Resistant starch reduces glycolysis by HK2 and suppresses high-fructose corn syrup-induced colon tumorigenesis.

BACKGROUND: The intake of high-fructose corn syrup (HFCS) may increase the risk of colorectal cancer (CRC). This study aimed to explore the potential effects and mechanisms of resistant starch (RS) in HFCS-induced colon tumorigenesis. METHODS: The azoxymethane/dextran sodium sulfate (AOM/DSS) and ApcMin/+ mice models were used to investigate the roles of HFCS and RS in CRC in vivo. An immunohistochemistry (IHC) staining analysis was used to detect the expression of proliferation-related proteins in tissues. 16S rRNA sequencing for microbial community, gas chromatography for short-chain fatty acids (SCFAs), and mass spectrometry analysis for glycolysis products in the intestines were performed. Furthermore, lactic acid assay kit was used to detect the glycolysis levels in vitro. RESULTS: RS suppressed HFCS-induced colon tumorigenesis through reshaping the microbial community. Mechanistically, the alteration of the microbial community after RS supplement increased the levels of intestinal SCFAs, especially butyrate, leading to the suppression of glycolysis and CRC cell proliferation by downregulating HK2. CONCLUSIONS: Our study identified RS as a candidate of protective factors in CRC and may provide a potential target for HFCS-related CRC treatment.

Fasting-mimicking diet remodels gut microbiota and suppresses colorectal cancer progression.

The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8+T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45+ and CD8+ T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.

Case report: A case of high virulence and multidrug resistant Klebsiella pneumoniae liver abscess in Ningxia, China.

RATIONALE: Highly virulent multidrug-resistant Klebsiella pneumoniae (KP) is becoming more and more common in clinical practice, especially the rise of carbapenem-resistant KP in clinical practice, resulting in the emergence of KP liver abscess in Ningxia, China. For the prognosis of liver abscess patients, it is particularly important to identify the types of pathogens and identify antibiotics that are sensitive to the pathogens. PATIENT CONCERNS: A 73-year-old man from China presents to our hospital with abdominal pain, jaundice and fever. Patients have no obvious cause of abdominal pain, abdominal distension, and abdominal pain is persistent. Abdominal examination showed hepatomegaly, no tenderness 2 cm from the right costal margin, abdominal distension and other general examinations did not have obvious abnormalities. He had no history of hypertension and diabetes, ERCP was performed for cholangiocarcinoma 1 year before the current visit, and no significant complications occurred. DIAGNOSES: His initial diagnosis was obstructive cholangitis, and computed tomographic images and liver drainage fluid bacterial culture and genetic polymerase chain reaction tests later determined that the patient had KP liver abscess. INTERVENTIONS: Drainage by liver catheter and antibiotic treatment for 7 weeks. OUTCOMES: The patient liver abscess is basically gone. LESSION: It is particularly important to optimize the diagnosis of liver abscess pathogens for timely and effective treatment of patients.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

Genome-Wide Identification and Characterization of R2R3-MYB Provide Insight into Anthocyanin Biosynthesis Regulation Mechanism of Ananas comosus var. bracteatus.

