<b><i>Background:</i></b> Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. <b><i>Summary:</i></b> Since the publication of <i>Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition)</i> in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition <i>(2019 Edition)</i> was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. <b><i>Key Messages:</i></b> Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

BACE1 is required for the release of ␤-amyloid (A␤) in vivo, and inhibition of BACE1 activity is targeted for reducing A␤ generation in Alzheimer's patients. To further our understanding of the safe use of BACE1 inhibitors in human patients, we aimed to study the physiological functions of BACE1 by characterizing BACE1-null mice. Here, we report the finding of spontaneous behavioral seizures in BACE1-null mice. Electroencephalographic recordings revealed abnormal spike-wave discharges in BACE1-null mice, and kainic acidinduced seizures also occurred more frequently in BACE1-null mice compared with their wild-type littermates. Biochemical and morphological studies showed that axonal and surface levels of Na v 1.2 were significantly elevated in BACE1-null mice, consistent with the increased fast sodium channel current recorded from BACE1-null hippocampal neurons. Patch-clamp recording also showed altered intrinsic firing properties of isolated BACE1-null hippocampal neurons. Furthermore, population spikes were significantly increased in BACE1-null brain slices, indicating hyperexcitability of BACE1-null neurons. Together, our results suggest that increased sodium channel activity contributes to the epileptic behaviors observed in BACE1-null mice. The knowledge from this study is crucial for the development of BACE1 inhibitors for Alzheimer's therapy and to the applicative study of epilepsy.

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PurposeTo evaluate whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict survival and metastasis in patients after transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (RHCC).Materials and MethodsClinical and laboratory data from 132 RHCC patients treated with TACE from January 2003 to December 2012 were retrospectively reviewed. Prognostic factors were assessed by multivariate analysis, and the predictive values of NLR and PLR for overall survival (OS) and extrahepatic metastases were compared.ResultsPretreatment mean NLR and PLR were 3.1 and 137, respectively. The 0.5-, 1-, and 2-year OS rates were 93.7%, 67.1%, and 10.1% in the low NLR group and 81.1%, 18.9%, and 3.8% in the high NLR group, respectively (P = 0.017). The corresponding OS rates in the low and high PLR groups were 92.5%, 58.1%, and 9.7% and 84.6%, 23.1%, and 2.6%, respectively (P = 0.030). The discriminatory performance predicting 1-year survival probability was significantly poorer for NLR (area under the curve [AUC] = 0.685, 95% confidence interval [CI] 0.598–0.763) than for PLR (AUC = 0.792, 95% CI 0.712–0.857; P = 0.0295), but was good for both ratios for predicting post-TACE extrahepatic metastasis. Multivariate analysis indicated that high PLR (hazard ratio [HR] = 0.373, 95% CI = 0.216-0.644, P < 0.001, vascular invasion (HR = 0.507, 95% CI = 0.310–0.832, P = 0.007), and multiple tumors (HR= 0.553, 95% CI = 0.333–0.919, P = 0.022) were independent prognostic factors for OS.ConclusionsHigh NLR and PLR were both associated with poor prognosis and metastasis in RHCC patients treated with TACE, but high PLR was a better predictor of 1-year OS. High PLR, vascular invasion, and multiple tumors were independent, unfavorable prognostic factors.

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Androgen deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer; ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated macrophages (TAM). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism. The association between enzalutamide-induced NED and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide-resistant mouse xenografts, and a coculture system. The underlying mechanisms were assessed using cytokine antibody arrays, ELISAs, chromatin immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model was established to evaluate the effects of combined IL6 receptor (IL6R) and high mobility group box 1 (HMGB1) inhibition on enzalutamide resistance. High CD163 expression was observed in ADT-treated prostate cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide-resistant xenografts, indicating the crucial roles of NED and TAMs in enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression facilitated TAM recruitment and polarization and drove NED via β-catenin stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited enzalutamide-induced resistance in an orthotopic prostate cancer mouse model. Enzalutamide elevates HMGB1 levels, which recruits and activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the enzalutamide-induced NED of prostate cancer, forming a positive feedback loop between NED in prostate cancer and TAMs. The combined inhibition of IL6R and HMGB1 may serve as a new treatment for enzalutamide resistance in patients with advanced or metastatic prostate cancer. .