3%±6.4%, Z=24.1>2.58, P=0.00), 1 year (89.2%±5.1% vs 40.7%±8.3%, Z=13.3>2.58, P=0.00) and 2 year (55.9%±8.6% vs 29.6%±8.2%, Z=7.2>2.58, P=0.00). The median OS were 42 months in (125)I + TACE+ RFA group and 30 months in TACE+ RFA group, χ(2)=4.76, P=0.029.The survival cumulative rate in (125)I+ TACE+ RFA group were higher than that in TACE+ RFA group at 1 year (92.1%±4.4% vs 83.8%±6.1%, Z=23.5>2.58, P=0.00), 2 year (75.8%±7.0% vs 59.8%±8.4%, Z=12.43>2.58, P=0.00), 3 year (59.0%±8.2% vs 41.7%±8.9%, Z=8.3>2.58, P=0.00), 5 year (34.2%±8.2% vs 18.2%±8.1%, Z=5.5>2.58, P=0.00). In addition, there was no statistical difference in liver function and complications between TACE+ RFA group and (125)I+ TACE+ RFA group. Conclusion: (125)I radioactive seed implantation plus TACE combined with RFA treatment is an effective and safe treatment for sub-capsular hepatocellular carcinoma.

[Effect of transcatheter arterial chemoembolization combined with thymosin alpha 1 on the autophagy of immune cells from advanced hepatocellular carcinoma].

Objective: To investigate the effect of transcatheter arterial chemoembolization(TACE)combined with thymosin alpha1(Tα1)on the autophagy of immune cells from advanced hepatocellular carcinoma. Methods: A total of 30 patients with advanced liver cancer enrolled in Lishui Central Hospital from September 2015 to June 2016 were collected in this study. The average age of patients was 16-75(56±12) years. All patients were treated with TACE after enrolled in hospital in a week. Patients were divided into TACE group and TACE+ Tα1 treatment group(15 cases in each group). Patients in TACE group received a conventional treatment, without any immunotherapy, while the TACE+ Tα1 treatment group accepted TACE following a subcutaneously injection of 1.6 mg Tα1 twice a week for 4 weeks. Flow cytometry was used to detect the T cell subsets in two groups both before and after TACE treatment for 1, 4 weeks and at 3 months follow-up. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The expression of Beclin-1, LC3 protein and mRNA were detected by Western blot (WB) and PCR respectively. Results: There was no statistical difference of the percentage of CD3(+) , CD4(+) , CD8(+) T cell subsets and Beclin-1, LC3 protein and mRNA expression between the two groups before TACE treatment (P>0.05). The percentage of CD3(+) , CD4(+) , CD8(+) T cell subsets in TACE+ Tα1 group at 1 week post-TACE treatment (58.45%±16.34%, 38.33%±15.16%, 27.31%±12.54%), at 4 weeks post-TACE treatment (62.38%±18.62%, 43.19%±13.86%, 29.54%±10.33%) and 3 months follow-up (64.15%±13.76%, 41.28%±14.65%, 29.38%±15.65%) were statistically higher than those in TACE group at 1 week post-TACE treatment (53.71%±11.17%, 32.12%±10.53%, 24.45%±13.72%) at 4 weeks post-TACE treatment (52.12%±14.26%, 31.16%±15.43%, 23.39%±15.33%) and 3 months follow-up (54.28%±13.15%, 32.17%±14.98%, 24.34%±14.12%) (P<0.05). The Beclin-1, LC3 protein and mRNA expression in TACE+ Tα1 group at 1 week post-TACE treatment (protein: 0.57±0.08, 2.26±0.36, mRNA: 0.62±0.11, 2.69±0.27), at 4 weeks post-TACE treatment (protein: 0.66±0.09, 3.11±0.45, mRNA: 0.78±0.13, 3.43±0.61) were higher than those in TACE group at 1 week post-TACE treatment (protein: 0.45±0.16, 1.43±0.30, mRNA: 0.52±0.15, 1.15±0.37), at 4 weeks post-TACE treatment (protein: 0.51±0.13, 1.81±0.35, mRNA: 0.56±0.10, 1.98±0.41) ( P<0.05). But there was no statistically significant difference in the expression of Beclin-1 and LC3 in two groups at 3 months follow-up (P>0.05). Conclusions: TACE combined with Tα1 significantly increase the level of autophagy in the immune cells of patients with advanced primary hepatocellular carcinoma.

