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It is reported that long noncoding RNA RHPN1-AS1 (lncRNA RHPN1-AS1) functions as an oncogene among multiple types of cancers; however, the effect of lncRNA RHPN1-AS1 in hepatocellular carcinoma (HCC) is left to be investigated. The main purpose of this work was to study the effects of lncRNA RHPN1-AS1/miR-485-5p system on proliferation, migration, and invasion in HCC and future investigate the latent mechanisms. Our work found that lncRNA RHPN1-AS1 was observably up-regulated in HCC tissues and cell lines, especially HCCLM3 and SMMC-7721 cells. LncRNA RHPN1-AS1 knockdown decreased the capacity of proliferation, invasion, and migration in HCCLM3 and SMMC-7721 cells, which could be crippled by miR-485-5p inhibitor. Besides, the expression of basigin (BSG) was decreased after lncRNA RHPN1-AS1 silence, indicating the function of lncRNA RHPN1-AS1/miR-485-5p/BSG axis in HCC progression. Our study opens novel insights to help understand the mechanisms of lncRNA RHPN1-AS1/miR-485-5p/BSG axis in HCC progression, which may provide a new therapeutic target for HCC treatment.

Objective To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. Summary/background Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. Methods Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. Results Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. Conclusions Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

TPS487 Background: In 2020, there were ̃905,000 new cases and ̃830,000 deaths from liver cancer globally, and a respective 410,038 and 391,152 in China (5-year overall survival [OS]: 14.1%).1,2,3 Hepatocellular carcinoma (HCC) accounts for 75%–85% of liver cancers.1 Transarterial chemoembolization (TACE) is the preferred treatment for patients with intermediate-stage unresectable HCC (uHCC); however, there are issues with the need for repeated dosing and the heterogenous target population (median OS: 13–43 mo). Treatment with TACE + systemic therapy may improve this. Although several trials reported negative results for TACE + sorafenib (sor) vs TACE alone in patients with uHCC, the TACTICS trial showed improved untreatable (unTACEable) progression-free survival (PFS) (25.2 vs 13.5 mo; P= 0.006).4 While promising, the unmet need for combination therapies remains. The recent IMbrave150 trial showed significantly improved OS with atezolizumab (atezo) + bevacizumab (bev) vs sor (19.2 vs 13.4 mo; P= 0.0009) in patients with uHCC5, making it an attractive option for combination with TACE. Methods: TALENTACE (NCT047126430) is a phase III, open-label, randomized study to evaluate the efficacy and safety of TACE + atezo + bev or TACE alone in patients with uHCC. Key inclusion criteria are ≥18 years old, HCC diagnosis, no prior systemic treatment, no prior locoregional treatment of target lesions, eligible for TACE treatment, tumor max diameter + tumor number ≥6, and not a candidate for curative therapy. Patients with tumors that have macrovascular invasion (MVI) or extrahepatic spread (EHS) are excluded. Patients will be randomized (1:1) to receive TACE + atezo + bev or TACE alone. TACE will be performed by clinical demand; atezo (1200 mg) and bev (15 mg/kg) will be administered by intravenous infusion on Day 1 of each 21-day cycle. Co-primary endpoints are independent review committee-determined TACE-PFS (randomization to unTACEable progression, TACE failure/refractoriness, or death) and OS. Secondary endpoints include investigator-determined TACE-PFS; time to unTACEable progression, progression, MVI, EHS, and MVI/EHS; objective response rate, duration of response, patient reported outcomes, and incidence of adverse events. References: Sung, H., et al. CA Cancer J Clin. 2021;71(3):209–249. World Health Organisation: Globocan 2020 – China Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf [accessed 1 June 2021] Allemani, C., et al. Lancet. 2018, 391(10125): 1023–1075. Kudo, M., et al. Gut. 2020;69(8):1492–1501. Finn, RS., et al. J Clin Oncol. 2021;39(no. 3_suppl):267–267. Clinical trial information: NCT04712643.

14‐3‐3ζ, a phosphopeptide‐binding molecule, is reportedly overexpressed in the cancerous tissues of patients with hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) protein X (HBx) draws intensive attention in HBV‐related HCC because it not only regulates HBV replication, but also promotes carcinogenesis by interacting with various tumor or antitumor molecules. This study is performed to investigate whether and how 14‐3‐3ζ interacts with HBx. The coimmunoprecipitation (Co‐IP) results showed that 14‐3‐3ζ bond to HBx in HBV‐infected Hep3B HCC cells and CSQT‐2 portal vein tumor thrombosis (PVTT) cells. By performing Co‐IP assay in HBV‐free Huh7 cells expressing wild‐type HBx, mutant HBx‐S31A, or HBx‐S31D (serine31 was mutated into alanine31 or aspartic acid31), we found that the phosphorylated serine31 with its near amino acid residues constituted a RPLphosphoS31 GP (R, arginine; P, proline; L, leucine; S, serine; G, glycine) motif in HBx for 14‐3‐3ζ docking. This 14‐3‐3ζ‐HBx interaction was partly impaired when Akt signaling transduction was blocked by LY294002. Furthermore, 14‐3‐3ζ silencing augmented HBx ubiquitination and decreased its expression in cancer cells and xenograft tumor. The migratory and invasive abilities of CSQT‐2 cells were inhibited upon 14‐3‐3ζ silencing, whereas partly restored by HBx overexpression. Additionally, 14‐3‐3ζ positively correlated with HBx to be overexpressed in the primary HCC tissues (r = 0.344) and metastatic PVTT (r = 0.348). In summary, findings of this study reveal a novel 14‐3‐3ζ‐HBx interaction in HCC cells and suggest 14‐3‐3ζ as a candidate target for treating HBV‐related HCC.

Clinically significant portal hypertension (CSPH) is associated with an incremental risk of esophageal varices and overt clinical decompensations. However, hepatic venous pressure gradient (HVPG) measurement, the gold standard for defining CSPH (HVPG≥10 mm Hg) is invasive and therefore not suitable for routine clinical practice. This study aims to develop and validate a radiomics-based model as a noninvasive method for accurate detection of CSPH in cirrhosis. The prospective multicenter diagnostic trial (CHESS1701, ClinicalTrials.gov identifier: NCT03138915 ) involved 385 patients with cirrhosis from five liver centers in China between August 2016 and September 2017. Patients who had both HVPG measurement and contrast-enhanced CT within 14 days prior to the catheterization were collected. The noninvasive radiomics model, termed rHVPG for CSPH was developed based on CT images in a training cohort consisted of 222 consecutive patients and the diagnostic performance was prospectively assessed in 163 consecutive patients in four external validation cohorts. rHVPG showed a good performance in detection of CSPH with a C-index of 0·849 (95%CI: 0·786–0·911). Application of rHVPG in four external prospective validation cohorts still gave excellent performance with the C-index of 0·889 (95%CI: 0·752–1·000, 0·800 (95%CI: 0·614–0·986), 0·917 (95%CI: 0·772–1·000), and 0·827 (95%CI: 0·618–1·000), respectively. Intraclass correlation coefficients for inter- and intra-observer agreement were 0·92–0·99 and 0·97–0·99, respectively. A radiomics signature was developed and prospectively validated as an accurate method for noninvasive detection of CSPH in cirrhosis. The tool of rHVPG assessment can facilitate the identification of CSPH rapidly when invasive transjugular procedure is not available.

