Preoperative high-sensitivity C-reactive protein to lymphocyte ratio index plays a vital role in the prognosis of hepatocellular carcinoma after surgical resection.

BACKGROUND: At present, the predictive ability of the prognostic indicator of hepatocellular carcinoma (HCC) is still limited. This study aims to analyze the relationship between the preoperative high-sensitivity C-reactive protein to lymphocyte ratio (HCLR) and the clinicopathologic characteristics of HCC. PATIENTS AND METHODS: A total of 229 HCC patients undergoing surgical resection were retrospectively analyzed. The majority of the patients (132/229) had tumors larger than 5 cm, and 45 out of 229 had more than one tumor focus. Receiver operating characteristic curve analysis was used to decide the cutoff value of HCLR. The overall survival (OS) and progression-free survival (PFS) rates were evaluated by adopting the Kaplan-Meier method. RESULTS: The cutoff value of HCLR for the best discrimination of HCC prognosis was 1.3 with a sensitivity of 75.5% and a specificity of 71.8%. The area under the receiver operating characteristic curve was 0.791 (95% CI, 0.731-0.840). Preoperative HCLR at a high level (>1.3) was positively correlated with large tumor size, TNM stage, microvascular invasion, and recurrence. The mean OS and PFS in patients with HCLR >1.3 were significantly shorter than in those with HCLR ≤1.3. Univariate and multivariate analyses revealed the HCLR was an independent predictor of OS and PFS. CONCLUSION: HCLR was an important independent predictor of dismal prognosis in HCC patients and can be used as a sensitive indicator for the dynamic monitoring of postoperative patients.

IDH1 mutation in human glioma induces chemical alterations that are amenable to optical Raman spectroscopy.

INTRODUCTION: Mutations in the isocytrate dehydrogenase 1 (IDH1) gene are early genetic events in glioma pathogenesis and cause profound metabolic changes. Because this genotype is found in virtually every tumor cell, therapies targeting mutant IDH1 protein are being developed. The intraoperative administration of those therapies would require fast technologies for the determination of IDH1 genotype. As of today, there is no such diagnostic test available. Recently, infrared spectroscopy was shown to bridge this gap. Here, we tested Raman spectroscopy for analysis of IDH1 genotype in glioma, which constitutes an alternative contact-free technique with the potential of being applicable in situ. METHODS: Human glioma samples (n = 36) were obtained during surgery and cryosections were prepared. IDH1 mutations were assessed using DNA sequencing and 100 Raman spectra were obtained for each sample. RESULTS: Analysis of Raman spectra revealed increased intensities in spectral bands related to DNA in IDH1 mutant glioma while bands assigned to molecular vibrations of lipids were significantly decreased. Moreover, intensities of Raman bands assigned to proteins differed in IDH1 mutant and IDH1 wild-type glioma, suggesting alterations in the protein profile. The selection of five bands (498, 826, 1003, 1174 and 1337 cm-1) allowed the classification of Raman spectra according to IDH1 genotype with a correct rate of 89%. CONCLUSION: Raman spectroscopy constitutes a simple, rapid and safe procedure for determination of the IDH1 mutation that shows great promise for clinically relevant in situ diagnostics.

Aldo-keto Reductase Family 1 Member B 10 Mediates Liver Cancer Cell Proliferation through Sphingosine-1-Phosphate.

AKR1B10 is involved in hepatocarcinogenesis via modulation of fatty acid and lipid synthesis. AKR1B10 inhibition results in apoptosis of tumor cells whose lipids, especially phospholipids, were decreased by over 50%, suggesting involvement of phospholipids like sphingosine-1-phosphate (S1P) in AKR1B10's oncogenic function. Using a co-culture system, we found that co-culture of QSG-7701 (human hepatocyte) with HepG2 (hepatoma cell line) increases QSG-7701's proliferation, in which AKR1B10-S1P signaling plays a pivotal role. Consistent with previous findings, AKR1B10 mRNA and protein levels were higher in primary hepatocellular carcinoma (PHC) tissues than in peri-tumor tissues. Interestingly, the level of S1P was also higher in PHC tissues than in peri-tumor tissues. After analyzing the correlation between AKR1B10 mRNA expression in PHC tissues and the clinical data, we found that AKR1B10 mRNA expression was associated with serum alpha-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, and lymph node metastasis, but not with other clinicopathologic variables. A higher AKR1B10 mRNA expression level is related to a shorter DFS (disease free survival) and OS (overall survival), serving as an independent predictor of DFS and OS in PHC patients with surgical resection.

Anti-profibrotic effects of artesunate on bleomycin-induced pulmonary fibrosis in Sprague Dawley rats.

The present study aimed to determine whether artesunate has beneficial effects on bleomycin-induced pulmonary fibrosis in rats and to examine the possible mechanisms underlying these effects. All experiments were performed with male Sprague Dawley rats weighing 180-250 g. Animals were randomly divided into four experimental groups that were administered either saline alone, artesunate alone, bleomycin alone or bleomycin + artesunate. Lung histopathology was investigated by hematoxylin and eosin staining and Masson staining. Lung profibrotic molecules were analyzed by reverse transcription polymerase chain reaction, immunoblotting and immunohistochemistry. In rats treated with artesunate, pulmonary fibrosis induced by bleomycin was significantly reduced. Administration of artesunate significantly improved bleomycin-induced morphological alterations. Profibrotic molecules, including transforming growth factor-ß1, Smad3, heat shock protein 47, α-smooth muscle actin and collagen type I were also reduced by artesunate. These findings suggest that artesunate improves bleomycin-induced pulmonary fibrosis pathology in rats possibly by inhibiting profibrotic molecules associated with pulmonary fibrosis.

