[Application of ARHGAP8 in Predicting the Efficacy of Neoadjuvant Chemotherapy for Locally Advanced Mid-Low Rectal Cancer].

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

Metabolic and Transcriptomic Profile Revealing the Differential Accumulating Mechanism in Different Parts of Dendrobium nobile.

Dendrobium nobile is an important orchid plant that has been used as a traditional herb for many years. For the further pharmaceutical development of this resource, a combined transcriptome and metabolome analysis was performed in different parts of D. nobile. First, saccharides, organic acids, amino acids and their derivatives, and alkaloids were the main substances identified in D. nobile. Amino acids and their derivatives and flavonoids accumulated strongly in flowers; saccharides and phenols accumulated strongly in flowers and fruits; alkaloids accumulated strongly in leaves and flowers; and a nucleotide and its derivatives and organic acids accumulated strongly in leaves, flowers, and fruits. Simultaneously, genes for lipid metabolism, terpenoid biosynthesis, and alkaloid biosynthesis were highly expressed in the flowers; genes for phenylpropanoids biosynthesis and flavonoid biosynthesis were highly expressed in the roots; and genes for other metabolisms were highly expressed in the leaves. Furthermore, different members of metabolic enzyme families like cytochrome P450 and 4-coumarate-coA ligase showed differential effects on tissue-specific metabolic accumulation. Members of transcription factor families like AP2-EREBP, bHLH, NAC, MADS, and MYB participated widely in differential accumulation. ATP-binding cassette transporters and some other transporters also showed positive effects on tissue-specific metabolic accumulation. These results systematically elucidated the molecular mechanism of differential accumulation in different parts of D. nobile and enriched the library of specialized metabolic products and promising candidate genes.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Efficacy and safety of precision-guided transjugular extrahepatic portosystemic shunt (TEPS) in the management of cavernous transformation of the portal vein with portal hypertension: a case series.

BACKGROUND AND AIMS: Performing a Transjugular intrahepatic portal system shunt (TIPS) in patients with portal vein cavernous transformation (CTPV) poses significant challenges. As an alternative, transjugular extrahepatic portal vein shunt (TEPS) may offer a potential solution for these patients. Nonetheless, the effectiveness and safety of TEPS remain uncertain. This case series study aimed to evaluate the efficacy and safety of TEPS in treating patients with CTPV portal hypertension complications. METHODS: The study encompassed a cohort of 22 patients diagnosed with CTPV who underwent TEPS procedures. Of these, 13 patients manifested recurrent hemorrhagic episodes subsequent to conventional therapies, 8 patients grappled with recurrent or refractory ascites, and 1 patient experienced acute bleeding but refused endoscopic treatment. Comprehensive postoperative monitoring was conducted for all patients to rigorously evaluate both the technical and clinical efficacy of the intervention, as well as long-term outcomes. RESULTS: The overall procedural success rate among the 22 patients was 95.5% (21/22).During the TEPS procedure, nine patients were guided by percutaneous splenic access, three patients were guided by percutaneous hepatic access, five patients were guided by transmesenteric vein access from the abdomen, and two patients were guided by catheter marking from the hepatic artery. Additionally, guidance for three patients was facilitated by pre-existing TIPS stents. The postoperative portal pressure gradient following TEPS demonstrated a statistically significant decrease compared to preoperative values (24.95 ± 3.19 mmHg vs. 11.48 ± 1.74 mmHg, p < 0.01).Although three patients encountered perioperative complications, their conditions ameliorated following symptomatic treatment, and no procedure-related fatalities occurred. During a median follow-up period of 14 months, spanning a range of 5 to 39 months, we observed four fatalities. Specifically, one death was attributed to hepatocellular carcinoma, while the remaining three were ascribed to chronic liver failure. During the follow-up period, no instances of shunt dysfunction were observed. CONCLUSIONS: Precision-guided TEPS appears to be a safe and efficacious intervention for the management of CTPV.

Andrographolide sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the EGFR/AKT and PDGFRß/AKT signaling pathways.