Background. We applied augmented reality (AR) techniques to flexible choledochoscopy examinations. Methods. Enhanced computed tomography data of a patient with intrahepatic and extrahepatic biliary duct dilatation were collected to generate a hollow, 3-dimensional (3D) model of the biliary tree by 3D printing. The 3D printed model was placed in an opaque box. An electromagnetic (EM) sensor was internally installed in the choledochoscope instrument channel for tracking its movements through the passages of the 3D printed model, and an AR navigation platform was built using image overlay display. The porta hepatis was used as the reference marker with rigid image registration. The trajectories of the choledochoscope and the EM sensor were observed and recorded using the operator interface of the choledochoscope. Results. Training choledochoscopy was performed on the 3D printed model. The choledochoscope was guided into the left and right hepatic ducts, the right anterior hepatic duct, the bile ducts of segment 8, the hepatic duct in subsegment 8, the right posterior hepatic duct, and the left and the right bile ducts of the caudate lobe. Although stability in tracking was less than ideal, the virtual choledochoscope images and EM sensor tracking were effective for navigation. Conclusions. AR techniques can be used to assist navigation in choledochoscopy examinations in bile duct models. Further research is needed to determine its benefits in clinical settings.

Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such “uncapturable and invisible” CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45−/CD31−) in patients subjected to surgical resection. Clinical significance of diverse subtypes of CTC was systematically investigated. Existence of small cell size CTCs (≤5 μm of WBCs) with cytogenetic abnormality of aneuploid chromosome 8, which constituted majority of the detected CTCs in HCC patients, was demonstrated for the first time. The stemness marker EpCAM+ aneuploid circulating tumor stem cells (CTSCs), and EpCAM− small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity of small triploid CTCs (≥5 cells/6 ml blood), multiploid (≥pentasomy 8) CTSCs or CTM (either one ≥ 1) significantly correlated to HCC patients' poor prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs in post-operative patients help predict neoplasm recurrence.

Adequate hepatopetal portal vein blood flow is obligatory to ensure proper liver function after liver transplantation. Large collateral veins as shunts impair portal vein flow and even cause hepatofugal blood flow and portal steal syndrome. In particular, splenorenal shunts in liver transplant recipients can lead to allograft dysfunction and possible allograft loss or hepatic encephalopathy. Restoration of portal flow through left renal vein ligation (LRVL) is a treatment option, which is much easier compared to splenectomy, renoportal anastomosis and shunt closure, but bears the risk of moderate and temporary impairment of renal function. In addition, a patent portal vein is mandatory for LRVL. However, although LRVL has been reported to be an effective, safe and easy method to control portacaval shunts and increase hepatopetal flow in some studies, indications and safety are still not clear. In this review, we summarize existing studies on LRVL during liver transplantation.

Unlike chemical pesticides, antiviral plants are biodegradable, replenishable and safe. In this study, 14 sesquiterpene compounds from Tithonia diversifolia were tested for their activities against Tobacco mosaic virus (TMV) using the half-leaf method. Tagitinin C (Ses-2) and 1β-methoxydiversifolin-3-0-methyl ether (Ses-5) were found to have in vivo curative activities of 62.86% and 60.27% respectively, at concentrations of 100μg/mL, respectively. In contrast, the in vivo curative inhibition rate of control agent ningnanmycin was 52.48%. Indirect enzyme-linked immunosorbent assay (ID-ELISA) also verified Ses-2 and Ses-5 had higher inhibition activities than the control agent ningnanmycin. Additionally, qRT-PCR showed that both Ses-2 and Ses-5 can partly inhibit the expression of CP and RdRp, two genes that play key roles in TMV infection. When TMV started to systemically spread, Ses-2 inhibited CP expression while Ses-5 inhibited RdRp expression. These results suggest that the two bio-agents have anti-TMV activities and may be used as bio-pesticides to control the plant virus.

Background The aim of this study was to determine the effect of anatomic resection (AR) versus non-anatomic resection (NAR) on recurrence rates in patients with hepatocellular carcinoma (HCC). Methods Eligible patients were randomized to AR or NAR from January 2006 to July 2007 at a single center. The primary outcome was the 2-year recurrence-free survival (RFS). Secondary outcomes were postoperative complications, time to first recurrence, 1-, 3-, and 5-year RFS, and overall survival (OS). Results Fifty-three (51%) and 52 (50%) patients underwent NAR and AR, respectively. A larger proportion of patients achieved margins ≥20 mm in the AR group (52% vs. 30%; P = 0.023). Complications (blood loss, transfusion requirement, and hospital stay) were similar between the two groups. Median follow-up was 33 (range, 2–77) months. Incidence of local recurrence at 2 years was 30% and 59% in the AR and NAR groups, respectively. Median time to first local recurrence in the AR group was significantly longer than in the NAR group (53 vs. 10 months, P = 0.010). There was no difference in overall RFS between the two groups (P = 0.290). Discussion AR decreased the 2-year local recurrence rate and increased the time to first local recurrence compared to NAR in patients with HCC.

Background Decision making and surgical planning are to achieve the precise balance of maximal removal of target lesion, maximal sparing of functional liver remnant volume, and minimal surgical invasiveness and therefore, crucial in liver surgery. The aim of this prospective study was to validate the accuracy and predictability of 3D interactive quantitative surgical planning approach (IQSP), and to evaluate the impact of IQSP on traditional surgical plans based on 2D images. Methods A total of 305 consecutive patients undergoing hepatectomy were included in this study. Surgical plans were created by traditional 2D approach using picture archiving and communication system (PACS) and 3D approach using IQSP respectively by two groups of physicians who did not know the surgical plans of the other group. The two surgical plans were submitted to the chief surgeon for selection before operation. The specimens were weighed. The two surgical plans were compared and analyzed retrospectively based on the operation results. Results The two surgical plans were successfully developed in all 305 patients and all the 3D IQSP surgical plans were selected as the final decision. Total 278 patients successfully underwent surgery, including 147 uncomplex hepatectomy and 131 complex hepatectomy. Twenty-seven patients were withdrawn from hepatectomy. In the uncomplex group, the two surgical plans were the same in all 147 patients and no statistically significant difference was found among 2D calculated resection volume (2D-RV), 3D IQSP calculated resection volume (IQSP-RV) and the specimen volume. In the complex group, the two surgical plans were different in 49 patients (49/131, 37.4%). According to the significance of differences, the 49 different patients were classified into three grades. No statistically significant difference was found between IQSP-RV and specimen volume. The coincidence rate of territory analysis of IQSP with operation was 92.1% (93/101) for 101 patients of anatomic hepatectomy. Conclusions The accuracy and predictability of 3D IQSP were validated. Compared with traditional surgical planning, 3D IQSP can provide more quantitative information of anatomic structure. With the assistance of 3D IQSP, traditional surgical plans were modified to be more radical and safe.

