Objective To evaluate the therapeutic value of alpha-fetoprotein (AFP) and cholinesterase (ChE) in patients with hepatitis B virus related acute onset chronic liver failure (HBV-ACLF). Methods A case-control observation was conducted. Sixty-seven patients with HBV-ACLF admitted to Tianjin Second People's Hospital from January 2009 to October 2015 were enrolled. According to the diagnostic criteria of ACLF, the patients were divided into early, middle, and late groups, and alternatively, according to the outcome, they were divided into survival group and death group. Serum samples were collected after 0, 2, 4, 8 weeks to determine the value of AFP and ChE and analyze the value of AFP and ChE in reflecting the changes during HBV-ACLF progression. The differences in AFP and ChE between the survival group and the death group were compared. The prognostic values of AFP and ChE for HBV-ACLF patients were evaluated. Results Among 67 patients, there were 24, 24, and 19 patients in the early, middle and late stage, respectively, and there were 0, 9, 18 deaths at 8 week. With the advance of HBV-ACLF, the levels of both AFP and ChE were decreased in the early, middle, and late stage, with the AFP value of 40.205 (14.663, 90.550), 23.445 (8.233, 64.213), 8.990 (6.120, 14.340) μg/L (F = 36.149, P = 0.000) and the ChE value of (4.217±1.408), (3.619±1.200), (2.503±1.248) kU/L, respectively (F = 19.575, P = 0.000). In the death group, the levels of serum AFP at 0, 2, 4, 8 weeks were significantly lower than those in survival group [μg/L: 21.540 (7.670, 50.470) vs. 60.680 (16.383, 146.100), 10.560 (6.170, 20.100) vs. 60.090 (27.662, 100.700), 8.750 (3.045, 10.105) vs. 51.875 (16.778, 88.833), 3.900 (2.120, 7.660) vs. 20.400 (12.950, 50.430), P < 0.05 or P < 0.01]. The levels of serum ChE at 2, 4, 8 weeks in the death group were significantly lower than those in the survival group (kU/L: 3.206±1.480 vs. 4.008±1.227, 2.893±1.478 vs. 4.140±1.236, 2.948±1.355 vs. 4.329±1.390, P < 0.05 or P < 0.01). The levels of AFP in 67 patients were 30.100 (10.100, 90.100) μg/L, and ChE was (3.685±1.382) kU/L at 2 weeks, and they showed no correlation between AFP and ChE according to the linear correlation analysis (r = 0.082, P = 0.508), suggesting that AFP and ChE could be used as two independent prognostic factors for HBV-ACLF patients. It was showed by receiver operating characteristic curve (ROC) analysis that the area under the curve of AFP (AUC) was 0.847 (P = 0.000), while the AUC of ChE was 0.681 (P = 0.012). The highest values of Youden index and the maximum effectiveness of testing were obtained when AFP and ChE reached 20.520 μg/L and 2.924 kU/L, respectively, with the sensitivity and the specificity of AFP being 85.0% and 77.8%, respectively, and of ChE being 77.5% and 59.3%, respectively. When using the value of AFP ≥ 20.520 μg/L combined with the value of ChE ≥ 2.924 kU/L, the sensitivity for predicting HBV-ACLF outcome was 65.9%, and its specificity was 91.0%. Conclusion Both AFP and ChE were helpful in providing accurate information for the progression and prognosis of HBV-ACLF patients due to the facts that their values were less interfered by the clinical treatment and that they have higher specificity.

Objective To evaluate the clinical effect and influential factors of intrauterine device (IUD) after insertion under B-type ultrasound guidance. Methods A total of 434 healthy women of childbearing potential, aged for 18 to 40 years were enrolled. After IUD insertion under ultrasound guidance, the uterine profile was observed during the procedure and the patients’ biological characteristic was recorded and gynecologic examiation was performed at month 1, 3, 6, 12, 18 during following up. All data were analyzed with SPSS software. Results There was no accident in operation.In 18 months after IUD insertion, the pregnancy rate with IUD was 1.94%,the expulsion rate was 4.59% and the removal rate was 5.54%. The risk factors of expulsion were the history with cesarean delivery and artificial abortion plus IUD insertion (P

