Efficacy and safety of transarterial chemoembolization combining sorafenib with or without immune checkpoint inhibitors in previously treated patients with advanced hepatocellular carcinoma: A propensity score matching analysis.

Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib and immune checkpoint inhibitors (T+S+ICIs) and TACE plus sorafenib (T+S) when treating patients with advanced hepatocellular carcinoma (HCC) who have previously received locoregional treatment. Materials and methods: A retrospective analysis was performed on the patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC from May 2019 to December 2020. These patients were treated with locoregional therapy and showed radiographic progression after the treatment. Patients received either T+S+ICIs or T+S. The outcomes, including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety, were compared. The propensity score matching (PSM) methodology was used to reduce the influence of confounding factors on the outcomes. Results: Forty-three patients were included in the T+S group and 33 in the T+S+ICI group. After PSM (n = 29 in each group), patients who received T+S+ICIs had a higher DCR (82.8% vs. 58.6%, p = 0.043), longer median PFS (6.9 vs. 3.8 months, p = 0.003), and longer median OS (12.3 vs. 6.3 months, p = 0.008) than those who underwent T+S. Eastern Cooperative Oncology Group performance status was an independent predictor of PFS, and age was an independent predictor of OS. The incidence of treatment-related adverse events in T+S+ICIs was well controlled. Conclusions: Compared with TACE combined with sorafenib, TACE combined with sorafenib plus ICIs is a potentially safe and effective treatment regimen for patients with advanced HCC who previously received locoregional treatment.

Case Report: Pediatric Malignant Atrophic Papulosis With Small Bowel Perforation and Positivity of Anticardiolipin Antibody.

Malignant atrophic papulosis (MAP) is a life-threatening vasculopathy affecting the skin, gastrointestinal tract, central nervous system, pleural membrane, and pericardium. MAP carries a poor prognosis primarily because of its systemic involvement. It is extremely rare in children. Herein, we report a pediatric case of MAP with small bowel perforation and anticardiolipin antibody positivity.

Minimally invasive treatment of calcaneal fractures via the sinus tarsi approach based on a 3D printing technique.

The sinus tarsi approach can be used for a limited exposure of the calcaneal fracture site. The reduction of the posterior articular surface, the shape of the calcaneus, the precise placement of the sustentacular screw (SS), the posterior articular surface screw of the calcaneal (PASS), and the long axis screw of the calcaneal (LAS) are still challenging. To that end, we proposed a minimally invasive technique for the treatment of calcaneal fractures via the sinus tarsi approach in combination with a three-dimensional (3D) printing technique. First, a 3D reconstructed model of the bilateral calcanei was obtained according to the computed tomography (CT) scan data and was used to simulate the placement of screws and acquire the screw trajectory parameters. Next, using 3D printing, a model of the calcaneus was printed, and the minimally invasive steel plate was pre-shaped to fit the lateral wall of the model. Finally, a total of 25 patients underwent this procedure. The results showed significant accuracy improvement in terms of the SS, PASS and LAS placement and in terms of the parameters including Bohler's angle, Gissane's angle, and the calcaneal width. In this work, the technique of the personalized minimally invasive treatment of calcaneal fractures improved the accuracy of screw placement (SP) and the reduction rate of posterior articular surface, improved the shape of the calcaneus, and increased the precision of the minimally invasive treatment of calcaneal fractures via the sinus tarsi approach.

Identification and characterization of myeloperoxidase in orange-spotted grouper (Epinephelus coioides).

