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Aim To obtain promising immunosuppressants from endophytic fungus. Methods and Results The endophytic fungus Mycosphaerella nawae (ZJLQ129) was isolated from the plant Smilax china L. and its secondary metabolites extracted and fractionated through column chromatography. The metabolites were further modified by a derivatization reaction with ammonium hydroxide. After isolation and derivatization, a new dibenzofuran named as (+)isomycousnine enamine (iME) was obtained. The structures of the derivatives were determined based on chemical evidences and extensive spectroscopic methods including 2D-NMR, DEPT and HRESI-MS spectra. The immune activities of iME were first evaluated on the proliferation and cytokines (IL-2 and IFN-γ) production of T and B cells by using MTT and ELISA methods respectively. Then, its effects on the proliferation of T-cell subsets (CD4+ and CD8+ T cells), as well as CD25 and CD69 expressions were also determined by flow cytometry. Finally, by using Cytometric Bead Array (CBA), the impacts of iME on the secretion of Th1/Th2/Th17 cytokines from purified CD4+ T cells were assayed. The results showed that iME not only selectively suppressed the immune responses of T cells, but also preferentially inhibited the activation and proliferation of CD4+ T cells. Conclusion A novel dibenzofuran derived from endophytic fungus Mycosphaerella nawae preferentially inhibits CD4+ T-cell activation and proliferation. Significance and Impact of the Study This work obtained iME, a new dibenzofuran derived from endophytic fungus. iME has the capacity to inhibit CD4+ T-cell activation and therefore is a novel potential immunosuppressant for development in the future.

A bacterial strain, designated AETb3-4

BACKGROUND: Oral squamous cell carcinoma (OSCC) usually originates from oral potentially malignant disorders (OPMD), such as oral leukoplakia (OLK) and oral lichen planus (OLP). Identifying biomarkers for the early diagnosis and evaluation of malignant transformation in OPMD could improve the survival rate of OSCC patients. OBJECTIVE: The present study aimed to screen for potential salivary biomarkers for evaluating the malignant transformation of OPMD. METHODS: Salivary proteases from OLK and OSCC patients or healthy donors and proteases in cultural medium from DOK and Cal-27 cells were detected with a human protease array kit. The concentrations of the salivary Kallikrein 5 (KLK5) and urokinase-type plasminogen activator (uPA) proteases were measured by ELISA. Receiver operating characteristics (ROC) to determine the potential value of these proteases in clinical diagnosis were calculated using SPSS software. Immunohistochemistry was used to detect the KLK5 and uPA expression in the oral organizations. RESULTS: The salivary protease spectrum was different among patients with OLK and OSCC and healthy donors. KLK5 and uPA levels in saliva tended to increase as the disease progressed (healthy < OPMD [OLK and OLP] < OSCC). ROC curves showed the optimum diagnostic cutoffs for KLK5 as a biomarker for OLK, OLP, and OSCC were 5.97, 6.03, and 9.45 pg/mL, respectively, while the cutoffs for uPA were 17.19, 17.26, and 20.96 pg/mL. Their combined analysis showed a higher sensitivity for the differential diagnosis of disease. Furthermore, higher levels of KLK5 and uPA were observed in OSCC tissues than in OLK and OLP. CONCLUSIONS: Salivary KLK5 and uPA are potential biomarkers for evaluating OLK and OLP malignant transformation and early diagnosis of OSCC.