The R2R3-MYB proteins comprise the largest class of MYB transcription factors, which play an essential role in regulating anthocyanin synthesis in various plant species. Ananas comosus var. bracteatus is an important colorful anthocyanins-rich garden plant. The spatio-temporal accumulation of anthocyanins in chimeric leaves, bracts, flowers, and peels makes it an important plant with a long ornamental period and highly improves its commercial value. We conducted a comprehensive bioinformatic analysis of the R2R3-MYB gene family based on genome data from A. comosus var. bracteatus. Phylogenetic analysis, gene structure and motif analysis, gene duplication, collinearity, and promoter analysis were used to analyze the characteristics of this gene family. In this work, a total of 99 R2R3-MYB genes were identified and classified into 33 subfamilies according to phylogenetic analysis, and most of them were localized in the nucleus. We found these genes were mapped to 25 chromosomes. Gene structure and protein motifs were conserved among AbR2R3-MYB genes, especially within the same subfamily. Collinearity analysis revealed four pairs of tandem duplicated genes and 32 segmental duplicates in AbR2R3-MYB genes, indicating that segmental duplication contributed to the amplification of the AbR2R3-MYB gene family. A total of 273 ABRE responsiveness, 66 TCA elements, 97 CGTCA motifs, and TGACG motifs were the main cis elements in the promoter region under response to ABA, SA, and MEJA. These results revealed the potential function of AbR2R3-MYB genes in response to hormone stress. Ten R2R3-MYBs were found to have high homology to MYB proteins reported to be involved in anthocyanin biosynthesis from other plants. RT-qPCR results revealed the 10 AbR2R3-MYB genes showed tissue-specific expression patterns, six of them expressed the highest in the flower, two genes in the bract, and two genes in the leaf. These results suggested that these genes may be the candidates that regulate anthocyanin biosynthesis of A. comosus var. bracteatus in the flower, leaf, and bract, respectively. In addition, the expressions of these 10 AbR2R3-MYB genes were differentially induced by ABA, MEJA, and SA, implying that these genes may play crucial roles in hormone-induced anthocyanin biosynthesis. Our study provided a comprehensive and systematic analysis of AbR2R3-MYB genes and identified the AbR2R3-MYB genes regulating the spatial-temporal anthocyanin biosynthesis in A. comosus var. bracteatus, which would be valuable for further study on the anthocyanin regulation mechanism of A. comosus var. bracteatus.

Long Non-Coding RNA DUXAP8 Acts as an Oncogene in Sinonasal Squamous Cell Carcinoma Through miR-584-5p/FNDC3B Pathway.

Sinonasal squamous cell carcinoma (SNSCC) is one of the least frequent carcinomas in the head and neck and accounts for 60% to 75% of sinonasal malignancies. The role of long non-coding RNAs (lncRNAs) in cancer development has drawn great attention over the years. The current study intended to assess the role and specific mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in SNSCC. Quantitative real-time PCR (qRT-PCR) analysis was implemented to assess the expression level of DUXAP8, microRNA-584-5p (miR-584-5p), and fibronectin type III domain containing 3B (FNDC3B). Proliferation assays included colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay. Transwell assays were implemented to monitor cell migration and invasion. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and JC-1 experiments. Mechanism experiments included RNA pull-down assay, RNA binding protein immunoprecipitation (RIP) assay, and luciferase reporter assay. DUXAP8 is overexpressed in SNSCC cells. Functionally, DUXAP8 silencing suppresses the malignant progression of SNSCC. Furthermore, DUXAP8 up-regulates the expression of FNDC3B via sponging miR-584-5p. Rescue experiments demonstrated that DUXAP8 mediates the progression of SNSCC via up-regulating FNDC3B expression. In conclusion, DUXAP8 acts as an oncogene in SNSCC, which may be a new molecular marker for SNSCC.

[Effect of computer navigation gap balance technology on lower limb recovery after total knee arthroplasty].

OBJECTIVE: To investigate the effect of computer navigation gap balance technology on the recovery of lower limb function after total knee arthroplasty. METHODS: The clinical data of 106 patients with knee osteoarthritis (OA) who underwent total knee arthroplasty from July 2018 to June 2019 were analyzed retrospectively. They were divided into measurement osteotomy group and space balance group according to different osteotomy techniques during total knee arthroplasty. There were 61 cases in osteotomy group, 24 males and 37 females;The age ranged from 45 to 77(63.35±4.26) years;According to K-L classification, 41 cases were grade Ⅲ and 20 cases were grade Ⅳ. intraoperative measurement osteotomy was performed. There were 45 cases in the gap balance group, 17 males and 28 females;Age 45 to 78(64.03±4.31) years;According to K-L classification, 29 cases were classified as grade Ⅲ and 16 cases as grade Ⅳ. computer navigation gap balance technology was implemented. The amount of intraoperative bleeding, operation time, incision length, hospital stay and postoperative complications were compared between two groups. The clinical efficacy was evaluated by Knee Society score(KSS) before operation and 12 months after operation. RESULTS: Total of 106 patients were followed up for 12 to 18(20.38±3.25) months. There were significant differences in intraoperative bleeding and operation time between two groups(P<0.05). There was no significant difference in incision length and hospital stay between the two groups(P>0.05). At 12 months after operation, the total score of KSS in the gap balance group (173.59±14.50) was better than that in the osteotomy group (164.95±12.10)(P<0.05). There were no serious complications of poor prosthesis loosening between two groups during follow-up, and there was no significant difference in the incidence of other complications between two groups(P>0.05). CONCLUSION: The application of computer navigation gap balance technology in total knee arthroplasty is conducive to the recovery of lower limb function in patients with OA, and there are no serious adverse complications and high safety.