A new isolate, 14YV733, of pepper chlorotic spot virus (PCSV) from chili peppers in Yunnan province of China was identified. The typical tospoviral particles of 80-120 nm in diameter were observed by electron microscopy. The virus caused systemic symptoms in several solanaceous plants and the Brassica rapa L. Chinensis group with mechanical inoculation. The sap from infected leaves reacted positively to a rabbit antibody to the N protein of watermelon silver mottle virus (WSMoV) in immunoblotting. The S, M, and L RNAs of PCSV-14YV733 are 3310 nts, 4711 nts, and 8913 nts long, respectively. This is the first report of complete sequences of PCSV in mainland China. Phylogenetic analysis of all tospoviral proteins indicated that PCSV-14YV733 is closely related to members of the WSMoV serogroup.

Although intratumor diversity driven by selection has been the prevailing view in cancer biology, recent population genetic analyses have been unable to reject the neutral interpretation. As the power to reject neutrality in tumors is often low, it will be desirable to have an alternative means to test selection directly. Here, we utilize gene expression data as a surrogate for functional significance in intra- and intertumor comparisons. The expression divergence between samples known to be driven by selection (e.g., between tumor and normal tissues) is always higher than the divergence between normal samples, which should be close to the neutral level of divergence. In contrast, the expression differentiation between regions of the same tumor, being lower than the neutral divergence, is incompatible with the hypothesis of selectively driven divergence. To further test the hypothesis of neutral evolution, we select a hepatocellular carcinoma tumor that has large intratumor SNV and CNV (single nucleotide variation and copy number variation, respectively) diversity. This tumor enables us to calibrate the level of expression divergence against that of genetic divergence. We observe that intratumor divergence in gene expression profile lags far behind genetic divergence, indicating insufficient phenotypic differences for selection to operate. All these expression analyses corroborate that natural selection does not operate effectively within tumors, supporting recent interpretations of within-tumor diversity. As the expected level of genetic diversity, hence the potential for drug resistance, would be much higher under neutrality than under selection, the issue is of both theoretical and clinical significance.

// Haowen Tang 1,* , Wenping Lu 1,* , Bingmin Li 2,* , Chonghui Li 1 , Yinzhe Xu 1 and Jiahong Dong 1,3 1 Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Haidian, Beijing, China 2 Chinese PLA Medical School, Haidian, Beijing, China 3 Center for Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University Medical Center, Changping, Beijing, China * These authors have contributed equally to this work Correspondence to: Jiahong Dong, email: // Keywords : neutrophil-lymphocyte ratio; biliary tract cancer; overall survival; relapse free survival; prognosis Received : December 27, 2016 Accepted : February 28, 2017 Published : March 12, 2017 Abstract Background: Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. Methods: MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. Results: Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. Conclusion: This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer.

The management of bile duct injury (BDI) remains a considerable challenge in hepatobiliary surgery. BDI is mainly iatrogenic, and mostly occurs in cholecystectomy. Laparoscopic cholecystectomy (LC) has been performed widely, however, the incidence of BDI associated with LC increases 2-3 times compared to that in open cholecystectomy (OC). BDI also occurs in robotic cholecystectomy. In China, the evidence-based Practice Guideline for Diagnosis and Treatment of BDI was published by the Biliary Surgery Group of Surgery Branch of Chinese Medical Association, with the purpose of reducing the incidence of BDI as well as promoting its optimal diagnosis and treatment. Surgery remains the mainstay of treatment for BDI and traumatic bile duct stricture. The definitive repair involves a series of procedures including exposing the proximal and distal bile duct, anastomotic bile duct tissue preparation, minimally invasive tissue anastomoses, and so on. Successful management is a surgical challenge requiring great specialized experience and precise surgical skill. The application of precision biliary surgery is recommended for promoting standardized management of BDI.

The aim of the present study was carried out to investigate the association of microRNA-133b (miRNA-133b) expression with the prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. In the present study, the expression of miRNA-133b in HCC tissues was determined to be lower than that noted in the adjacent normal tissues. Overall and disease-free survival of the HCC patients with high miRNA-133b expression was observably extended, compared with the HCC patients with low miRNA‑133b expression. Moreover, the overexpression of miRNA-133b inhibited cell proliferation, increased lactate dehydrogenase (LDH) activity, induced apoptosis and promoted caspase‑3/-8 activities and Bax/Bcl-2 protein expression in HCC cells, whereas the protein expression of epidermal growth factor receptor (EGFR) was significantly decreased. The overexpression of miRNA-133b significantly suppressed PI3K, phosphorylated (p)-Akt and p-mTOR protein expression in HCC cells. GW2974, an EGFR inhibitor, suppressed the protein expression of EGFR, inhibited cell proliferation, increased LDH activity, induced apoptosis and promoted caspase-3/-8 activities and Bax/Bcl-2 protein expression, downregulated PI3K, p-Akt and p-mTOR protein expression in the transfected HCC cells overexpressing miRNA-133b. Taken together, our results indicate that the overexpression of miRNA-133b is associated with the increased survival of HCC patients after curative hepatectomy. The effects of miRNA-133b in HCC are mediated through the EGFR/PI3K/Akt/mTOR signaling pathway.

Unlike hematological malignancies, solid tumors have proved to be less susceptible to chimeric antigen receptor (CAR)-T cell therapy, which is partially caused by reduced accumulation of therapeutic T cells in tumor site. Since efficient trafficking is the precondition and pivotal step for infused CAR-T cells to exhibit their anti-tumor function, strategies are highly needed to improve the trafficking ability of CAR-T cells for solid tumor treatment. Here, based on natural lymphocyte chemotaxis theory and characteristics of solid tumor microenvironments, we explored the possibility of enhancing CAR-T cell trafficking by using chemokine receptors. Our study found that compared with other chemokines, several CXCR2 ligands showed relatively high expression level in human hepatocellular carcinoma tumor tissues and cell lines. However, both human peripheral T cells and hepatocellular carcinoma tumor infiltrating T cells lacked expression of CXCR2. CXCR2-expressing CAR-T cells exhibited identical cytotoxicity but displayed significantly increased migration ability in vitro. In a xenograft tumor model, we found that expressing CXCR2 in CAR-T cells could significantly accelerate in vivo trafficking and tumor-specific accumulation, and improve anti-tumor effect of these cells.