Cryptocaryon irritans is an important protozoan ciliate, which has led to heavy economic losses in marine aquaculture. Previous studies have indicated that C. irritans infection could induce the migration of neutrophils to infection sites. Myeloperoxidase (MPO) mainly exists in the cytoplasmic granules of the neutrophil and performs its function by a unique enzymatic capacity to produce hypohalous acid and other toxic oxidants. To determine the involvement of MPO and neutrophils against C. irritans infection in the host, we amplified MPO cDNA (EcMPO) from orange-spotted grouper (Epinephelus coioides). The open reading frame (ORF) of EcMPO encodes a putative polypeptide of 770 amino acids and has typical structural characteristics of mammalian MPO, including a signal peptide, a propeptide, a light chain, a heavy chain, and a peroxidase domain. Bioinformatics analysis has demonstrated that the most important functional sites in mammalian MPO were also conserved in grouper and other piscine MPO, implying the functional conservation of this protein during evolution. A rabbit anti-MPO recombinant protein polyclonal antibody was produced, which could recognize the native MPO protein. The expression of EcMPO was higher in the lympho-hematopoietic organs, such as head kidney, trunk kidney, spleen, but lower in muscle, heart, and brain. After infection with C. irritans, the EcMPO transcript was significantly up-regulated at specific time points in the infection sites (skin and gill) and systemic immune organs (head kidney and spleen); The number of EcMPO positive cells first increased and then decreased in the gill, but was still higher than the control after 7 days. These results demonstrated that EcMPO and its positive cells may be involved in anti-C. irritans infection in the grouper, which is attributed to the innate immune mechanisms of the host against parasite infection.

Identification and expression analysis of three XCR1-like receptors from Epinephelus coioides after Cryptocaryon irritans infection.

The unique receptor XCR1 of the XC subfamily of chemokines is specially expressed in CD8α-like dendritic cells. This receptor has one ligand in mice (XCL1) and two ligands in humans (XCL1 and XCL2). In mammals, the XCR1-XCL1 complex performs a vital role in regulating the localization and function of T cells, dendritic cells, and other cell types. In this study, three XCR1-like receptors (EcXCR1, EcXCR1L, and EcCCR12) were identified from a transcriptome database of orange-spotted grouper. The open reading frames (ORFs) of EcXCR1, EcXCR1L, and EcCCR12 predictably encode 337, 348, and 358 amino acids, respectively. All receptors are seven trans-membrane proteins, and contain conserved functional regions, and conserved sites, that are crucial for the role of chemokine receptors in mammals. Conserved features include four cysteine residues in the extracellular regions, a "DRY" motif in the second intracellular loop, and common characteristics at the N-terminus that are important for ligand interaction. In healthy grouper, EcXCR1, EcXCR1L, and EcCCR12 were broadly expressed in all the tissues tested. EcXCR1 was expressed at high levels in the liver, and EcXCR1L, and EcCCR12 in the thymus. After grouper infection with Cryptocaryon irritans, EcXCR1 and EcCCR12 were up-regulated in the skin and the spleen, and EcCCR12 in the skin, gill, and spleen. EcXCR1L expression changed only slightly. These results imply that EcXCR1 and EcCCR12 may be involved in host defense against parasite infection. A polyclonal antibody was produced against EcCCR12, and used to detect EcCCR12-positive cells in peripheral blood. These results will contribute considerably to elucidate the biological role of piscine XCR1-like receptors and their ligands system in the future.

Prognostic value of DNA repair based stratification of hepatocellular carcinoma.

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.

Development and validation of a predictive score for perioperative transfusion in patients with hepatocellular carcinoma undergoing liver resection.

BACKGROUND: Liver resection is a major surgery requiring perioperative blood transfusion. Predicting the need for blood transfusion for patients undergoing liver resection is of great importance. The present study aimed to develop and validate a model for predicting transfusion requirement in HBV-related hepatocellular carcinoma patients undergoing liver resection. METHODS: A total of 1543 consecutive liver resections were included in the study. Randomly selected sample set of 1080 cases (70% of the study cohort) were used to develop a predictive score for transfusion requirement and the remaining 30% (n=463) was used to validate the score. Based on the preoperative and predictable intraoperative parameters, logistic regression was used to identify risk factors and to create an integer score for the prediction of transfusion requirement. RESULTS: Extrahepatic procedure, major liver resection, hemoglobin level and platelets count were identified as independent predictors for transfusion requirement by logistic regression analysis. A score system integrating these 4 factors was stratified into three groups which could predict the risk of transfusion, with a rate of 11.4%, 24.7% and 57.4% for low, moderate and high risk, respectively. The prediction model appeared accurate with good discriminatory abilities, generating an area under the receiver operating characteristic curve of 0.736 in the development set and 0.709 in the validation set. CONCLUSIONS: We have developed and validated an integer-based risk score to predict perioperative transfusion for patients undergoing liver resection in a high-volume surgical center. This score allows identifying patients at a high risk and may alter transfusion practices.