A novel Gram-stain-negative, aerobic and rod-shaped bacterium with a single polar flagellum or a stalk at the end of the cell, was isolated from maize roots in the Fangshan District of Beijing, People’s Republic of China. The new strain designated 774T produced indole acetic acid (IAA). The 16S rRNA gene sequence analysis indicated that strain 774T belongs to the genus Caulobacter and is closely related to Caulobacter flavus RHGG3T, Caulobacter zeae 410Tand Caulobacter radices 695T, all with sequence similarities of 99.9%. The genome size of strain774T was 5.4 Mb, comprising 5042 predicted genes with a DNA G+C content of 68.7%.Three striking lasso peptide biosynthetic gene clusters and two IAA synthesis genes belonging to the TPM pathway were also found in the genome of strain 774T. The average nucleotide identity values and digital DNA–DNA hybridization values of the strain774T with its closely phylogenetic neighbours were less than 91.5% and 45.0%, respectively, indicating a new Caulobacter species. The major fatty acids of strain774T were identified as C16: 0 (27.7%), summed feature 3 (C16: 1ω6c and/or C16: 1ω7c) (12.6%) and summed feature 8 (C18: 1ω7c and/or C18: 1ω6c) (42.9%).The major polar lipids consisted of phosphatidyl–glycerol and glycolipids. The predominant ubiquinone was identified as Quinone 10. Based on the polyphasic characterization, strain 774T represents a novel species of the genus Caulobacter, for which the name Caulobacter endophyticus sp. nov. is proposed with 774T (= CGMCC 1.16558T = DSM 106777T) as the type strain.

Objectives: To evaluate the clinical effect of magnesium aluminum carbonate combined with rabeprazole-based triple therapy in the treatment of patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage. Methods: A total of 80 patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage admitted to the Baoding First Central Hospital from January 2019 to December 2020 were selected and randomly divided into two groups, with 40 cases in each group. The control group were given rabeprazole-based triple therapy, while the experimental group were treated with magnesium aluminum carbonate on the basis of the control group. The changes of symptoms and signs such as abdominal pain, abdominal distension, nausea, vomiting and hematochezia were compared between the two groups before and after treatment. Serological changes of the gastric mucosal microenvironment, such as the serum levels of extracellular regulatory protein kinase (ERK), superoxide dismutase (SOD) and epidermal growth factor receptor (EGFR), were compared between the two groups. Moreover, the differences in the results of gastroscopy between the two groups before and after treatment were compared and analyzed. Results: The scores of gastrointestinal symptoms in the experimental group after treatment were significantly improved compared with the control group (p=0.00). The levels of ERK and EGFR in the experimental group were significantly lower than those in the control group (ERK, p=0.01; EGRF, p=0.00), while the level of SOD was significantly increased (p=0.02). After treatment, the total effective rate of ulcer healing in the experimental group was 82.5%, which was significantly better than 60% in the control group (p=0.03). After treatment, moderate to severe gastric mucosal inflammation in the experimental group decreased to 10%, significantly better than that in the control group (decreased to 30%) (p=0.03). Conclusion: Magnesium aluminum carbonate combined with rabeprazole-based triple therapy is preferred for the treatment of patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage. With such a highly effective treatment regimen, the internal environment and blood supply of gastric mucosal cells can be significantly improved, gastric mucosal inflammation and gastrointestinal symptoms can be ameliorated, and the healing of ulcer surfaces can be accelerated. doi: https://doi.org/10.12669/pjms.38.5.5174 How to cite this:Zhou P, Gao L, Wang L, Zhang Y, Song W, Hao Y. Clinical observation of magnesium aluminum carbonate combined with rabeprazole-based triple therapy in the treatment of helicobacter pylori-positive gastric ulcer associated with hemorrhage. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5174 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Two nifH gene-harbouring bacterial strains were isolated from rhizospheres of different vegetable plants grown in different regions of northern PR China. The two strains possessed almost identical 16S rRNA gene sequences. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the two strains were 99.21 and 93.6% respectively, suggesting they belong to one species. Based on 16S rRNA gene phylogeny, the two strains were clustered together with Paenibacillus rhizophilus 7197T, Paenibacillus sabinae T27T and Paenibacillus forsythiae T98T, but on a separate branch. Novelty of the species was confirmed by ANI and dDDH comparisons between the type strain 7124T and its closest relatives, since the obtained values were considerably below the proposed thresholds for the species delineation. The genome size of strain 7124T was 5.40 Mb, comprising 5050 predicted genes with a DNA G+C content of 52.3 mol%. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The major cellular fatty acids were anteiso-C15 : 0 (52.9%) and C16 : 0 (23.4 %). Menaquinone-7 was reported as the major respiratory quinone. The diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. Based on phylogenetic, genomic, chemotaxonomic and phenotypic data, the two isolates are considered to represent a novel species of the genus Paenibacillus , for which the name Paenibacillus apii sp. nov. is proposed, with 7124T (=DSM 103172T=CGMCC 1.15689T) as type strain.