Immunotherapy might be an effective treatment in extrahepatic cholangiocarcinoma (eCCA), a tumor with extremely limited therapeutic options. Our study is to characterize the programmed death ligand-1 (PD-L1) protein expression and cancer microenvironment profiles in surgically resected eCCA samples. PD-L1 positivity was observed on tumor cells (32.3%) as well as on tumor-associated macrophages (74.2%). PD-L1 expression by eCCA correlated significantly with immune parameters such as intra-tumoral CD3+ tumor infiltrating lymphocytes (TILs) density (P = 0.002), intra-tumoral CD8+ TILs density (P < 0.001), and the expression pattern of human leukocyte antigen (HLA) class I (P < 0.001). Immunofluorescence showed that PD-L1 positive tumor cells were adjacent to PD-1 positive cells and the stroma covered with interferon-γ. Correlation with clinicopathological parameters and survival analyses revealed that PD-L1 positivity in eCCA was related to the absence of venous invasion (P = 0.030), improved overall survival (P = 0.020) and progressionfree survival (P = 0.011). HLA class I molecules defect, which is an important mechanism of immune evasion, was frequently observed in eCCA (50.0%) and was associated with a decreased number of intra-tumoral CD8+ TIL density (P = 0.028). Additionally, the presence of unusually high numbers of tumor-associated macrophages (TAMs) subsets M2 in most of eCCA (74.2%) was noted. Our study indicated that PD-L1 expression in association with intra-tumoral TILs infiltration and HLA class I expression in 32.3% of the eCCA reflects an active immune microenvironment potentially responsive to PD-1/PD-L1 inhibitors. In addition, the combination of macrophage-targeting agents may provide therapeutic synergy for future immunotherapy.

Potatoes (Solanum tuberosum) are one of the most important crops in China following rice, wheat, and corn. Aster yellows phytoplasma appeared to be widespread in China; it was found to cause diseases on alfalfa, oranges, peaches, periwinkles, bamboo (1), and cactus (4). However, scant information of this pathogen on potatoes is available except for a few short reports published during the 1950s. During the potato disease surveys conducted from 2005 to 2010 in Yunnan and Inner Mongolia, 10 to 35% of potato plants exhibited symptoms of yellowing or purpling of apical leaves, with the top leaves rolling inward and aerial tubers formation. Total DNA was extracted from midveins of leaves and roots of 125 diseased and asymptomatic plants with a DNeasy Plant Mini Kit (Qiagen, Valencia, CA) according to the manufacturer's instructions. A nested PCR was carried out with the first round primer pair P1/P7 followed by the second round primer pair R16F2n/R16R2 (2,3). A PCR product of approximately 1.2 kb was amplified from diseased plants but not from asymptomatic plants. Restriction fragment length polymorphism (RFLP) patterns were analyzed by digesting a 1.2-kb product using restriction enzymes AluI, BfaI, BstUI, HhaI, HpaI, KpnI, MseI, and RsaI. Comparing the RFLP patterns with previously published phytoplasma strains (2), aster yellows phytoplasma found on potato plants in Yunnan and Inner Mongolia belong to group I, subgroup B (16SrI-B). The PCR product from P1/P7, diluted 1:30, was amplified by using primer pair P1A/P7A (3) and P1A/16S-SR (3). The nested-PCR products from P1A/P7A and P1A/16S-SR were cloned into pCR8/GW/TOPO vector (Invitrogen, Carlsbad, CA) and sequenced by the Core Lab of the University of Alaska–Fairbanks and GENEWIZ (South Plainfield, NJ). The nucleotide sequence (GenBank Accession No. HQ599228) was analyzed by iPhyClassifier software and had 99.53% sequence identity to the reference strain (GenBank Accession No. M30790) for ‘Candidatus Phytoplasma asteris’. The RFLP similarity is identical (coefficient 1.00) to the reference pattern of 16Sr group I, subgroup B (GenBank Accession No. NC_005303). To our knowledge, this is the first report revealing the molecular characteristics of a phytoplasma associated with aster yellows-diseased potatoes in China. References: (1) H. Cai et al. Plant Prot. 31:38, 2005. (2) I.-M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (3) I.-M. Lee et al. Int. J. Syst. Evol. Microbiol. 54:337, 2004. (4) W. Wei et al. Plant Dis. 91:461, 2007.

Phytoplasmas have been reported from more than 70 plant species in China, most of which are from woody plants and very few are from potatoes (Solanum tuberosum). During the growing seasons of 2005 through 2011, potato disease surveys were conducted in seed and commercial fields in Yunnan Province and Inner Mongolia. Potato plants displayed symptoms of curled, yellowish and purplish leaves, shortened internodes, aerial tuber formation, and few small malformed underground tubers. Although the location of the fields surveyed each year varied, the disease seems to have become increasingly prevalent. In Yunnan, disease incidence was 5 to 24% in 2005 and 15 to 100% in 2010 and 2011. In Inner Mongolia, disease incidence in seed potato fields was 5 to 15% in 2006 and 25 to 50% in 2011. Total DNA was extracted from the leaves, stems, and roots of symptomatic and asymptomatic plants with a DNeasy Plant Mini Kit (Qiagen, Valencia, CA) according to the manufacturer's instruction. A nested PCR was performed by using primer pair P1/P7 followed by R16F2n/R16R2 to detect the presence of phytoplasmas (1,3). An approximate 1.25-kb PCR product was amplified from symptomatic plants but not from asymptomatic plants. Restriction fragment length polymorphism (RFLP) patterns were analyzed by digesting the 1.2-kb amplicon singly with restriction enzymes AluI, BfaI, HhaI, HpaI, KpnI, MseI, and TaqI. Comparing the RFLP patterns of samples with previously published phytoplasma strains, the phytoplasmas matched patterns of the stolbur group, subgroup E (16SrXII-E) (1). In addition, the PCR product from P1/P7, diluted 1:30, was amplified by using primer pair P1A/P7A (2). The nested PCR product was cloned into pCR8/GW/TOPO vector (Invitrogen, Carlsbad, CA) and sequenced by the Core Lab of the University of Alaska Fairbanks and GENEWIZ (South Plainfield, NJ). Nucleotide sequences (GenBank Accession No. EU293841) were analyzed by iPhyClassifier software (4), confirming the relationship of this phytoplasma to ‘Candidatus Phytoplasma fragariae’ with RFLP patterns identical to group 16SrXII-E. To our knowledge, this is the first molecular characterization of the stolbur group phytoplasmas associated with potato disease in China. The potato is becoming increasingly important in China. The impacts of stolbur on potato yield losses, disease distributions, and insect vectors are currently under investigation. References: (1) I.-M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (2) I.-M. Lee et al. Int. J. Syst. Evol. Microbiol 54:337, 2004. (3) C. D. Smart et al. Appl. Environ. Microbiol. 62:2988, 1996. (4) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

