Synthesis of 1-Benzyl-2,4-diarylimidazole through I2/CuI-Catalyzed Cyclization of Benzylamine and Hydrazone.

In this paper, we report an innovative method for synthesizing 1-benzyl-2,4-diarylimidazole utilizing 1-phenylethanone-2-(2-pyridinyl) hydrazine and benzylamine, catalyzed by an I2/CuI system. This approach represents a significant departure from traditional methods for synthesizing polysubstituted imidazoles; it employs the I2/CuI catalyst to replace rare metal catalysts, thereby achieving high yields of substitution products (≤85%). This method for the generation of 1,2,4-triimidazole derivatives is characterized by its exceptional chemical selectivity and extensive substrate compatibility.

A comparative metabolomics study between grain-sized moxibustion and suspended moxibustion on rats with gastric ulcers.

Grain-sized moxibustion (GS-Moxi) and suspended moxibustion (S-Moxi) represent the two typical local heat therapies in Traditional Chinese Medicine (TCM) and have been extensively used in treating gastric ulcers (GU) in China. However, the difference in biological response between the two moxibustion therapies in treating GU remains unclear. Here we investigated the therapeutic effect and potential mechanistic difference underlying the two moxibustion methods. Ethanol-induced GU model was established and was treated with GS-Moxi or S-Moxi at ST36 and ST21 for 5 days separately. And then, gastric histopathological examination, immunohistochemical staining for repair factors (EGFR, VEGF, Ki67), and 1H NMR-based metabolomics analysis of plasma and stomach of rats were conducted. We found GS-Moxi and S-Moxi effectively alleviated gastric damage and significantly increased the expression of related repair factors. However, S-Moxi corrected aberrant energy metabolism and lipids metabolism in GU rats but had little effect on neurotransmitter-related metabolism, while GS-Moxi regulated energy metabolism and neurotransmitter-related metabolism in GU rats but had no effect on lipids metabolism. We further proposed that the main target of S-Moxi may be liver and vasculature, whereas GS-Moxi specially targeted the stomach via regulating nervous system. This study strongly verified the outstanding gastroprotective effects of moxibustion and enriched our understanding of the varied biological responses triggered by different moxibustion methods.

Population structure and genome-wide evolutionary signatures reveal putative climate-driven habitat change and local adaptation in the large yellow croaker.

The large yellow croaker (Larimichthys crocea) is one of the most economically valuable marine fish in China and is a notable species in ecological studies owing to a serious collapse of wild germplasm in the past few decades. The stock division and species distribution, which have important implications for ecological protection, germplasm recovery, and fishery resource management, have been debated since the 1960s. However, it is still uncertain even how many stocks exist in this species. To address this, we evaluated the fine-scale genetic structure of large yellow croaker populations distributed along the eastern and southern Chinese coastline based on 7.64 million SNP markers. Compared with the widely accepted stock boundaries proposed in the 1960s, our results revealed that a climate-driven habitat change probably occurred between the Naozhou (Nanhai) Stock and the Ming-Yuedong (Mindong) Stock. The boundary between these two stocks might have shifted northwards from the Pearl River Estuary to the northern area of the Taiwan Strait, accompanied by highly asymmetric introgression. In addition, we found divergent landscapes of natural selection between the stocks inhabiting northern and southern areas. The northern population exhibited highly agminated signatures of strong natural selection in genes related to developmental processes, whereas moderate and interspersed selective signatures were detected in many immune-related genes in the southern populations. These findings establish the stock status and genome-wide evolutionary landscapes of large yellow croaker, providing a basis for conservation, fisheries management and further evolutionary biology studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00165-2.

Genome-wide evolutionary signatures of climate adaptation in spotted sea bass inhabiting different latitudinal regions.

Consideration of the thermal adaptation of species is essential in both evolutionary biology and climate-change biology because it frequently leads to latitudinal gradients of various phenotypes among populations. The spotted sea bass (Lateolabrax maculatus) has a broad latitudinal distribution range along the marginal seas of the Northwest Pacific and thus provides an excellent teleost model for population genetic and climate adaptation studies. We generated over 8.57 million SNP loci using whole-genome resequencing from 100 samples collected at 14 geographic sites (five or ten samples per site). We estimated the genetic structure of the sampled fish and clustered them into three highly differentiated populations. The genetic differentiation pattern estimated by multivariable models combining geographic distance and sea surface temperature differences suggests that isolation by distance and isolation by environment both have significant effects on this species. Further investigation of genome-wide evolutionary signatures of climate adaptation identified many genes related to growth, muscle contraction, and vision that are under positive natural selection. Moreover, the contrasting patterns of natural selection in high-latitude and low-latitude populations prompted different strategies of trade-offs between growth rate and other traits that may play an essential role in adaptation to different local climates. Our results offer an opportunity to better understand the genetic basis of the phenotypic variation in eurythermal fishes inhabiting different climatic regions.

