Study on the time conversion method of early warning indicators of flash flood disaster: A case of Qufu City, Shandong Province.

To solve the problem of imperfect flash flood warning indicators in mountainous watersheds, this study proposes a conversion method of critical rainfall for different warning periods on the basis of the existing stormwater calculation formulae and applies it to typical mountainous watersheds. The specific method is to use the multiplicative power function method to interpolate and extend the early warning indicators of other time periods through the known early warning indicators of some time periods, apply them to Hengmiao Village and Gaolou Village, typical disaster prevention objects in Qufu City, Shandong Province, China, and verify the rationality of the results. The results show that the multiplicative power function method interpolates and extends the early warning indexes of 0.5, 1, 3, 6, 12, and 24 h under the same soil moisture condition. Based on the historical actual mountain flood disaster rainfall, the correlation coefficient R2 and Nash coefficient Ens are calculated to be 0.85 and 0.86, respectively, which verifies the applicability of this method. This study provides a convenient and quick way to unify the time series of regional early warning indicators and a feasible way for other regions to study regional overall early warning.

Modified quantitative and volumetric response evaluation criteria for patients with hepatocellular carcinoma after transarterial chemoembolization.

Objective: This study aimed to investigate the cutoff value of quantitative and volumetric response evaluation criteria for patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) and compare the performance of the modified criteria to one-dimensional criteria in survival prediction. Methods: A retrospective single-center study was performed for treatment-naive patients with HCC who underwent initial TACE between June 2015 and June 2019. Treatment response assessment was performed after the first observation by contrast CT or MRI, with the measurement of diameters by modified Response Evaluation Criteria in Solid Tumors (mRECIST) and volumes by quantitative European Association for Study of the Liver (qEASL). Overall survival (OS) was the primary endpoint of this study. The new cutoff value for volumetric response evaluation criteria was created using restricted cubic splines. The performance of modified qEASL (mqEASL, with the new cutoff value) and mRECIST on survival prediction was compared by Cox regression models in internal and external validation. Results: A total of 129 patients (mean age, 60 years ± 11 [standard deviation]; 111 men) were included and divided into training (n=90) and validation (n=39) cohorts. The cutoff value for the viable volume reduction was set at 57.0%. The mqEASL enabled separation of non-responders and responders in terms of median OS (p<0.001), 11.2 months (95% CI, 8.5-17.2 months) vs. 31.5 months (95% CI, 25.5-44.0 months). Two multivariate models were developed with independent prognostic factors (tumor response, metastasis, portal vein tumor thrombus, and subsequent treatment) to predict OS. Model 2 (for mqEASL) had a greater Harrel's C index, higher time-dependent area under the receiving operator characteristic curve (AUROC), and more precise calibration on 6-month survival rates than Model 1 (for mRECIST). Conclusions: With the modified cutoff value, the quantitative and volumetric response of HCC patients to TACE becomes a precise predictor of overall survival. Further studies are needed to verify this modification before application in clinical practice.

Emergent Transjugular Intrahepatic Portosystemic Shunt as a First-Line Therapy in Patients with Cirrhosis with Acute Gastroesophageal Variceal Hemorrhage.

PURPOSE: To investigate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) as first-line therapy in patients with advanced cirrhosis with acute variceal hemorrhage. MATERIALS AND METHODS: From July 2016 to June 2019, 76 patients with advanced cirrhosis and acute variceal hemorrhage were included in this retrospective study. All patients underwent emergent TIPS as first-line therapy within 24 hours. Gastroesophageal varices in patients with cirrhosis were diagnosed with contrast-enhanced computed tomography because emergent endoscopy has not been routinely performed in this center. The primary outcomes were the control rate of bleeding and the rate of rebleeding. Secondary outcomes were the technical success rate of procedure, transplantation-free survival, the mean hospitalization time, the time of stay in the intensive care unit, and adverse events. RESULTS: All patients underwent TIPS creation successfully and were transferred to general wards. The median follow-up time was 21.7 months (interquartile range, 12.6-28.1 months). The control rate of bleeding (≤5 days) was 100%. The rates of early (>5 days to 6 weeks) and late (>6 weeks to 2 years) rebleeding were 6.6% and 1.3%, respectively. The 6-week, 1-year, and 2-year transplantation-free survival rates were 94.7%, 93.4%, and 84.6%, respectively. The incidences of acute liver failure, hepatic encephalopathy, and shunt dysfunction were 5.3%, 25%, and 5.3%, respectively. CONCLUSIONS: Emergent TIPS as a first-line therapy in patients with advanced cirrhosis with acute variceal hemorrhage is safe and effective. This study provides an alternative approach for medical centers without emergent endoscopy facility to manage the condition.

