Correlation Analysis between Microbial Communities and Flavor Compounds during the Post-Ripening Fermentation of Traditional Chili Bean Paste.

Chili bean paste is a traditional flavor sauce, and its flavor compounds are closely related to its microflora. This study focused on investigating the content of bioactive compounds, flavor compounds, and microbial communities during the post-ripening fermentation of chili bean paste, aiming to provide a reference for improving the flavor of chili bean paste by regulating microorganisms. Compared to no post-ripening fermentation, the content of organic acids increased significantly (p < 0.05), especially that of citric acid (1.51 times). Glutamic acid (Glu) was the most abundant of the 17 free amino acids at 4.0 mg/g. The aroma profiles of the samples were significantly influenced by fifteen of the analyzed volatile compounds, especially methyl salicylate, methyl caproate, and 2-octanol (ROAV > 1). Latilactobacillus (27.45%) and Pseudomonas (9.01%) were the dominant bacterial genera, and Starmerella (32.95%) and Pichia (17.01%) were the dominant fungal genera. Weissella, Lacticaseibacillus, Pichia, and Kazachstania had positive effects on volatile flavoring compounds, which enriched the texture and flavor of the chili bean paste. Therefore, the microbial-community activity during the post-ripening fermentation is the key to enhance the flavor quality of the product.

Synthesis of Benzofuro[3,2-b]indol-3-one Derivatives via Dearomative (3 + 2) Cycloaddition of 2-Nitrobenzofurans and para-Quinamines.

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions and affords a series of benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up to 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis and versatile derivatizations demonstrate the potential synthetic application of the protocol. A plausible reaction mechanism is also proposed to account for the observed reaction process. This work represents the first instance of the N-triggered dearomative (3 + 2) cycloaddition of 2-nitrobenzofurans.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Effects of extracted oil of fermented Tartary buckwheat on lipid-lowering, inflammation modulation, and gut microbial regulation in mice.

This study investigated the composition of Tartary buckwheat oil fermented by Monascus purpureus and extracted under supercritical CO2 conditions (FTBO) and evaluated its effects on lipid-lowering, inflammation modulation, and gut microbial regulation in mice that were fed a high-fat diet (MOD). Compared with the raw oil (TBO), the γ-oryzanol content reached 27.09 mg g-1; the monounsaturated fatty acid (MUFA) content (such as oleic acid and palmitic acid) was elevated; and the antioxidant capacities of DPPH, ABTS, and hydroxyl were improved in FTBO (p < 0.0001). Then, supplementation with FTBO had a remarkable effect on reducing the body weight and visceral obesity as well as alleviating hyperglycemia, dyslipidemia, inflammatory reactions, and liver damage. The TC, TG, and LDL-C levels in the liver and plasma were reduced, and the HDL-C levels in the liver were increased (p < 0.05). In particular, the high-dose group (FTBOH) exhibited the most significant effect on reducing the pro-inflammatory cytokines ET, TNF-α, IL-1ß, and IL-6 in the liver, which were 18.85, 570.12, 50.47, and 26.22 pg mL-1, respectively (p < 0.05). Moreover, FTBO reversed intestinal disorders and increased the intestinal microbial diversity and richness. The relative abundance of beneficial bacteria, such as Bifidobacterium, Lactobacillus, Limosilactobacillus, and Lachnospiraceae_UCG-006, were increased, and the relative abundance of the harmful bacteria Staphylococcus and Lachnoclostridium were reduced. In summary, FTBO has potential applications as a dietary supplement or dietary modifier in lowering blood lipids, modulating immune activity, and reversing intestinal disorders. This study provides reference guidance for the subsequent industrialization and development of Tartary buckwheat, the extension of the industrial chain, the development of new products, and the extraction of functional components.