Intercross population study reveals that co-mutation of mitfa genes in two subgenomes induces red skin color in common carp ( Cyprinus carpio wuyuanensis).

Common carp are among the oldest domesticated fish in the world. As such, there are many food and ornamental carp strains with abundant phenotypic variations due to natural and artificial selection. Hebao red carp (HB, Cyprinus carpio wuyuanensis), an indigenous strain in China, is renowned for its unique body morphology and reddish skin. To reveal the genetic basis underlying the distinct skin color of HB, we constructed an improved high-fidelity (HiFi) HB genome with good contiguity, completeness, and correctness. Genome structure comparison was conducted between HB and a representative wild strain, Yellow River carp (YR, C. carpio haematopterus), to identify structural variants and genes under positive selection. Signatures of artificial selection during domestication were identified in HB and YR populations, while phenotype mapping was performed in a segregating population generated by HB×YR crosses. Body color in HB was associated with regions with fixed mutations. The simultaneous mutation and superposition of a pair of homologous genes ( mitfa) in chromosomes A06 and B06 conferred the reddish color in domesticated HB. Transcriptome analysis of common carp with different alleles of the mitfa mutation confirmed that gene duplication can buffer the deleterious effects of mutation in allotetraploids. This study provides new insights into genotype-phenotype associations in allotetraploid species and lays a foundation for future breeding of common carp.

Comparative genomics analysis and genome assembly integration with the recombination landscape contribute to Takifugu bimaculatus assembly refinement.

Takifugu genus has been brought to the fore in scientific and practical research due to its compact genome, explosive speciation progress and economic value. Here we updated the chromosome-level genome of Takifugu bimaculatus by an ultra-high-density linkage map, a classic and accurate way of chromosome assembly. The map constituted a robust assembly frame, with 92.2% (372.77 Mb) of the draft genome cumulatively placed. With intraspecies and interspecies comparative genomic analysis, we developed a criterion to quantify the differences between assemblies and established a novel way to integrate information from multiple assemblies. The integrated assembly rectified potential mis-assemblies, greatly improving the genome contiguity and correctness. Our results rendered profound information on the genetic recombination of T. bimaculatus and provided new insights into effective genome assembly. The consolidated assembly will be a contributory tool of T. bimaculatus and broadly across the Takifugu by providing a convincing reference for genomic research.

Assessing the determinants of teachers' job happiness in the private universities.

Teachers' job happiness in private universities is an important element for the healthy and orderly development of universities and an inevitable requirement for the construction of university faculty, and it has become a hot topic of research in the field of private higher education at present. However, there is still a lack of empirical studies on the factors influencing job happiness in private universities. This study constructs a theoretical model between professional identity, job competence, professional motivation, professional prospects, perceived fairness, job achievements and job happiness, and explores the specific drivers of teachers' job happiness in private universities based on empirical research. The results of the data analysis showed that professional identity, job competence, professional prospects, perceived fairness, job achievements, and professional motivation all had significant effects on teachers' job happiness, and the effects were decreasing. This study examined the effects of job happiness in practice in private universities, which helped private universities to enhance teachers' professional identity, strengthen organizational support for teacher development, promote teachers' teaching ability, improve job competence, and build a developmental teacher evaluation mechanism.

Piston Sensing for Golay-6 Sparse Aperture System with Double-Defocused Sharpness Metrics via ResNet-34.

In pursuit of high imaging quality, optical sparse aperture systems must correct piston errors quickly within a small range. In this paper, we modified the existing deep-learning piston detection method for the Golay-6 array, by using a more powerful single convolutional neural network based on ResNet-34 for feature extraction; another fully connected layer was added, on the basis of this network, to obtain the best results. The Double-defocused Sharpness Metric (DSM) was selected first, as a feature vector to enhance the model performance; the average RMSE of the five sub-apertures for valid detection in our study was only 0.015λ (9 nm). This modified method has higher detecting precision, and requires fewer training datasets with less training time. Compared to the conventional approach, this technique is more suitable for the piston sensing of complex configurations.