Anterior vs conventional approach hepatectomy for large liver cancer: a meta-analysis.

AIM: To evaluate the clinical outcomes and safety of anterior- and conventional-approach hepatectomy for patients with large liver tumors. METHODS: PubMed, EMBASE, Google Scholar and the Cochrane Library databases were searched for randomized controlled trials (RCTs) and controlled clinical trials comparing anterior-approach hepatectomy (AAH) and conventional-approach hepatectomy (CAH). Two observers independently extracted the data using a spreadsheet and assessed the studies for inclusion. Studies that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed using either fixed effects or random effects models. RESULTS: Two RCTs and six controlled clinical trials involving 807 patients met the predefined inclusion criteria. A total of 363 patients underwent AAH and 444 underwent CAH. Meta-analysis indicated that the AAH group had fewer requirements for transfusion (OR = 0.37, 95%CI: 0.21-0.63), less recurrence (OR = 0.57, 95%CI: 0.37-0.87), and lower mortality (OR = 0.29, 95%CI: 0.13-0.63). There were no significant differences between AAH and CAH with regard to perioperative complications (OR = 0.94, 95%CI: 0.58-1.51), intraoperative tumor rupture (OR = 0.98, 95%CI: 0.40-2.40), or length of hospital stay (weighted mean difference = -0.17, 95%CI: -2.36-2.02). CONCLUSION: AAH has advantages of decreased transfusion, mortality and recurrence compared to CAH. It is a safe and effective method for large cancers requiring right hepatectomy.

Low immediate postoperative platelet count is associated with hepatic insufficiency after hepatectomy.

AIM: To investigate the relationship between low immediate postoperative platelet count and perioperative outcome after liver resection in patients with hepatocellular carcinoma (HCC). METHODS: In a cohort of 565 consecutive hepatitis B-related HCC patients who underwent major liver resection, the characteristics and clinical outcomes after liver resection were compared between patients with immediate postoperative platelet count < 100 × 10(9)/L and patients with platelet count ≥ 100 × 10(9)/L. Risk factors for postoperative hepatic insufficiency were evaluated by multivariate analysis. RESULTS: Patients with a low immediate postoperative platelet count (< 100 × 10(9)/L) had more grade III-V complications (20.5% vs 12.4%, P = 0.016), and higher rates of postoperative liver failure (6.8% vs 2.6%, P = 0.02), hepatic insufficiency (31.5% vs 21.2%, P < 0.001) and mortality (6.8% vs 0.5%, P < 0.001), compared to patients with a platelet count ≥ 100 × 10(9)/L. The alanine aminotransferase levels on postoperative days 3 and 5, and bilirubin on postoperative days 1, 3 and 5 were higher in patients with immediate postoperative low platelet count. Multivariate analysis revealed that immediate postoperative low platelet count, rather than preoperative low platelet count, was a significant independent risk factor for hepatic insufficiency. CONCLUSION: A low immediate postoperative platelet count is an independent risk factor for hepatic insufficiency. Platelets can mediate liver regeneration in the cirrhotic liver.

Microbial side-chain cleavage of phytosterols by mycobacteria in vegetable oil/aqueous two-phase system.