BACKGROUND: Cetuximab, an inhibitor targeting EGFR, is widely applied in clinical management of colorectal cancer (CRC). Nevertheless, drug resistance induced by KRAS-mutations limits cetuximab's anti-cancer effectiveness. Furthermore, the persistent activation of EGFR-independent AKT is another significant factor in cetuximab resistance. Nevertheless, the mechanism that EGFR-independent AKT drives cetuximab resistance remains unclear. Thus, highlighting the need to optimize therapies to overcome cetuximab resistance and also to explore the underlying mechanism. PURPOSE: This work aimed to investigate whether and how andrographolide enhance the therapeutic efficacy of cetuximab in KRAS-mutant CRC cells by modulating AKT. METHODS: The viabilities of CRC cell lines were analyzed by CCK-8. The intracellular proteins phosphorylation levels were investigated by Human Phospho-kinase Antibody Array analysis. Knockdown and transfection of PDGFRß were used to evaluate the role of andrographolide on PDGFRß. The western blotting was used to investigate Wnt/ß-catenin pathways, PI3K/AKT, and EMT in KRAS-mutant CRC cells. The animal models including subcutaneous tumor and lung metastasis were performed to assess tumor response to therapy in vivo. RESULTS: Andrographolide was demonstrated to decrease the expression of PI3K and AKT through targeting PDGFRß and EGFR, and it enhanced cetuximab effect on KRAS-mutant CRC cells by this mechanism. Meanwhile, andrographolide helped cetuximab to inhibit Wnt/ß-catenin, CRC cell migration and reduced Vimentin expression, while increasing that of E-cadherin. Lastly, co-treatment with cetuximab and andrographolide reduced the growth of KRAS-mutant tumors and pulmonary metastases in vivo. CONCLUSIONS: Our findings suggest that andrographolide can overcome the KRAS-mutant CRC cells' resistance to cetuximab through inhibiting the EGFR/PI3K/AKT and PDGFRß /AKT signaling pathways. This research provided a possible theory that andrographolide sensitizes KRAS-mutant tumor to EGFR TKI.

Revealing of Intracellular Antioxidants in Dendrobium nobile by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

The medicinal plant Dendrobium nobile is an important natural antioxidant resource. To reveal the antioxidants of D. nobile, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed for metabolic analysis. The H2O2-induced oxidative damage was used in human embryonic kidney 293T (H293T) cells to assess intracellular antioxidant activities. Cells incubated with flower and fruit extracts showed better cell survival, lower levels of reactive oxygen species (ROS), and higher catalase and superoxide dismutase activities than those incubated with root, stem, and leaf extracts (p < 0.01). A total of 13 compounds were newly identified as intracellular antioxidants by association analysis, including coniferin, galactinol, trehalose, beta-D-lactose, trigonelline, nicotinamide-N-oxide, shikimic acid, 5'-deoxy-5'-(methylthio)adenosine, salicylic acid, isorhamnetin-3-O-neohespeidoside, methylhesperidin, 4-hydroxybenzoic acid, and cis-aconitic acid (R2 > 0.8, Log2FC > 1, distribution > 0.1%, and p < 0.01). They showed lower molecular weight and higher polarity, compared to previously identified in vitro antioxidants in D. nobile (p < 0.01). The credibility of HPLC-MS/MS relative quantification was verified by common methods. In conclusion, some saccharides and phenols with low molecular weight and high polarity helped protect H293T cells from oxidative damage by increasing the activities of intracellular antioxidant enzymes and reducing intracellular ROS levels. The results enriched the database of safe and effective intracellular antioxidants in medicinal plants.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Skeletal muscle abnormalities, such as muscle mass depletion (sarcopenia) and fatty infiltration of the muscle (myosteatosis), are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt (TIPS). AIM: To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy (HE) and mortality after TIPS. METHODS: The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved. The transversal psoas muscle thickness (TPMT) and psoas muscle attenuation (PMA) measured from the unenhanced abdominal computed tomography (CT) at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis, respectively. The area under curve (AUC) was used to evaluate the discriminative power of TPMT, PMA, and relevant clinical parameters. Fur-thermore, log-rank test was performed to compare the incidence of overt HE and survival between the different groups, and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models. RESULTS: A total of 108 patients were collected. Among these patients, 45.4% of patients developed overt HE after TIPS treatment. Furthermore, 32.4% and 28.7% of these patients were identified to have myosteatosis and sarcopenia, respectively. Myosteatosis (51.0% vs 16.9%, P < 0.001) and sarcopenia (40.8 vs 18.6%, P = 0.011) were found to be more frequent in patients with overt HE, when compared to patients without overt HE. The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE (AUC = 0.713 and 0.778, respectively) was higher when compared to the neutrophil lymphocyte ratio (AUC = 0.636). The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis, followed by patients with myosteatosis or sarcopenia, while this was the lowest in patients without sarcopenia and myosteatosis. In addition, sarcopenia and myosteatosis were inde-pendently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients. CONCLUSION: CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.