Prognostic significance of CCND1 amplification/overexpression in smoking patients with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer, with 5-year survival rate less than 30%. In order to offer an individual therapeutic approach, it is necessary to identify novel prognostic factors to recognize high-risk patients. Given the high frequency of CCND1 abnormalities and the important biological effects of smoking in ESCC, we explored the potential relationship between CCND1 abnormalities and smoking in ESCC patients. CCND1 status was examined by fluorescence in situ hybridization and immunohistochemical staining in ESCC tissue microarrays (n = 519). CCND1 amplification and cyclinD1 overexpression were found in 53.2 and 34.1% ESCC, respectively. CCND1 amplification (P = 0.142 for DFS and P = 0.191 for OS) and cyclinD1 overexpression (P = 0.035 for DFS and P = 0.092 for OS) tended to be poorer prognostic factors in all patients. Among smoking patients, those with CCND1 amplification had significantly poorer prognosis, with a median DFS and OS of 25.0 and 30.0 months compared to not reached and 52.0 months for those without CCND1 amplification (P = 0.020 and 0.018). A similar trend was found in the 68 patients with cyclinD1 overexpression (P = 0.043 and 0.048). Further univariate and multivariate analysis revealed CCND1 amplification was independently poorer prognostic factor in smoking patients, which was not found in non-smoking patients. Smokers with CCND1 amplification or cyclinD1 overexpression have poorer survival, which help us to identify distinct groups of patients with apparently poorer outcome and would enable appropriate follow-up and treatment strategies.

Autophagy suppression facilitates macrophage M2 polarization via increased instability of NF-κB pathway in hepatocellular carcinoma.

The tumor microenvironment is a highly heterogeneous circumstance composed of multiple components, while tumor-associated macrophages (TAMs) are major innate immune cells with highly plastic and are always educated by tumor cells to structure an advantageous pro-tumor immune microenvironment. Despite emerging evidence focalizing the role of autophagy in other immune cells, the regulatory mechanism of autophagy in macrophage polarization remains poorly understood. Herein, we demonstrated that hepatocellular carcinoma (HCC) cells educated macrophages toward M2-like phenotype polarization under the condition of coculture. Moreover, we observed that inhibition of macrophage autophagy promoted M2-like macrophage polarization, while the tendency was impeded when autophagy was motivated. Mechanistically, macrophage autophagy inhibition inactivates the NF-κB pathway by increasing the instability of TAB3 via ubiquitination degradation, which leads to the M2-like phenotype polarization of macrophages. Both immunohistochemistry staining using human HCC tissues and experiment in vivo verified autophagy inhibition is correlated with M2 macrophage polarization. Altogether, we illustrated that macrophage autophagy was involved in the process of HCC cells domesticating M2 macrophage polarization via the NF-κB pathway. These results provide a new target to interfere with the polarization of macrophages to M2-like phenotype during HCC progression.

Inhibition of autophagy in macrophage promotes IL-1ß-mediated hepatocellular carcinoma progression via inflammasome accumulation and self-recruitment.

Hepatocellular carcinoma (HCC) has a complex and changeable tumor microenvironment. Despite emerging evidence focusing on autophagy process within immune cells, the function and regulatory mechanism of macrophage autophagy in tumor progression remains unclear. Our results of multiplex-immunohistochemistry and RNA-sequencing identified the reduced levels of autophagy in tumor macrophages in the HCC microenvironment, associated with a poor prognosis and increased microvascular metastasis in HCC patients. Specifically, HCC suppressed the macrophage autophagy initiation through the up-regulation of mTOR and ULK1 phosphorylation at Ser757. Knockdown of autophagy-related proteins to further inhibit autophagy significantly boosted the metastatic potential of HCC. Mechanistically, the accumulation of NLRP3 inflammasome mediated by autophagy inhibition promoted the cleavage, maturation, and release of IL-1ß, which facilitated the HCC progression, eventually accelerating HCC metastasis via the epithelial-mesenchymal transition. Autophagy inhibition provoked macrophage self-recruitment through the CCL20-CCR6 signaling was also a crucial account of HCC progression. Recruited macrophages mediated the cascade amplification of IL-1ß and CCL20 to form a novel pro-metastatic positive feedback loop through promoting HCC metastasis and increased macrophage recruitment, respectively. Notably, targeting IL-1ß/IL-1 receptor signaling impaired lung metastasis induced by macrophage autophagy inhibition in a mice HCC lung metastasis model. In summary, this study highlighted that inhibition of tumor macrophage autophagy facilitated HCC progression by increasing IL-1ß secretion via NLRP3 inflammasome accumulation and by macrophage self-recruitment through the CCL20 signaling pathway. Interruption of this metastasis-promoting loop by IL-1ß blockade may provide a promising therapeutic strategy for HCC patients.

