Background
Percutaneous radiofrequency ablation (RFA) is used as a first‐line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate ...its therapeutic efficacy compared to repeated surgical resection.
Methods
A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases.
Results
Sixty‐one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion‐basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3‐year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5‐year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36).
Conclusions
Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients.
As far as we know, this article is the first to compare the clinical results of radiofrequency ablation (RFA) versus repeated surgery for resectable colorectal liver metastases recurrence. We found that recurrence occurred more frequently and in shorter interval after RFA, especially in patients with tumor size >3 cm. Liver resection and percutaneous RFA achieved similar overall survival.
ABSTRACT
In eukaryotes, autophagy is induced as an innate defense mechanism against pathogenic microorganisms by self-degradation. Although trichinellosis is a foodborne zoonotic disease, there are ...few reports on the interplay between
Trichinella spiralis
survival strategies and autophagy-mediated host defense. Therefore, this study focused on the association between
T. spiralis
and autophagy of host small intestinal cells. In this study, the autophagy-related indexes of host small intestinal cells after
T. spiralis
infection were detected using transmission electron microscopy, hematoxylin and eosin staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting. The results showed that autophagosomes and autolysosomes were formed in small intestinal cells, intestinal villi appeared edema, epithelial compactness was decreased, microtubule-associated protein 1A/1B-light chain 3B (LC3B) was expressed in lamina propria stromal cells of small intestine, and the expression of autophagy-related genes and proteins was changed significantly, indicating that
T. spiralis
induced autophagy of host small intestinal cells. Then, the effect of
T. spiralis
on autophagy-related pathways was explored by Western blotting. The results showed that the expression of autophagy-related pathway proteins was changed, indicating that
T. spiralis
regulated autophagy by affecting autophagy-related pathways. Finally, the roles of
T. spiralis
serine protease inhibitors (
Ts
SPIs), such as
T. spiralis
Kazal-type SPI (
Ts
KaSPI) and
T. spiralis
Serpin-type SPI (
Ts
AdSPI), were further discussed
in vitro
and
in vivo
experiments. The results revealed that
Ts
SPIs induced autophagy by influencing autophagy-related pathways, and
Ts
AdSPI has more advantages. Overall, our results indicated that
T. spiralis
induced autophagy of host small intestinal cells, and its
Ts
SPIs play an important role in enhancing autophagy flux by affecting autophagy-related pathways. These findings lay a foundation for further exploring the pathogenesis of intestinal dysfunction of host after
T. spiralis
infection, and also provide some experimental and theoretical basis for the prevention and treatment of trichinellosis
.
Purpose: Quercetin is a potent chemotherapeutic drug. Clinical trials exploring different schedules of administration of quercetin
have been hampered by its extreme water insolubility. To overcome ...this limitation, this study is aimed to develop liposomal
quercetin and investigate its distribution in vivo and antitumor efficacy in vivo and in vitro .
Experimental Design: Quercetin was encapsulated in polyethylene glycol 4000 liposomes. Biodistribution of liposomal quercetin i.v. at 50 mg/kg
in tumor-bearing mice was detected by high-performance liquid chromatography. Induction of apoptosis by liposomal quercetin
in vitro was tested. The antitumor activity of liposomal quercetin was evaluated in the immunocompetent C57BL/6N mice bearing LL/2
Lewis lung cancer and in BALB/c mice bearing CT26 colon adenocarcinoma and H22 hepatoma. Tumor volume and survival time were
observed. The mechanisms underlying the antitumor effect of quercetin in vivo was investigated by detecting the microvessel density, apoptosis, and heat shock protein 70 expression in tumor tissues.
Results: Liposomal quercetin could be dissolved in i.v. injection and effectively accumulate in tumor tissues. The half-time of liposomal
quercetin was 2 hours in plasma. The liposomal quercetin induced apoptosis in vitro and significantly inhibited tumor growth in vivo in a dose-dependent manner. The optimal dose of liposomal quercetin resulted in a 40-day survival rate of 40%. Quantitative
real-time PCR showed that liposomal quercetin down-regulated the expression of heat shock protein 70 in tumor tissues. Immunohistochemistry
analysis showed that liposomal quercetin inhibited tumor angiogenesis as assessed by CD31 and induced tumor cell apoptosis.
Conclusions: Our data indicated that pegylated liposomal quercetin can significantly improve the solubility and bioavailability of quercetin
and can be a potential application in the treatment of tumor.
is the main cause of grape anthracnose, and the majority of grapevine cultivars are susceptible to this fungus. Some Chinese wild grape cultivars are resistant, however. It is therefore apt to ...compare the pathogenesis and immune responses in susceptible and resistant cultivars of grapevine to explore the detailed molecular and biochemical mechanisms of resistance to this fungus. In this study, ultrastructural and histopathological observations were used to demonstrate the resistance responses to
in the resistant Chinese wild cultivar
clone 'Shang-24' and the susceptible cultivars
'Tangwei' and
'Thompson Seedless'. Seventy-two hours postinoculation (hpi) with
, brown necrotic spots were clearly visible on the leaves of the susceptible 'Tangwei' and 'Thompson Seedless'. The infection was characterized by rapid colonization of the host cells by hyphae and massive spread of the pathogen in the intercellular spaces, ultimately leading to host cell collapse, cuticle dissolution, and extensive hyphal growth. In the resistant clone 'Shang-24', the conidia were lysed, a large quantity of electronically dense matter appeared, the hyphal growth was suppressed, and the host cells remained intact. In addition, six genes associated with disease resistance were differentially expressed in the susceptible and resistant cultivars. These disease-related genes were significantly up-regulated following infection with
. This study illustrates the differences in infection and colonization of
in resistant and susceptible grape leaves.