Neutralizing epitopes on Clostridioides difficile toxin A revealed by the structures of two camelid VHH antibodies.

Toxin A (TcdA) and toxin B (TcdB) are two key virulence factors secreted by Clostridioides difficile, which is listed as an urgent threat by the CDC. These two large homologous exotoxins are mainly responsible for diseases associated with C. difficile infection (CDI) with symptoms ranging from diarrhea to life threatening pseudomembranous colitis. Single-domain camelid antibodies (VHHs) AH3 and AA6 are two potent antitoxins against TcdA, which when combined with two TcdB-targeting VHHs showed effective protection against both primary and recurrent CDI in animal models. Here, we report the co-crystal structures of AH3 and AA6 when they form complexes with the glucosyltransferase domain (GTD) and a fragment of the delivery and receptor-binding domain (DRBD) of TcdA, respectively. Based on these structures, we find that AH3 binding enhances the overall stability of the GTD and interferes with its unfolding at acidic pH, and AA6 may inhibit the pH-dependent conformational changes in the DRBD that is necessary for pore formation of TcdA. These studies reveal two functionally critical epitopes on TcdA and shed new insights into neutralizing mechanisms and potential development of epitope-focused vaccines against TcdA.

Identification of TFPI as a receptor reveals recombination-driven receptor switching in Clostridioides difficile toxin B variants.

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with Clostridioides difficile infection. Its sequence variations among clinical isolates may contribute to the difficulty in developing effective therapeutics. Here, we investigate receptor-binding specificity of major TcdB subtypes (TcdB1 to TcdB12). We find that representative members of subtypes 2, 4, 7, 10, 11, and 12 do not recognize the established host receptor, frizzled proteins (FZDs). Using a genome-wide CRISPR-Cas9-mediated screen, we identify tissue factor pathway inhibitor (TFPI) as a host receptor for TcdB4. TFPI is recognized by a region in TcdB4 that is homologous to the FZD-binding site in TcdB1. Analysis of 206 TcdB variant sequences reveals a set of six residues within this receptor-binding site that defines a TFPI binding-associated haplotype (designated B4/B7) that is present in all TcdB4 members, a subset of TcdB7, and one member of TcdB2. Intragenic micro-recombination (IR) events have occurred around this receptor-binding region in TcdB7 and TcdB2 members, resulting in either TFPI- or FZD-binding capabilities. Introduction of B4/B7-haplotype residues into TcdB1 enables dual recognition of TFPI and FZDs. Finally, TcdB10 also recognizes TFPI, although it does not belong to the B4/B7 haplotype, and shows species selectivity: it recognizes TFPI of chicken and to a lesser degree mouse, but not human, dog, or cattle versions. These findings identify TFPI as a TcdB receptor and reveal IR-driven changes on receptor-specificity among TcdB variants.

Structure of the glucosyltransferase domain of TcdA in complex with RhoA provides insights into substrate recognition.

Clostridioides difficile is one of the most common causes of antibiotic-associated diarrhea in developed countries. As key virulence factors of C. difficile, toxin A (TcdA) and toxin B (TcdB) act by glucosylating and inactivating Rho and Ras family small GTPases in host cells, which leads to actin cytoskeleton disruption, cell rounding, and ultimately cell death. Here we present the co-crystal structure of the glucosyltransferase domain (GTD) of TcdA in complex with its substrate human RhoA at 2.60-angstrom resolution. This structure reveals that TcdA GTD grips RhoA mainly through its switch I and switch II regions, which is complemented by interactions involving RhoA's pre-switch I region. Comprehensive structural comparisons between the TcdA GTD-RhoA complex and the structures of TcdB GTD in complex with Cdc42 and R-Ras reveal both the conserved and divergent features of these two toxins in terms of substrate recognition. Taken together, these findings establish the structural basis for TcdA recognition of small GTPases and advance our understanding of the substrates selectivity of large clostridial toxins.

Structure and conformational dynamics of Clostridioides difficile toxin A.

Clostridioides difficile toxin A and B (TcdA and TcdB) are two major virulence factors responsible for diseases associated with C. difficile infection (CDI). Here, we report the 3.18-Å resolution crystal structure of a TcdA fragment (residues L843-T2481), which advances our understanding of the complete structure of TcdA holotoxin. Our structural analysis, together with complementary single molecule FRET and limited proteolysis studies, reveal that TcdA adopts a dynamic structure and its CROPs domain can sample a spectrum of open and closed conformations in a pH-dependent manner. Furthermore, a small globular subdomain (SGS) and the CROPs protect the pore-forming region of TcdA in the closed state at neutral pH, which could contribute to modulating the pH-dependent pore formation of TcdA. A rationally designed TcdA mutation that trapped the CROPs in the closed conformation showed drastically reduced cytotoxicity. Taken together, these studies shed new lights into the conformational dynamics of TcdA and its roles in TcdA intoxication.