Objective To investigate whether SIS3, a specific inhibitor of Smad3 phosphorylation, can reverse the stemness of multidrug?resistant ( MDR ) hepatocellular carcinoma cells. Methods MDR HCC Huh7. 5. 1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK?8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry ( FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting ( WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl?2, Bax and p?Smad3 in different conditions. Results ADM treatment of HCC cells in vitro resulted in a development of subline, Huh7. 5. 1/ADM cells, with CSC phenotypes: stable MDR phenotype ( besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50:0.215±0.018 vs. 0.123± 0.004, 0.145±0.009 vs. 0.014±0.002, 1.021± 0.119 vs. 0.071± 0.006, 27.007±1.606 vs. 1.919±0.032)(unit: μg/ml)(P<0.05). Huh7.5.1/ADM cells enriched the cancer stem?like cell fraction (CD133?positive subpopulation) (76.06±2.948% vs. 25.38±4.349%)(P<0.05) , had stronger tumorigenicity in vivo and colony formation ability, and activated the Smad3 activity. Inhibition of Smad3 activity by SIS3 decreased stemness of the Huh7. 5. 1/ADM cells: CD133?positive subpopulation (48.49±2.304% vs. 76.06±2.948%)(P<0.05); ADM IC50: (0.112±0.019 vs. 0.215± 0.018), VCR IC50(0.065±0.013 vs. 0.145±0.009), MMC IC50(0.749±0.121 vs. 1.021±0.119), CTX IC50 (10.576±1.248 vs. 27.007±1.606)(unit:μg/ml)(P<0.05), and decreased tumorigenicity and colony formation ability. Conclusion SIS3 as a specific inhibitor of Smad3 signal is involved in the stemness of
multidrug resistant hepatocellular carcinoma cells.

Objective To investigate whether SIS3, a specific inhibitor of Smad3 phosphorylation, can reverse the stemness of multidrug?resistant ( MDR ) hepatocellular carcinoma cells. Methods MDR HCC Huh7. 5. 1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK?8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry ( FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting ( WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl?2, Bax and p?Smad3 in different conditions. Results ADM treatment of HCC cells in vitro resulted in a development of subline, Huh7. 5. 1/ADM cells, with CSC phenotypes: stable MDR phenotype ( besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50:0.215±0.018 vs. 0.123± 0.004, 0.145±0.009 vs. 0.014±0.002, 1.021± 0.119 vs. 0.071± 0.006, 27.007±1.606 vs. 1.919±0.032)(unit: μg/ml)(P<0.05). Huh7.5.1/ADM cells enriched the cancer stem?like cell fraction (CD133?positive subpopulation) (76.06±2.948% vs. 25.38±4.349%)(P<0.05) , had stronger tumorigenicity in vivo and colony formation ability, and activated the Smad3 activity. Inhibition of Smad3 activity by SIS3 decreased stemness of the Huh7. 5. 1/ADM cells: CD133?positive subpopulation (48.49±2.304% vs. 76.06±2.948%)(P<0.05); ADM IC50: (0.112±0.019 vs. 0.215± 0.018), VCR IC50(0.065±0.013 vs. 0.145±0.009), MMC IC50(0.749±0.121 vs. 1.021±0.119), CTX IC50 (10.576±1.248 vs. 27.007±1.606)(unit:μg/ml)(P<0.05), and decreased tumorigenicity and colony formation ability. Conclusion SIS3 as a specific inhibitor of Smad3 signal is involved in the stemness of
multidrug resistant hepatocellular carcinoma cells.