Transarterial Chemoembolization Combined with Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors versus Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Advanced Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (TACE+IT) versus ICIs plus TKIs (IT) for advanced hepatocellular carcinoma (HCC). Materials and Methods: Data of consecutive advanced HCC patients receiving TACE+IT or IT between January 2019 and December 2021 were included and were retrospectively analyzed. Propensity score matching (PSM) was performed to reduce bias due to confounding variables. The primary outcome of the study was overall survival (OS). The secondary outcomes were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs), respectively. Results: Sixty-four patients were enrolled in the study, among which 24 and 40 received TACE+IT and IT, respectively. The PSM cohort included 24 patients receiving TACE+IT (TACE+IT group) and 24 patients receiving IT (IT group) alone. During a median follow-up of 23 months, patients in TACE+IT group had significantly longer OS (median, 17.3 vs 11.8 months, P = 0.023), better ORR (41.7% vs 12.5%, P = 0.023) and DCR (79.2% vs 50.0%, P = 0.035) than those in the IT group, whereas a non-significant trend in PFS (median, 7.4 vs 6.7 months, P = 0.23) was observed. According to multivariable cox regression analysis, it was found that treatment modality was the only independent risk factor for OS (HR = 0.404, 95% CI = 0.179-0.911, P < 0.05). There were no remarkable differences in AEs associated with ICIs and TKIs between the two groups, with the exception of gastrointestinal reaction. Conclusion: TACE combined with ICIs plus TKIs significantly improved OS, ORR, and DCR and showed a relatively longer PFS trend over ICIs combined with TKIs for advanced HCC.

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence.

Transarterial chemoembolization (TACE) is widely applied for the treatment of hepatocellular carcinoma. Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session. However, repeated TACE procedures can impair liver function and increase treatment-related adverse events, all of which prompted the introduction of the concept of "TACE failure/refractoriness". Mainly based on evidence from two retrospective studies conducted in Japan, sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness. Several studies have investigated the outcomes of other subsequent treatments, including locoregional, other molecular targeted, anti-programmed death-1/anti-programed death ligand-1 therapies, and combination therapies after TACE failure/refractoriness. In this review, we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

Efficacy comparison of acupuncture and balanced acupuncture combined with TongduZhengji manipulation in the treatment of acute lumbar sprain.

OBJECTIVE: To compare the curative effect of balanced acupuncture combined with TongduZhengji manipulation vs acupuncture in the treatment of acute lumbar sprain. METHODS: Clinical data of 71 patients with acute lumbar sprains in our hospital from January 2020 to December 2020 were retrospectively analyzed. Patients were divided into single group (n=35) and combined group (n=36) based on treatment methods. The single group received only acupuncture treatment, while the combined group received balanced acupuncture combined with TongduZhengji manipulation. The treatment efficacy, pain level, lumbar function and motion of the lumbar spine were compared between the two groups. RESULTS: The Visual Analogue Scale (VAS) scores of the combined group were lower than those of the single group after 3, 4, and 5 days of treatment (P<0.05). There was no significant difference in VAS scores between the two groups after 1 and 2 days of treatment (P>0.05). The Roland-Morris Disability Questionnaire (RMDQ) score of the combined group showed no significant difference compared with that of the single group after 1 and 2 days of treatment (P>0.05), and were lower than those of the single group after 3, 4, and 5 days of treatment (P<0.05). The Japanese Orthopedic Association (JOA) score of the combined group after 1, 2, and 3 days of treatment showed no significant difference compared with the single group (P>0.05), and was higher than that of the single group after 4 and 5 days of treatment (P<0.05). The Range of Motion (ROM) score of the combined group showed no significant difference compared with the single group after 1 and 2 days of treatment (P>0.05), and was lower than that of the single group after 3, 4, and 5 days of treatment (P<0.05). The total effective rate of treatment in the combined group was significantly higher than that in the single group (91.67% vs. 71.43%) (P<0.05). CONCLUSION: Compared with acupuncture alone, balanced acupuncture combined with TongduZhengji manipulation can significantly reduce the pain level and improve lumbar spine mobility as well as lumbar spine function, exhibiting better curative effect than acupuncture only.

Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition.

Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response.

Background: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. Materials and Methods: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. Results: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5-10.5) and PFS was 8.5 months (95% CI, 5.4-11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. Conclusion: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

Percutaneous transhepatic intrahepatic portosystemic shunt for variceal bleeding: A series of six cases and literature review.

OBJECTIVES: To present a case series of modified transjugular intrahepatic portosystemic shunts (TIPS) and percutaneous transhepatic intrahepatic portosystemic shunts (PTIPS) in cirrhotic patients with variceal bleeding (VB). In addition, the scientific literature pertaining to PTIPS was reviewed. METHODS: This retrospective clinical case series included six cirrhotic patients with VB who were treated with PTIPS after the failure of endoscopic band ligation or endoscopic injection sclerotherapy combined with vasoactive drugs. The treatment was conducted between January 2017 and June 2019 at a single institution. Three patients suffered from severe atrophy of the right or left lobar of the liver as well as the main right or left branch of the portal vein. The remaining three patients showed severe atrophy of the whole liver and portal vein, resulting in widening of the liver fissure. A paired t-test was used to compare the changes in portal pressure gradient between before and after the PTIPS operation. The rebleeding rate, treatment efficacy, complications, and technical success rate were all assessed during follow-up. RESULTS: All six PTIPS procedures were performed successfully, with no severe procedural-related complications observed. None of the patients experienced VB during a mean follow-up of 22.8 (range, 18.0-28.0) months. The mean portosystemic pressure gradient decreased from 28.3 â€‹± â€‹4.3 â€‹mmHg pre-procedure to 12.3 â€‹± â€‹2.6 â€‹mmHg immediately post-procedure (P â€‹< â€‹0.001). At follow-up, one patient was found to have developed grade 2 hepatic encephalopathy thrice during the first year, according to the West Haven criteria. However, this was resolved following medical treatment. CONCLUSIONS: When the patient's portal venous anatomy is unconducive to the performance of TIPS using the transjugular approach, PTIPS can be considered as a safe, effective complementary surgical approach for patients with VB.

Re-evaluating Transarterial Chemoembolization Failure/Refractoriness: A Survey by Chinese College of Interventionalists.

BACKGROUND AND AIMS: The recognition of transarterial chemoembolization (TACE) failure/refractoriness among Chinese clinicians remains unclear. Using an online survey conducted by the Chinese College of Interventionalists (CCI), the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma (HCC) treatment in clinical practice. METHODS: From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting, a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment. RESULTS: A total of 257 clinicians participated and responded to the survey. Most participants agreed that the concept of "TACE failure/refractoriness" has scientific and clinical significance (n=191, 74.3%). Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness (n=88, 46.1%). None of the existing TACE failure/refractoriness definitions were widely accepted by the participants; thus, it is necessary to re-define this concept for the treatment of HCC in China (n=235, 91.4%). Most participants agreed that continuing TACE should be performed for patients with preserved liver function, presenting portal vein tumor thrombosis (n=242, 94.2%) or extrahepatic spread (n=253, 98.4%), after the previous TACE treatment to control intrahepatic lesion(s). CONCLUSIONS: There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions. Further work should be carried out to re-define TACE failure/refractoriness.

Single-Centre Retrospective Training Cohort Using Artificial Intelligence for Prognostic Prediction of Encephalopathy, Mortality, and Liver Dysfunction after Early TIPS Creation.

OBJECTIVES: Based on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3 months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally. RESULTS: A total of 207 patients were included, with 33 (15.9%) experienced OHE within 3 months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65 years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy. CONCLUSIONS: The ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

Integrated I-125 Seed Implantation Combined with Transarterial Chemoembolization for Treatment of Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombus.

