Adjuvant transarterial chemoembolization timing after radical resection is an independent prognostic factor for patients with hepatocellular carcinoma.

Background: It has been reported that postoperative adjuvant TACE (PA-TACE) treatment decreases recurrence and significantly improves the survival of patients who undergo radical resection of hepatocellular carcinoma (HCC) with high-risk recurrence factors. However, when to perform PA-TACE has not been fully studied. Methods: We retrospectively collected the clinicopathologic characteristics of the patients with HCC between October 2013 and June 2020. The optimal cutoff value for PA-TACE time was determined based on the R package "maxstat". Logistic regression and Cox regression analysis were used to determine the effect of the choice of PA-TACE timing on prognosis. Results: The analysis was performed on 789 patients with HCC, and 484 patients were finally involved and were divided into training cohort (378) and validation cohort (106). The PA-TACE timing was found to be associated with survival outcomes. Multivariate logistic analysis found independent predictors of the PA-TACE timing, including gender and history of HBV. Multivariate Cox analysis showed that Ki-67, tumor size, MVI and the PA-TACE timing were independent prognostic factors for RFS in HCC patients. Conclusions: Based on this study, HCC patients with high-risk recurrence factors can receive personalized assistance in undergoing PA-TACE treatment and improve their survival outcomes.

Clinical Practice of Targeted Capture Sequencing to Identify Actionable Alterations in Cholangiocarcinoma.

The early diagnosis and treatment of cholangiocarcinoma (CCA) remain a challenge worldwide. Genetic testing promises to solve these problems. Due to the different mutation landscapes across populations and the paucity of sequencing data of Chinese patients with CCA, the existing mutation landscape is insufficient to reflect the mutation characteristics of Chinese patients. Thus, we retrospectively analyzed 72 Chinese patients with CCA who had received genetic testing of targeted capture sequencing. A total of 2152 somatic mutations were detected in 56 (77.78%) patients, of which, the frequently mutated driver genes were TP53 (27.78%), KMT2D (23.81%), KMT2C (20.63%), BCOR (18.06%), APC (15.28%), BAP1 (13.89%), ARID1A (12.50%), NF1 (12.50%), PIK3CA (12.50%), KRAS (11.11%), and LRP1B (11.11%). Most mutations were enriched in NRF2, TP53, and TGF-Beta oncogenic signaling pathways and cadherin repeat domains which were associated with intercellular adhesion. Based on cancer-related public databases and multiple protein function prediction algorithms, we identified 118 novel pathogenic or likely pathogenic somatic mutations and 77 actionable alterations. Molecular analysis of tumors from a precision oncology perspective can provide potential targets for early diagnosis and treatment of CCA and assist physicians in clinical decision making.

Establishment and Application of a Novel Difficulty Scoring System for da Vinci Robotic Pancreatoduodenectomy.

Background: Robotic pancreatoduodenectomy (RPD) technology is developing rapidly, but there is still a lack of a specific and objective difficulty evaluation system in the field of application and training of RPD surgery. Methods: The clinical data of patients who underwent RPD in our hospital from November 2014 to October 2020 were analyzed retrospectively. Univariate and multivariate logistic regression analyses were used to determine the predictors of operation difficulty and convert into a scoring system. Results: A total of 72 patients were enrolled in the group. According to the operation time (25%), intraoperative blood loss (25%), conversion to laparotomy, and major complications, the difficulty of operation was divided into low difficulty (0-2 points) and high difficulty (3-4 points). The multivariate logistic regression model included the thickness of mesenteric tissue (P1) (P = 0.035), the thickness of the abdominal wall (B1) (P = 0.017), and the preoperative albumin (P = 0.032), and the nomogram was established. AUC = 0.773 (0.645-0.901). Conclusions: The RPD difficulty evaluation system based on the specific anatomical relationship between da Vinci's laparoscopic robotic arm and tissues/organs in the operation area can be used as a predictive tool to evaluate the surgical difficulty of patients before operation and guide clinical practice.