A novel Gram-stain-negative, aerobic, rod-shaped and indole acetic acid-producing strain, designated 7209-2T, was isolated from rhizosphere of rape (Brassica napus L.) grown in the Yakeshi City, Inner Mongolia, PR China. The 16S rRNA gene sequence analysis indicated that strain 7209-2T belongs to the genus Rhizobium and is closely related to Rhizobium rosettiformans W3T, Rhizobium ipomoeae shin9-1T and Rhizobium wuzhouense W44T with sequence similarities of 98.2, 98.1 and 97.9 %, respectively. Phylogenetic analysis based on concatenated housekeeping recA and atpD gene sequences showed that strain 7209-2T formed a group together with R. wuzhouense W44T and R. rosettiformans W3T, with sequences similarities of 92.6 and 91.1 %, respectively. The genome size of strain 7209-2T was 5.25 Mb, comprising 5027 predicted genes with a DNA G+C content of 61.2 mol%. The average nucleotide identity and digital DNA–DNA hybridization comparisons among 7209-2T and reference strains for the most closely related species showed values below the accepted threshold for species discrimination. The major fatty acids of strain 7209-2T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 2 (C12 : 0 aldehyde and/or unknown 10.953) . The major polar lipids were found to consist of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as quinone 10. Based on all the above results, strain 7209-2T represents a novel species of the genus Rhizobium , for which the name Rhizobium rhizophilum sp. nov. is proposed with 7209-2T (=CGMCC 1.15691T=DSM 103161T) as the type strain.

A series of novel N-alkyl-N-hydroxyl carboximates derived from β-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound β-elemene (1). Notably, compound 11i exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound 11i could significantly induce cell apoptosis. Further in vivo study in the H460 xenograft mouse model validated the anti-tumour activities of 11i with a greater tumour growth inhibition (TGI, 68.3%) than β-elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such N-alkyl-N-hydroxyl carboximate class of compounds exemplified as 11i demonstrated potent anticancer activities both in vitro and in vivo, and should warrant further investigation for potential anticancer therapy.

A novel 1-aminocyclopropane-1-carboxylate deaminase producing bacterium, Gram- stain-negative, aerobic, motile, rod-shaped strain designated YM1C-6-2T was isolated from rhizosphere of maize grown in Northeast China. The 16S rRNA gene sequence analysis indicated that strain YM1C-6-2T belongs to the genus Mesorhizobium and is closely related to Mesorhizobium alhagi CCNWXJ12-2T and M. camelthorni CCNWXJ40-4T with sequence similarities of 98.4% and 97.9%, respectively. Multilocus sequence analysis of other housekeeping genes revealed that the new isolates YM1C-6-2T forms a phylogenetically group with some species in the genus Mesorhizobium. The genome size of strain YM1C-6-2T was 5.51 Mb, comprising 5378 predicted genes with a DNA G+C content of 64.5%. The average nucleotide identity and digital DNA–DNA hybridization comparisons between YM1C-6-2T and the most related type strains showed values below the accepted threshold for species discrimination. The major fatty acids of strain YM1C-6-2T were C19:0 cyclo ω8c (47.5%), summed feature 8 (C18:1ω7c and/or C18:1ω6c) (19.5%) and C16:0 (15.1%), which differed from the closely related reference strains in their relative abundance. The major polar lipids consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as Quinone 10. Phenotypic and biochemical analysis results indicated that strain YM1C-6-2T can be distinguished from closely related type strains. Based on the above results, strain YM1C-6-2T represents a novel species of the genus Mesorhizobium, for which the name Mesorhizobium rhizophilum sp. nov. is proposed with YM1C-6-2T (= CGMCC 1.15487T = DSM 101712T) as the type strain.