Paenibacillus dendrobii sp. nov., an indole-3-acetic acid-producing endophytic bacterium isolated from Dendrobium nobile.

A novel rod-shaped, Gram-stain-positive, spore-forming and motile by peritrichous flagella strain, designated HJL G12T, was isolated from the root of Chinese herb Dendrobium nobile. Strain HJL G12T grew optimally at pH 7.0, 30 °C and in the presence of 1.0 % NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene and genomic sequences showed that HJL G12T clustered with Paenibacillus chibensis NBRC 15958T and Paenibacillus dokdonensis YH-JAE5T with 98.3 and 98.2 % sequence similarity. The DNA-DNA hybridization values between strain HJL G12T and the two reference strains were 23.6 % and 24.9 %, respectively. Menaquinone-7 was the only respiratory quinone and meso-diaminopimelic acid was present in the cell-wall peptidoglycan. Antesio-C15 : 0 and iso-C16 : 0 were detected to be the major cellular fatty acids. The cellular polar lipid profile contained diphosphatidyglycerol, phosphatidylglycerol, phosphatidylethanolamine, lysyl-phospatidylglycerol and three unidentified aminophospholipids. Based on these results, strain HJL G12T is considered to represent a novel species within the genus Paenibacillus, for which the name Paenibacillus dendrobii sp. nov. is proposed, with HJL G12T (=NBRC 115617T=CGMCC 1.18520T) as the type strain.

As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy.

Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.

Predicting Outcome in Combination Treatment of TACE and Camrelizumab for Advanced Hepatocellular carcinoma: Tumor Hypervascularity and Reactive Cutaneous Capillary Endothelial Proliferation.

Objective: To validate the robust predictive values of tumor vascularity and reactive cutaneous capillary endothelial proliferation (RCCEP) in combination treatment of transarterial chemoembolization (TACE) and camrelizumab for patients with advanced hepatocellular carcinoma (HCC) and then select the potential candidates who would survive best from such treatment. Methods: The clinical data of 113 patients with advanced HCC treated with TACE and camrelizumab from January 2019 to December 2021 were analyzed retrospectively. Mann Whitney U-test was used to evaluate the correlation between vascular distribution and RCCEP and tumor response; Kaplan Meier technique was used to evaluate time to progress (TTP) and overall survival (OS), and log rank test was used for comparison; multivariate Cox regression analysis was used to evaluate the related influencing factors. Results: The TTP and OS of TACE combined with carrelizumab in patients with advanced HCC were 7.1 and 14.3 months. Hypervascularity and development of RCCEP were good predictors of TTP (HR 2.561, P < 0.001; HR 1.486, P = 0.032) and OS (HR 2.854, P < 0.001; HR 1.634, P = 0.011). The median TTP and OS of patients with hypervascularity and RCCEP were 10.6 and 19.3 months, which were better than those with only hypervascularity (6.8 months, P = 0.016; 11.6 months, P = 0.003) and only RCCEP (6.2 months, P = 0.039; 13.5 months, P = 0.042), as well as those with neither (3.8 months, P < 0.001; 7.4 months, P < 0.001). Conclusion: Tumor hypervascularity and development of RCCEP were favorable predictive factors for the combination treatment of TACE and carrelizumab, with both of which the patients survived longest and might be the potential candidates.