[Nuclear magnetic resonance-based metabolomics revealed metabolite profiles participate in intervention effect of refined moxibustion in gastric ulcer model rats].

OBJECTIVE: To investigate the effect of refined moxibustion on expression of gastric mucosal epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), and changes of metabolite profiles in gastric ulcer (GU) rats, so as to analyze its mechanism underlying improvement of GU. METHODS: Male SD rats were randomized into control, model, acupoint moxibustion groups (n=6 per group). The GU model was induced by cold-restraint stress. The ignited refined moxa was applied to bilateral "Liangmen" (ST21) and "Zusanli" (ST36) for 3 cones/acupoint, once daily for 7 days. Then, we employed 1H NMR-based metabolomics approach to analyze the metabolic profiles of serum and stomach tissue samples. The conventional histopathological changes of the gastric mucosa were observed by H.E. stain and the expressions of EGFR and VEGF in the gastric mucosa were detected by immunohistochemistry. RESULTS: Compared to the control group, the expression levels of EGFR and VEGF were significantly increased in the model group (P<0.01, P<0.05), and further notably up-regulated in the acupoint moxibustion group (P<0.001, P<0.01). Results of H.E. staining showed damage of the folds of gastric mucosa, disordered arrangement of the glands, infiltration of inflammatory cells and unclear structure of gastric mucosa in the model group, which was relatively milder in the acupoint moxibustion group. 1H-NMR technical analysis showed that in comparison with the control group, 11 and 11 metabolites in the stomach extract and plasma were increased, 10 in the gastric tissue and 3 in the plasma were decreased in the GU model group; while in comparison with the model group, 17 differently expressed metabolites in the gastric extract and 10 metabolites in the plasma restored to their levels of control group after the acupoint moxibustion intervention. These metabolites participate in 12 metabolic pathways including glycine, serine and threonine metabolism, glutathione metabolism, glycine metabolism, alanine, aspartic acid and glutamic acid metabolism, purine metabolism, glyoxylic acid and digarboxylic acid metabolism, biosynthesis of aminoacyl-tRNA, amino sugar and nucleotide sugar metabolism, cysteine and methionine metabolism, citrate cycle, pyruvate metabolism, and the mutual conversion of pentose and glucuronate，suggesting their involvement in moxibustion-induced improvement of GU. CONCLUSION: Refined moxibustion at ST21 and ST36 can up-regulate the expression of EGFR and VEGF in the gastric mucosa and lessen gastric mucosal injury, which may be related to its effects in reducing GU-induced metabolic disorders, including sugar, purine, amino acid, and phospholipid metabolism and antioxidant defense system.

Clinical Study of Stellate Ganglion Block Combined with General Anesthesia on Hemodynamics, Cognitive Function, and Gastrointestinal Function in Elderly Patients Undergoing Partial Hepatectomy.

Partial hepatectomy under general anesthesia is prone to hemodynamic alterations, and stress reactions are the main contributing factors to postoperative cognitive function in elderly partial hepatectomy patients. Postoperative cognitive dysfunction increases the incidence of postoperative complications and long-term morbidity and mortality in elderly patients. With the increasing trend of aging population and the gradual increase of elderly people undergoing surgical treatment, it is especially important to study the corresponding prevention and treatment measures. In this study, a total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. The changes in hemorheology, stress-related indexes, cognitive function, postoperative pain, and gastrointestinal function were compared between the two groups The results showed that SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.

Chromosome-level genome of Poropuntius huangchuchieni provides a diploid progenitor-like reference genome for the allotetraploid Cyprinus carpio.