The working principle of Programmable Logic Controller (PLC) is introduced. Three kinds of PLC programming method, logic based method, function based method and Petri Net based method are emphasized. The example is also given. It also points out that function based PLC programming method is a practical engineering method.

The relative efficacy and safety of first-line metastatic colorectal cancer (mCRC) treatment regimens, capecitabine with irinotecan (CAPIRI) and 5-fluorouracil/leucovorin plus irinotecan (FOLFIRI), are not well defined. We identified and subsequently examined seven independent, randomized controlled clinical trials, performing a meta-analysis to compare these two treatment regimens. Using Medline, EMBASE, Cochrane Library (CENTRAL), and the American Society of Clinical Oncology Annual Meeting to search available literature until February 2014, we identified seven studies comparing safety and efficacy of CAPIRI and FOLFIRI in mCRC patients. These studies were pooled and evaluated for rates of progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and diarrhea. CAPIRI and FOLFIRI demonstrated similar efficacy outcomes, though CAPIRI was associated with a higher incidence of diarrhea. CAPIRI and FOLFIRI are equally effective options for first-line treatment of mCRC.

Clostera anastomosis (L.) granulovirus (CaLGV) and Clostera anachoreta granulovirus (ClanGV) are both capable of infecting each other's native host insects. Despite this, we have little information on their genetic relationship. The complete nucleotide sequence of CaLGV was determined and compared with that of the genome of ClanGV. The circular, double-stranded DNA CaLGV genome (GenBank accession no. KC179784) had a G+C content of 46.7 % and was 101,818 bp in size (331 bp larger than the ClanGV genome). Overall, the CaLGV nucleotide sequence was found to be 90 % identical to that of ClanGV. It contained a total of 123 ORFs, 119 of which had ClanGV homologues, with an identical transcription direction and ORF organization. Seventy-five of the 119 ORFs showed 90 % or greater identity to their ClanGV homologues. CaLGV contained only a single identifiable homologous region (hrs)/repeat region (similar to ClanGV hr4). The mean frequency of nucleotide substitutions in the CaLGV/ClanGV coding regions was 8.33 %. CaLGV contained four unique ORFs (CaL23, CaL39, CaL48 and CaL92). Eight ORFs found in both CaLGV and ClanGV have no homologues in other baculoviruses. Intergenic regions of CaLGV and ClanGV occupied 6.6 % and 7 % of their respective genomes. CaLGV appears closer phylogenetically to ClanGV than to any other baculoviruses.

Based on the established indoor experimental platform for the leakage of buried oil pipeline, the characteristics of leakage under varied transfer pressure have been studied and simulated according to the experimental model by using FLOEFD—an analysis software of fluid & heat transfer. By comparing and analyzing the result of simulation, experiment and applying correlate theory of fluid dynamics，the theoretical model is established.

This article aims to simulate fire smoke spread in atrium-corridor structure with different factors, reveal the relation between spread time and each single factor, which may provide guidance for further fire design in the atrium-corridor structure.

Large amounts of sludge are produced in China each year. Its safe disposal and the recycling technology is the only way to solve the problem of sludge pollution, in which the sludge solidification technology is very important. Since the hygroscopic property and self-hardening property of paper sludge ash are important factors for developing cheap and effective sludge curing agent formulations, the research is practically valuable. The present research studies the basic engineering properties of paper sludge ash, its PH value, heavy metals in the extracting solution, hygroscopic property, microstructure and shear strength. The results show: the PS ash was weakly alkaline; the extracting heavy metals are of little pollution; hygroscopic property decreases with increasing pressure and there is a minimum water absorption; shear strength decreases as the water content increases.

