Evaluation of China's live streaming e-commerce industry policies based on a three-dimensional analysis framework.

As an emerging business modality and Internet format, live streaming e-commerce has developed rapidly since its emergence in 2016, especially since the outbreak of the COVID-19 epidemic in late 2019, when an increasing number of businesses from other industries attracted participation. However, with the development of the live streaming e-commerce industry, the industry's market environment is becoming increasingly chaotic. Therefore, during this period, government departments continuously formulate and implement relevant industry policies. In order to exploring the cooperation network structure, policy content distribution, and implementation effectiveness characteristics among publishers, this paper constructs a three-dimensional analysis framework of policy from the perspective of policy tools, policy effectiveness evaluation and policy publishers. The results show that in terms of policy tools, the overall structure of policy tools in the live streaming e-commerce industry is unreasonable, and different types of policy tools are significantly diverse. The proportion of environmental policy tools is greater than that of demand-based and supply-based policy tools, accounting for 62.97%, and among them, the tools related to industry regulation and management account for the largest proportion of the total, which greatly suppresses the enthusiasm of various entities in the industry for development. In terms of policy effectiveness evaluation, most of the policies do not formulate detailed long-, medium-, or short-term goals, nor are the policy priorities, incentive measures, or action modes perfect, indicating that the government's pushing and pulling forces for the live streaming e-commerce industry are insufficient. Finally, in the subject dimension of policy release, the synergy of relevant subjects is constantly improving, but there is also a phenomenon of over-concentration in the synergistic departments.

Insulin Determines Transforming Growth Factor ß Effects on Hepatocyte Nuclear Factor 4α Transcription in Hepatocytes.

Loss of hepatocyte nuclear factor 4α (HNF4α) expression is frequently observed in end-stage liver disease and associated with loss of vital liver functions, thus increasing mortality. Loss of HNF4α expression is mediated by inflammatory cytokines, such as transforming growth factor (TGF)-ß. However, details of how HNF4α is suppressed are largely unknown to date. Herein, TGF-ß did not directly inhibit HNF4α but contributed to its transcriptional regulation by SMAD2/3 recruiting acetyltransferase CREB-binding protein/p300 to the HNF4α promoter. The recruitment of CREB-binding protein/p300 is indispensable for CCAAT/enhancer-binding protein α (C/EBPα) binding, another essential requirement for constitutive HNF4α expression in hepatocytes. Consistent with the in vitro observation, 67 of 98 patients with hepatic HNF4α expressed both phospho-SMAD2 and C/EBPα, whereas 22 patients without HNF4α expression lacked either phospho-SMAD2 or C/EBPα. In contrast to the observed induction of HNF4α, SMAD2/3 inhibited C/EBPα transcription. Long-term TGF-ß incubation resulted in C/EBPα depletion, which abrogated HNF4α expression. Intriguingly, SMAD2/3 inhibitory binding to the C/EBPα promoter was abolished by insulin. Two-thirds of patients without C/EBPα lacked membrane glucose transporter type 2 expression in hepatocytes, indicating insulin resistance. Taken together, these data indicate that hepatic insulin sensitivity is essential for hepatic HNF4α expression in the condition of inflammation.

Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis.

Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.

Intrahepatic Cholangiocarcinoma Cells Promote Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Cells by Secreting LAMC2.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma cells are common primary hepatic tumor cells in the liver. Combined hepatocellular cholangiocarcinoma (CHC) contains both hepatocellular carcinoma cells and intrahepatic cholangiocarcinoma cells in one tumor lesion and these tumors show poor prognosis. Here we examined the potential interaction between hepatocellular carcinoma cells and intrahepatic cholangiocarcinoma cells using cell culture studies. The results showed that culture supernatant from intrahepatic cholangiocarcinoma cells induced endothelial-mesenchymal transition and facilitated the migration and invasion of hepatocellular carcinoma cells, although it did not accelerate the proliferation of hepatocellular carcinoma cells. Furthermore, culture supernatant from intrahepatic cholangiocarcinoma cells increased the chemoresistance of hepatocellular carcinoma cells. Laminin subunit gamma 2 (LAMC2) was detected in the culture supernatant of intrahepatic cholangiocarcinoma cells but not in that of hepatocellular carcinoma cells. Using established LAMC2 knockout intrahepatic cholangiocarcinoma cells, our results demonstrated that intrahepatic cholangiocarcinoma cells promoted the epithelial-mesenchymal transition of hepatocellular carcinoma cells through secreting LAMC2. Our results have revealed a novel mechanism of interaction between intrahepatic cholangiocarcinoma cells and hepatocellular carcinoma cells, which may provide new insight into developing effective treatments for CHC.