Adventitious root primordia formation and development in the stem of Ananas comosus var. bracteatus slip.

There are about 4-6 slips on a fruit, and they are good materials for effective regeneration of Ananas comosus var. bracteatus. Adventitious root (AR) induction is essential for the propagation of Ananas comosus var. bracteatus slips. Growth regulator treatment, and culture medium are imperative factors that affect slip growth and rooting. In order to screen the optimal methods for slips rooting and reveal the anatomic procedure of slip rooting, this study induced slip rooting by different treatment of growth regulator, culture medium, observed the slip stem structure, AR origination and formation procedure through paraffin sections. The results showed that, slip cuttings treated with 100 mg/L of Aminobenzotriazole (ABT) for 6 hrs, cultured in river sand: coconut chaff: garden soil 2:2:1 medium is the optimal method for rooting. The proper supplementary of ABT can enhance the soluble sugar content, soluble protein content, polyphenol oxidase (PPO) activity and peroxidase (POD) enzyme activity, which resulted in the improvement of rooting. The slip stem structure is quite different from other monocots, which consists of epidermis, cortex, and stele with vascular tissues distributed in the cortex and stele. The AR primordia originates from the parenchyma cells located on the borderline between the cortex and stele. The vascular tissues in the AR develop and are connected with vascular tissue of the stem before the AR grew out the stem. The number of primary xylem poles in AR is about 30.

Identification of inhibitors targeting HIF-2α/c-Myc by molecular docking and MM-GBSA technology.

The treatment of ccRCC by targeting hypoxia-inducible factor HIF-2α is currently a direct and effective method. Studies have shown that HIF-2α and c-Myc cooperate to promote ccRCC tumor progression, and the overexpression of c-Myc is related to the progress and drug resistance of most human cancers. Although HIF-2α and c-Myc are important drug targets, their dual inhibitors are still lacking. We used virtual screening tools (mainly including molecular docking and MM-GBSA technology) to obtain some well-listed compounds that can potentially target HIF-2α and c-Myc and used molecular dynamics simulations to study their binding with these protein systems. Using a structure-based screening scheme, a batch of top-ranking compounds were selected, and their binding affinities were predicted of these compounds were performed. Representative compound C93106, C43257, and C41580 all showed good comprehensive binding score. Our results indicate that the target compounds can all form key interactions with the active site of the protein, and 30 ns molecular dynamic simulation of the complex system indicates a stable binding conformation. This research laid the foundation for the development of more effective and specific HIF-2α and c-Myc dual-target inhibitors.

Design and screening of FAK, CDK 4/6 dual inhibitors by pharmacophore model, molecular docking, and molecular dynamics simulation.

Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates integrin and growth factor signaling pathways, which is a promising therapeutic target because of involving in the migration, proliferation and survival of cancer cell. Overexpression and amplification of cyclin-dependent kinase 4/6 (CDK4/6) occur in many cancers and may be the cause of resistance to CDK4/6 inhibitors in preclinical models. The latest research shows that the combination of FAK and CDK4/6 can be dually targeted to enhance the antitumor effects. In this study, FAK and CDK4/6 dual target inhibitors were designed by computer-aided drug design. Seven million molecules were screened by the pharmacophore model and molecular docking. Finally, 6 compounds were obtained. Molecular dynamics simulation of compound 1, 2 and 3 showed that it has good binding stability to both receptors. According to the binding modes of compound 1 with two receptors, corresponding modifications were made, and 7 novel designed compounds were obtained. The docking energy of these novel designed compounds were lower than that of compound 1, and they can be tested in future.Communicated by Ramaswamy H. Sarma.