Aim: Previous studies have demonstrated that glycine (GLY) markedly reduces lipopolysaccharide (LPS)-induced myocardial injury. However, the mechanism of this effect is still unclear. The present study investigated the effect of GLY on cytosolic calcium concentration ([Ca 2+ ] c ) and tumor necrosis factor-α (TNFα) production in cardiomyocytes exposed to LPS, as well as whether the glycine-gated chloride channel is involved in this process. Methods: Neonatal rat cardiomyocytes were isolated, and the [Ca 2+ ] c and TNFα levels were determined by using Fura-2 and a Quantikine enzyme-linked immunosorbent assay, respectively. The distribution of the GLY receptor and GLY-induced currents in cardiomyocytes were also investigated using immunocytochemistry and the whole-cell patch-clamp technique, respectively. Results: LPS at concentrations ranging from 10 ng/mL to 100 μg/mL significantly stimulated TNFα production. GLY did not inhibit TNFα production induced by LPS at concentrations below 10 ng/mL but did significantly decrease TNFα release stimulated by 100 μg/mL LPS and prevented an LPS-induced increase in [Ca 2+ ] c , which was reversed by strychnine, a glycine receptor antagonist. GLY did not block the isoproterenol-induced increase in [Ca 2+ ] c , but did prevent the potassium chloride-induced increase in [Ca 2+ ] c in cardiomyocytes. Strychnine reversed the inhibition of the KCl–stimulated elevation in [Ca 2+ ] c by GLY. In chloride-free buffer, GLY had no effect on the dipotassium hydrogen phosphate-induced increase in [Ca 2+ ] c . Furthermore, GLY receptor α1 and β subunit-immunoreactive spots were observed in cardiomyocytes, and GLY-evoked currents were blocked by strychnine. Conclusion: Cardiomyocytes possess the glycine-gated chloride channel, through which GLY prevents the increase in [Ca 2+ ] c and inhibits the TNFα production induced by LPS at high doses in neonatal rat cardiomyocytes.

The microbial production of 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae XJPD-Li under different aeration strategies were investigated. In batch fermentation, the results showed that the final concentration of 1,3-PD and yield on glycerol were 13.44 g/l and 0.73 mol/mol under the anaerobic condition (N2, 0.4 vvm), 11.55 g/l and 0.62 mol/mol without aeration, and 8.73 g/l and 0.47 mol/mol under the aerobic condition (air, 0.4 vvm), respectively. Under the aerobic condition, the yield of 1,3-PD on glycerol was the lowest, while the biomass (optical density at 650 nm) was the highest among these three conditions. In the fed-batch culture, the final concentration and the yield of 1,3-PD was 60.82 g/l and 0.61 mol/mol under the anaerobic condition (N2, 0.4 vvm), 56.43 g/l and 0.53 mol/mol without aeration, and 65.26 g/l and 0.56 mol/mol under the aerobic condition. All these three conditions had good productivities of 1,3-PD, which were 3.35 g/lxh under the anaerobic condition (N2, 0.4 vvm), 3.13 g/lxh without aeration, and 3.16 g/lxh under the aerobic condition within the initial 12 h.

In a survey of endophytic fungal biodiversity, an antimicrobial endophytic isolate zjwcf069 was obtained from twigs of Forsythia viridissima, Zhejiang Province, Southeast China. Zjwcf069 was then identified as Pezicula sp. through combination of morphological and phylogenetic analysis based on ITS-rDNA. Zjwcf069 here represented the first endophytic fungus in Pezicula isolated from host F. viridissima. From the fermentation broth, four compounds were obtained through silica gel column chromatography and Sephadex LH-20 under the guide of bioassay. Their structures were elucidated by spectroscopic analysis as mellein (1), ramulosin (2), butanedioic acid (3), and 4-methoxy-1(3H)-isobenzofuranone (4). Compound 4 here stood for the very first time as natural product from microbes. In vitro antifungal assay showed that compound 1 displayed growth inhibition against 9 plant pathogenic fungi, especially Botrytis cinerea and Fulvia fulva with EC50 values below 50 μg/mL. Endophytic fungi in medicinal plants were good resources for bioactive secondary metabolites.