Microbial side-chain cleavage of natural sterols to 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD) by Mycobacteria has received much attention in pharmaceutical industry, while low yield of the reaction owing to the strong hydrophobicity of sterols is a tough problem to be solved urgently. Eight kinds of vegetable oils, i.e., sunflower, peanut, corn, olive, linseed, walnut, grape seed, and rice oil, were used to construct oil/aqueous biphasic systems in the biotransformation of phytosterols by Mycobacterium sp. MB 3683 cells. The results indicated that vegetable oils are suitable for phytosterol biotransformation. Specially, the yield of AD carried out in sunflower biphasic system (phase ratio of 1:9, oil to aqueous) was greatly increased to 84.8 % with 10 g/L feeding concentration after 120-h transformation at 30 °C and 200 rpm. Distribution coefficients of AD in different oil/aqueous systems were also determined. Because vegetable oils are of low cost and because of their eco-friendly characters, there is a great potential for the application of oil/aqueous two-phase systems in bacteria whole cell biocatalysis.

Effect of lentinan on membrane-bound protein expression in splenic lymphocytes under chronic low-dose radiation.

We investigated the protective effects of lentinan against damages to chronic and low-dose radiation (CL-radiation) by using mouse models. The mice were randomized divided into four groups: normal control mice (Ctr), mice exposed to radiation (Rad), irradiated mice treated with low-dose lentinan (0.1mg/(kg.d), RL), and irradiated mice treated with high-dose lentinan (0.5mg/(kg.d), RH). All the mice were injected intraperitoneally once a day at a dose of 0.5mL (Ctr and Rad with normal sodium while RL and RH with lentinan). The success of radiation models was confirmed by HE stain and cell morphology by a transmission electron microscope (TEM). On the basis of radiation models, we investigated the expression of proteins on the membrane of splenic cells through MALDI-TOF-MS/MS. The results demonstrated that both RT-radiation and lentinan affected the expression of membrane proteins, but lentinan protected the splenic cells and tissue from the injuries caused by CL-radiation. Therefore, we speculated that CL-radiation mainly damages the genetic materials and membrane-bound proteins, while lentinan protects membrane-bound proteins by regulating signal transduction and the appearance of the cells.

Angiotensin-converting enzyme I/D polymorphism and aortic aneurysm risk: a meta-analysis.

OBJECTIVES: Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated in aortic aneurysm risk, but individual published studies show inconclusive results. The aim of this study was to explore a more precise estimation of its relation with aortic aneurysm using meta-analysis. METHODS: Electronic searches of PubMed and EMBASE databases were conducted for all publications through February 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the strength of this association in the random-effects model or fixed-effects model. RESULTS: Fourteen case-control studies, including a total of 3938 cases and 5748 controls, were included. This meta-analysis showed a significant association between ACE I/D polymorphism and aortic aneurysm risk (OR = 1.53, 95% CI 1.26-1.87, P <0.01). In the subgroup analysis by ethnicity, a statistically significant association was found in Caucasians (OR = 1.46, 95% CI 1.20-1.77, P <0.01), but not in Asians. In the subgroup analysis by type of aortic aneurysm, this polymorphism was significantly associated with abdominal aortic aneurysm risk (OR = 1.38, 95% CI 1.10-1.74, P <0.01), thoracic aortic aneurysm risk (OR = 1.59, 95% CI 1.11-2.29, P = 0.01) and aortic dissection risk (OR = 2.43, 95% CI 1.07-5.52, P = 0.03). Stratification by hypertension status showed that hypertensive patients with this polymorphism were associated with increased aortic aneurysm risk (OR = 1.47, 95% CI 1.03-2.09, P = 0.03), whereas normotensive individuals with this polymorphism did not have an increased aortic aneurysm risk. CONCLUSIONS: This meta-analysis suggested that ACE I/D polymorphism was associated with aortic aneurysm risk.

Liver resection in hepatitis B related-hepatocellular carcinoma: clinical outcomes and safety in elderly patients.