[Correlation between TNM staging of primary cholangiocarcinoma and the maximum standard uptake value of (18)F-2-deoxy-D-glucose positron emission tomography with computerized tomography].

Objective: To investigate the correlation between TNM staging of primary cholangiocarcinoma and the maximum standard uptake value (SUVmax) of (18)F-2-deoxy-D-glucose positron emission tomography with computerized tomography ((18)F-FDG PET/CT). Methods: A retrospective analysis of 36 patients with confirmed primary cholangiocarcinoma from October 2014 to July 2016 was carried out. All the patients underwent preoperative PET/CT in the Fifth Affiliated Hospital of Wenzhou Medical University from November 2014 to July 2016, the SUVmax was calculated by drawing region of interest around the primitive tumor area.According to the American Cancer Joint Committee (AJCC) guidelines for the clinical staging of intrahepatic and extrahepatic cholangiocarcinoma, the differences of SUVmax were compared in the patients with different age, gender and staging, and the correlation between TNM staging and SUVmax was determined.Data were compared with independent sample t test between groups. Results: The mean SUVmax of 36 patients with primary cholangiocarcinoma was 7.87±3.17 (2.1-14.6). The SUVmax values of patients with lymph node metastasis or distant metastasis were significantly higher than those without lymph node metastasis or distant metastasis (t=0.364, 0.343, both P<0.05), respectively. There was significant difference in SUVmax between patients with different TNM staging (F=1.352, P=0.021). There was no significant differences in SUVmax between patient with different gender, age (>70 years or<70 years) and T staging (t=1.058, 1.980, F=1.252, all P>0.05). Spearman correlation analyses showed that the TNB stage of primary cholangiocarcinoma was positively correlated with its SUVmax (r=0.658, P=0.007). Conclusion: The SUVmax is positively correlated with the TNM staging of primary cholangiocarcinoma, which is helpful for the clinical staging and prognosis of the patients.

[The role of FOXO3a-Bim signaling in triptolide induced bladder cancer T24 cells apoptosis].

Objective: To investigate the role of FOXO3a-Bim signaling in triptolide induced bladder cancer T24 cells apoptosis. Methods: T24 cells were used and divided into control group, triptolide group(50 nmol/L), MK2206 group(50 nmol/L triptolide+ 5 µmol/L MK2206), FOXO3a-siRNA group(50 nmol/L triptolide+ 100 nmol/L FOXO3a-siRNA), Bim-siRNA group (50 nmol/L triptolide+ 100 nmol/L Bim-siRNA). MTT assay was used to analyze the cells growth inhibition.Annexin V/PI staining was implemented to detect cell apoptosis rate, the expression of p-Akt, Akt, p-FOXO3a, FOXO3a, Bim, Bax.Cleaved-caspase 3 was analyzed by Western blot. Results: After treatment with triptolide 25, 50, 100, 250 nmol/L, the cell growth inhibition rates at 24 hours(17%±9%, 24%±5%, 43%±8%, 61%±8%), 48 hours (20%±7%, 34%±6%, 56%±7%, 74%±5%) and 72 hours(32%±8%, 41%±7%, 69%±7%, 84%±3%) were significantly higher than control group respectively.The IC(50) at 24, 48, 72 hours were (113±10), (91±8), (68±5) nmol/L; the cell apoptosis rates at 24 hours (10%±4%, 15%±5%, 29%±8%, 46%±8%), 48 hours (16%±5%, 24%±6%, 40%±7%, 55%±9%) and 72 hours (27%±4%, 38%±5%, 50%±9%, 65%±8%) were significantly increased (P<0.05). Western blot showed that triptolide reduced the expression of p-Akt, p-FOXO3a and increased the expression of Bim, Bax, cleaved-caspase 3.The cell inhibition rate in Triptolide group (30%±8%) was significantly higher than that in the control group (P<0.05) and the rates in MK2206 group (54% ±6%), FOXO3a-siRNA group (18%±7%) and Bim-siRNA group (11%±6%) were also higher than the control group.Compared with the triptolide group, the inhibition rate in MK2206 group was significantly increased, but decreased in FOXO3a-siRNA group and Bim-siRNA group(P<0.05). Conclusion: Triptolide induces T24 cells apoptosis through FOXO3a-Bim signaling pathway.