Multiple primary carcinoma (MPC) is defined as two or more carcinomas without subordinate relationship detected in the same or other organs of an individual patient. The diagnosis of MPC must comply with the following standards: each of the tumors must present a definite picture of malignancy, each tumor must be histologically distinct, and the probability of one being a metastasis of the other must be excluded. MPC often occurs in the digestive system, but its pathogenesis remains unclear involving genetic susceptibility, tumor immunity and iatrogenic factors, including radiotherapy and chemotherapy. Most MPC patients are double primary malignancy; the occurrence of quadruple primary malignancy is below 0.1%. Here we present a rare case of quadruple primary malignancy involving the small intestine, descending colon, renal pelvis and pancreas. Due to its rarity, the relevant literature is also reviewed. In general, the incidence of MPC is rising, so prevention, early diagnosis and treatment will become necessary and important. Therefore, further research should focus on the etiology and mechanism of MPC.

Background: Trial design neuroinflammation and postoperative pain after surgery are increasingly reported in association with postoperative cognitive dysfunction (POCD). Parecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for postoperative analgesia for its potent anti-inflammatory and analgesic effects. This study aimed to evaluate parecoxib's effects on POCD in elderly patients undergoing total knee arthroplasty.

This study was performed to investigate the impact of a family history of type 2 diabetes (T2DM) on insulin resistance and beta-cell dysfunction in populations with varying glucose tolerance.Among the total of 142 participants, 73 subjects with no family history of T2DM (FH-) included 42 with normal glucose tolerance (NGT/FH-) and 31 with impaired glucose tolerance (IGT/FH-); and 69 first-degree relatives of patients with T2DM (FH+) included 36 with NGT (NGT/FH+) and 33 with IGT (IGT/FH+). Insulin resistance was evaluated by Insulin Sensitivity Index (ISI) based on the euglycemic hyperinsulinemic clamp. Islet beta-cell function was assessed by disposition index (DI) for the acute insulin response to glucose (AIRg) using intravenous glucose tolerance test. Metabolic data were compared between groups after adjustment for age, sex, body mass index and waist-to-hip ratio.The NGT/FH+ group showed lower level of ISI (P = 0.023) than the NGT/FH- group, whereas no difference was found in AIRg or DI between these 2 subgroups. In the FH- individuals, both ISI and DI of the IGT/FH- group decreased compared with the NGT/FH- group (both P0.05). In the FH+ individuals, no difference was found in ISI between the IGT/FH+ and NGT/FH+ groups, whereas the IGT/FH+ group had a lower level of AIRg and DI than the NGT/FH+ group (both P0.0001).This study showed that the pathophysiological changes were different between individuals with and without a family history of T2DM during the glucose tolerance aggravation.

Through bioassay-guided fractionation, the EtOAc extract of a culture broth of the endophytic fungus Phoma species ZJWCF006 in Arisaema erubescens afforded a new α-tetralone derivative, (3S)-3,6,7-trihydroxy-α-tetralone (1), together with cercosporamide (2), β-sitosterol (3), and trichodermin (4). The structures of compounds were established on the basis of spectroscopic analyses. Compounds 1, 2, and 3 were obtained from Phoma species for the first time. Additionally, the compounds were subjected to bioactivity assays, including antimicrobial activity, against four plant pathogenic fungi (Fusarium oxysporium, Rhizoctonia solani, Colletotrichum gloeosporioides, and Magnaporthe oryzae) and two plant pathogenic bacteria (Xanthomonas campestris and Xanthomonas oryzae), as well as in vitro antitumor activities against HT-29, SMMC-772, MCF-7, HL-60, MGC80-3, and P388 cell lines. Compound 1 showed growth inhibition against F. oxysporium and R. solani with EC50 values of 413.22 and 48.5 μg/mL, respectively. Additionally, compound 1 showed no cytotoxicity, whereas compound 2 exhibited cytotoxic activity against the six tumor cell lines tested, with IC50 values of 9.3 ± 2.8, 27.87 ± 1.78, 48.79 ± 2.56, 37.57 ± 1.65, 27.83 ± 0.48, and 30.37 ± 0.28 μM, respectively. We conclude that endophytic Phoma are promising sources of natural bioactive and novel metabolites.