Application of a surgical nursing cooperation program in laparoscopic pancreaticoduodenectomy.

BACKGROUND: To evaluate the value of programmed surgical nursing in laparoscopic pancreaticoduodenectomy (LPD) and summarize the experience. METHODS: The clinical data of 80 patients who received LPD in Sun Yat-sen Memorial Hospital from January 2017 to December 2018 were analyzed retrospectively. A total of 40 patients were treated with traditional surgical nursing as the control group in the earlier stage. Afterwards, another 40 cases in the experimental group were treated using the surgical nursing program. Operation time, blood loss, and satisfaction of surgeons were analyzed. RESULTS: In all, 80 cases were successfully completed, and no significant difference was observed in the preoperative data statistics between these two groups (P>0.05). Compared with the control group, the average operation time and the average blood loss of the experimental group were significantly reduced (288.9±11.14 vs. 364.5±10.84 min, P<0.05; 135.3±20.12 vs. 364.8±77.39 mL, P<0.05), and the satisfaction of surgeons was significantly higher (95% vs. 80%, P<0.05). CONCLUSIONS: Skilled execution of nursing cooperation is crucial in LPD. Through appropriate preoperative preparation, gaining mastery operation steps, remaining in sync with surgeons, and perfecting the management details, the surgical nursing cooperation program can improve the satisfaction of the surgeons and make operations more efficient.

Enhanced recovery after surgery (ERAS) program in elderly patients undergoing laparoscopic hepatectomy: a retrospective cohort study.

BACKGROUND: Enhanced recovery after surgery (ERAS) has shown sufficient superiority in terms of cutting down hospital stay and costs, and reducing complications in patients undergoing laparoscopic hepatectomy (LH). However, the benefit of ERAS in elderly patients undergoing LH remains unclear, and clinical studies on this topic are still limited. METHODS: In total, 177 elderly patients (aged over 65 and underwent LH) were divided into two groups. The 107 patients in the control group received standard care, while the 70 patients in the ERAS group underwent the ERAS program after hepatectomy. The primary endpoint was the postoperative hospital stay. The secondary endpoints were resumption of oral intake, readmission rate and complications. RESULTS: ERAS had a positive effect on reducing length of hospital stay {6 [4-8] vs. 9 [7-14] days; P<0.001}. Although there was no significant reduction of overall complications in the ERAS group compared with the control group (0.500 vs. 0.626; P=0.097), the Clavien-Dindo classification of compliances in the ERAS group was lower among the patients with complications (Grade I: 0.829 vs. 0.597; P=0.018; Grade II: 0.143 vs. 0.328; P=0.044), which indicated that the patients in the control group might experience more severe complications. The readmission rates remained unaffected between the two groups. CONCLUSIONS: Consistent with younger patients, ERAS program is considered to be effective and safe, which can distinctly promote recovery after hepatectomy for elderly patients accepting LH.

Upregulated long noncoding RNA LINC01296 indicates a dismal prognosis for pancreatic ductal adenocarcinoma and promotes cell metastatic properties by affecting EMT.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to chemotherapy and radiotherapy and whose incidence has increased worldwide. Long noncoding RNAs have been demonstrated to play important roles in cancer initiation and progression. Long intergenic non-coding RNA 01296 (LINC01296) has been reported to be upregulated in several malignancies, but the clinical relevance and biological role of LINC01296 in PDAC are still unclear. METHODS: RT-qPCR was performed to evaluate the expression of LINC01296 in 85 pared PDAC tissue samples and a panel of PDAC cell lines. The clinical value and prognostic role of LINC01296 in patients with PDAC were further explored. Furthermore, we explored the functional roles of LINC01296 depletion in PANC-1 and SW1990 cells, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT). RESULTS: LINC01296 was enhanced in PDAC tissues and cell lines, and this overexpression was correlated with advanced tumor stages and positive lymph node metastasis in patients with PDAC. In addition, upregulation of LINC01296 was an independent prognostic predictor for patients with PDAC after surgery. Moreover, silencing of LINC01296 followed by treatment with small interfering RNAs suppressed cell proliferation and promoted cell apoptosis by affecting the Bcl-2/caspase-3 pathway. Importantly, LINC01296 attenuation impaired the migratory and invasive potential partly by reversing EMT. CONCLUSIONS: Overall, our work may help to develop a novel prognostic biomarker and therapeutic target for PDAC.