Clinical-Radiomic Analysis for Pretreatment Prediction of Objective Response to First Transarterial Chemoembolization in Hepatocellular Carcinoma.

BACKGROUND: The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. OBJECTIVE: To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. METHODS: A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model's performance. RESULTS: The final CR model consisted of 5 independent predictors, including TPR-signature (p < 0.001), AFP (p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (p = 0.01), tumor location (p = 0.039), and arterial hyperenhancement (p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60-3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. CONCLUSIONS: The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.

Hepatectomy strategy for T2 gallbladder cancer between segment IVb and V resection and wedge resection: A propensity score-matched study.

BACKGROUND: Liver resection is recommended for T2 gallbladder cancer, but the optimal hepatectomy strategy remains controversial. We aimed to assess the safety and effectiveness of segment IVb and V resection versus wedge resection in patients with T2 gallbladder cancer. METHODS: This is a retrospective multicenter propensity score-matched study in China. Overall survival, disease-free survival, perioperative complications, and hospital length of stay were used to evaluate safety and effectiveness. RESULTS: There are a total of 512 patients. 112 of 117 patients undergoing segment IVb and V resection were matched to 112 patients undergoing wedge resection. After matching, segment IVb and V resection demonstrated no statistical difference in overall survival (hazard ratio, 0.970 [0.639-1.474]; P = .886), but significance in disease-free survival (hazard ratio, 0.708 [0.506-0.991]; P = .040). Patients with incidental gallbladder cancer (hazard ratio, 0.390 [0.180-0.846]; P = .019), stage T2b (hazard ratio, 0.515 [0.302-0.878]; P = .016), and negative lymph nodes status (hazard ratio, 0.627 [0.406-0.991]; P = .043) were associated with improved disease-free survival after segment IVb and V resection, but not in wedge resection. However, perioperative complications occurred more frequently after segment IVb and V resection (28.5% vs 9.1%, P < .001) along with the longer hospital length of stay (17.3 vs 10.2 days, P < .001). Notably, patients with jaundice (odds ratio, 4.053 [1.361-12.23]; P = .013), undergoing laparoscopic resection (odds ratio, 2.387 [1.059-4.484]; P = .028) or surgeon performing per the first 10 segment IVb and V resections (odds ratio, 2.697 [1.035-6.998]; P = .041), were the independent risk factors for perioperative complications in the segment IVb and V resection group. CONCLUSION: T2 gallbladder cancer patients undergoing segment IVb and V resection rather than wedge resection have an improved disease-free survival, especially for incidental gallbladder cancer or hepatic-sided (T2b) gallbladder cancer. However, high rates of perioperative complications and longer hospital length of stay after segment IVb and V resection indicated that surgeons must rely on their own surgical skills and the patient profile to decide the optimal hepatectomy strategy.

Pterostilbene inhibits gallbladder cancer progression by suppressing the PI3K/Akt pathway.

Gallbladder cancer is the most common malignant tumor of the biliary system and is characterized by difficulty to diagnose in early stages, a high degree of malignancy, and poor prognosis. Finding new drugs may improve the prognosis for this dismal cancer. Herein, we investigated the potential application of pterostilbene (PTS) against gallbladder cancer in vivo and in vitro. PTS potently inhibited cell proliferation, migration and invasion of gallbladder cancer cells. Moreover, PTS also had a function of inducing apoptosis in vitro. Meanwhile, PTS reversed EMT with a correlated inhibition of PI3K/Akt activation. Tumor xenograft models showed that PTS inhibited tumor growth and had low toxicity in vivo, which were consistent with the in vitro data. These findings indicate that PTS arrests cell growth through inhibition of PI3K/AKT signaling and is a potential drug for the therapy of gallbladder cancer.

