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Background: The identification of patients at high risk of developing postoperative complications is important to improve surgical safety. We sought to develop an individualized tool to predict post-hepatectomy major complications in hepatitis B virus (HBV)-infected patients with hepatocellular carcinoma (HCC).Methods: A multicenter database of patients undergoing hepatectomy for HCC were analyzed; 2/3 and 1/3 of patients were assigned to the training and validation cohorts, respectively. Independent risks of postoperative 30-day major complications (Clavien-Dindo grades III-V) were identified and used to construct a web-based prediction model, which predictive accuracy was assessed using C-index and calibration curves, which was further validated by the validation cohort and compared with conventional scores.Results: Among 2762 patients, 391 (14.2%) developed major complications after hepatectomy. Diabetes mellitus, concurrent hepatitis C virus infection, HCC beyond the Milan criteria, cirrhosis, preoperative HBV-DNA level, albumin-bilirubin (ALBI), and aspartate transaminase to platelet ratio index (APRI) were identified as independent predictors of developing major complications, which were used to construct the online calculator ( http://www.asapcalculate.top/Cal11_en.html ). This model demonstrated good calibration and discrimination, with the C-indexes of 0.752 and 0.743 in the training and validation cohorts, respectively, which were significantly higher than those conventional scores (the training and validation cohorts: 0.565 ~ 0.650 and 0.568 ~ 0.614, all P < 0.001).Conclusions: A web-based prediction model was developed to predict the probability of post-hepatectomy major complications in an individual HBV-infected patient with HCC. It can be used easily in the real-world clinical setting to help management-related decision-making and early warning, especially in areas with endemic HBV infection. [ABSTRACT FROM AUTHOR]

Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001). Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival. [ABSTRACT FROM AUTHOR]

Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC. The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity. Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126–1.451; P < 0.001) and recurrence (1.187; 1.058–1.331; P = 0.004). This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important. [ABSTRACT FROM AUTHOR]

Background Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase ( TERT ) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets. [ABSTRACT FROM AUTHOR]

A novel salicylaldehyde-4-hydoxy phenylacetyl acylhydrazone (C 15 H 14 N 2 O 3 , HL) and its three new mononuclear complexes, [CuLPy]NO 3 (1), [CuLCl(EtOH)] (2) and [CoL 2 ]NO 3 ·EtOH (3), were synthesized. The interactions of the four compounds with DNA/BSA have been studied by UV–Vis spectroscopy, fluorescence spectroscopy, microcalorimetry and molecular docking methods. Furthermore, the antibacterial activities of the four compounds were determined. [Display omitted] A salicylaldehyde-4-hydroxy phenyl acetyl acyl hydrazone (C 15 H 14 N 2 O 3 , HL) and its three complexes ([CuLPy]NO 3 (1), [CuLCl(EtOH)] (2) and [CoL 2 ]NO 3 ·EtOH, (3)) were synthesized. The single crystal X-ray diffraction results of 1 , 2 and 3 showed that the coordination atoms (N and O atoms) in the complexes exhibited four-coordinated pyramidal, five-coordinated and six-coordinated octahedral geometries centered on the metal ions, respectively. TG-DTG techniques illustrated that the maximum thermal decomposition peak temperatures of these compounds were all higher than 200 ℃, exhibiting strong thermal stabilities. All four compounds, HL , 1 , 2 and 3 , quenched the intrinsic fluorescence of BSA by means of static processes, as investigated by fluorescence spectra, which suggested that these compounds could effectively combine with BSA to form non-fluorescent ground state complexes. The UV–vis spectra showed that HL , 1 , 2 and 3 effectively combined with CT-DNA through intercalative modes. Microcalorimetry tests indicated that the interaction processes of HL , 1 and 2 with BSA and CT-DNA were all spontaneously exothermic and entropy reducing, and each of the interaction durations was within 50 min. The interactions of the four compounds with BSA and CTDNA were also simulated by the molecular docking method, showing that the four compounds had hydrogen bonds and hydrophobic interactions with BSA and CT-DNA. The antibacterial activities of HL , 1 , 2 and 3 against S. aureus, P. aeruginosa, B. subtilis and E. coli were determined, revealing that 1 and 2 exhibit stronger inhibition activities against P. aeruginosa than gentamicin sulfate. Complexes 1 and 2 are potential alternative drugs to gentamicin sulfate in the future. [ABSTRACT FROM AUTHOR]

Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy. [ABSTRACT FROM AUTHOR]

Two novel transition metal complexes ZnL 2 ·H 2 O (I) and [CrL 2 ]NO 3 ·EtOH (II) were synthesized by C 15 H 14 N 2 O 3 (HL) with Zn(NO 3) 2 ·6H 2 O and Cr(NO 3) 3 ·9H 2 O. The binding modes of I and II with CT-DNA/BSA had been studied by UV-vis spectroscopy, fluorescence spectroscopy and microcalorimetry. Furthermore, antibacterial activities of two complexes were also determined. [Display omitted] Two salicylaldehyde-4-hydroxy phenylacetyl acylhydrazone transition metal complexes ZnL 2 ·H 2 O (I) and [CrL 2 ]NO 3 ·EtOH (II) were synthesized by C 15 H 14 N 2 O 3 (HL) with Zn(NO 3) 2 ·6H 2 O and Cr(NO 3) 3 ·9H 2 O. Structures of HL , I and II were characterized by single crystal X-ray diffraction. With the ligand HL belonging to the monoclinic crystal system and the P 2 1 / c space group, the coordinating atoms (N and O atoms) in both two complexes I and II exhibited a six-coordinated octahedral geometry centered on the metal ion. Thermal stabilities of the two complexes were analyzed by TG-DTG techniques, which illustrated the maximum thermal decomposition peak temperatures of two complexes were both higher than 170 °C, exhibiting strong thermal stabilities. UV–vis absorption spectroscopy and microcalorimetry were used to determine interaction patterns of I and II with CT-DNA, showing that I and II effectively bound to CT-DNA through the intercalation mode and the interactions processes of I and II with CT-DNA were spontaneous, exothermic entropy reduction reactions. Fluorescence spectroscopy and microcalorimetry were used to determine the interactions of I and II with BSA, presenting that the two complexes can effectively bind to BSA and form non-fluorescent matrix complexes and the interactions processes were spontaneous exothermic and entropy reducing, and each of interaction duration was within 48 min. In addition, the antimicrobial activities of complexes I and II against S. aureus, P. aeruginosa, B. subtilis and E. coli were determined, revealing II exhibited stronger inhibition activity against P. aeruginosa than gentamicin sulfate at 0.5 mg·L-1. Complexes I and II were expected to be used as alternative drugs of gentamicin sulfate in the future. [ABSTRACT FROM AUTHOR]

The Eastern Staging System, which was specially developed for patients undergoing surgical resection for hepatocellular carcinoma (HCC), has been proposed for more than ten years. To prospectively validate the predictive accuracy of the Eastern staging on long-term survival after HCC resection. Patients who underwent hepatectomy for HCC from 2011 to 2020 at 10 Chinese hospitals were identified from a prospectively collected database. The survival predictive accuracy was evaluated and compared between the Eastern Staging with six other staging systems, including the JIS, BCLC, Okuda, CLIP, 8th AJCC TNM, and HKLC staging. Among 2365 patients, the 1-, 3-, and 5-year overall survival rates were 84.2%, 64.5%, and 52.6%, respectively. Among these seven staging systems, the Eastern staging was associated with the best monotonicity of gradients (linear trend χ2: 408.5) and homogeneity (likelihood ratio χ2: 447.3), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.776, 0.787, and 0.768, respectively). In addition, the Eastern staging was the most informative staging system in predicting survival (Akaike information criterion: 2982.33). Using a large multicenter prospectively collected database, the Eastern Staging was found to show the best predictive accuracy on long-term overall survival in patients with resectable HCC than the other 6 commonly-used staging systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the compressive performance of 24 laminated bamboo specimens made from three different growth portions of the source bamboo. The cross-section of each specimen was 100mm×100mm. The load–strain and load–displacement relationships are obtained from compression tests, and the detailed failure modes, compressive strength and elastic modulus for all specimens are reported. The results show that the mean compressive strength increases with growth portion height, but that the variation in compressive strength also increases with growth portion height. The net result is that the characteristic strength (typically used in the design process) decreases slightly with growth portion height, but not significantly. In contrast, laminated bamboo manufactured from the middle growth portion exhibits the highest elastic modulus, with the variation again increasing with height. Although the source growth portion has a clear effect on the behaviour of laminated bamboo under compression, the paper concludes that the effect is not significant from a design perspective. The results of all the tests are combined to produce a model stress–strain relationship suitable for predicting the performance of laminated bamboo under compression for design purposes. The stress–strain relationship shows that under compression laminated bamboo fails in a ductile manner. Based on the compressive properties obtained in this research, laminated bamboo is a suitable construction material for engineering structures. [Copyright &y& Elsevier]