Quantitative Identification of Antioxidant Basis for Dendrobium Nobile Flower by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

Dendrobium nobile is a beautiful orchid and a widely used medicinal plant. In vitro antioxidant assays suggested that D. noblie flower extracts showed significantly higher 2, 2'-azinobis-3-ethylbenzthiazoline-6-sulfonate (ABTS) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging rates and much more ferric-reducing power than those of root, stem, leaf and fruit. To better understand the antioxidant basis of D. nobile flower, high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used for metabolic identification and quantification. Finally, there were 72 metabolites among the total of 712 identified components showed significant association (coefficient >0.8, p < 0.05) with ABTS scavenging rates, DPPH scavenging rates, and ferric-reducing power. The three enriched classes of flower metabolites, including amino acids and their derivatives, organic acids and their derivatives, and flavonoids, formed the main antioxidant basis. The significantly accumulated rutin, astragalin, isomucronulatol-7-O-glucoside, quercetin 4'-O-glucoside, methylquercetin O-hexoside, caffeic acid, caffeic acid O-glucoside, and p-coumaric acid (Log2(fold change) >2, p < 0.01, distribution in flower >0.1%) made a key contribution to the higher antioxidant activities in flower. The relative quantification results of HPLC-MS/MS were verified by the common quantification methods. The antioxidant basis revealed of D. nobile flower will be helpful in the production of healthy or beauty products.

Gut mucosal microbiota profiles linked to colorectal cancer recurrence.

BACKGROUND: Emerging evidence links gut microbiota to various human diseases including colorectal cancer (CRC) initiation and development. However, gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet, especially in a Chinese cohort. AIM: To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. METHODS: We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy controls. The patients were followed up by regular examination to determine whether tumors recurred. Triplet-paired samples from on-tumor, adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA sequencing. Next, we carried out bioinformatic analyses, Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. RESULTS: We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis. A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis, including Anaerotruncus, Bacteroidales, Coriobacteriaceae, Dialister, Eubacterium, Fusobacterium, Filifactor, Gemella, Haemophilus, Mogibacteriazeae, Pyramidobacter, Parvimonas, Porphyromonadaceae, Slackia, Schwartzia, TG5 and Treponema. CONCLUSION: Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.

Novel roles of lipopolysaccharide and TLR4/NF-κB signaling pathway in inflammatory response to liver injury in Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow. To date, the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown. AIM: To assess the role of NF-κB-mediated inflammation in BCS-induced liver injury in humans and rats. METHODS: A total of 180 rats were randomly assigned into nine groups, including four BCS model groups (1, 3, 6 and 12 wk), four sham-operated groups (1, 3, 6 and 12 wk), and a control group. Lipopolysaccharide (LPS) levels in each group were detected by the Tachypleus Amebocyte Lysate assay. The mRNA and protein levels of TLR4, NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-2 and interferon (IFN)-γ were quantified. In addition, 60 patients with BCS and 30 healthy controls were enrolled, and their blood samples were analyzed. RESULTS: Hepatic and plasma LPS levels were significantly increased in rats. The mRNA and protein expression levels of TLR4, NF-κB and inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in liver tissues were significantly higher in the BCS model groups compared with the other two groups. In addition, the model groups (1, 3, 6 and 12 wk after BCS induction) showed significant differences in the levels of LPS, TLR4, NF-κB, TNF-α, IL-2 and IFN-γ. Notably, there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4, NF-κB and inflammatory cytokines. Importantly, it was revealed that the levels of LPS, TLR4, NF-κB and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients. CONCLUSION: LPS level is markedly elevated in BCS, in turn activating the TLR4/NF-κB signaling pathway, leading to induction of inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in response to BCS-induced liver injury.