AIM: To compare the morbidity and mortality in young and elderly hepatocellular carcinoma (HCC) patients undergoing liver resection. METHODS: We retrospectively enrolled 1543 consecutive hepatitis B (HBV)-related HCC patients undergoing elective hepatic resection in our cohort, including 207 elderly patients (≥ 65 years) and 1336 younger patients (＜ 65 years). Patient characteristics and clinical outcomes after liver resection were compared between the two groups. RESULTS: Elderly patients had more preoperative comorbidities and lower alanine aminotransferase and aspartate aminotransferase levels. Positive rates for hepatitis B surface antigen (P ＜ 0.001), hepatitis B e antigen (P ＜ 0.001) and HBV DNA (P = 0.017) were more common in younger patients. Overall complications and their severity classified using the Clavien system were similar in the two groups (33.3% vs 29.6%, P = 0.271). Elderly patients had a higher rate of postoperative cardiovascular complications (3.9% vs 0.6%, P = 0.001), neurological complications (2.9% vs 0.4%, P ＜ 0.001) and mortality (3.4% vs 1.2%, P = 0.035), and had more hospital stay requirement (13 d vs 12 d , P < 0.001) and more intensive care unit stay (36.7% vs 27.8%, P = 0.008) compared with younger patients. However, postoperative hepatic insufficiency was more common in the younger group (7.7% vs 3.4%, P = 0.024). CONCLUSION: Hepatectomy can be safely performed in elderly patients. Age should not be regarded as a contraindication to liver resection with expected higher complication and mortality rates.

11α-Hydroxylation of 16α,17-epoxyprogesterone by Rhizopus nigricans in a biphasic ionic liquid aqueous system.

11α-Hydroxylation of 16α,17-epoxyprogesterone (EP) by Rhizopus nigricans is an essential step in the synthesis of many steroidal drugs, while low conversion of the biohydroxylation is a tough problem to be solved urgently in industry. Two ionic liquids (ILs) of [BMIm][PF(6)] and [BMIm][NTf(2)] were used in the biotransformation of EP by R. nigricans. The results indicated that the conversion carried out in [BMIm][PF(6)]-aqueous biphasic system was greatly increased to above 90% at 18 g/L feeding concentration. A simplified mechanism was proposed to explain the improvement of the bioconversion in a biphasic ionic liquid aqueous system. Besides, successive three batches of bioconversion were carried out in the biphasic system with a total conversion of 87% at phase ratio 10 and 75% at phase ratio 5, respectively. Since recycling of the [BMIm][PF(6)] is quite easy, there is a great potential for the application of ILs in fungi biotransformation to implement green production.

AtKP1, a kinesin-like protein, mainly localizes to mitochondria in Arabidopsis thaliana.

Kinesins and kinesin-like proteins (KLPs) constitute a large family of microtubule-based motors that play important roles in many fundamental cellular and developmental processes. To date, a number of kinesins or KLPs have been identified in plants including Arabidopsis thaliana. Here, a polyclonal antibody against AtKP1 (kinesin-like protein 1 in A. thaliana) was raised by injection the expressed AtKP1 specific C-terminal polypeptides in rabbits, and immunoblot analysis was conducted with the affinity-purified anti-AtKP1 antibody. The results indicated that this antibody recognized the AtKP1 fusion proteins expressed in E. coli and proteins of ~125 kDa in the soluble fractions of Arabidopsis extracts. The molecular weight was consistent with the calculated molecular weight based on deduced amino acids sequence of AtKP1. To acquire the subcellular localization of the protein, AtKP1 in Arabidopsis root cells was observed by indirect immunofluorescence microscopy. AtKP1 was localized to particle-like organelles in interphase or dividing cells, but not to mitotic microtubule arrays. Relatively more AtKP1 was found in isolated mitochondria fraction on immunoblot of the subcellular fractions. The AtKP1 protein could not be released following a 0.6 M KI washing, indicating that AtKP1 is tightly bind to mitochondria and might function associated with this kind of organelles.