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Abstract Objective To compare therapeutic outcomes of predicted proliferative and nonproliferative hepatocellular carcinoma (HCC) after microwave ablation (MWA) using a previously developed imaging-based predictive model, the SMARS score. Methods This multicenter retrospective study included consecutive 635 patients with unresectable HCC who underwent MWA between August 2013 and September 2020. Patients were stratified into predicted proliferative and nonproliferative phenotypes according to the SMARS score. Overall survival (OS) and recurrence-free survival (RFS) were compared between the predicted proliferative and nonproliferative HCCs before and after propensity score matching (PSM). OS and RFS were also compared between the two groups in subgroups of tumor size smaller than 30 mm and tumor size 30–50 mm. Results The SMARS score classified 127 and 508 patients into predicted proliferative and nonproliferative HCCs, respectively. The predicted proliferative HCCs exhibited worse RFS but equivalent OS when compared with nonproliferative HCCs before (p < 0.001 for RFS; p = 0.166 for OS) and after (p < 0.001 for RFS; p = 0.456 for OS) matching. Regarding subgroups of tumor size smaller than 30 mm (p = 0.098) and tumor size 30–50 mm (p = 0.680), the OSs were similar between the two groups. However, predicted proliferative HCCs had worse RFS compared to nonproliferative HCCs in the subgroup of tumor size 30–50 mm (p < 0.001), while the RFS did not differ in the subgroup of tumor size smaller than 30 mm (p = 0.141). Conclusion Predicted proliferative HCCs have worse RFS than nonproliferative ones after MWA, especially in tumor size larger than 30 mm. However, the phenotype of the tumor may not affect the OS. Critical relevance statement Before performing microwave ablation for hepatocellular carcinoma, the tumor phenotype should be considered because it may affect the therapeutic outcome. Key Points Proliferative hepatocellular carcinoma (HCC) may be identified using the SMARS score, an imaging-based predictive model. SMARS predicted proliferative HCCs have worse recurrence-free and equivalent overall survival compared to nonproliferative HCC after microwave ablation. Tumor phenotype should be considered before performing microwave ablation. Graphical Abstract

Abstract The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss‐of‐function and gain‐of‐function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

BackgroundBoth the Barcelona Clinic Liver Cancer (BCLC) staging and the Hong Kong Liver Cancer (HKLC) staging have their own definitions of ideal patients for liver resection (IPLR) in hepatocellular carcinoma (HCC). This study aimed to compare the prognosis of IPLRs between the BCLC and HKLC staging systems, and to identify patients who may benefit from liver resection (LR) in the HKLC staging but beyond the BCLC staging.MethodsThis retrospective study evaluated 1,296 consecutive patients with HCC who underwent LR between August 2013 and April 2021 (457 patients and 1,046 patients were IPLR according to the BCLC and HKLC staging systems, respectively). Overall survival (OS) was compared between the two groups. To assess potential benefit of LR for IPLR in the HKLC staging but beyond the BCLC staging, univariate and multivariate Cox regression analysis was performed to determine prognostic factors of OS, and prognostic stratification was performed based on the selected prognostic factors. The IPLRs in the HKLC staging but beyond the BCLC staging were divided into subgroups according to the prognostic stratification and separately compared with the IPLRs in the BCLC staging.ResultsOS was different between the two staging systems (P = 0.011). All the 457 IPLRs in the BCLC staging were also the IPLRs in the HKLC staging. Diameter of the largest tumor5 cm (HR = 1.58; 95% CI: 1.18–2.10; P = 0.002) and liver cirrhosis (HR = 1.61; 95% CI: 1.19–2.20; P = 0.002) were risk factors for poor OS in IPLRs in the HKLC staging but beyond the BCLC staging; hence, patients were divided into the low-risk (n = 104), intermediate-risk (n = 369), and high-risk groups (n = 116) accordingly. There was no difference in OS between patients in the BCLC staging and patients in low-risk group (P = 0.996). However, OS was significantly different between patients in the BCLC staging and those in intermediate-risk (P = 0.003) and high-risk groups (P < 0.001).ConclusionIPLRs in the BCLC staging system have better prognosis. However, IPLRs in the HKLC staging system but beyond the BCLC staging may have equivalent prognosis to IPLRs in the BCLC staging if the tumor size is ≤ 5 cm and liver cirrhosis is absent.

BackgroundHepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy.MethodsHepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR.ResultsIn this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR.ConclusionThis study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

Pulmonary fibrosis (PF) is a severe chronic lung disease with little effective treatment options other than lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using bleomycin- (BLM-) induced mice PF model and green fluorescent protein– (GFP–) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell RNA sequencing (scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR, ANNEXIN, HGF, and PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2+ antiinflammatory lung macrophages and lowered further inflammation and fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better therapeutic effects in PF.