Soluble major histocompatibility complex (MHC) class I antigens released from hepatocytes and the passenger leukocyte population of the liver allograft have both been considered as important contributors for spontaneous liver tolerance upon allogeneic transplantation into fully MHC-mismatched hosts. This study was conducted to delineate the role of “passenger leukocytes” (PL) as well as local intra-graft defence mechanisms of long-term accepted liver allografts in more detail. Orthotopic liver transplantation was performed in male inbred rats as follows (n = 4–6): (i) Lewis (LEW; RT1.l) → LEW; (ii) DA (RT1.av1) → DA; (iii) DA → LEW; (iv) LEW → DA; (v) LEW (10-Gy whole body irridiation [WBI], d-7) → DA; (vi) LEW (10-Gy WBI, d-7) → LEW; (vii) LEW (10-Gy WBI, d-7) → LEW (parked for 36 hours) → DA; and (viii) LEW (10-Gy WBI, d-7) → DA (parked for 36 hours) → DA. The model specifically investigated the role of PLs as potential contributors to liver tolerance as WBI destroys this nonresident liver population. Characterization of Fas/FasL expression and the frequency of apoptotic cell death was performed by immunohistochemistry and TUNEL staining. Reverse transcriptase—polymerase chain reaction, by the use of Fas and FasL-specific cDNA probes, was performed on isolated hepatocytes of tolerized and rejected livers at various time points after transplantation. Animal survival in the various experimental groups was calculated using Kaplan-Meier survival statistics and related log-rank statistics as follows: (i) < 100 days; (ii) ≥ 100 days; (iii) > 100 days; (iv) 11.3 ± 1.0 day; (v) 9.0 ± 0.5 days; (vi) > 100 days; (vii) 5/6 > 100 days; and (viii) 8.0 ± 1.5 days. Immunohistochemistry revealed high numbers of proliferating cells in tolerized liver allografts. Apoptotic cell death of hepatocytes could be detected in both rejecting and to a lower extent in tolerized animals. Conversely, only tolerized but not rejected liver allografts revealed upregulation of FasL-expression on hepatic parenchymal cells from day 3 onwards. Irridiated LEW livers, in turn, loose their ability to survive in allogeneic DA hosts (group v) whereas they survive in syngeneic hosts (group vi), indicating that irridiation itself does not destroy the liver parenchyma. Reconstitution of irridiated LEW livers with syngeneic (group vii) but not with allogeneic (group viii) PLs restored tolerance induction. The underlying mechanisms of immune-privilege observed with liver allografts appear to share characteristics of clonal exhaustion suggesting that alloreactive lymphocytes are depleted by AICD via the FasL/Fas signal transduction pathway. The high frequency of apoptotic lymphocytes found in the portal tract of tolerized (but not rejected) LEW grafts supposes that functional FasL expression on graft hepatocytes mediates specific elimination of graft-directed effector lymphocytes. This mechanism constitutes peripheral deletion as one of the possible tolerogenic mechanisms involved. Chimerical liver grafts consisting of donor (LEW) parenchyma and host (DA) passenger leukocytes loose their tolerogenic capacity. In contrast, syngeneic reconstitution with LEW-PLs, restores liver graft acceptance upon transplantation into allogeneic DA hosts. This phenomenon is not relying on the induction of micro- or macrochimeric hosts, as no LEW PLs were found in spleen, thymus or the blood compartment from long-term surviving DA rats. Thus, non-resident liver cells contribute significantly to liver graft acceptance. Subsequently, liver tolerance appears to be mainly induced in the graft itself. [Copyright &y& Elsevier]