Inhibition of heat shock protein 90 alleviates cholestatic liver injury by decreasing IL-1ß and IL-18 expression.

Severe cholestatic liver injury diseases, such as obstructive jaundice and the subsequent acute obstructive cholangitis, are induced by biliary tract occlusion. Heat shock protein 90 (HSP90) inhibitors have been demonstrated to be protective for various organs. The potential of HSP90 inhibitors in the treatment of cholestatic liver injury, however, remains unclear. In the present study, rat models of bile duct ligation (BDL) were established, the HSP90 inhibitor 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG) was administered, and its ability to ameliorate the cholestasis-induced liver injuries was evaluated. In the BDL rat models and clinical samples, increased HSP90 expression was observed to be associated with cholestatic liver injury. Furthermore, 17-DMAG alleviated cholestasis-induced liver injury in the rat models, as revealed by the assessment of pathological changes and liver function. In addition, 17-DMAG protected hepatocytes against cholestatic injury in vitro. Further assays indicated that 17-DMAG administration prevented cholestasis-induced liver injury in the rats by decreasing the expression of interleukin (IL)-1ß and IL-18. Moreover, 17-DMAG also decreased the cholestasis-induced upregulation of IL-1ß and IL-18 in liver sinusoidal endothelial cells in vitro. In conclusion, the HSP90 inhibitor 17-DMAG is able to prevent liver injury in rats with biliary obstruction, and this phenomenon is associated with the reduction of IL-1ß and IL-18 expression.

Silencing ARAF Suppresses the Malignant Phenotypes of Gallbladder Cancer Cells.

ARAF is a member of the RAF kinase family that is necessary for mitogen-activated protein kinase (MAPK) activation in various malignancies, including lung, colorectal, pancreatic, and breast cancers. As the most common biliary tract tumor, gallbladder cancer (GBC) seriously harms human health while the function of ARAF in GBC remains elusive. Here, we found that ARAF expression was upregulated in gallbladder cancer tissues. In vitro, ARAF silencing mediated by RNA interference effectively inhibited cell proliferation, colony formation, migration, and invasion of GBC cells. Moreover, knocking down ARAF suppressed tumor growth in vivo. Our results indicated that ARAF functions as an oncogene in GBC and, thus, could be a potential therapeutic target for GBC.

Laparoscopic procedure is associated with lower morbidity for simultaneous resection of colorectal cancer and liver metastases: an updated meta-analysis.

BACKGROUND: It has been demonstrated that simultaneous resection of both primary colorectal lesion and metastatic hepatic lesion is a safe approach with low mortality and postoperative complication rates. However, there are some controversies over which kind of surgical approach is better. The aim of study was to compare the efficacy and safety of laparoscopic surgeries and open surgeries for simultaneous resection of colorectal cancer (CRC) and synchronous colorectal liver metastasis (SCRLM). METHODS: A systemic search of online database including PubMed, Web of Science, Cochrane Library, and Embase was performed until June 5, 2019. Intraoperative complications, postoperative complications, and long-term outcomes were synthesized by using STATA, version 15.0. Cumulative and single-arm meta-analyses were also conducted. RESULTS: It contained twelve studies with 616 patients (273 vs 343, laparoscopic surgery group and open surgery group, respectively) and manifested latest surgical results for the treatment of CRC and SCRLM. Among patients who underwent laparoscopic surgeries, they had lower rates of postoperative complications (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), less intraoperative blood loss (weight mean difference (WMD) = - 113.31, 95% CI: - 189.03 to - 37.59, P = 0.003), less time in the hospital and recovering after surgeries (WMD = - 2.70, 95% CI: - 3.99 to - 1.40, P = 0.000; WMD = - 3.20, 95% CI: - 5.06 to - 1.34, P = 0.001), but more operating time (WMD = 36.57, 95% CI: 7.80 to 65.35, P = 0.013). Additionally, there were no statistical significance between two kinds of surgical approaches in disease-free survival and overall survival. Moreover, cumulative meta-analysis indicated statistical difference in favor of laparoscopic surgery in terms of morbidity was firstly detected in the 12th study in 2018 (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028) as the 95% CI narrowed. CONCLUSION: Compared with open surgeries, laparoscopic surgeries are safer (postoperative complications and intraoperative blood loss) and more effective (length of hospital stay and postoperative stay), and it can be considered as the first option for management of SCRLM in high-volume laparoscopic centers. TRIAL REGISTRATION: CRD42020151176.