Purpose: Pancreatic cancer is a highly aggressive malignant tumour with poor prognosis. The median survival is only 6 months. This study investigated the prognostic value of nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) expression in pancreas cancer. Methods: CRM1 expression was detected, by Western blot, in pancreatic tissue from 69 cancer patients and 10 normal subjects. Results: CRM1 showed increased expression in pancreatic cancer tissue (P = 0.007). The high expression of CRM1 was associated with increased serum levels of CEA (P = 0.002) and CA19-9 (P = 0.005). There was an association between CRM1 expression and tumour size (P = 0.01), lymphadenopathy (P = 0.004) and liver metastasis (P = 0.003). High CRM1 expression was not correlated with the other clinicopathological parameters. High CRM1 expression was a prognostic indicator for progression-free survival (PFS) (P = 0.006) as well as overall survival (OS) (P = 0.001). Expression of CRM1 was an independent prognostic parameter for poorer PFS and OS (95% CI, 1.27–5.39). Conclusions: CRM1 expression demonstrated prognostic value in pancreatic cancer. Prospective studies are required to determine the prognostic role of high expression of CRM1 in pancreatic cancer.

This study aimed to investigate multi-slice CT contrast-enhanced presentation of gastric cancer and its correlation with histo-differentiation and p53 and P-glycoprotein (P-gp) expression.Sixty-six patients with gastric cancer in the present study underwent a multi-slice CT preoperative routine and dual-phase contrast-enhanced examination of the upper abdomen; postoperative specimens were used to determine histo-differentiation and the expression of p53 and P-gp. The correlation of multi-slice CT contrast-enhanced presentation with histo-differentiation and expression of p53 and P-gp was analyzed.The dual-phase contrast-enhanced ratio (CER) was not correlated with the histo-differentiation of gastric cancer (P0.05). Positive expression of p53 and P-gp was significantly higher in the cases of layered or heterogeneous enhancement than in the cases of homogenous enhancement (P0.05). Positive expression of p53 was also correlated with the arterial phase CER, tumor size and lymph node metastasis (P0.05), but not with infiltration thickness of the gastric wall, nor was it correlated with the portal phase CER (P0.05). Positive expression of P-gp was only correlated with the portal phase CER (P = 0.005).Differently enhanced pattern and CER of the arterial and portal phase in gastric cancer correlate with its different histo-differentiation and expression of p53 and P-gp respectively. In addition, tumor size and lymph node metastasis of gastric cancer relate to the expression of p53.

A new flavonoid glycoside, 5,7-dihydroxy-4'-methoxyflavone-7-O-[6-O-(4-O-acetyl-alpha-L-rhamnosyl)-3-O-beta-D-glucosyl]-6-O-acetyl-beta-D-glucoside and three known flavonoid glycosides, 5,7-dihydroxy-4-methoxyflavone-7-0-[6-0-(4-0-acetyl-alpha-L-rhamnosyl)]-beta-D-glucoside, 3,5,7, 4'-tetrahydroxyflavonol-3-O-beta-D-glucoside and 5,7-dihydroxy-4'-methoxyflavone-7-O-(6-O-alphaL-rhamnosyl)-beta-D-glucoside were isolated from the whole plant of Thalictrum przewalskii. Their structures were determined on the basis of spectroscopic evidences.