Objective To investigative whether the odds tumor enhancement ratio (OTER) on cross-sectional imaging is a prognostic factor for hepatocellular carcinoma after transarterial chemoembolization (TACE). Methods This study involved 126 patients who underwent TACE from May 2015 to March 2019. The signal intensity/Hounsfield units (HU) was measured by placing regions of interest on the tumor and surrounding liver in unenhanced and arterial-phase contrast-enhanced cross-sectional images. The OTER was calculated as follows: OTER = (HU TUMORart − HU TUMORun )/ (HU LIVERart − HU LIVERun ). Univariate analysis was performed to determine the factors associated with overall survival (OS). Variables with a P value of

Objectives: To develop and validate a predictive model for early refractoriness of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).Methods: In this multicenter retrospective study, a total of 204 consecutive patients who initially underwent TACE were included. Early TACE refractoriness was defined as patients presented with TACE refractoriness after initial two consecutive TACE procedures. Of all patients, 147 patients (approximately 70%) were assigned to a training set, and the remaining 57 patients (approximately 30%) were assigned to a validation set. Predictive model was established using forward stepwise logistic regression and nomogram. Based on factors selected by logistic regression, a one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) between patients who were present or absent of early TACE refractoriness. PFS curve was estimated by Kaplan-Meier method and compared by log-rank test.Results: Logistic regression revealed that bilobar tumor distribution (p = 0.002), more than three tumors (p = 0.005) and beyond up-to-seven criteria (p = 0.001) were significantly related to early TACE refractoriness. The discriminative abilities, as determined by the area under the receiver operating characteristic (ROC) curve, were 0.788 in the training cohort and 0.706 in the validation cohort. After PSM, the result showed that patients who were absent of early TACE refractoriness had a significantly higher PFS rate than those of patients who were present (p < 0.001).Conclusion: This study presents a predictive model with moderate accuracy to identify patients with high risk of early TACE refractoriness, and patients with early TACE refractoriness may have a poor prognosis.

P2X7 receptor (P2X7) is a non-selective and ATP-sensitive ligand-gated cation channel. Studies have confirmed that it is expressed in a variety of cells and correlates with their function, frequently in immune cells and tumor cells. We found increased expression of this receptor in many tumor cells, and it has a role in tumor survival and progression. In immune cells, upregulation of the receptor has a double effect on tumor suppression as well as tumor promotion. This review describes the structure of P2X7 and its role in the tumor microenvironment and presents possible mechanisms of P2X7 in tumor invasion and metastasis. Understanding the potential of P2X7 for tumor treatment, we also present several therapeutic agents targeting P2X7 and their mechanisms of action. In conclusion, the study of P2X7 is an important guideline for the use of clinical tumor therapy and may be able to provide a new idea for tumor treatment, but considering the complexity of the biological effects of P2X7, the drugs should be used with caution in clinical practice.

Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases.

The present study aimed to explore the mechanism of action of Gegen Qinlian decoction (GGQLD) in experimental non-alcoholic fatty liver disease (NAFLD). A total of 30 rats were randomly divided into five groups: The chow, model, high- and low-dose GGQLD (GGQLD-H and GGQLD-L, respectively) and resveratrol (Resl) groups, and were treated with saline, GGQLD and Resl when a model of high-fat diet (HFD)-induced NAFLD was established. Blood lipid and liver enzymes were detected following treatment for 8 weeks and liver tissue pathology was observed using Oil Red O and haematoxylin and eosin staining. Furthermore, the liver protein and mRNA expression of sirtuin (Sirt)1, peroxisome proliferator-activated receptor-β coactivator (PGC)-1α and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were measured using western blotting and reverse transcription-quantitative polymerase chain reaction. Compared with the chow group, the model group demonstrated significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P<0.01). GGQLD doses and Resl attenuated the elevated serum ALT and AST levels. GGQLD-H and Resl significantly increased the serum high-density lipoprotein cholesterol level compared with that in the model group (P<0.01), while GGQLD-L and Resl significantly decreased serum low-density lipoprotein cholesterol levels (P<0.01). The GGQLDs and Resl groups revealed an evident improvement in Sirt1 protein and mRNA expression. Although GGQLD and Resl significantly decreased NF-κB gene expression compared with the model group (P<0.01), the effect on NF-κB protein expression was not significant. Furthermore, the PGC-1α gene and protein expression in the HFD rat group slightly decreased compared to the levels in the chow group, but the decrease was insignificant. However, an evident increase in PGC-1α mRNA expression was observed in the GGQLD-H group compared with the model group (P<0.01). Histological staining revealed that GGQLD and Resl decreased the lipid droplets in hepatocytes and normalized steatosis in rats fed with a HFD. The results indicated that GGQLD treatment may be a potent strategy for managing NAFLD by managing lipid metabolism and inflammatory and histological abnormalities by triggering the Sirt1 pathway. [ABSTRACT FROM AUTHOR]