Scientometric analysis of mTOR signaling pathway in liver disease.

BACKGROUND: The mTOR pathway is vital for homeostasis, metabolism, cancer transplantation and regeneration in the liver. The aim of this study is to use a bibliometric method to reveal current research hotspots and promising future trends in mTOR signaling in liver diseases. METHODS: Publications were searched and downloaded from the Web of Science Core Collection (WOSCC) Database. CiteSpace, Carrot2, and VOSviewer programs were utilized to analyze the contribution of various countries/regions, institutes, and authors; and to reveal research hotspots and promising future trends in this research area. RESULTS: Until May 21, 2019, a total of 2,232 papers regarding mTOR signaling pathway in liver disease were included, and each paper was cited 23.21 times on average. The most active country was the USA. 5 landmark articles with centrality and burstiness were determined by co-citation analysis. Research hotspots included "liver transplantation" "hepatic stellate cell proliferation" "NAFLD" "therapy of HCC". Moreover, six key clusters were discovered during the procedure of "clustering", including "liver transplantation" "protein synthesis" "mTOR inhibitor" "following early cyclosporine withdrawal" "srebp-1 activation", and "hepatocellular cancer". CONCLUSIONS: Various scientific methods were applied to reveal scientific productivity, collaboration, and research hotspots in the mTOR signaling pathway in liver disease. Liver transplantation, hepatic stellate cell proliferation, non-alcoholic fatty liver disease (NAFLD), therapy of hepatocellular carcinoma (HCC), cell growth and autophagy, are research hotspots and are likely to be promising in the next few years. Further studies in this field are needed.

Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma.

BACKGROUND: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the prognostic and predictive factors remain unclear. AIM: To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODS: Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS. In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers were included after a propensity-score 1:1 matching analysis. Compared to the group receiving surgery alone, PA-TACE prolonged the OS rate in patients with resected HCC (P < 0.001). The Barcelona Clinic Liver Cancer system and ferritin-to-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups. Age (P = 0.023) and microscopic vascular invasion (MVI) (P = 0.002) were also identified in the PA-TACE group, while gender (P = 0.027), hepatitis B virus (P = 0.034) and albumin-bilirubin grade (P = 0.027) were also selected in the surgery alone group. In addition, PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone) < 1]. Notably, a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P = 0.038) and without MVI (P = 0.048). CONCLUSION: FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS. Moreover, high FHR and the absence of MVI were important predictive factors, which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

Complete duodenal obstruction induced by groove pancreatitis: A case report.

BACKGROUND: Groove pancreatitis (GP) is a type of chronic pancreatitis occurring in an anatomic area between the duodenum, head of the pancreas, and common bile duct. Duodenal obstruction is always caused by malignant pancreatic diseases, such as pancreatic head carcinoma, while is rarely induced by benign pancreatic diseases, such as pancreatitis. CASE SUMMARY: A 39-year-old man presented with a 1-mo history of upper abdominal discomfort. His concomitant symptoms were abdominal distension, postprandial nausea, and vomiting. Contrast-enhanced computed tomography of the abdomen showed thickening of the intestinal wall with enhancement of the descending segment of the duodenum, which could not be clearly differentiated from the head of the pancreas. Upper gastrointestinal radiographs and gastrointestinal endoscopy showed a complete obstruction of the descending duodenum. An operation found that a 3-cm mass was located in the "groove part" of the pancreas and oppressing the descending duodenum. Pancreaticoduodenectomy was performed to relieve the obstruction and thoroughly remove the pancreatic lesions. The pathologic diagnosis was pancreatitis. The patient had an uneventful recovery with no complications. CONCLUSION: Because of the special location and the contracture induced by long-term chronic inflammation, our case reminds surgeons that some benign pancreatic diseases, such as GP, can also present with symptoms similar to those of pancreatic cancer. This knowledge can help to avoid an unnecessary radical operation.