[Effects and mechanism ofitraconazole on prostate cancer PC-3 cell apoptosis].

Objective: To investigate the effects and mechanisms of itraconazole on prostate cancer PC-3 cells proliferation. Methods: The PC-3 cells were divided into four group: control group, itraconazole group, itraconazole+ CerS-1-shRNA group and itraconazole+ PDMP group.3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide(MTT)assay was used to detect the growth of PC-3 cells.Apoptosis was detected by Annexin V-FITC /PI.The intracellular ceramide production was assayed by high performance liquid chromatography(HPLC). The expression of Bax, Bcl-2, cleaved-caspase3 and the expression and phosphorylation of Akt, mTORC1 were detected by Western blot. Results: After treatment with 0, 5, 10, 20 µmol/L itraconazole, apoptosis rate was 3.23%±1.32%, 5.87%±2.45%, 23.22%±5.29%, 48.57%±8.37%.The percentage content of ceramide was 100%, 109%±18%, 156%±12%, 197%±22%.Compared with the control group, there were statistically differences when the concentration of itraconazole were 10 and 20 µmol/L(all P<0.05). Western blot analysis showed that the Bax, cleaved-caspase 3 expression of itraconazole group and itraconazole+ PDMP group was significantly higher than control group, while Bcl-2 expression was significantly lower than the control; the Bax, cleaved-caspase 3 expression ofitraconazole+ CerS1-shRNA group was significantly lower than itraconazole group, while Bcl-2 expression was significantly higher than the itraconazole group.After 5, 10, 20 µmol/L itraconazole treatment, the expression of p-Akt and p-mTORC1 were significantly lower than the control group; the expression of p-Akt and p-mTORC1 in itraconazole+ CerS-1-shRNA group were significantly higher than itraconazole group. Conclusion: Itraconazole induces apoptosis of PC-3 cell through increasing the intracellular ceramide content, which might relate to upregulation of cleavage-caspase 3 and Bax, downregulation of Bcl-2 and inactivation of Akt-mTORC signal pathway.

[Association between ultrasound screening frequency and mortality in patients with hepatocellular carcinoma].

Objective: To discuss the association between ultrasound screening frequency and total mortality in patients with HCC before diagnosing HCC, and explore the optimal ultrasound screening frequency for HCC high-risk groups. Methods: Retrospectively collected clinical data of 615 cases of liver cirrhosis who developed to HCC from January 1, 2010 to December 31, 2015. Before diagnosing HCC, all patients were divided into five groups according to ultrasound screening frequency: 0-6, 7-12, 13-24, 25-36 months and not screened within 3 years (never screened). The chance to receive curative therapy, 5-year cumulative mortalities and independent factors of mortality in patients with HCC were analyzed. Results: Chances to receive curative therapy among the 0-6, 7-12, 13-24, 25-36 months and never screened groups were 38.2%, 27.2%, 25.4%, 23.8% and 19.7%, respectively (P<0.05). The 5-year overall mortality rates were 76.4%, 77.7%, 79.3%, 82.5% and 84.6%, respectively. Compared with 0-6 months, the adjusted OR of mortality for the other groups were 1.112, 1.235, 1.305 and 1.451, respectively (all P<0.05). Multivariate analysis showed that ultrasound screening frequency, curative treatment and Child-Pugh (class A/B) were the factors to affect long-term survival in patients with HCC (all P<0.05). Conclusion: For HCC high-risk groups, optimal ultrasound screening frequency is within 6 months, and high-frequency ultrasound screening can increase the chance of receiving curative treatment, reduce total mortality, and improve overall survival.

[Effect comparison of ultrasound-guided lower extremity nerve block and spinal anesthesia in ankle surgery].