This paper is to explore the effect and mechanism of Gegenqinlian decoction on experimental nonalcoholic fatty liver disease (NAFLD) in vivo and in vitro. The final aim is to make clear whether Gegenqinlian decoction would impact NAFLD through improving PPARγ to suppress inflammation and regulate lipid. The data in this research suggested that Gegenqinlian decoction is a potent way to manage NAFLD through improving PPARγ to regulate lipid and suppress inflammation. [ABSTRACT FROM AUTHOR]

A 68-year-old male patient with a history of nonobstructive hypertrophic cardiomyopathy was admitted to the cardiac intensive care unit due to sudden onset of near syncope and hypotension. The diagnosis of acute bilateral pulmonary embolism was confirmed by pulmonary computed tomographic angiography. On day 2 of admission, left ventricular outflow tract (LVOT) obstruction was demonstrated by increased peak systolic blood flow (454 cm/s) and increased transvalvular pressure gradient (83 mmHg), as well as systolic anterior motion of the mitral valve leaflet. LVOT obstruction underwent a gradual normalization and was completely resolved on day 21 after symptom onset, and the patient was discharged. Acute pulmonary embolism is a rare cause of LVOT obstruction. In this case, the concomitant existence of nonobstructive hypertrophic cardiomyopathy exacerbated LVOT obstruction due to right ventricle overload-induced leftward deviation of interventricular septum and may render the patients at higher risk for sudden death. More active anticoagulation therapy should be considered in this situation.

Suffering from structural deterioration and natural disasters, the resilience of civil structures in the face of extreme loadings inevitably drops, which may lead to catastrophic structural failure and presents great threats to public safety. Earthquake-induced extreme loading is one of the major reasons behind the structural failure of buildings. However, many buildings in earthquake-prone areas of China lack safety monitoring, and prevalent structural health monitoring systems are generally very expensive and complicated for extensive applications. To facilitate cost-effective building-safety monitoring, this study investigates a method using cost-effective MEMS accelerometers for buildings’ rapid after-earthquake assessment. First, a parameter analysis of a cost-effective MEMS sensor is conducted to confirm its suitability for building-safety monitoring. Second, different from the existing investigations that tend to use a simplified building model or small-scaled frame structure excited by strong motions in laboratories, this study selects an in-service public building located in a typical earthquake-prone area after an analysis of earthquake risk in China. The building is instrumented with the selected cost-effective MEMS accelerometers, characterized by a low noise level and the capability to capture low-frequency small-amplitude dynamic responses. Furthermore, a rapid after-earthquake assessment scheme is proposed, which systematically includes fast missing data reconstruction, displacement response estimation based on an acceleration response integral, and safety assessment based on the maximum displacement and maximum inter-story drift ratio. Finally, the proposed method is successfully applied to a building-safety assessment by using earthquake-induced building responses suffering from missing data. This study is conducive to the extensive engineering application of MEMS-based cost-effective building monitoring and rapid after-earthquake assessment.

This paper studies a substitution secant/finite difference (SSFD) method for solving large scale sparse unconstrained optimization problems. This method is a combination of a secant method and a finite difference method, which depends on a consistent partition of the columns of the lower triangular part of the Hessian matrix. A q-superlinear convergence result and an r-convergence rate estimate show that this method has good local convergence properties. The numerical results show that this method may be competitive with some currently used algorithms. [ABSTRACT FROM AUTHOR]

High salt (HS) diet can accelerate the progress of hypertensive left ventricular (LV) remodeling. But the detailed mechanism remains poorly understood. We hypothesized HS intake could impact cardiac lymphangiogenesis through tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway which might play an important role in HS intake accelerated LV remodeling. Eight-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were randomized to 0.5% NaCl (Low salt, LS) and 8% NaCl (high salt, HS) diets for 12 weeks. LV remodeling was determined by echocardiography. LV invasive hemodynamic analysis and morphologic staining (cardiomyocyte hypertrophy, collagen deposition, TonEBP expression, macrophage infiltration and lymphatic density) were performed at the time of sacrifice. The blood pressure of SHR-HS group was significantly increased compared to SHR-LS and WKY groups. Meanwhile, The LV chamber size was markedly enlargement, LV function apparently compromised accompanied with a severe macrophage infiltration, and fibrosis in the perivascular and interstitium of LV compared with SHR-LS group. Furthermore, the expression levels of VEGF-C, TonEBP, and lymphatic markers in SHR-HS group were significantly increased parallel with apparent lymphangiogenesis compared with SHR-LS group. Our work indicates that TonEBP/VEGF-C signaling pathway was up-regulated in HS intake accelerated hypertensive LV remodeling process that may be valuable for further investigation.