The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis. METHODS: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort. PNI-related genomic and transcriptomic profiles were analyzed in MSK and ZS-ICC cohorts. GO, KEGG, and ssGSEA analyses were performed. Immunohistochemistry was used to investigate the relationship between PNI and markers of neurons, hydrolases, and immune cells. The efficacy of adjuvant therapy in ICC patients with PNI was also assessed. RESULTS: A total of 30.6% and 20.7% ICC patients had PNI in MSK and TMA cohorts respectively. Patients with PNI presented with malignant phenotypes such as high CA19-9, the large bile duct type, lymph node invasion, and shortened overall survival (OS) and relapse-free survival (RFS). Nerves involved in PNI positively express tyrosine hydroxylase (TH), a marker of sympathetic nerves. Patients with PNI showed high mutation frequency of KRAS and an immune suppressive metastasis prone niche of decreased NK cell, increased neutrophil, and elevated PD-L1, CD80, and CD86 expression. Patients with PNI had an extended OS after adjuvant therapy with TEGIO, GEMOX, or capecitabine. CONCLUSION: Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with PNI. Patients with PNI showed a poor prognosis after surgery but a good response to adjuvant chemotherapy.

Enhancement of Anti-Proliferative Activity of the Extracts from Dehulled Adlay by Fermentation with Bacillus subtilis.

Dehulled adlay was fermented with Bacillus subtilis BJ3-2, the anti-proliferative activities of the extracts from fermented dehulled adlay were investigated with six types of tumor cells, and then the bioactive components and the anti-proliferative mechanism were primarily explored. Results showed that all the extracts of B. subtilis-fermented dehulled adlay (BDA) and dehulled adlay (DA) had no inhibition effect on human embryonic kidney 239T cells. The anti-proliferative activities of the extracts from BDA against six types of tumor cells were almost always significantly higher than DA. Compared with others, the n-butanol extract of BDA (BDA-Nb) exhibited stronger anti-proliferative activities against human leukemia K562 cells and human non-small cell lung cancer A549 cells. Importantly, the anti-proliferative activity of fermented dehulled adlay against K562 cells was firstly discovered. Meanwhile, BDA-Nb was rich in tetramethylpyrazine, γ-aminobutyric acid, protocatechuic, 2,3,4-trihydroxybenzoic, chlorogenic, p-hydroxybenzoic, caffeic, trans-cinnamic, ferulic acids, and rutin. BDA-Nb induced the proliferative inhibition of K562 and A549 cells due to abnormal cell morphology, the increased cell population in G1 phase and apoptosis rate, the downregulation of Bcl-2, and the upregulation of Bax and caspase-3/8/9. These results indicate that dehulled adlay fermented with B. subtilis could be a potential therapeutic agent for leukemia and lung cancer.

Amplification of spatially isolated adenosine pathway by tumor-macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma.

BACKGROUND: Immune checkpoint blockade resistance narrows the efficacy of cancer immunotherapies, but the underlying mechanism remains elusive. Delineating the inherent mechanisms of anti-PD1 resistance is important to improve outcome of patients with advanced HCC. METHOD: The level of cricTMEM181 was measured in HCC patients with anti-PD1 therapy by RNA sequencing and then confirmed by qPCR and Sanger sequencing. Immune status in tumor microenvironment of HCC patients or mice models was evaluated by flow cytometry and IHC. Exosomes from HCC cell lines were isolated by ultracentrifugation, and their internalization by macrophage was confirmed by immunofluorescence. The underlying mechanism of HCC-derived exosomal circTMEM181 to macrophage was confirmed by SILAC, RNA FISH and RNA immunoprecipitation. The ATP-ADO pathway amplified by HCC-macrophage interaction was evaluated through ATP, AMP and ADO measurement and macrophage-specific CD39 knockout mice. The role of circTMEM181 in anti-PD1 therapy and its clinical significance were also determined in our retrospective HCC cohorts. RESULTS: Here, we found that circTMEM181 was elevated in hepatocellular carcinoma (HCC) patients responding poorly to anti-PD1 therapy and in HCC patients with a poor prognosis after operation. Moreover, we also found that high exosomal circTMEM181 favored the immunosuppressive microenvironment and endowed anti-PD1 resistance in HCC. Mechanistically, exosomal circTMEM181 sponged miR-488-3p and upregulated CD39 expression in macrophages. Using macrophage-specific CD39 knockout mice and pharmacologic approaches, we revealed a novel mode of anti-PD1 resistance in HCC. We discovered that cell-specific CD39 expression in macrophages and CD73 expression in HCC cells synergistically activated the eATP-adenosine pathway and produced more adenosine, thereby impairing CD8+ T cell function and driving anti-PD1 resistance. CONCLUSION: In summary, HCC-derived exosomal circTMEM181 contributes to immunosuppression and anti-PD1 resistance by elevating CD39 expression, and inhibiting the ATP-adenosine pathway by targeting CD39 on macrophages can rescue anti-PD1 therapy resistance in HCC.