Tomato spotted wilt virus (TSWV) causes major losses of many crops worldwide. Several strategies have been attempted to control disease caused by TSWV. However, many challenges for the effective control of this disease remain. A promising approach is the use of abiotic or biotic inducers to enhance plant resistance to pathogens. We screened a diterpenoid compound from Wedelia trilobata, 3α-Angeloyloxy-9β-hydroxy-ent-kaur-16-en-19-oic acid (AHK), which had higher curative and protective effects against TSWV than the ningnanmycin control. The rapid initiation of the expression of all the TSWV genes was delayed by more than 1d in the curative assay, and the expression of the NSs, NSm and RdRp genes was inhibited. In addition, the replication of all TSWV genes in systemic leaves was inhibited in the protective assay, with an inhibition rate of more than 90%. The concentrations of jasmonic acid (JA) and jasmonic acid isoleucine (JA-ILE) in the AHK-treated and systemic leaves of the treated plants were significantly higher than those observed in the control. The results suggested that AHK can induce systemic resistance in treated plants. The transcription of the NtCOI1 gene, a key gene in the JA pathway, was significantly higher in both the inoculated and systemic leaves of the AHK-treated plants compared to the control. The AHK-induced resistance to TSWV in Nicotiana benthamiana could be eliminated by VIGS-mediated silencing of the NtCOI1 gene. These results indicated that AHK can activate the JA pathway and induce systemic resistance to TSWV infection.

Various minimally invasive approaches have been described for infected necrotizing pancreatitis. This article describes a modified minimal-access retroperitoneal pancreatic necrosectomy (MARPN) procedure assisted by gas insufflation.This retrospective, observational study documented patients who had undergone a step-up MARPN between 1 January 2010 and 31 December 2016. A minimum follow-up of 1 year was required for inclusion. The step-up approach involved percutaneous catheter drainage followed by the modified MARPN and necrosectomy. If more than one access site was needed it was categorized as complex MARPN.Of 212 patients with infected necrotizing pancreatitis, 164 (77·4 per cent) underwent a step-up approach. The median number of percutaneous catheter drains and MARPN procedures was 3 (range 1-7) and 1 (1-6) respectively. Ninety patients (54·9 per cent) underwent complex MARPN. For residual necrosis after MARPN, three patients (1·8 per cent) underwent sinus tract gastroscopy, and 11 (6·7 per cent) had sinography combined with a tube change. However, operations in 13 patients (7·9 per cent) required conversion to open surgery. Postoperative complications developed in 103 patients (62·8 per cent). The mortality rate was 6·1 per cent (10 deaths).A step-up approach using a modified MARPN for infected necrotizing pancreatitis is a reasonable option.Los procedimientos mínimamente invasivos se han convertido en los más frecuentes para el tratamiento de necrosis pancreáticas infectadas. El objetivo de este estudio fue presentar un procedimiento de necrosectomía pancreática retroperitoneal de acceso mínimo (minimal-access retroperitoneal pancreatic necrosectomy, MARPN) modificado y asistido mediante insuflación de gases, así como evaluar su seguridad y eficacia. MÉTODOS: Se realizó un análisis retrospectivo y observacional de los datos de un hospital desde el 1 de enero de 2010 hasta el 31 de diciembre de 2016. Se incluyeron en el análisis todos los pacientes en los que realizó un abordaje por etapas, que consistía en el drenaje percutáneo mediante la colocación de un catéter seguido de un procedimiento MARPN modificado, en los que se dispusiese de un seguimiento postoperatorio mínimo de 1 año. El MARPN en el lado derecho y la necrosectomía realizada a través de más de un acceso se clasificaron como MARPN complejo. Se evaluaron los resultados radiológicos y quirúrgicos.De 212 pacientes con necrosis pancreática infectada, en 164 (77,4%) se realizó un abordaje por etapas. La mediana del número de drenajes percutáneos y procedimientos MARPN fue 3 (rango, 1-7) y 1 (rango, 1-6), respectivamente. En 90 pacientes (54,9%) se realizó un MARPN complejo. Para la exéresis de necrosis residual después de un MARPN, en 3 pacientes (1,8%) se realizó mediante gastroscopia y en 11 pacientes (6,7%) con un recambio de drenaje bajo control radiológico. En 13 pacientes (7,9%) fue necesaria la reconversión a cirugía abierta. Hubo complicaciones postoperatorias en 103 pacientes (62,8%). La tasa de mortalidad fue del 6,1% (n = 10). CONCLUSIÓN: El abordaje por etapas con un MARPN modificado es seguro y efectivo en el tratamiento de la necrosis pancreática infectada.

306 Background: Combined therapy of an immune checkpoint inhibitor with a targeted antiangiogenic agent had been proved to be effective for the treatment of uHCC. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely, where ADCC/ADCP effects could induce T-cell apoptosis and clearance and then compromise anti-tumor activity. Penpulimab demonstrated a slower PD-1 antigen binding off-rate, which resulted in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and might contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Methods: In this open-label, multicenter phase Ib/II study, patients (pts) without prior systemic treatment, and classified as BCLC stage B (not amenable for locoregional therapy) or C, Child-Pugh ≤7, and ECOG PS ≤ 1 received Penpulimab (200mg IV Q3W) and Anotinib (8 mg PO 2weeks on/1 week off). Primary endpoint was ORR (RECIST v1.1); secondary endpoints were safety, DCR, DoR, TTP, PFS and OS. Results: 31 pts (median age 56 years [23–74], ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy. As of August 31, 2020, median follow-up time was 11.9 mons (range 3.7-17.7). Median PFS was 7.6 mons with 6-mons PFS rate was 57.6% while median TTP was 8.5 mons with 6-mons TTP rate was 62.7%. Median overall survival had not been met and 6-mons OS rate was 93.2%. The ORR was 31.0% (9/29) and DCR was 82.8% (24/29). At data cutoff, 77.8% of responders remained ongoing and still on treatment. Treatment-related adverse events (TRAEs) occurred in 90.3% of pts (≥G3 in 16.1% [5/31], no G5, treatment discontinuation in 9.7% [3/31]). Most common TRAEs (≥15%) were increased AST (38.7%) and ALT (35.5%), increased blood bilirubin (22.6%),asthenia (22.6%),decreased platelet count (19.4%) and rash (16.1%). Conclusions: Penpulimab plus Anlotinib showed favorable antitumor efficacy and an acceptable safety profile in pts with uHCC. The further randomized, phase 3 study of Penpulimab in combination with Anlotinib at a higher dose (10 mg PO 2 weeks on/1 week off) in this setting is ongoing (NCT04344158).