[Correlation analysis and breeding application of agronomic traits and quality indexes in Dendrobium nobile].

The present study aimed to explore the correlation between agronomic traits and quality indexes of Dendrobium nobile and its application value in agricultural breeding. The cultivated strains of D. nobile in Hejiang-Chishui producing areas were extensively collected,and the main agronomic traits and quality indexes were measured. The agronomic traits with significant correlation with quality indexes were screened out by the correlation analysis,and then the parental lines and self-bred F_1 generation plants were furtherverified. Among 96 lines of D. nobile,the content of soluble polysaccharides showed a significant negative correlation with dendrobine( P < 0. 01),and no significant correlation with agronomic traits in stems and leaves. The content of dendrobine exhibited a significant positive correlation with the stem width-thickness ratio( at the largest cross section; P < 0. 01),and no significant correlation with other agronomic traits. Regression analysis further verified the positive correlation between dendrobine content and stem width-thickness ratio( R2> 0. 9). Two lines,JC-10 and JC-35,with significant differences in stem width-thickness ratio were screened out( P <0. 05). The corresponding F1 generation plants by self-pollination both showed that the dendrobine content was higher with greater stem width-thickness ratio( P < 0. 01). The experimental results suggested that within a certain range,the dendrobine content was higher in D. nobile with flatter stem. Therefore,in the breeding of D. nobile,this specific trait could be used for screening plants with high content of quality indexes such as dendrobine.

Zinc affects the physiology and medicinal components of Dendrobium nobile Lindl.

The growth of Dendrobium nobile is often influenced by zinc. Here, D. nobile was regularly sprayed with different concentrations (0, 50, 100, 200, 400, 800, 1000, 2000 µmol L-1) of zinc to study its effect on the growth and biosynthesis of medicinal components. Samples were taken at 0, 7, 14, and 21 days to detect physiological and medicinal components. The results showed that the net photosynthetic rate, transpiration rate, stomatal conductance, and Chl A and Chl B levels of leaves first increased and then decreased as the concentration of zinc increased. At 400 µmol L-1 concentration, these parameters reached their maximum values. Thus, a certain dose of zinc could promote the photosynthesis of D. nobile. There was an obvious increase in the synthesis of superoxide dismutase (SOD), while the content of ascorbate peroxidase and ascorbic acid (AsA) were the highest after treatment with 400 µmol L-1 zinc. Maximum levels of polysaccharides and polyphenols were observed on day 7 and 14, respectively, at a zinc concentration of 400 µmol L-1. These results suggest that exogenous zinc may promote the accumulation of medicinal components in D. nobile. It was also found that polysaccharides could combine well with zinc to form a polysaccharide-zinc chelate and transform inorganic zinc into organic form, which is stored in the form of polysaccharide-Zn and is known to reduce the damage induced by Zn stress.

Nutcracker syndrome accompanied by hypertension: a case report and literature review.

Nutcracker syndrome (NCS) refers to characteristic clinical symptoms that develop secondary to the nutcracker phenomenon (NCP), defined as compression of the left renal vein between the superior mesenteric artery and the aorta. A 22-year-old Chinese man presented with a 2-year history of hypertension and left flank pain after activity; his blood pressure fluctuated within 130-150/90-100 mmHg without treatment. He had microscopic hematuria (2+) and increased plasma renin activity. The findings of both color Doppler ultrasound and computed tomography angiography were consistent with a diagnosis of NCS. The patient had no history of familial hypertension or special medications. Secondary hypertension-related examinations showed no significant abnormalities. After placement of an endovascular stent in the left renal vein, normal blood flow resumed and the collateral circulation was reduced. Both the hypertension and flank pain were alleviated within 3 days after the intervention and did not reappear during the following 11 months. NCP/NCS accompanied by hypertension is very rare. The possibility of NCP/NCS should be considered when secondary hypertension cannot be explained by other factors. The mechanism by which hypertension is caused by NCP/NCS is rather complex and deserves further investigation.