Background The UGT1A1*28 polymorphism, although closely linked with CPT-11-related adverse effects, cannot be used alone to guide individualized treatment decisions. However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics. Our study is designed to investigate whether there is a relationship between SN-38 peak or valley concentrations and efficacy or adverse effects of CPT-11-based chemotherapy. We retrospectively studied 98 patients treated with advanced colorectal cancer in various UGT1A1*28 genotype groups (mainly (TA)6/(TA)6 and (TA)6/(TA)7 genotypes) treated with CPT-11 as first-line chemotherapy in Shanghai. Methods One hundred and sixty-four advanced colorectal cancer patients were enrolled. To understand differences in genotype expression, the frequency of UGT1A1*28 thymine–adenine (TA) repeats in TATA box arrangement was assessed by PCR with genomic DNA extracted from peripheral blood. For ninety-eight cases with the (TA)6/(TA)6 and (TA)6/(TA)7 genotypes treated with CPT-11 as first-line chemotherapy, the plasma concentration of SN-38 was detected by HPLC 1.5 and 49 h after CPT-11 infusion. Efficacy and adverse effects were observed subsequently, and the relationship between SN-38 plasma concentration and efficacy or adverse effects within genotype groups, as well as differences in efficacy and adverse effects between (TA)6/(TA)6 and (TA)6/(TA)7 genotypes were analyzed statistically. Results One hundred and fourteen patients (69.51 %) were identified with the (TA)6/(TA)6 genotype, forty-eight patients (29.27 %) with the (TA)6/(TA)7 genotype, and two patients (1.22 %) with the (TA)7/(TA)7 genotype. The average peak and valley concentrations of SN-38 after CPT-11 infusion and plasma bilirubin average levels before and after CPT-11 treatment in the (TA)6/(TA)7 genotype group were all higher than those in (TA)6/(TA)6 group, and the difference was statistically significant (p = 0.00). Stepwise regression analysis showed that SN-38 peak and valley concentration was correlated with PFS in the (TA)6/(TA)6 genotype. In the (TA)6/(TA)7 group, SN-38 peak concentration was correlated with CPT-11 starting dose and OS, valley concentration correlated with plasma bilirubin levels before CPT-11 treatment, delayed diarrhea, and OS. For the (TA)6/(TA)6 genotype, mPFS of the SN-38 peak concentration >43.2 ng/ml subgroup was significantly longer than that of ≤43.2 ng/ml subgroup (8.0 ± 0.35 vs. 6.5 ± 0.79 months, χ2 = 17.18, p = 0.00) with a relatively high incidence of Grade I/II° myelosuppression; for the (TA)6/(TA)7 genotype, there was no significant difference in mOS between the SN-38 valley concentration >16.83 ng/ml and ≤16.83 subgroups (17.3 ± 0.45 vs. 18.8 ± 0.50 months, χ2 = 1.38, p = 0.24), but the former had a higher incidence of Grade III/IV° mucositis and delayed diarrhea. For 2 (TA)7/(TA)7 cases, although 25 % dose reduction of CPT-11, which is calculated according to body surface area, Grade IV° bone marrow suppression and Grade III° delayed diarrhea still occurred after CPT-11 treatment, though both adverse effects resolved and did not recur again after a 50 % dose reduction. Conclusion The (TA)6/(TA)6 genotype and (TA)6/(TA)7 genotype accounted for the most, and (TA)7/(TA)7 genotype only account for a very small portion of advanced colorectal cancer patients in Shanghai. For the (TA)6/(TA)6 genotype, CPT-11 dosage can be increased gradually to improve efficacy for patients with SN-38 peak concentration ≤43.2 ng/ml after CPT-11 infusion; and for (TA)6/(TA)7 genotype patients, CPT-11 dosage may be lowered appropriately to reduce serious adverse effects such as bone marrow suppression and delayed diarrhea without affecting the efficacy for those with SN-38 valley concentration >16.83 ng/ml. For (TA)7/(TA)7 genotype patients, adverse effects should be closely observed after treatment even if CPT-11 dosage has been reduced.