Objective: To compare the anesthesia effect between ultrasound-guided lower extremity nerve block and spinal anesthesia in ankle surgery. Methods: Upon the approval of institutional Ethics Committee and informed consent, 80 patients American Society of Anesthesiology (ASA)Ⅰ-Ⅱaged 18-70 yr, undergoing ankle surgery from December 2014 to May 2015 in the Fifth Affiliated Hospital of Wen Zhou Medical College, were randomly divided by random numbers into two groups (n=40): nerve block group (group N) and spinal anesthesia (group S). The group N was combined with ultrasound-guided femoral nerve, obturator nerve, lateral femoral cutaneous nerve and sacral plexus block; group S was selected spinal anesthesia in the gap of L3-L4. Times of anesthesia procedure (Tr), sensory block (Tfb), motor block (Tmb), duration of sensory block (Tfr) and duration of motor block (Tmr) were recorded. The incidence of hypotension within 30 min after anesthesia and 24 hours postoperatively analgesic were also recorded. The effect of anesthesia was evaluated. Results: The Tr, Tfb, Tmb, Tfr and Tmr in group N and group S were (15.0±1.5), (11.2±1.2), (13.4±1.4), (816.0±112.9), (432.0±138.9)min and (8.7±1.2), (2.3±0.6), (3.8±1.1), (436.7±130.5), (320.0±34.6)min, respectively. Tr, Tfb, Tmb, Tfr and Tmr in group N were significantly longer than that in group S (t=20.742, 41.945, 34.101, 13.901, 4.948, all P<0.05). There was no significant difference in the incidences of hypotension within 30 min after anesthesia (0 vs 7.5%, P>0.05). The incidence of 24 hours postoperatively analgesic in group N were significantly lower than that in group S (45.0% vs 77.5%, P<0.05). Compared with group S, there was no significant difference in the percentage of anesthetic effect reached gradeⅠ(95% vs 100%, P>0.05) in group N. Conclusion: Ultrasound-guided nerve block could be safe and effective in patients undergoing ankle surgery, and postoperative analgesia time of nerve block is longer than that of spinal anesthesia.

[The activity of moxalactam against Enterobacteriaceae and anaerobia in vitro].

OBJECTIVE: To observe the antibacterial activity of moxalactam against Enterobacteriaceae bacteria and anaerobic bacteria in vitro, and to compare with other antibacterial drugs, for providing experimental basis for the clinical application of moxalactam. METHODS: Minimum inhibitory concentrations (MICs) of moxalactam and other antibacterial agents against 491 Enterobacteriaceae spp. and anaerobic spp.collecting from clinical settings were determined by agar dilution methods and E-test strips according to the Clinical and Laboratory Standards Institute (CLSI)(2014). RESULTS: Moxalactam showed great antibacterial activity to Enterobacteriaceae spp., including ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp., with the MIC(50), MIC(90), and susceptibility rates of 0.25-4 mg/L, 0.5-8 mg/L, and >90%, respectively. The susceptibility rates of Enterobacteriaceae with ESBLs-producing or non-ESBLs-producing to imipenem and meropenem were both higher than 90%. The susceptibility rates of ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.to piperacillin/tazobactam and cefoperazone/sulbactam were 90%, 68%, 53% and 76%, 66%, 76.6%, respectively, while the susceptibility rates of non-ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.were all more than 95%. The susceptibility rates of Enterobacter spp. and other Enterobacter to piperacillin/tazobactam were 80%, 80%and that to cefoperazone/sulbactam were 80%, 76.7%, respectively.The MICs range of moxalactam on anaerobic spp.was from ≤0.064 to >256 mg/L, while MIC(50) was 2 mg/L and MIC(90) was 64 mg/L. CONCLUSIONS: Moxalactam showed well activity against ESBLs-producing and non-ESBLs-producing Enterobacteriaceae and anaerobia.

[Efficacy analysis of radiofrequency ablation combined with 125I seed for multiple nodular hepatocellular carcinoma].