CTLA-4 Synergizes With PD1/PD-L1 in the Inhibitory Tumor Microenvironment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan-Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4+ lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues (P <.001), and patients with a high density of CTLA-4+ tumor-infiltrating lymphocytes (TILsCTLA-4 High) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILsCTLA-4 Low (P <.001 and P = .024, respectively). Similarly, patients with high FOXP3+ TILs (TILsFOXP3 High) had poorer prognoses than patients with low FOXP3+ TILs (P = .021, P = .034, respectively), and the density of CTLA-4+ TILs was positively correlated with FOXP3+ TILs (Pearson r = .31, P <.001). Furthermore, patients with high PD-L1 expression in tumors (TumorPD-L1 High) and/or TILsCTLA-4 High presented worse OS and a higher recurrence rate than patients with TILsCTLA-4 LowTumorPD-L1 Low. Moreover, multiple tumors, lymph node metastasis, and high TumorPD-L1/TILsCTLA-4 were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors (P = .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. TumorPD-L1/TILsCTLA-4 is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.

Increases of Lipophilic Antioxidants and Anticancer Activity of Coix Seed Fermented by Monascus purpureus.

Lipophilic tocols, γ-oryzanol, and coixenolide in coix seed before and after fermentation by Monascus purpureus were determined. Antioxidant and anticancer activities of raw and fermented coix seed were evaluated using free-radical-scavenging assays and polyunsaturated fatty acid oxidation model, and human laryngeal carcinoma cell HEp2, respectively. Compared to the raw seed, the tocols, γ-oryzanol, and coixenolide contents increased approximately 4, 25, and 2 times, respectively, in the fermented coix seed. Especially, γ-tocotrienol and γ-oryzanol reached 72.5 and 655.0 µg/g in the fermented coix seed. The lipophilic extract from fermented coix seed exhibited higher antioxidant activity in scavenging free radicals and inhibiting lipid oxidation. The inhibitory concentrations for 50% cell survival (IC50) of lipophilic extract from fermented coix seed in inhibiting HEp2 cells decreased by 42%. This study showed that coix seed fermented by M. purpureus increased free and readily bioavailable lipophilic antioxidants and anticancer activity. Therefore, fermentation could enhance the efficacy of the health promoting function of coix seeds.

Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically.

OBJECTIVE: Differentiation-inducing therapy for tumors is a strategy that aims to induce the differentiation and maturation of cancer stem cells (CSCs). The differentiation-inducing capacity of arsenic trioxide (ATO) in hepatocellular carcinoma (HCC) and the underlying mechanism were previously unknown. METHODS: In the present study, we explored the ATO-induced differentiation of CSCs in HCC by detecting the expression of CSC-related markers and tumorigenicity variation in vivo and in vitro. We developed a combined chemotherapeutic approach to HCC by characterizing the effects of combinatorial treatment with 5-fluorouracil (5-FU)/cisplatin and ATO in vitro and in patient-derived xenograft models. Changes in gene expression patterns were investigated by gene microarray analysis. RESULTS: ATO effectively induced differentiation of CSCs by downregulation of CSC-related genes and suppression of tumorigenicity capability. Combinatorial treatment with ATO and 5-FU/cisplatin significantly enhanced therapeutic effects in HCC cells compared with the treatment with 5-FU/cisplatin alone. Synergistic inhibition of the LIF/JAK1/STAT3 and NF-kB signaling pathways by ATO and 5-FU/cisplatin is a potential molecular mechanism underlying the differentiation effect. CONCLUSIONS: ATO induced the differentiation of HCC CSCs and potentiated the cytotoxic effects of 5-FU/cisplatin through synergistic inhibition of the LIF/JAK1/STAT3 and NF-kB signaling pathways. These results offer new insights for the clinical treatment of HCC.

S100A4 overexpression in pancreatic ductal adenocarcinoma: imaging biomarkers from whole-tumor evaluation with MRI and texture analysis.