Three new phenazine-type compounds, named phenazines SA—SC (1—3), together with four new natural products (4—7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. ...NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1—5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.
Quality control of Chinese medicine injections remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the ...best-selling injections, Shenqi Fuzheng (SQ) injection (SQI), via a full component quantitative analysis. A total of 15 representative small molecular components of SQI were simultaneously determined using ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole tandem time-of-flight mass spectrometry (Q-TOF-MS); saccharide composition of SQI was also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on an amino column before and after acid hydrolysis. The existence of polysaccharides was also examined on a gel permeation chromatography column. The method was well validated in terms of linearity, sensitivity, precision, accuracy and stability, and was successfully applied to analyze 13 SQI samples. The results demonstrate that up to 94.69% (w/w) of this injection product are quantitatively determined, in which small molecules and monosaccharide/sucrose account for 0.18%-0.21%, and 53.49%-58.2%, respectively. The quantitative information contributes to accumulating scientific evidence to better understand the therapy efficacy and safety of complex Chinese medicine injections.
Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the ...underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome.
Complex chemical composition is an important reason for restricting herbal quality evaluation. Despite the multi-components determination method significantly promoted the progress of herbal quality ...evaluation, however, which mainly concerned the total amount of multiple components and ignored the activity variation between each one, and did not accurately reflect the biological activity of botanical medicines. In this manuscript, we proposed a toxicity calibrated contents determination method for hyper toxic aconite, called toxic constituents index (TCI). Initially, we determined the minimum lethal dose value of mesaconitine (MA), aconitine (AC), and hypaconitine (HA), and established the equation TCI = 100 × (0.3387 ×X MA + 0.4778 ×X AC + 0.1835 ×X HA). Then, 10 batches of aconite were selected and their evaluation results of toxic potency (TP), diester diterpenoid alkaloids (DDAs), and TCI were compared. Linear regression analysis result suggested that the relevance between TCI and TP was the highest and the correlation coefficient R was 0.954. Prediction error values study also indicated that the evaluation results of TCI was highly consistent with that of TP. Moreover, TCI and DDAs were both applied to evaluate 14 batches of aconite samples oriented different origins; from the different evaluation results, we found when the proportion of HA was reached 25% in DDAs, the pharmacopeia method could generate false positive results. All these results testified the accuracy and universality of TCI method. We believe that this study method is rather accurate, simple, and easy operation and it will be of great utility in studies of other foods and herbs.
In mammals, active DNA demethylation involves oxidation of 5-methylcytosine (5mC) into 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by Tet dioxygenases and excision of these two oxidized ...bases by thymine DNA glycosylase (TDG). Although TDG is essential for active demethylation in embryonic stem cells and induced pluripotent stem cells, it is hardly expressed in mouse zygotes and dispensable in pronuclear DNA demethylation. To search for other factors that might contribute to demethylation in mammalian cells, we performed a functional genomics screen based on a methylated luciferase reporter assay. UNG2, one of the glycosylases known to excise uracil residues from DNA, was found to reduce DNA methylation, thus activating transcription of a methylation-silenced reporter gene when co-transfected with Tet2 into HEK293T cells. Interestingly, UNG2 could decrease 5caC from the genomic DNA and a reporter plasmid in transfected cells, like TDG. Furthermore, deficiency in Ung partially impaired DNA demethylation in mouse zygotes. Our results suggest that UNG might be involved in Tet-mediated DNA demethylation.
Dynamic changes of traffic features in unstructured road networks challenge the scene-cognitive abilities of drivers, which brings various heterogeneous traffic behaviors. Modeling traffic with these ...heterogeneous behaviors would have significant impact on realistic traffic simulation. Most existing traffic methods generate traffic behaviors by adjusting parameters and cannot describe those heterogeneous traffic flows in detail. In this paper, a cognition-driven trafficsimulation method inspired by the theory of cognitive psychology is introduced. We first present a visual-filtering model and a perceptual-information fusion model to describe drivers’ heterogeneous cognitive processes. Then, logistic regression is used to model drivers’ heuristic decision-making processes based on the above cognitive results. Lastly, we apply the high-level cognitive decision-making results to low-level traffic simulation. The experimental results show that our method can provide realistic simulations for the traffic with those heterogeneous behaviors in unstructured road networks and has nearly the same efficiency as that of existing methods.
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