OBJECTIVE: To investigate the clinical efficacy of radiofrequency ablation(RFA)combined with (125)I seed in patients with multiple nodular hepatocellular carcinoma(HCC). METHODS: The clinical data of 47 patients with multiple nodular HCC confirmed clinically or pathologically in the Fifth Affiliated Hospital of Wenzhou Medical University between January 2009 and September 2014 were retrospectively analyzed. All patients were divided into two groups depending on treatment: RFA group(n=29); RFA combined with (125)I seed group(n=18). Survival time was estimated with the Kaplan-Meier analysis. The survival curve was compared by Log-rank test. RESULTS: The clinical data and tumor situation of patients between two groups did not show significant differences. The follow-up time ranged from 2 to 55 months. At the end of the study, the median progression-free survival of two groups were 18 months and 11 months, and the differences were statistically significant(P=0.036). The overall survival rates in RFA combined with (125)I seed group at 1, 2, and 3 years (94.4%, 78.0%, 66.8%, respectively) were higher than those in RFA group (88.5%, 68.6%, 57.1%, respectively). However, the differences between the two groups were not statistically significant(P=0.554). CONCLUSIONS: For multiple nodular HCC, RFA combined with (125)I seed can prolong progression-free survival, have an advantage in local control rate, and is better than single RFA at short-term curative effect.However, its long-term outcomes should be further explored by a large-sample, multi-center and randomized trial.

Criteria for decision making after endoscopic resection of well-differentiated rectal carcinoids with regard to potential lymphatic spread.

BACKGROUND AND STUDY AIM: Rectal carcinoids are low-grade malignancies that are usually treated by endoscopic resection. However, on pathologic examination, resection margins that are positive for carcinoid cells are frequently found. Patient outcomes were reviewed after endoscopic resection of rectal carcinoids and the clinical significance of possible residual disease, as defined by pathologic and endoscopic examination, was evaluated. PATIENTS AND METHODS: The medical records and endoscopic findings of 347 patients presenting with rectal carcinoids to 14 university hospitals in Korea between January 1999 and June 2007 were retrospectively analyzed. RESULTS: A total of 304 patients were treated with endoscopic resection, and 43 patents were treated with surgery. In the endoscopic resection group, the complete resection rate was 88.2% based on endoscopic appearance (CR-E) and 60.2% based on pathologic evaluation (CR-P). The agreement between CR-E and CR-P was low (κ=0.192). No residual tumors were found in 77 of 85 patients (90.6%) who were CR-E but not CR-P and who had endoscopic biopsy taken at 24-month follow-up. The receiver-operating characteristic curve identified an optimal cut-off value of 10.5 mm, at which the sensitivity and the specificity for metastasis were 100% and 89%, respectively. The risk factors for metastasis by multivariate analysis were tumor size, increased mitotic rate, and lymphovascular invasion. CONCLUSIONS: Endoscopic resection is a safe and effective modality for treating well-differentiated rectal carcinoids smaller than 10 mm in diameter. Discrepancies were observed between CR-E and CR-P. The risk factors for metastasis were tumor size, increased mitotic rate, and lymphovascular invasion.

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study.

PURPOSE: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. METHODS: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. RESULTS: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. CONCLUSION: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

Comparative study of several microinvasive treatments for large hepatocellular carcinoma.

OBJECTIVE: To study the prognosis of large hepatocellular carcinoma after interventional radiology and to compare the efficacy of different microinvasive treatments. PATIENTS AND METHODS: The clinical data of 46 large hepatocellular carcinoma patients confirmed by clinical treatment or pathological examination were retrospectively analyzed. Patients were divided into two groups (TACE+RFA n=23 cases, and Combination group n=23 cases), according to the treatments method. two groups were followed up for 5-48 months. Survival was estimated using the Kaplan-Meier method and the survival curve was compared by log-rank test. RESULTS: Median follow-up time was 33 months in both groups. The median survival time in Combination group (n=41 months) was significantly longer than TACE+RFA group (n=33 months) (p = 0.052). Median progress-free survival (PFS) is 10 months in Combination group and 8 months in TACE+RFA group. The difference was statistically significant (p = 0.023). The tumor inhibition rate was 82.6% and 52.2%, respectively and the difference was statistically significant (p = 0.028). The overall survival rate at l, 2 and 3 years was 100%, 95.7% and 55.8% respectively in Combination group was higher than TACE+RFA group at 91.3%, 55.8% and 38.3% respectively. The difference was not statistically significant. CONCLUSIONS: For large hepatocellular carcinoma, combined method was superior to TACE+RFA and comprehensive treatment can improve the local-control rate.