The diploid Poropuntius huangchuchieni in the cyprinid family, which is widely distributed in the Mekong and Red River basins, is one of the most closely related diploid progenitor-like species of allotetraploid common carp, which was generated by merging of two diploid genomes during evolution. Therefore, the P. huangchuchieni genome is essential for polyploid evolution studies in Cyprinidae. Here, we report a high-quality chromosome-level genome assembly of P. huangchuchieni by integrating Oxford Nanopore and Hi-C technologies. The assembled genome size was 1,021.38 Mb, 895.66 Mb of which was anchored onto 25 chromosomes with a N50 of 32.93 Mb. The genome contained 486.28 Mb repetitive elements and 24,099 protein-coding genes. Approximately 95.9% of the complete BUSCOs were detected, suggesting a high completeness of the genome. Evolutionary analysis revealed that P. huangchuchieni diverged from Cyprinus carpio at approximately 12 Mya. Genome comparison between P. huangchuchieni and the B subgenome of C. carpio provided insights into chromosomal rearrangements during the allotetraploid speciation. With the complete gene set, 17,474 orthologous genes were identified between P. huangchuchieni and C. carpio, providing a broad view of the gene component in the allotetraploid genome, which is critical for future genetic analyses. The high-quality genomic data set created for P. huangchuchieni provides a diploid progenitor-like reference for the evolution and adaptation of allotetraploid carps.

Genome-wide identification and characterization of olfactory receptor genes in common carp (Cyprinus carpio).

The environment contains a large extent of chemical information, which could be detected as olfactory sense. Olfactory in vertebrates plays important roles on many aspects during life time, including localizing prey or food, avoiding predators, mating behavior and social communication. Considering the essential role of olfactory receptors in the specific recognition of diverse stimuli, understanding the evolutionary dynamics of olfactory receptors in teleost means a lot, especially in the allotetraploid common carp, who has undergone the fourth whole-genome duplication event. Here, we identified the whole set of olfactory receptor genes in representative teleosts and found a significant contraction in common carp when compared with other teleosts. Odorant receptor genes (OR) occupy the most among four groups of olfactory receptors, including 33 functional genes and 16 pseudogenes. Furthermore, 6 trace amine-associated receptor (TAAR) genes (including 1 pseudogene), 7 odorant-related-A receptor genes, and 10 olfactory C family receptor genes (including 3 pseudogenes) were identified in common carp. Phylogenetic and motif analysis were performed to illustrate the phylogenetic relationship and structural conservation of teleost olfactory receptors. Selection pressure analysis suggested that olfactory receptor groups in common carp were all under relaxed purifying-selection. Additionally, gene expression divergences for olfactory receptor genes were investigated during embryonic development stages of common carp. We aim to determine the abundance of common carp olfactory receptor genes, explore the evolutionary fate and expression dynamics, and provide some genomic clues for the evolution of polyploid olfactory after whole-genome duplication and for future studies of teleost olfactory.

Identification and Expression Analysis of Long Non-coding RNA in Large Yellow Croaker (Larimichthys crocea) in Response to Cryptocaryon irritans Infection.

Large-scale transcription studies have revealed numerous lncRNAs (long non-coding RNAs). lncRNAs have been proposed to participate in the regulation of a diverse range of biological processes, including transcriptional regulation. Although lncRNAs have attracted increasing attention, the studies in large yellow croaker (Larimichthys crocea) are still rare, and they lack systematic analysis. In this study, 101 RNA-seq datasets varied in ages, sexes, and tissues were retrieved from the NCBI database to generate a comprehensive catalog of large yellow croaker transcriptome database. A set of 14,599 high-confidence lncRNAs from 13,673 loci were identified and characterized. Furthermore, RNA-seq datasets obtained from the infection of C. irritans were employed to investigate the differential expression pattern of lncRNAs and analyze potential biological functions. A total of 77 differentially expressed lncRNAs targeting to 567 protein-coding genes were identified by using expression analysis. Several immune genes, including TLR5, CD2AP, and MMP9, were highlighted. With GO enrichment and KEGG pathway analysis, the immune-related terms or pathways were enriched. This study created a comprehensive dataset of lncRNAs for large yellow croaker, which would be helpful for the researches of functional roles of lncRNAs in large yellow croaker.

Development and Evaluation of a High-Throughput Single-Nucleotide Polymorphism Array for Large Yellow Croaker (Larimichthys crocea).