Development and Validation of a Nomogram for Early Detection of Malignant Gallbladder Lesions.

OBJECTIVES: Preoperative decision-making for differentiating malignant from benign lesions in the gallbladder remains challenging. We aimed to create a diagnostic nomogram to identify gallbladder cancer (GBC), especially for incidental GBC (IGBC), before surgical resection. METHODS: A total of 587 consecutive patients with pathologically confirmed gallbladder lesions from a hospital were randomly assigned to a training cohort (70%) and an internal validation cohort (30%), with 287 patients from other centers as an external validation cohort. Radiological features were developed by the least absolute shrinkage and selection operator logistic regression model. Significant radiological features and independent clinical factors, identified by multivariate analyses, were used to construct a nomogram. RESULTS: A diagnostic nomogram was established by age, CA19.9, and 6 radiological features. The values of area under the curve in the internal and external validation cohorts were up to 0.91 and 0.89, respectively. The calibration curves for probability of GBC showed optimal agreement between nomogram prediction and actual observation. Compared with previous methods, it demonstrated superior sensitivity (91.5%) and accuracy (85.1%) in the diagnosis of GBC. The accuracy using the nomogram was significantly higher in GBC groups compared with that by radiologists in the training cohort (P < 0.001) and similarly in each cohort. Notably, most of the IGBC, which were misdiagnosed as benign lesions, were successfully identified using this nomogram. DISCUSSION: A novel nomogram provides a powerful tool for detecting the presence of cancer in gallbladder masses, with an increase in accuracy and sensitivity. It demonstrates an unprecedented potential for IGBC identification.

Survival benefits of neoadjuvant chemo(radio)therapy versus surgery first in patients with resectable or borderline resectable pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Pancreatic adenocarcinoma is a highly lethal malignancy. Neoadjuvant chemo(radio)therapy [NAC(R)T] is recommended to use for borderline resectable pancreatic cancer (BRPC) and high-risk resectable pancreatic cancer (RPC), but no high-level evidence exists. METHODS: We searched PubMed, EMBASE, Web of Science, and Cochrane library to identify trials comparing survival data of NAC(R)T with SF for RPC or BRPC. Overall survival (OS) was synthesized in analysis of all the patients (intention-to-treat [ITT] analysis) and resected patients respectively. RESULTS: The meta-analysis included 17 trials with 2286 participants. For BRPC, NAC(R)T improved OS both in ITT analysis (HR, 0.49; 95% CI, 0.37-0.65; P < 0.001) and in analysis of resected patients (HR, 0.66; 95% CI, 0.51-0.85; P = 0.001) in comparison to SF, accompanied with comparable overall resection rate [odds ratio (OR), 0.69; 95% Cl, 0.41-1.16; P = 0.159]. Disease-free survival, R0 rate, and recurrence were also in favor of NAC(R)T. For RPC, OS in analysis of resected patients was higher with NAC(R)T (HR, 0.75; 95% CI, 0.63-0.89; P = 0.001), but OS in ITT analysis was similar (HR, 1.02; 95% CI, 0.85-1.22; P = 0.818). The overall resection rate (OR, 0.50; 95% Cl, 0.25-0.99; P = 0.048) was lower, but R0 rate was higher with NAC(R)T. No differences in disease-free survival and recurrence between NAC(R)T and SF. Survival benefits of NAC(R)T basically persisted across sensitivity and subgroup analyses. CONCLUSIONS: This meta-analysis demonstrates that NAC(R)T can provide survival benefits in BRPC patients and a subgroup of RPC patients compared with SF. Future research should focus on investigating the potential biomarkers to screen the subgroup of RPC patients who can benefit from neoadjuvant therapy. TRIAL REGISTRATION: CRD42018103086.