A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells.

BACKGROUND: The combined application of immune cells and specific biomarkers related to the tumor immune microenvironment has a better predictive value for the prognosis of HCC. The purpose of this study is to construct a new prognostic model based on immune-related genes that regulate cross-talk between immune and tumor cells to assess the prognosis and explore possible mechanisms. METHOD: The immune cell abundance ratio of 424 cases in the TCGA-LIHC database is obtained through the CIBERSORT algorithm. The differential gene analysis and cox regression analysis is used to screen IRGs. In addition, the function of IRGs was preliminarily explored through the co-culture of M2 macrophages and HCC cell lines. The clinical validation, nomogram establishment and performing tumor microenvironment score were validated. RESULTS: We identified 4 immune cells and 9 hub genes related to the prognosis. Further, we identified S100A9, CD79B, TNFRSF11B as an IRGs signature, which is verified in the ICGC and GSE76427 database. Importantly, IRGs signature is closely related to the prognosis, tumor microenvironment score, clinical characteristics and immunotherapy, and nomogram combined with clinical characteristics is more conducive to clinical promotion. In addition, after co-culture with M2 macrophages, the migration capacity and cell pseudopod of MHCC97H increased significantly. And CD79B and TNFRSF11B were significantly down-regulated in MHCC97H, Huh7 and LM3, while S100A9 was up-regulated. CONCLUSION: We constructed an IRGs signature and discussed possible mechanisms. The nomogram established based on IRGs can accurately predict the prognosis of HCC patients. These findings may provide a suitable therapeutic target for HCC.

A new aromatic glycoside and its anti-proliferative activities from the leaves of Bergenia purpurascens.

Chemical investigation of the ethanolic extracts of the dried leaves of Bergenia purpurascens led to the isolation and identification of a new aromatic glycoside, 1-O-ß-D-glucopyranosyl-2-methoxy-3-hydroxyl-phenylethene (1), along with other 19 known compounds (2-20). The structure of compound 1 was determined by a detailed analysis using various analytical techniques, including 1D and 2D NMR. In vitro anti-proliferative activities of compound 1 on five human cancer cell lines were evaluated. The results showed that compound 1 possessed the most potent effects with the IC50 values of 14.36 ± 1.04 µM against T24 cells. The further bioactivity analysis showed that compound 1 induced apoptosis of T24 cells, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activation of caspase-3 for causing cell apoptosis. The present investigation illustrated compound 1 might be used as a potential antitumour chemotherapy candidate.

Chemical Constituents of the Aerial Parts of Euphorbia nematocypha.

Chemical constituents of the dried aerial parts of Euphorbia nematocypha were investigated. A new oleanane triterpenoid, trans, trans-2',4'- hexadienedioicacid-1'-ß-amyrin ester (1), together with, ß-amyrin (2), ß-amyrin acetate (3), betulinic acid (4), ellagic acid (5), oleanolic acid (6), ß-sitosterol (7), kaempferol (8), quercetin (9), lupeol (10) and pseudo-taraxasterol (11) were isolated from the methylene chloride extract. Their structures were elucidated on the basis of extensive spectroscopic (1D- & 2D-NMR) and ESI-MS analysis and comparison with data reported in the literature. The new isolated triterpenoid showed moderate cytotoxic activities against HeLa and MCF-7cell lines.

Pyrolytic synthesis and luminescence of porous lanthanide Eu-MOF.

A lanthanide metal coordination polymer [Eu2(BDC)3(DMSO)(H2O)] was synthesized by the reaction of europium oxide with benzene-1,3-dicarboxylic acid (H2BDC) in a mixed solution of dimethyl sulfoxide (DMSO) and water under hydrothermal conditions. The crystal structure of Eu2(BDC)3(DMSO)(H2O) was characterized by X-ray diffraction (XRD). Thermo-gravimetric analysis of Eu2(BDC)3(DMSO)(H2O) indicated that coordinated DMSO and H2O molecules could be removed to create Eu2(BDC)3(DMSO)(H2O)-py with permanent microporosity, which was also verified by powder XRD (PXRD) and elemental analysis. Both Eu2(BDC)3(DMSO)(H2O) and Eu2(BDC)3(DMSO)(H2O)-py showed mainly Eu-based luminescence and had characteristic emissions in the range 550-700 nm.