Dendrobium liquor eliminates free radicals and suppresses cellular proteins expression disorder to protect cells from oxidant damage.

Dendrobium liquor obtained by soaking Dendrobium in Chinese liquor is considered as a health drink in China. Here, we found the pretreatment of extract of Dendrobium nobile Lindl. liquor (DNLE) attenuated the oxidative damage to cells caused by H2 O2 , while the abilities of DNLE of eliminating extracellular free radicals and promoting the activities of intracellular antioxidant enzymes were observed. Quantitative proteomics identified 375 differentially expressed proteins caused by H2 O2 treatment in 293T cells. However, only 12 differentially expressed proteins were found in DNLE-pretreated cells which under the same oxidative damage. This suggested that the pretreatment of DNLE could suppress the disorder of protein expressions caused by oxidative stress which could induce cell death. Besides, DNLE was helpful for avoiding the unfolded protein response (UPR) and cell cycle disorder caused by oxidative stress. Taken together, these results demonstrated that Dendrobium liquor could be a healthy herbal drink with antioxidant function. PRACTICAL APPLICATIONS: Dendrobium is used as an edible herb and a tonic food in traditional Chinese medicine. Dendrobium liquor obtained by soaking Dendrobium with Chinese liquor is also regarded as a nourishing health drink. However, there is rare research data on biological activity of Dendrobium liquor. Our current results demonstrated that the extract of Dendrobium nobile Lindl. liquor (DNLE) possessed the ability of eliminating free radicals in/out the human cells. More importantly, DNLE could help cells to resist the interference on cell life activities caused by oxidative stress. Since many evidences suggested that oxidative stress is linked to human disease and aging, and chemical antioxidant has some side effects on health, Dendrobium liquor can serve as a natural health drink with antioxidant function. Furthermore, the active ingredients in DNLE also possess the potential to be developed as natural antioxidant additive in food and cosmetics.

Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma.

PURPOSE: Transcatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC. METHODS: The clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups. RESULTS: One month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05). CONCLUSION: Compared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.

Transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid-related hepatic sinusoidal obstruction syndrome.

BACKGROUND: Treatments for hepatic sinusoidal obstruction syndrome (HSOS) are limited. AIM: To evaluate transjugular intrahepatic portosystemic shunting (TIPS) as a treatment for pyrrolidine alkaloid-related HSOS (PA-HSOS). METHODS: This retrospective analysis included patients with PA-HSOS admitted to the First Affiliated Hospital of the University of Science and Technology of China (June 2015 to January 2019). Baseline clinical characteristics and follow-up data were extracted from the medical records. All patients included in this study experienced failure of initial therapy. Patients were divided into the TIPS and conservative treatment groups according to the therapy they received. Liver function, maximal ascites depth, imaging characteristics, pathology findings, and survival were compared between groups. RESULTS: The TIPS group included 37 patients (28 males), and the conservative treatment group included 17 patients (11 males). Baseline characteristics were similar between groups. There were two deaths in the TIPS group and seven deaths in the conservative treatment group during follow-up (3-48 mo). The 3-, 6-, 12- and 24-mo survival rates were 94.6%, 94.6%, 94.6% and 94.6%, respectively, in the TIPS group and 70.6%, 57.8%, 57.8% and 57.8%, respectively, in the conservative treatment group. Kaplan-Meier analysis revealed significantly longer survival for the TIPS group than for the conservative treatment group (P = 0.001). Compared with the pre-treatment value, maximal ascites depth was significantly lower at 1 wk, 2 wk, 1 mo, and 3 mo for the TIPS group (all P < 0.05) but not in the conservative treatment group. Contrast-enhanced computed tomography demonstrated the disappearance of patchy liver enhancement after TIPS. Pathology showed that liver congestion and hepatocyte swelling improved with time after TIPS placement. CONCLUSION: TIPS may achieve better outcomes than conventional symptomatic treatment in patients with PA-HSOS.