PURPOSE: To compare the safety and efficacy of integrated iodine-125 (I-125) seed implantation (sequential implantation of helical I-125 seed implant into the main portal vein and of I-125 seeds into the branch tumor thrombus directly forming main portal vein tumor thrombus (MPVTT)) combined with transarterial chemoembolization (TACE) versus TACE alone for hepatocellular carcinoma (HCC) with MPVTT. MATERIALS AND METHODS: From December 2016 to January 2020, 46 HCC patients with MPVTT were analyzed. In the combination group, 21 patients received helical I-125 seed implantation in the main portal vein through a patent small portal vein branch and TACE in a single session. After 7-10 days, I-125 seeds were implanted percutaneously into the branch tumor thrombus directly forming MPVTT. In the TACE group, 25 patients received TACE alone. Thereafter, TACE was repeated as needed in both groups. Adverse events, tumor response, and overall survival (OS) of the two groups were compared. RESULTS: No adverse events grade ≥ 3 were observed in either group. The optimal objective response rate and disease control rate for MPVTT in the combination group and TACE group were 52.4% versus 4.0% (P < 0.001) and 85.7% versus 32.0% (P < 0.001), respectively. Median OS in the combination group (9.8 months) was longer than in the TACE group (5.2 months) (P = 0.024). Multivariate analysis revealed that, compared with the TACE group, the mortality risk in the combination group significantly decreased (hazard ratio: 0.444; P = 0.020). CONCLUSION: Integrated I-125 seed implantation combined with TACE is a safe and effective treatment for HCC with MPVTT. LEVEL OF EVIDENCE: Level 3, Non-randomized controlled cohort/follow-up study.

Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma.

BACKGROUND: Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness. METHODS: Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells. RESULTS: miR-145 directly targeted the PD-L1 3'-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues. CONCLUSION: Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.

Prognosis Nomogram for Hepatocellular Carcinoma Patients with Portal Vein Invasion Undergoing Transarterial Chemoembolization Plus Sorafenib Treatment: A Retrospective Multicentre Study.

OBJECTIVES: To explore the outcomes of combined transarterial chemoembolization (TACE) with sorafenib in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) and to establish a prognostic prediction nomogram to differentiate target patients and stratify risk. MATERIALS AND METHODS: This multicentre, retrospective study consisted of 185 consecutive treatment-naïve patients with HCC and PVTT treated with TACE plus sorafenib from three institutions between January 1st, 2012 and December 31st, 2017. The primary outcome measurement of the study was overall survival (OS). The type of PVTT was classified by the Liver Cancer Study Group of Japan. The prognostic nomogram was established based on the predictors and was performed with interval validation. RESULTS: The median OS of the Vp1-3 and Vp4 groups was 12.4 months (11.7-18.9) and 8.5 months (7.6-11.2) (P = 0.00098), respectively, and there was a significant difference in the median OS between the Vp1-2 and Vp3 subgroups (16.4 months (12.2-27.9) vs. 10.9 months (8.4-18.1), P = 0.041). The multivariate Cox regression analysis suggested that tumour size, albumin-bilirubin grade, and PVTT type were independent prognostic factors. The C-index value of the nomogram based on these predictors in the entire cohort was 0.731 (0.628-0.833). CONCLUSIONS: After the combined therapy of TACE and sorafenib, advanced HCC patients with segmental or subsegmental PVTT showed better survival than those with main PVTT. The nomogram can be applied to identify advanced HCC patients with PVTT who may benefit most from the combination treatment and be helpful for making decision in clinical practice.

Performance of artificial intelligence for prognostic prediction with the albumin-bilirubin and platelet-albumin-bilirubin for cirrhotic patients with acute variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt.