Background & Aims Noninvasive and accurate methods are needed to identify patients with clinically significant portal hypertension (CSPH). We investigated the ability of deep convolutional neural network (CNN) analysis of computed tomography (CT) or magnetic resonance (MR) to identify patients with CSPH. Methods We collected liver and spleen images from patients who underwent contrast-enhanced CT or MR analysis within 14 days of transjugular catheterization for hepatic venous pressure gradient measurement. The CT cohort comprised participants with cirrhosis in the CHESS1701 study, performed at 4 university hospitals in China from August 2016 through September 2017. The MR cohort comprised participants with cirrhosis in the CHESS1802 study, performed at 8 university hospitals in China and 1 in Turkey from December 2018 through April 2019. Patients with CSPH were identified as those with a hepatic venous pressure gradient of 10 mm Hg or higher. In total, we analyzed 10,014 liver images and 899 spleen images collected from 679 participants who underwent CT analysis, and 45,554 liver and spleen images from 271 participants who underwent MR analysis. For each cohort, participants were shuffled and then sampled randomly and equiprobably for 6 times into training, validation, and test data sets (ratio, 3:1:1). Therefore, a total of 6 deep CNN models for each cohort were developed for identification of CSPH. Results The CT-based CNN analysis identified patients with CSPH with an area under the receiver operating characteristic curve (AUC) value of 0.998 in the training set (95% CI, 0.996–1.000), an AUC of 0.912 in the validation set (95% CI, 0.854–0.971), and an AUC of 0.933 (95% CI, 0.883–0.984) in the test data sets. The MR-based CNN analysis identified patients with CSPH with an AUC of 1.000 in the training set (95% CI, 0.999–1.000), an AUC of 0.924 in the validation set (95% CI, 0.833–1.000), and an AUC of 0.940 in the test data set (95% CI, 0.880–0.999). When the model development procedures were repeated 6 times, AUC values for all CNN analyses were 0.888 or greater, with no significant differences between rounds (P > .05). Conclusions We developed a deep CNN to analyze CT or MR images of liver and spleen from patients with cirrhosis that identifies patients with CSPH with an AUC value of 0.9. This provides a noninvasive and rapid method for detection of CSPH ( ClincialTrials.gov numbers: NCT03138915 and NCT03766880 ).

BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. MATERIAL AND METHODS Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. RESULTS A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02-1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03-1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01-1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99-1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99-1.24, P=0.09). CONCLUSIONS Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions.

Background/Aims: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. Methods: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. Results: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). Conclusion: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

4592 Background: Advanced HCC is a deadly disease with few systemic therapeutic options. VEGF blockade potentiates the effect of PD-1 inhibition by opposing the immunosuppressive effects of VEGF-A (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors). A sBLA has been submitted for an anti-PD-L1 + anti-VEGF combination as 1L treatment for advanced HCC. Penpulimab is a novel humanized anti-PD-1 IgG1 antibody with complete removal of Fc receptor mediated effect, and featuring slow antigen binding off-rate and high receptor occupancy. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Methods: In this open-label, multicenter phase Ib/II study, treatment-naive pts with advanced HCC received penpulimab 200mg Q3W in combination with anlotinib 8mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary objectives were to assess antitumor activity by ORR (RECIST v1.1). The secondary objectives were to assess antitumor activity by DCR, DoR, TTP, and to assess the safety and tolerability of the combination. Results: As of Jan 14, 2020, 31 pts (median age 56 years [23-74], male 81%, ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy (a median of 6 [1-15] doses). Treatment-related adverse events (TRAEs) occurred in 93.5% of pts (G3 in 9.7% [3/31], no G4, and leading to treatment discontinuation in 6.5% [2/31]). Most frequent TRAEs were increased AST (35.5%), increased ALT (29%), asthenia (22.6%), decreased platelet count (19.4%), increased blood bilirubin (19.4%), increased bilirubin conjugated (19.4%), and rash (16.1%). Of 25 evaluable pts (with the opportunity to be followed-up for ≥2 scans, 12 weeks), confirmed ORR was 24% (6/25) and DCR was 84% (21/25). Five responders remained in response with DoR ranging 1.4+ to 6.9+ months. Median TTP was not reached and 6m-TTP rate was 63% (95% CI: 38%, 81%). Conclusions: Penpulimab in combination with anlotinib had a manageable safety profile and encouraging antitumor activities in patients with advanced HCC. No unexpected AEs were identified beyond the established safety profile for each agent. Evaluation of penpulimab + anlotinib (10 mg QD) in a phase 3 study for 1L HCC is currently underway. Clinical trial information: NCT04172571 .

Background This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). Methods We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. Results A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. Conclusions The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.

Aim To evaluate the application value of a three-dimensional (3D) printing model in the training of choledochoscopy techniques. Materials and methods Imaging data from two patients with biliary dilatation were used to produce two 3D reconstruction models which were subsequently constructed into 3D printing models (No. 1 and No. 2). Four hepatobiliary surgeons evaluated the anatomical accuracy and academic teaching value of the printed models. Twenty resident trainees with no prior experience in any kind of endoscopic techniques were randomly and symmetrically divided into two groups. The training group (A) used the 3D model No. 1 in the learning of biliary tract anatomy and practice techniques of choledochoscopy. The control group (B) got the virtual 3D image of the same model on computer for learning. After 4 weeks, the model No. 2 was used to reassess the trainees’ subjective and objective progress in anatomy familiarity and choledochoscopy manipulations. Results All consulted surgeons agreed that the 3D models realistically reproduced the anatomy of the biliary system. All trainees in group A agreed or strongly agreed that the 3D models provided good anatomical realism, enhanced their experience in the training of choledochoscopy techniques, and aided in their learning of biliary anatomy. With the practice went on, they increased the accuracy and showed a reduction in operation time on the model No. 1. During final examination with model No. 2, the rate of correct anatomical structure identification in training group was significantly higher than group B (p

This study seeks to compare the impact of selective partial portal vein ligation (PPVL) or the combination of simultaneous hepatic artery ligation (PPVAL) with in situ splitting (ISS) on liver regeneration and injury. Rats were randomized into three groups; namely: selective PVL, PPVL + ISS and PPVAL + ISS. The changes in hepatic hemodynamics, liver regeneration and hepatocytic injury were examined. Blood flow to the left portal branch and the microcirculation of the left median lobe after PPVL or PPVAL was significantly reduced. Liver regeneration of PPVAL + ISS group was more pronounced than that in the PPVL + ISS and PVL groups at 48 and 72 hours as well as 7 d postoperatively. The serum biochemical markers and histopathological examination demonstrated reduced levels of liver injury in the PPVL + ISS group. Injury to hepatocytes was more pronounced with PPVAL + ISS than PVL. HGF, TNF-α and IL-6 expression in the regenerated lobes in both PPVAL + ISS and PPVL + ISS groups increased significantly when compared to the PVL group. We demonstrated that both PPVL + ISS and PPVAL + ISS were effective and feasible means of inducing remnant liver hypertrophy and could serve as a rapid clinical application for qualified patients.