Salix viminalis L., a dioecious species, is widely distributed in riparian zones, and flooding is one of the most common abiotic stresses that this species suffers. In this study, we investigated the morphological, anatomical, and physiological responses of male vs. female plants of S. viminalis to flooding. The results showed that the plant height and root collar diameter were stimulated by flooding treatment, which corresponded with higher dry weight of the stem and leaf. However, the dry weight of the underground part decreased, which might be due to the primary root having stopped growing. The little-influenced net photosynthesis rate (Pn) under flooding treatment could guarantee rapid growth of the aboveground part, while the unaffected leaf anatomical structure and photosynthetic pigment contents could ensure the normal operation of photosynthetic apparatus. Under a flooding environment, the production ratio of superoxide free radical (O2∙-) and malondialdehyde (MDA) contents increased, indicating that the cell membrane was damaged and oxidative stress was induced. At the same time, the antioxidant enzyme system, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and osmotic adjustment substances, involving proline (Pro) and solute protein (SP), began to play a positive role in resisting flooding stress. Different from our expectation, the male and female plants of S. viminalis performed similarly under flooding, and no significant differences were discovered. The results indicate that both male and female plants of S. viminalis are tolerant to flooding. Thus, both male and female plants of S. viminalis could be planted in frequent flooding zones.

L. is an important shrub that has potential for use as a bioenergy crop, for phytoremediation of heavy metal contaminated soil and sewage sludge treatment. It is mainly distributed in the northeast of China, but the species has not yet been used a resource here. We examined the genetic diversity and population structure of populations from the Ergun basin and West Liao basin using 20 microsatellite markers. A high level of genetic diversity (Nâ=â16.45, Hâ=â0.742) was detected for , and populations from the Ergun basin exhibited higher genetic diversity and private alleles numbers than the West Liao basin. The 12 populations could be divided into two clusters by both Bayesian analysis and UPGMA clustering which were consistent with the populations derived from the two basins. Moderate population differentiation (Fâ=â0.076) was shown in , and AMOVA analysis confirmed that most of the genetic variation (86.13%) was attributed to individual differences within populations, while 11.49% was attributed to differences between basins and 2.38% to differences within each basin. Significant correlations of F/(1âF) with log (geographic distance) among 12 populations (râ=â0.634, pâ

In this paper, the design method for a two-dimensional (2D) beam-scanning reflectarray based on liquid crystals (LCs) and static driving technique in the millimeter-wave band is proposed. The reflectarray is composed of multi-resonant elements which obtain the phase shift by applying the driving voltage on the LC. The LC elements of the reflectarray are controlled by static driving method. In order to reduce the negative impact of the densely distributed LC driving lines on the performance of the reflectarray, a novel LC driving strategy is presented to further reduce the number of driving lines. Subarray partition is employed, and more importantly, the ground plane of the reflectarray is divided into several segments so that about one third part of the driving lines can be transferred from the patch layer to the ground plane layer. A 32  ×  30 reflectarray is designed and taken for an example to demonstrate the proposed method. Full wave numerical simulations are conducted, and the results show large beam scanning ranges of the reflectarray over 50° in the plane containing the offset feed and over 40° in the plane perpendicular to the feed plane. [ABSTRACT FROM AUTHOR]

Clonal plants could modify phenotypic responses to nutrients heterogeneously distributed both in space and time by physiological integration. It will take times to do phenotypic responses to modifications which are various in different growth periods. An optimal phenotype is reached when there is a match between nutrient conditions and foraging ability. A single plantlet of Buchloe dactyloides with two stolons was transplanted into heterogeneous nutrient conditions. One stolon grew in homogeneous nutrient patch, while the other cultured in different scales of heterogeneous nutrient patches. As compared to the other nutrient treatment, heterogeneous nutrient treatments with small scale of 25×25 cm resulted in a higher biomass, and larger number of ramets, clumps and stolons in B. dactyloides at both genet and clonal fragment levels. Significant differences of number of ramets, clumps and stolons were detected at the rapid growth stage, but not in the early stage of the experiment. Foraging ability was more efficient in heterogeneous than in homogeneous nutrient conditions as assessed by higher root mass and root to shoot ratio. Different nutrient treatments did not prompt significant differences in internode and root length. Physiological integration significantly increased biomass, but did not influence other growth or morphological characters. These results suggest that physiological integration modifies phenotypic plasticity of B. dactyloides for efficient foraging of nutrients in heterogeneous nutrient conditions. These effects are more pronounced at genet and clonal fragment levels when the patch scale is 25×25 cm. Time is a key factor when phenotypic plasticity of B. dactyloides in heterogeneous nutrient conditions is examined.