PURPOSE: The aim of this study was to validate and compare the prognostic performance of the albumin-bilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, Child-Pugh (CP) grade, and Model for End-Stage Liver Disease (MELD) score in predicting the 1-year variceal rebleeding probability using artificial intelligence for patients with cirrhosis and variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt (TIPS) procedures. MATERIALS AND METHODS: This dual-center retrospective study included two cohorts, with patients enrolled between January 2016 and September 2018 in the training cohort and January 2017 and September 2018 in the validation cohort. In the training cohort, independent risk factors associated with the 1-year variceal rebleeding probability were identified using univariate and multivariate logistic analyses. ALBI-, PALBI-, Child-Pugh-, and MELD-based nomograms and an artificial neural network (ANN) model were established and validated internally in the training cohort and externally in the validation cohort, which included patients with variceal bleeding who were treated with preventive TIPS. RESULTS: A total of 259 patients were included. The median follow-up periods were 24.1 and 18.9 months, and the 1-year variceal rebleeding rates were 12.3% (14/114) and 10.3% (15/145) in the training and validation cohorts, respectively. In the training cohort, all four variables were identified as independent risk factors. Four nomograms were then established and showed comparable prognostic performances after internal (C-index: 0.879, 0.829, 0.874, and 0.798) and external (C-index: 0.720, 0.719, 0.718, and 0.703) validation. The ANN demonstrated that these four variables had comparable importance in predicting the 1-year variceal rebleeding probability. CONCLUSION: None of the four variables are optimal in predicting the 1-year variceal rebleeding probability for patients with cirrhosis and variceal bleeding undergoing early TIPS.

Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma.

PURPOSE: To explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: From August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan-Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS). RESULTS: In total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively. CONCLUSIONS: TACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.

Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells.

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this study, we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells. METHODS: Initially, the sorafenib-resistant HCC cell lines HepG2 SR and Huh7 SR were established. Western-blot assays were used to detect the expression of PD-L1, E-cadherin, and N-cadherin. The intervention and overexpression of PD-L1 were used to explore the role of PD-L1 in the regulation of EMT in HepG2 SR and Huh7 SR cells. Cell migration and invasion were assessed by transwell assays. PD-L1 or Sterol regulatory element-binding protein 1 (SREBP-1) overexpression and knock-down were performed in order to study the mechanism of PD-L1 in sorafenib-resistant HCC cells. RESULTS: PD-L1 expression was upregulated, whereas E-cadherin levels were downregulated and N-cadherin expression was increased in HepG2 SR and Huh7 SR cells. The cell viabilities of HepG2 and Huh7 cells were lower than those of HepG2 SR and Huh7 SR cells. PD-L1 overexpression reduced E-cadherin expression and increased N-cadherin levels, whereas PD-L1 knock-down increased E-cadherin expression and decreased N-cadherin expression. PD-L1 expression promoted EMT and the migratory and invasive abilities of HepG2 SR and Huh7 SR cells. PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells. CONCLUSIONS: The findings reveal that PD-L1 expression promotes EMT of sorafenib-resistant HCC cells.

Deep Learning Predicts Overall Survival of Patients With Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization Plus Sorafenib.

OBJECTIVES: To develop and validate a deep learning-based overall survival (OS) prediction model in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus sorafenib. METHODS: This retrospective multicenter study consisted of 201 patients with treatment-naïve, unresectable HCC who were treated with TACE plus sorafenib. Data from 120 patients were used as the training set for model development. A deep learning signature was constructed using the deep image features from preoperative contrast-enhanced computed tomography images. An integrated nomogram was built using Cox regression by combining the deep learning signature and clinical features. The deep learning signature and nomograms were also externally validated in an independent validation set of 81 patients. C-index was used to evaluate the performance of OS prediction. RESULTS: The median OS of the entire set was 19.2 months and no significant difference was found between the training and validation cohort (18.6 months vs. 19.5 months, P = 0.45). The deep learning signature achieved good prediction performance with a C-index of 0.717 in the training set and 0.714 in the validation set. The integrated nomogram showed significantly better prediction performance than the clinical nomogram in the training set (0.739 vs. 0.664, P = 0.002) and validation set (0.730 vs. 0.679, P = 0.023). CONCLUSION: The deep learning signature provided significant added value to clinical features in the development of an integrated nomogram which may act as a potential tool for individual prognosis prediction and identifying HCC patients who may benefit from the combination therapy of TACE plus sorafenib.

Retraction of "UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC".

[This retracts the article DOI: 10.7150/thno.32738.].