Objective:To summarize the clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach (TOETSLVA).Methods:We retrospectively reviewed the medical record of patients who underwent TOETSLVA in our department from November 2011 to May 2020, including 3 males and 95 females, aged from 18 to 57 years old. Initial 81 cases were categorized in "Period A (November 2011-November 2015)" and subsequent 17 cases in "Period B (August 2019-May 2020)" . Data about demographics, operation time and complications were collected. SPSS 22.0 software was used for statistical analysis.Results:In Period A, the average age of patients was (34.2±9.4) years old; the mean tumor diameter was (2.33±0.80) cm; postoperative pathology showed benign nodules in 76 cases and malignant carcinoma in 5 cases; there were 65 cases of unilateral subtotal thyroid lobectomy, 6 cases of isthmus lobectomy, and 5 cases of bilateral subtotal thyroid lobectomy, with the mean operation time of (132.70±47.22) min; in 5 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (185.4±31.40) min; postoperative neck infections occurred in 6 cases; temporary vocal cord paralysis occurred in 1 case, which it recovered within two months; and CO 2 gas embolism occurred in 2 cases. In Period B, the average age of patients was (35.1±8.5) years old; mean tumor diameter was (1.32±0.67) cm; postoperative pathology indicated malignant nodules in 15 cases and benign nodules in 2 cases; in 2 cases of unilateral thyroid lobectomy, the mean operation time was (153.5±34.64) min; in 15 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (123.73±14.26) min; and none of patients developed postoperative neck infections or CO 2 gas embolism. All patients had different degree of cutaneous numbness in the submandibular region after surgery, which recovered within 1-2 weeks. There were no complications such as postoperative secondary hemorrhage, permanent vocal cord paralysis, hypoparathyroidism in both the periods. The median follow-up time was 86 months (57-105 months) in Peroid A and 5 months (3-12 months) in Peroid B. During the follow-up periods, there were no obvious abnormalities in swallowing, chewing, oral sensory function and neck activity, and also no tumor recurrence or metastasis. Conclusions:TOETSLVA is a safe and feasible surgery method, with a good cosmetic result. This approach will not lead to a postoperative cutaneous numbness of the submandibular region for a long time.

OBJECTIVETo investigate whether SIS3, a specific inhibitor of Smad3 phosphorylation, can reverse the stemness of multidrug-resistant(MDR) hepatocellular carcinoma cells.

METHODSMDR HCC Huh7.5.1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK-8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry (FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting (WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl-2, Bax and p-Smad3 in different conditions.

RESULTSADM treatment of HCC cells in vitro resulted in a development of subline, Huh7.5.1/ADM cells, with CSC phenotypes: stable MDR phenotype (besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50: 0.215 ± 0.018 vs. 0.123 ± 0.004, 0.145 ± 0.009 vs. 0.014 ± 0.002, 1.021 ± 0.119 vs. 0.071 ± 0.006, 27.007 ± 1.606 vs. 1.919 ± 0.032) (unit: µg/ml) (P<0.05). Huh7.5.1/ADM cells enriched the cancer stem-like cell fraction (CD133-positive subpopulation) (76.06 ± 2.948% vs. 25.38 ± 4.349%) (P<0.05), had stronger tumorigenicity in vivo and colony formation ability, and activated the Smad3 activity. Inhibition of Smad3 activity by SIS3 decreased stemness of the Huh7.5.1/ADM cells: CD133-positive subpopulation (48.49 ± 2.304% vs. 76.06 ± 2.948%) (P<0.05); ADM IC50: (0.112 ± 0.019 vs. 0.215 ± 0.018), VCR IC50 (0.065 ± 0.013 vs. 0.145±0.009), MMC IC₅₀ (0.749 ± 0.121 vs. 1.021 ± 0.119), CTX IC50 (10.576 ± 1.248 vs. 27.007 ± 1.606) (unit: µg/ml) (P<0.05), and decreased tumorigenicity and colony formation ability.

CONCLUSIONSIS3 as a specific inhibitor of Smad3 signal is involved in the stemness of multidrug resistant hepatocellular carcinoma cells.

AC133 Antigen ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antigens, CD ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; pathology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Glycoproteins ; metabolism ; Heterografts ; Humans ; Isoquinolines ; pharmacology ; Liver Neoplasms ; drug therapy ; metabolism ; pathology ; Mice ; Neoplasm Proteins ; metabolism ; Neoplastic Stem Cells ; drug effects ; Peptides ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pyridines ; pharmacology ; Pyrroles ; pharmacology ; Smad3 Protein ; antagonists & inhibitors ; metabolism ; Tumor Stem Cell Assay ; bcl-2-Associated X Protein ; metabolism