Mini-ALPPS-based multidisciplinary treatment leading to long-term survival in a patient with a large HCC: A case report.

Background: The future liver remnant (FLR) induced by stage I associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma (HCC) might be limited due to liver fibrosis/cirrhosis or incomplete liver parenchymal transection. Case presentation: A 51-year-old male with hepatitis B liver fibrosis was diagnosed with a large HCC (13.5 cm × 12.5 cm × 13.8 cm). The FLR of the patient was insufficient to permit one-stage tumor resection. Therefore, the two-stage ALPPS surgery was planned. Stage I ALPPS was performed with incomplete liver parenchymal transection due to bleeding (which is why we called it Mini-ALPPS). On postoperative day (POD) 18, CT revealed that the FLR hypertrophy was poor. The FLR/standard liver volume (SLV) had only increased from 22.00% to 34.63%. Salvage transhepatic arterial chemoembolization (TACE) was performed on POD 22 days to control possible tumor progression during the waiting period and to further facilitate FLR growth. About 16 days later, a CT reassessment of FLR revealed a 42.5% FLR/SLV. A right hepatectomy was then uneventfully performed. Although HCC recurred after 586 days, the patient survived for more than 1,920 days after stage II ALPPS. Discussion: Damage control during a difficult conventional stage I ALPPS was important. TACE during the interstage and postoperative periods of this Mini-ALPPS was safe and beneficial. A multidisciplinary based on Mini-ALPPS treatment could provide patients long-term survival; however, Mini-ALPPS should not be selected as the primary solution for such patients today, as some other minimally invasive and effective strategies are available.

Effects of Huangqin Decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. OBJECTIVE: To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). METHODS: The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H-C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. RESULTS: The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H-C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. CONCLUSIONS: HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.

Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach.

BACKGROUND: Inflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) and Paeonia lactiflora Pall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair. METHODS: A systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets. RESULTS: The results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect. CONCLUSION: This study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.

FXYD6 overexpression in HBV-related hepatocellular carcinoma with cirrhosis.

OBJECTIVE: The aim of this study was to investigate the expression of FXYD domain-containing ion transport regulator 6 (FXYD6) mRNA and protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues with cirrhosis, the corresponding paracancerous tissues and the normal liver tissues, and to explore the clinical significance of FXYD6 expression in HBV-related HCC with cirrhosis. METHODS: The FXYD6 mRNA and protein were examined by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. RESULTS: The FXYD6 mRNA in HBV-related HCC tissues was significantly higher than that in the cirrhosis tissues or that in the normal liver tissues. The positive expression rate of FXYD6 protein was statistically higher in HBV-related HCC tissues than that in HBV-related cirrhosis or that in normal liver tissues. There was no significant correlation between the expression of FXYD6 protein and gender, age, histological differentiation, tumor diameter, tumor number, integrity of tumor capsule or not and alpha fetoprotein (AFP) concentration in serum, but the protein expression was associated with microvascular invasion, pathological stage, and early recurrence after operation within 1 year. CONCLUSION: FXYD6 might be involved in hepatocyte carcinogenesis and tumor progression in HBV-related HCC with cirrhosis and indicated a poor prognosis.

Prognostic role of PD-L1 for HCC patients after potentially curative resection: a meta-analysis.

BACKGROUND: A series of studies has investigated the prognostic role and clinical significance of programmed death ligand 1 (PD-L1) in hepatocellular carcinoma (HCC). However, the results were inconsistent. We aimed to clarify the prognostic role of PD-L1 and relationship between PD-L1 expression and several important clinicopathological features. METHODS: PubMed, EMBASE and the Science Citation Index Expanded were systematically searched. All cohort or case-control studies comparing the prognosis and clinical features between the high PD-L1 and low PD-L1 groups were included. Publication bias was evaluated using funnel plots and Begg's test. Subgroup analysis, sensitivity analysis and meta-regression analysis were performed. RESULTS: Seventeen studies including 2979 patients were eligible. The overall survival (OS) was not significantly different between the high and low PD-L1 groups (hazard ratio [HR]: 1.27; 95% confidence interval [CI] 0.98-1.65: P = 0.07) with significant heterogeneity (P < 0.001; I2 = 81%). The recurrence-free survival (RFS) was not significantly different between the high and low PD-L1 groups (HR: 1.22; 95% CI 0.97-1.53; P = 0.09) with significant heterogeneity (P < 0.001; I2 = 78%). The expression of PD-L1 was found to be significantly correlated with alpha-fetoprotein, hepatitis history, and tumour-infiltrating lymphocytes. Begg's test found no significant publication bias for OS and RFS. Sensitivity analysis established the robustness of our results. Subgroup analysis and meta-regression analysis found the region of research as a significant contributor to inter-study heterogeneity in RFS, indicating some racial differences in the prognostic role of PD-L1. CONCLUSIONS: Our study found no significant prognostic role of PD-L1 in HCC patients after potential curative hepatectomy based on our included studies. The expression of PD-L1 was significantly correlated with AFP, hepatitis history, and TILs. The prognostic role of PD-L1 in HCC warrants further investigation.

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways.

OBJECTIVE: Huangqin decoction (HQD), a classical traditional Chinese medicinal formula, has been commonly used to treat gastrointestinal diseases for thousands of years. We investigated the anti-inflammatory effects and underlying mechanisms of HQD on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). METHODS: Experimental mice were given 3% DSS, and HQD (2.275, 4.55, and 9.1 g/kg), or mesalazine (ME, 200 mg/kg) orally for 7 days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory cytokines were measured to evaluate the effects of HQD on colitis. The effects of HQD on the Ras-phosphoinositide-3-kinase (PI3K)-Akt-hypoxia inducible factor 1 alpha (HIF-1α) and nuclear factor-kappa B (NF-κB) pathways were evaluated by Western blot analysis. In addition, the gut microbiota was characterized using high-throughput Illumina MiSeq sequencing. RESULTS: The results showed that HQD significantly reduced the body weight loss, ameliorated DAI, restored colon length, and improved the intestinal epithelial cell barrier in mice with DSS-induced colitis. The messenger RNA (mRNA) expression levels of inflammatory mediators were decreased following HQD treatment. Furthermore, the Ras-PI3K-Akt-HIF-1α and NF-κB pathways were significantly inhibited by HQD. Finally, treatment with HQD resulted in recovery of gut microbiota diversity. CONCLUSIONS: HQD ameliorates DSS-induced colitis through regulation of the gut microbiota, and suppression of Ras-PI3K-Akt-HIF-1α and NF-κB pathways. Our results suggested that HQD may be a potential candidate for treatment of UC.