Two new 2,3-seco-hopane triterpene derivatives from Megacodon stylophorus and their antiproliferative and antimicrobial activities.

Chemical investigation of the ethanol extract of the whole plant of Megacodon stylophorus led to the isolation and identification of two new seco-hopane triterpenoids, 2,3-seco-22(29)-hopene-2-carboxyl-3-aldehyde (1) and 2,3-seco-4(23),22(29)-hopene-2-carboxyl-3-aldehyde (2), along with 10 known compounds, 3-12. All the isolates were reported from this plant for the first time. The structures of compounds 1 and 2 were determined by detailed analysis of their spectral data including 1D and 2D NMR. In addition, compound 1 was further analyzed by X-ray crystallography. Compounds 1-3 were evaluated for their in vitro anti-proliferative activities on HeLa, MCF-7, and Hep-G2 tumor cell lines. Compound 2 was active against the three cell lines with IC50 values of 3.6, 7.5, and 13.6 µM, respectively, while compound 1 exhibited cytotoxicity on MCF-7 (IC50 14.0 µM) and HeLa (IC50 18.2 µM) cell lines. Antimicrobial activities of compounds 1-2 (minimum inhibitory concentration values in the range of 3.12-12.50 mg/mL) were also observed.

Two new sesquiterpenes from Artemisia sieversiana.

Two new sesquiterpenes, together with 32 known compounds(3-34), were isolated from Artemisia sieversiana Ehrhart ex willd. and the compounds 3-21 were isolated from this plant for the first time. The new compounds were elucidated as 2α,9α-dihydroxymuurol-3(4)-en-12-oic acid (1) and 13α-methyl-(5αH,6αH,7αH,8αH)-austricin 8-O-ß-D-glucopyranoside (2), respectively. The structural identification of these compounds was mainly achieved by spectroscopic methods including 1D and 2D NMR techniques, and the structure of compound 1 was confirmed by a single crystal X-ray diffraction experiment. Compounds 1-2 were evaluated for cytotoxic activity in vitro against MCF-7, NCI-H460 and Hep-G2 cell lines, respectively.

Norlathyrane diterpenes from the root of Euphorbia kansuensis.

Phytochemical investigation of the EtOH extract obtained from the root of the Euphorbia kansuensis Proch. grown in China resulted in the isolation of two novel norlathyrane diterpenes, named ekanpenoids A and B (1 and 2, resp.). Their structures were established by extensive 1D- and 2D-NMR spectroscopy, as well as other spectra. The isolated diterpenes exhibited potent cytotoxic activities against the HeLa and Hep-G2 cell lines with the IC50 values ranging from 3.6 to 9.7 µg/ml.

Triterpenoids of Chrysosplenium carnosum.

A phytochemical study of the ethanolic extract of Chrysosplenium carnosum Hook. f. et Thoms. led to the isolation of two new oleanane-type triterpenoids, 6ß-hydroxy-3-oxoolean-12-en-27-oic acid (1) and 3ß, 21α-dihydroxyolean-12-en-27-oic acid (2), along with fourteen known compounds (3-16), all of which were isolated from this plant for the first time. The structures of these compounds were established on the basis of spectroscopic methods. Compounds 1-4 were evaluated for their in vitro anti-tumor activities on B16F10, SP2/0 and Hep-G2 cells lines. Compounds 1, 3 and 4 exhibited strong inhibitory activity against B16F10 and SP2/0 cells' growth, compared with moderate cytotoxic activity against Hep-G2 cells. However, compound 2 showed to be inactive against these tumor cells.