Preoperative Neutrophil-to-Lymphocyte Ratio as a New Prognostic Marker in Hepatocellular Carcinoma after Curative Resection.

BACKGROUND: Preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cutoff value of NLR in several studies is not consistent. This study aims to investigate the correlation of preoperative NLR with clinicopathologic features and the prognosis in patients who have undergone resection for HCC. METHODS: Clinical data of 256 patients with HCC who underwent radical hepatectomy were retrospectively analyzed. The patients were divided into the low-NLR group (NLR ≤ 2.31) and the high-NLR group (NLR > 2.31). A univariate analysis was performed to assess clinicopathologic characteristics that influenced disease-free survival (DFS) and overall survival (OS) in patients. The significant variables were further analyzed by a multivariate analysis using Cox regression. The Kaplan-Meier method was used to assess the DFS and OS rate. RESULTS: The value of NLR was associated with tumor size, clinical tumor-node-metastasis (TNM) stage, portal vein tumor thrombus (PVTT), distant metastasis, and aspartate aminotransferase (AST) in HCC. NLR > 2.31, size of tumor > 5 cm, number of multiple tumors, III-IV of TNM stage, PVTT, distant metastasis, and AST > 40 U/l were predictors of poorer DFS and OS. NLR > 2.31, size of tumor >5 cm, III-IV of TNM stage, and AST > 40 U/l were independent predictors of DFS and OS. CONCLUSION: Preoperative NLR > 2.31 was an adverse predictor of DFS and OS in HCC after hepatectomy. This study suggested that NLR might be a novel prognostic biomarker in HCC after curative resection.

Autophagy inhibition contributes to the synergistic interaction between EGCG and doxorubicin to kill the hepatoma Hep3B cells.

(-)-Epigallocatechin-3-O-gallate(EGCG), the highest catechins from green tea, has promisingly been found to sensitize the efficacy of several chemotherapy agents like doxorubicin (DOX) in hepatocellular carcinoma (HCC) treatment. However, the detailed mechanisms by which EGCG augments the chemotherapeutic efficacy remain unclear. Herein, this study was designed to determine the synergistic impacts of EGCG and DOX on hepatoma cells and particularly to reveal whether the autophagic flux is involved in this combination strategy for the HCC. Electron microscopy and fluorescent microscopy confirmed that DOX significantly increased autophagic vesicles in hepatoma Hep3B cells. Western blot and trypan blue assay showed that the increasing autophagy flux by DOX impaired about 45% of DOX-induced cell death in these cells. Conversely, both qRT-PCR and western blotting showed that EGCG played dose-dependently inhibitory role in autophagy signaling, and that markedly promoted cellular growth inhibition. Amazingly, the combined treatment caused a synergistic effect with 40 to 60% increment on cell death and about 45% augmentation on apoptosis versus monotherapy pattern. The DOX-induced autophagy was abolished by this combination therapy. Rapamycin, an autophagic agonist, substantially impaired the anticancer effect of either DOX or combination with EGCG treatment. On the other hand, using small interference RNA targeting chloroquine autophagy-related gene Atg5 and beclin1 to inhibit autophagy signal, hepatoma cell death was dramatically enhanced. Furthermore, in the established subcutaneous Hep3B cells xenograft tumor model, about 25% reduction in tumor growth as well as 50% increment of apoptotic cells were found in combination therapy compared with DOX alone. In addition, immunohistochemistry analysis indicated that the suppressed tendency of autophagic hallmark microtubule-associated protein light chain 3 (LC3) expressions was consistent with thus combined usage in vitro. Taken together, the current study suggested that EGCG emerges as a chemotherapeutic augmenter and synergistically enhances DOX anticancer effects involving autophagy inhibition in HCC.

[Observation on therapeutic effect of muscular needling combined with scarring moxibustion on active stage of rheumatoid arthritis].

OBJECTIVE: To observe the therapeutic effect of muscular needling combined with scarring moxibustion on active stage of rheumatoid arthritis (RA). METHODS: Sixty cases of RA were randomly divided into a muscular needling group and a medication group, 30 cases in each group. The muscular needling group was treated by muscular needling on Quchi (LI 11), Sanyinjiao (SP 6), etc. combined with scarring moxibustion on Dazhui (GV 14), Zusanli (ST 36) etc., while the medication group was treated by oral administration of Diclofenac sodium and intramuscular injection of Methotrexate. The therapeutic effects, main symptoms and signs, erythrocyte sedimentation rate (ESR) and rheumatoid factor were observed in two groups before and after treatment. RESULTS: The total effective rate of muscular needling group was 76.7%, and that of medication group was 73.3%, there was no significant difference between two groups (P > 0.05). The clinical symptoms, signs, and E8R of two groups were improved obviously compared with those before treatment (P < 0.01, P < 0.05), however there were no significant differences between the two groups after treatment (all P > 0.05). The adverse reactions of medication group were more eminent compared to the muscular needling group. CONCLUSION: Muscular needling can obviously relieve the symptoms and signs of active stage rheumatoid arthritis and the effect is equivalent to oral administration of western medicine, the incidence of adverse reactions in the muscular needling group is obviously lower than that of western medication. Muscular needling is a safe and effective method for treatment of RA.