High-density single-nucleotide polymorphism (SNP) genotyping array is an essential tool for genetic analyses of animals and plants. Large yellow croaker (Larimichthys crocea) is one of the most commercially important marine fish species in China. Although plenty of SNPs have been identified in large yellow croaker, no high-throughput genotyping array is available. In this study, a high-throughput SNP array named NingXin-I with 600K SNPs was developed and evaluated. A set of 82 large yellow croakers were collected from different locations of China and re-sequenced. A total of 9.34M SNPs were identified by mapping sequence reads to the large yellow croaker reference genome. About 1.98M candidate SNPs were selected for further analyses by using criteria such as SNP quality score and conversion performance in the final array. Finally, 579.5K SNPs evenly distributed across the large yellow croaker genome with an average spacing of 1.19 kb were proceeded to array production. The performance of NingXin-I array was evaluated in 96 large yellow croaker individuals from five populations, and 83.38% SNPs on the array were polymorphic sites. A further test of the NingXin-I array in five closely related species in Sciaenidae identified 26.68-56.23% polymorphic SNP rate across species. A phylogenetic tree inferred by using the genotype data generated by NingXin-I confirmed the phylogenetic distance of the species in Sciaenidae. The performance of NingXin-I in large yellow croaker and the other species in Sciaenidae suggested high accuracy and broad application. The NingXin-I array should be valuable for quantitative genetic studies, such as genome-wide association studies (GWASs), high-density linkage map construction, haplotype analysis, and genome-based selection.

Transarterial chemoembolization combined with microwave ablation versus microwave ablation only for Barcelona clinic liver cancer Stage B hepatocellular carcinoma: A propensity score matching study.

PURPOSE: We aimed to compare the outcomes of microwave ablation (MWA) alone with those of transarterial chemoembolization combined with MWA (TACE-MWA) for Barcelona clinic liver cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and to identify the prognostic factors associated with the two treatments. MATERIALS AND METHODS: This retrospective study was conducted in 150 BCLC Stage B HCC patients from April 2006 to November 2017. Of these, 88 patients were treated with MWA alone while 62 with TACE-MWA. Propensity score matching (PSM) was conducted to adjust for imbalances in clinical parameters. Procedure-related complications, local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) were analyzed. RESULTS: Before PSM, the maximal tumor diameters were 6.0 ± 1.0 cm and 6.7 ± 1.3 cm in the TACE-MWA and MWA groups, respectively, with a significant difference (P = 0.002); a significant difference was also detected in α-fetoprotein level (P = 0.013). After PSM, no difference was found in the two parameters (P = 0.067, 0.470). Before and after PSM, no difference was detected in the procedure-related complications (P = 0.803 vs. 1.000, P = 1.000 vs. 1.000), RFS (P = 0.786 vs. 0.689), and OS (P = 0.684 vs. 0.929). Tumor size and α-fetoprotein level were independent influencing factors for OS before and after PSM (P = 0.009, 0.023), while tumor size (D > 7) was an independent risk factor for poor OS (P = 0.011). Tumor number was an independent risk factor for RFS before and after PSM (P = 0.007 vs. P = 0.008). A significant difference was detected in LTP between the two groups with single tumor before and after PSM (P = 0.059 vs. P = 0.006). CONCLUSIONS: The MWA alone group had RFS and OS comparable to that of the TACE-MWA group. TACE-MWA was effective in controlling LTP in patients with a single tumor.

Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer.

Troxipide is widely used to treat gastric ulcer (GU) in the clinic. However, a lack of systematic metabolic, pharmacokinetic and pharmacological studies limits its clinical use. This study aimed to firstly explore the metabolic, pharmacokinetic and pharmacological mechanisms of troxipide in rats with GU compared to normal control (NC) rats. First, metabolic study was perormed by a highly selective, high-resolution mass spectrometry method. A total of 45 metabolites, including 9 phase I metabolites and 36 phase II metabolites, were identified based on MS/MS spectra. Subsequently, the pharmacokinetics results suggested that the Cmax, Ka, t1/2, AUC(0-t) and AUC(0-∞) of troxipide were significantly increased in rats with GU compared with NC rats. The Vz, K10 and absolute bioavailability of troxipide were obviously decreased in rats with GU compared with NC rats, and its tissue distribution (in the liver, lung and kidney) was significantly different between the two groups of rats. Additionally, the pharmacodynamic results suggested that the levels of biochemical factors (IL-17, IL-6, TNF-α, IFN-γ, AP-1, MTL, GAS, and PG-II) were significantly increased, the PG-Ӏ level was obviously decreased, and the protein expression levels of HSP-90, C-Cas-3 and C-PARP-1 were markedly increased in rats with GU compared with NC rats. The above results suggested that the therapeutic mechanisms underlying the metabolic, pharmacokinetic and pharmacological properties of troxipide in vivo in rats deserve further attention based on the importance of troxipide in the treatment of GU in this study, and these mechanisms could be targets for future studies.