Enhanced recovery care versus traditional care after laparoscopic liver resections: a randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS), with several evidence-based elements, has been shown to shorten length of hospital stay and reduce perioperative hospital costs in many operations. This randomized clinical trial was performed to compare complications and hospital stay of laparoscopic liver resection between ERAS and traditional care. METHODS: A randomized controlled trial was performed for laparoscopic liver resection from August 2015 to August 2016. Patients were randomly divided into ERAS group and traditional care group. The primary outcome was length of hospital stay (LOS) after surgery. Second outcomes included postoperative complications, hospital cost, and 30-day readmissions. Elements used in ERAS group included more perioperative education, nurse navigators, nutrition support for liver diseases, respiratory therapy, oral carbohydrate 2 h before operation, early mobilization and oral intake, goal-directed fluid therapy, less drainages, postoperative nausea and vomiting (PONV) prophylaxis and multimodal analgesia. RESULTS: The study included 58 (two conversion to laparotomy) patients in ERAS group and 61 (three conversion to laparotomy) patients in the traditional care group. Postoperative LOS was significantly shorter in the ERAS group than traditional care group (5 vs. 8 days; p < 0.001). ERAS program significantly reduced the hospital costs (CNY 45413.1 vs. 55794.1; p = 0.006) and complications (36.2 vs. 55.7%; p = 0.033). Duration till first flatus and PONV were significantly reduced in ERAS group. Pain control was better in ERAS (Visual analogue scale (VAS) POD1 (≥ 4) 19.0 vs. 39.3%, p = 0.017; VAS POD1 2.5 vs. 3.1, p = 0.010). There was no difference in the rate of 30-day readmissions (6.9 vs. 8.2%; p = 1.000). CONCLUSION: ERAS protocol is feasible and safe for laparoscopic liver resection. Patients in ERAS group have less pain and complications.

Simultaneous determination and pharmacokinetic study of polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII in beagle dog plasma after oral administration of Rhizoma Paridis extracts by LC-MS-MS.

For the first time, a rapid and specific LC-MS-MS method has been developed for the analysis of polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII in beagle dog plasma. The method was applied to study the pharmacokinetics of Rhizoma Paridis extracts containing polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII. The analysis was carried out on an Agilent Zorbax XDB-C(18) reversed-phase column (100 × 2.1 mm, 1.8 µm) by isocratic elution with acetonitrile and water (50:50, v/v). The flow rate was 0.25 mL/min. All analytes including internal standards were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII ranging from 10 to 5000 ng/mL. The intra-and inter-day precisions (RSDs) were less than 6.66 and 9.15%. The extraction recovery ranged from 95.53 to 104.21% with RSD less than 8.69%. Stability studies showed that polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII were stable in preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII.

Identification and characterization of an amphioxus matrix metalloproteinase homolog BbMMPL2 responding to bacteria challenge.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases mainly involved in extracellular matrix (ECM) degradation. We have cloned and identified BbMMPL2 as homolog of MMPs from adult amphioxus. Recombinant BbMMPL2 proteins underwent self-processing during refolding in vitro. The final ~23 kDa polypeptide displayed proteolytic activity against ECM components like casein, gelatin, collagen IV and fibrinogen, but not laminin, fibronectin or α1-PI. This activity could be inhibited by GM6001 and TIMP-1/2. In addition, real-time RT-PCR analysis revealed that BbMMPL2 expressed in all issues/organs in adult amphioxus we tested. Its transcription was significantly up-regulated 12 h post immune challenge by Escherichia coli in epidermis and hepatic diverticulum but only slightly increased by Staphyloccocus aureus in epidermis. Furthermore, recombinant BbMMPL2-EGFP expressed in 293T and NIH/3T3 cells showed aggregation in cytoplasm and induced cell death. Our results provided new evidence that MMP was involved in immune response which could be conserved through evolution.