OBJECTIVE: To investigate the relationship between imaging findings and S100A4 overexpression in pancreatic ductal adenocarcinoma (PDAC) and to determine imaging biomarkers of S100A4 overexpression from whole-tumor evaluation with MRI and texture analysis. METHODS: A total of 60 patients with pathologically confirmed PDAC were included in the study. All patients underwent preoperative abdominal contrast-enhanced MRI examination with Magnetom Aera (Siemens Healthcare, Germany, 1.5 T) at our institute. Whole-tumor evaluation including texture analysis was performed. Sections of specimens were reviewed, and the S100A4 expression status was quantitatively evaluated. Univariate and multivariate logistic regression analyses were conducted to find imaging biomarkers that could predict S100A4 overexpression. RESULTS: Twenty-four tumors (40.0%) had negative results for S100A4 overexpression, and 36 tumors (60.0%) exhibited overexpression. After univariate and multivariate analysis, distal pancreatic duct dilatation, T1WI_10th percentile and the enhancement rate difference between delayed phase (DP) and portal venous phase (PVP) were identified to predict S100A4 overexpression in PDAC independently (p = 0.009, 0.012 and 0.044), with odds ratios (ORs) of 0.102, 0.139 and 4.645, respectively. The area under the ROC curve (AUC) values were 0.715, 0.707 and 0.691. The AUC value of the proposed model was 0.877 with a sensitivity of 80.6% and specificity of 75.0%. CONCLUSION: A model including distal pancreatic duct dilatation, T1WI_10th percentile and the enhancement rate difference between the DP and PVP could predict S100A4 overexpression in PDAC as imaging biomarkers.

Tetramethylpyrazine from adlay (Coix lacryma-jobi) biotransformation by Bacillus subtilis and its quality characteristics.

Adlay, as a traditional Chinese medicine, has been used in nourishing foods, which are rich in a variety of nutrients (special biological compounds). The study was designed to optimize the fermentation parameters of dehulled, polished and broken adlay fermented by Bacillus subtilis BJ3-2 with regard to tetramethylpyrazine (TMP) yield and fibrinolytic enzyme activity. Then the proximate and bioactive components of B. subtilis-fermented adlay were evaluated. Box-Behnken design results showed that the TMP yield was 6.93 mg/g DW (dried weight) of B. subtilis-fermented polished adlay, which was about 136 times higher than that of B. subtilis-fermented soybean (BSB). The fibrinolytic enzyme activity was 2236.17 U/g in B. subtilis-fermented dehulled adlay, and slightly less than in BSB. B. subtilis-fermented adlay contained higher fat, free amino acids and fatty acids contents but lower protein and starch contents than raw adlay. Except for coixol and coixan, the levels of γ-aminobutyric acid, triterpenes, phenolics, flavonoids and coixenolide in B. subtilis-fermented adlay increased by 14.05, 2.02, 2.31 and 1.36 times, respectively. The contents of phenolic acids including caffeic, gallic, catechinic and chlonogenic acids in the free phenolic extracts significantly increased (p < 0.05). The results demonstrated that the biotransformation of high-yield TMP, fibrinolytic enzyme and other bioactive components of B. subtilis-fermented adlay products was realized. B. subtilis-fermented adlay could be a promising value-added food, and that is more suitable for human consumption.

Comprehensive evaluation of physicochemical properties and antioxidant activity of B. subtilis-fermented polished adlay subjected to different drying methods.

The physicochemical properties and antioxidant activity of B. subtilis-fermented polished adlay (BPA) subjected to different drying methods (hot-air drying, HAD; infrared-radiation drying, IRD; vacuum drying, VD; microwave-vacuum drying, MVD; and freeze-vacuum drying, FVD) were evaluated in this study. Results showed FVD was ideal for maintaining the natural appearance and higher contents of proximate compositions, free fatty acids, tetramethylpyrazine (6.91 mg/g DW), coixol (0.62 mg/g DW), coixenolide (4.21% DW), coixan (35.10% DW), and triterpenoids (17.41 mg/g DW). The higher contents of total phenolics and flavonoids, stronger antioxidant activity, and higher color differences were observed in HAD and IRD samples. MVD displayed the shorter drying time, higher γ-aminobutyric acid content, and higher retention ratios of tetramethylpyrazine (75.54%), coixol (87.10%), coixenolide (98.57%), and coixan (99.11%). Pearson's correlation coefficient exhibited that the positive correlation between the contents of phenolics and flavonoids and the antioxidant activities of all dried BPA samples was observed (R 2 > 0.881, p < .05). Principal component analysis showed that the top three categories of comprehensive quality were FVD-, MVD-, and VD-treated BPA samples. In conclusion, MVD should be a potential preservation method to obtain high-quality dried BPA for short drying time and high comprehensive quality.