Clinically significant portal hypertension (CSPH) is associated with an incremental risk of esophageal varices and overt clinical decompensations. However, hepatic venous pressure gradient (HVPG) measurement, the gold standard for defining CSPH is invasive and impractical for routine clinical practice. This study aims to develop and validate a radiomics-based model as a noninvasive method for accurate detection of CSPH in cirrhosis. The prospective multicenter diagnostic trial (CHESS1701, ClinicalTrials.gov identifier: NCT03138915) involved 385 patients with cirrhosis from 5 liver centers in China between August 2016 and September 2017. Patients who had a HVPG measurement and contrast-enhanced CT within 14 days prior to the catheterization were collected. The noninvasive radiomics model, termed rHVPG for CSPH was developed based on CT images in a primary cohort that consisted of 222 consecutive patients and the diagnostic performance was prospectively assessed in 163 consecutive patients in 4 external validation cohorts. rHVPG showed a high diagnostic accuracy for detection of CSPH with a C-index of 0.849 (95%CI: 0.786-0.911). Application of rHVPG in 4 external prospective validation cohorts still gave excellent performance with the C-index of 0.889 (95%CI: 0.752-1.000, 0.800 (95%CI: 0.614-0.986), 0.917 (95%CI: 0.772-1.000), and 0.827 (95%CI: 0.618-1.000), respectively. Intraclass correlation coefficients for inter- and intra-observer agreement were 0.92-0.99 and 0.97-0.99, respectively. A novel radiomics signature was developed and prospectively validated as an accurate method for noninvasive detection of CSPH in cirrhosis. The tool of rHVPG assessment can facilitate the identification of CSPH rapidly when invasive transjugular procedure is not available. Trial Registration Number: ClinicalTrials.gov identifier: NCT03138915 Funding: This work was supported by the grants from National Natural Science Foundation of China (81600510, 81672725); Guangzhou Industry-Academia-Research Collaborative Innovation Major Project (201704020015); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (ZYLX201610), Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20151602), Application Research on Clinical Characteristics of the Capital (z161100000516197), Capital’s Funds for Health Improvement and Research (2018-1-2081). Conflict of Interest: No author has any potential conflict to disclose (financial, professional or personal) relevant to the manuscript. Ethical Approval Statement: The study was performed according to Helsinki declaration and approved by all institutional review board.

In China, potato is widely cultivated economic crop. Recently, potato diseases with characteristic symptoms of phytoplasma infections were found in potato fields. In 2006 and 2007, samples exhibiting symptoms including rosette and upright growth, upward rolling, yellowing and purpling of leaves, shortened and thickened internodes and formation of aerial tubers were collected from plants in Yunnan and Inner Mongolia and analyzed for the presence of phytoplasmas. DNA was extracted from tissues of 63 symptomatic and 10 asymptomatic plants. Phytoplasma 16S rRNA was amplified by PCR with primer pair P1/P7, followed by nested PCR with P1A/P7A, P1A/16S-SR or R16F2n/R16R2n. Twenty nine symptomatic plants (46 %), but no asymptomatic plants, tested positive for phytoplasmas. Nested PCR products were cloned and sequenced. Sequence analysis indicated that the phytoplasmas from diseased potatoes shared 98.1–99.8 % similarity with ‘Candidatus Phytoplasma fragariae’ (16SrXII-E) and other strains in 16SrXII subgroups. RFLP and phylogenetic analyses also indicated that phytoplasmas of group 16SrXII were associated with phytoplasma infected potatoes in China; these strains are most closely related to subgroup 16SrXII-E. Our results showed that five strains belonged to 16SrXII-E; 11 strains were designated as a new 16SrXII subgroup, 16SrXII-I; and subgroup affiliations of all others were not determined. The genetic diversity of the strains was corroborated by sequence analysis of ribosomal protein genes, the elongation factor Tu gene (tuf) and the pre-protein translocase membrane subunit gene (secY). The results illustrated the complexity and diversity of phytoplasmas associated with potatoes in China.

Hydrogel as three-dimensional (3D) substrate has been employed in miniaturized high throughput protein detection platforms to increase the number of effective antibodies and signal augmentation. However, the high water content of the hydrogel can dilute samples and create barrier to mass transfer, limiting hydrogel height to several microns in most platforms. Moreover, these platforms cannot achieve widespread use in common laboratories as they usually rely heavily on expensive robotic liquid handlers and custom-built components. Here we developed a ready-to-use, easy to store and handle, versatile and multiplex-able 3D scaffold-based immunoassay chip (3D immunoChip) possible for high throughput protein quantification using bench-top equipment in common laboratories. Sample dilution, mass transfer, signal scattering and storage problems can be avoided by using dry scaffolds that regain transparency upon rehydration. When combined with hydrophilic-hydrophobic patterned reagent loading slides, manual high throughput handling of samples can be achieved. As these micro-scaffolds are patterned without barriers in between, simultaneous and effortless washing of all the reaction zones is possible in a Petri dish. Such features aid the 3D immunoChip in saving up to 100 times reagent and about 6 times labour. The 3D immunoChip is able to detect albumin (ALB), as a model analyte, from 5 ng mL(-1) to 1000 ng mL(-1), making it comparable to the commercialized ELISA kit based on a 96-well plate (0.22-400 ng mL(-1)). This thus enables the 3D immunoChip to directly detect ALB secreted by HepaRG cells cultured in a 3D cell culture array chip for high throughput drug hepatotoxicity evaluation, which could potentially accelerate drug screening.

3-Acetonyl-3-hydroxyoxindole (AHO) induces systemic acquired resistance (SAR) in Nicotiana. However, the underlying molecular mechanism is not well understood. To understand the molecular regulation during SAR induction, we examined mRNA levels, microRNA (miRNA) expression, and their regulatory mechanisms in control and AHO-treated tobacco leaves. Using RNA-seq analysis, we identified 1,445 significantly differentially expressed genes (DEGs) at least 2 folds with AHO treatment. The DEGs significantly enriched in six metabolism pathways including phenylpropanoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis for protective cuticle and wax. Key DEGs including PALs and PR-10 in salicylic acid pathway involved in SAR were significantly regulated. In addition, we identified 403 miRNAs belonging to 200 miRNA families by miRNA sequencing. In total, AHO treatment led to 17 up- and 6 down-regulated at least 2 folds (Wald test, P SPL6 and AP2. We concluded that both mRNA and miRNA regulation enhances AHO-induced SAR. These data regarding DEGs, miRNAs, and their regulatory mechanisms provide molecular evidence for the mechanisms involved in tobacco SAR, which are likely to be present in other plants.

Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such "uncapturable and invisible" CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45

Hypertrophic scars/keloids are pathogenic scars that are characterized by collagen and fibroblast accumulation. The endothelia in the lesions are mechanosensitive and participate actively in the pathogenesis of these scars. The present review summarizes how endothelium responds to mechanical stimuli such as shear, stretch and hydrostatic pressure. It also shows that in heart, liver, kidney and lung fibrosis, endothelial dysfunctions (EDs) associate with changes in vascular tone, endothelial permeability, coagulation and vasomodulation that result in inflammation, hypertension and coagulation. Pathological scars exhibit similar EDs during their development and progression. Mechanopharmaceutical or mechanotherapeutic interventions that rescue EDs may be useful scar treatments.

Background Augmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes. Data Sources The keywords “augmented reality”, “liver”, “laparoscopic” and “hepatectomy” were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles. Results In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology. Conclusions With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.

Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure. Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure. Preoperative UIs are highly correlated with Child score (P

Based on the serological relationships of nucleocapsid proteins (NPs), a tospovirus species can be classified as a member of a serogroup or a distinct serotype, which greatly helps virus identification and disease diagnosis. Recent studies reported that distinct tospovirus species sharing above 51.8 % amino acid (aa) identity in their NPs may be serologically related. Two phylogenetically related peanut-infecting tospovirus species, Peanut chlorotic fan-spot virus (PCFV) in Taiwan and Peanut yellow spot virus (PYSV) in India, were previously considered as distinct serotypes, since no serological relationship has been established. To verify the serological relationship of PCFV and PYSV, the NP of PCFV was purified from leaf tissues of the infected Chenopodium quinoa plants and used to produce polyclonal antiserum (RAs-PCFV NP) and a monoclonal antibody (MAb-PCFV NP). Polyclonal antiserum to the bacterially expressed NP of PYSV (RAs-PYSV NP) was also prepared. RAs-PCFV NP reacted with the homologous PCFV NP and the bacterial-expressed PYSV NP and tissue extracts of PYSV-infected plants. Reciprocally, RAs-PYSV NP reacted with the homologous bacterial-expressed PYSV NP and the tissue extracts of PYSV-infected or PCFV-infected plants. In addition, MAb-PCFV NP reacted only with the tissue extracts of PCFV-infected plants. Our results demonstrate that PCFV NP is serologically related to PYSV NP and they should be classified as members of a unique serogroup.

The complete genome sequence of a new potato virus M (PVM) isolate (PVM-YN), collected from potato (Solanum tuberosum) in Yunnan, China, was determined. It was 8,530 nucleotides (nt) in length, excluding the poly(A) tail at the 3′ end, and shared 71.4–72.0% nucleotide sequence identity with available PVM isolates in the NCBI database. The coat proteins (CP) of PVM-YN shared 79.0–97.4% amino acid sequence identity with that of other isolates. It is the first report of the complete genomic sequence of a new PVM isolate infecting S. tuberosum in China.

Targeted cell delivery to lesion sites via minimally invasive approach remains an unmet need in regenerative medicine to endow satisfactory therapeutic efficacy and minimized side-effects. Here, we rationally designed a pathology-targeted cell delivery strategy leveraging injectable micro-scaffolds as cell-loading capsule and endogenous tissue transglutaminase (TGase) at lesion site as adhesive. Up-regulated TGase post-liver injury catalyzed chemical bonding between the glutamine and lysine residues on liver surface and micro-scaffolds both ex vivo and in vivo, facilitating sufficient adhesion on the pathological liver. Upon intraperitoneal injection, Mesenchymal Stem Cell-loaded capsules, exhibiting cell protection from shear-induced damage and post-transplantation anoikis, adhered to the CCl4-treated liver with a hundred-fold improvement in targeting efficiency (70.72%) compared to free-cell injection, which dramatically improved mice survival (33.3% vs. 0% for free-cell therapy) even with low-dosage treatment. This unique and widely-applicable cell delivery mechanism and strategy hold great promise for transforming cell therapy for refractory diseases.

Adequate hepatopetal portal vein blood flow is obligatory to ensure proper liver function after liver transplantation. Large collateral veins as shunts impair portal vein flow and even cause hepatofugal blood flow and portal steal syndrome. In particular, splenorenal shunts in liver transplant recipients can lead to allograft dysfunction and possible allograft loss or hepatic encephalopathy. Restoration of portal flow through left renal vein ligation (LRVL) is a treatment option, which is much easier compared to splenectomy, renoportal anastomosis and shunt closure, but bears the risk of moderate and temporary impairment of renal function. In addition, a patent portal vein is mandatory for LRVL. However, although LRVL has been reported to be an effective, safe and easy method to control portacaval shunts and increase hepatopetal flow in some studies, indications and safety are still not clear. In this review, we summarize existing studies on LRVL during liver transplantation.

Mechanical stapling devices have been established as a mainstay in laparoscopic splenectomy (LS), but limited data are available regarding stapleless LS for splenomegaly with individual vessel dissection (IVD). This study aimed to investigate the feasibility of stapleless LS for splenomegaly and its potential advantage over staple-based LS. A total of 51 patients with splenomegaly underwent stapleless LS and were subsequently reviewed. The data collected include the patients’ demographics, operative outcomes, and the rates of conversion to open surgery, complications, and mortality. Multiple linear and logistic regression analyses were used to assess the impact of the primary diagnosis, body mass index (BMI), and massive splenomegaly on the perioperative conversion rate. There were no deaths. The mean for various parameters are as follows: spleen length 21.6 cm; spleen weight 1,184 g, operating time 148 min, hospital stay 5.2 days, estimated blood loss 245 ml. The total conversion rate was 9.8 % (including one reoperation for bleeding). The presence of a BMI >30 % and hematologic malignancy—cofactors of portal hypertension (PH)—and a spleen weight >1,000 g were independent predictors of conversion to open surgery. Stapleless LS for splenomegaly is feasible and safe in selected patients. It has advantages over traditional procedures using staples, at least in patients with benign splenomegaly. Patients with hematologic malignancy, BMI >30 %, coexistence of PH, and spleen weight >1,000 g are susceptible to bleeding during dissection of the splenic hilum, with use of IVD being relatively limited.