Co-Administration of Multiple Childhood Vaccines - Guangdong Province, 2019.

What is already known about this topic? The Co-Administration of Multiple Vaccines were implemented in many countries and have been shown to significantly reduce many times of visiting the vaccination clinic. What is added by this report? It is the first time to calculate the cost of visiting vaccination clinic from transportation and work-absence for children's families in Guangdong. What are the implications for public health practice? We demonstrated the importance of Co-Administration of Multiple Vaccines that reduce the vaccination cost of children's families. The policy should be promoted as soon as possible.

Cap-Assisted Endoscopic Sclerotherapy vs Ligation in the Long-Term Management of Medium Esophageal Varices: A Randomized Trial.

INTRODUCTION: Compared with endoscopic variceal ligation (EVL), cap-assisted endoscopic sclerotherapy (CAES) improves efficacy in the treatment of small esophageal varices (EVs) but has not been evaluated in the management of medium EVs. The aim of this study was to compare CAES with EVL in the long-term management of patients exhibiting cirrhosis with medium EVs and a history of esophageal variceal bleeding (EVB), with respect to variceal eradication and recurrence, adverse events, rebleeding, and survival. METHODS: Cirrhotic patients with medium EVs and a history of EVB were divided randomly into EVL and CAES groups. EVL or CAES was repeated each month until variceal eradication. Lauromacrogol was used as a sclerosant. Patients were followed up until 1 year after eradication. RESULTS: In total, 240 patients (age: 51.1 ± 10.0 years; men: 70.8%) were included and randomized to the EVL and CAES groups. The recurrence rate of EVs was much lower in the CAES group than in the EVL group (13.0% vs 30.7%, P = 0.001). The predictors for variceal recurrence were eradication by EVL (hazard ratio [HR]: 2.37, P = 0.04), achievement of complete eradication (HR: 0.27, P < 0.001), and nonselective ß-blocker response (HR: 0.32, P = 0.003). There was no significant difference in the rates of eradication, rebleeding, requirement for alternative therapy, and mortality or the incidence of complications between groups. DISCUSSION: CAES reduces the recurrence rate of EVs with comparable safety to that of EVL in the long-term management of patients presenting cirrhosis with medium EVs and a history of EVB.

Mortalin stabilizes CD151-depedent tetraspanin-enriched microdomains and implicates in the progression of hepatocellular carcinoma.

Background: Our previous studies showed that tetraspanin CD151 was implicated in the progression of hepatocellular carcinoma (HCC), mainly depending on the formation of functional complexes with molecular partners, including Mortalin. In this study, we investigate the role of mortalin in CD151-depedent progression of HCCs. Methods: Immunofluorescent staining, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to investigate the expression and location of CD151 and Mortalin in four HCC cell lines with different metastatic ability. The relationship between Mortalin and CD151 was investigated in HCCLM3 cells using co-immunoprecipitation. CD151 or Mortalin expression in HCC cells were modified by transfection technology. Wound-healing assay and Transwell assay were used to assay the role of CD151 and Mortalin in cell migration and invasion. The expression and prognostic implication of CD151 and Mortalin in 187 cases of HCCs were analyzed. Results: Expression of Mortalin in HCC cells was positive related to their metastatic ability and its tendency was in line with the expression of CD151. Immunofluorescent staining showed that Mortalin was located in cytoplasm, while positive staining for CD151 was observed in cytoplasm and membrane of HCC cells. co-IP revealed that Mortalin formed a complex with CD151. Down-regulation of Mortalin induced a moderate decreased CD151 protein, but not CD151 mRNA, while inhibition of CD151 did not influence the expression of Mortalin at the level of both protein and mRNA. Interference of Mortalin significantly inhibited the invasion and migration of HCC cells with high CD151 expression and partially restored the invasion and migration of HCC cells induced by CD151 over-expression. Clinically, high Mortalin expression correlated with malignant phenotype of HCC, such as microvascular invasion (p=0.017) and tumor diameter (p=0.001). HCC patients expressing high Mortalin were tend to have higher expression of CD151. HCC patients expressing high level of CD151 showed the poorer prognosis in a Mortalin-dependent manner. Conclusions: Mortalin maybe stabilize of the structure of CD151-dependent tetraspanin-enriched microdomains and implicate in the progression of HCC.