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OBJECTIVES: To characterize nosocomial transmission and rearrangement of the resistance-virulence plasmid between two ST11-K64 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strains (JX-CR-hvKP-10 and JX-CR-hvKP-9) with low fitness. METHODS: Phenotypic tests were used to assess the virulence of JX-CR-hvKP-10 and JX-CR-hvKP-9. Whole-genome sequencing was used to analyze JX-CR-hvKP-10 and JX-CR-hvKP-9 chromosomes and plasmids. Fitness and conjugation experiments were also conducted using these two CR-hvKP isolates. RESULTS: Phenotypic tests indicated that both JX-CR-hvKP-10 and JX-CR-hvKP-9 were multidrug-resistant and hypervirulent K. pneumoniae. Whole-genome sequencing and clinical information demonstrated that the super large resistance-virulence fusion plasmid pJX10-1 formed precisely by the fusion of pJX9-1 and pJX9-2 via the nosocomial transmission. Interestingly pJX9-1 itself was also a classic resistance-virulence fusion plasmid by way of the blaKPC-carrying resistance plasmid and pLVPK-like virulence plasmid. Compared with classic K. pneumoniae ATCC700603, fitness analysis revealed no significant difference in growth was observed between JX-CR-hvKP-10 and JX-CR-hvKP-9. CONCLUSION: Nosocomial transmission and rearrangement of a blaKPC-harboring plasmid and a pLVPK-like virulence plasmid with a low fitness cost in ST11 K. pneumoniae enhances drug resistance and virulence simultaneously. Thus, active surveillance of this hybrid plasmid is needed to prevent these efficient resistance-virulence plasmids from disseminating in hospital settings.

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BACKGROUND: Calcification in primary gastric cancer is very rare. In this report, we describe the computerized tomography (CT) changes in calcification in a patient with locally advanced signet-ring gastric cancer treated with chemotherapy. CASE PRESENTATION: A 49-year-old man presented with 5 months' history of abdominal pain, anorexia, and rapid weight loss. He had undergone Billroth-II subtotal gastrectomy for a bleeding gastric ulcer 30 years ago. Abdominal CT showed irregular thickening of the gastric wall and miliary calcifications. Histologic examination of specimen obtained by endoscopic biopsy showed poorly differentiated calcified signet-ring gastric cancer. The patient was clinically staged T4N2M0 and treated with docetaxel, cisplatin, and fluorouracil (DCF)/oxaliplatin and S-1 (XLOX)/S-1. After five cycles of chemotherapy, the general condition of the patient improved and tumor markers (CEA, CA125, CA199) decreased. However, follow-up CT scans showed continuing increase in the calcification. CONCLUSIONS: To conclude, in this case report we have described the dynamic changes in calcification in a gastric cancer patient receiving chemotherapy. One explanation for the observed increase in calcifications could be that the ischemic necrosis resulting from chemotherapy creates an alkaline environment, which promotes deposition of calcium salts. Our theory needs to be confirmed with histological evidence from a large series of patients. Nevertheless, we hope that these findings will improve understanding of the mechanism of calcification in gastric cancer.

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Objective: This study aims to investigate the effect of astragaloside IV on adipose lipolysis and hepatic gluconeogenesis. Methods: High-fat diet (HFD) feeding induced adipose dysfunction with enhanced endogenous glucose production in mice. The effects of Astragaloside IV on lipolysis and hepatic glucose production were investigated. Results: HFD feeding induced cAMP accumulation through reducing PDE3B expression and activity in adipose tissue. As a result, HFD feeding increased adipose lipolysis in mice. Astragaloside IV enhanced Akt phosphorylation and promoted Akt binding to PDE3B to preserve PDE3B content, resultantly reducing adipose cAMP accumulation. Knockdown of Akt1/2 diminished the effect of astragaloside IV on PDE3B induction, indicative of the role of Akt in astragaloside IV action. As a result from blocking of cAMP/PKA signaling, astragaloside IV suppressed hormone-sensitive lipase (HSL) activation and inhibited inflammation-associated adipose lipolysis. Moreover, astragaloside IV reduced ectopic fat deposition in the liver and inhibited FoxO1 activation via regulation of Akt, resultantly restraining excess hepatic glucose production. Conclusion: We showed that preserving PDE3B content by Akt is a key regulation to prevent lipolysis. Astragaloside IV inhibited lipolysis by reducing cAMP accumulation via regulation of Akt/PDE3B, contributing to limiting hepatic lipid deposition and restraining excessive hepatic glucose production.

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OBJECTIVE: This study was designed to investigate the hypothesis that metformin and resveratrol exhibited the same effect on inhibition of NLRP3 inflammasome activation with regulation of AMPK in adipose tissue exposed to high glucose. METHODS: To induce adipose tissue dysfunction, we treated epididymal adipose tissue of mice or differentiated 3T3-L1 adipocytes with high glucose (33 mM) for 24 h. Meanwhile, mice were injected with streptozotocin STZ to induce diabetes and followed by oral administration of metformin (200 mg/kg), resveratrol (50 mg/kg) or ER stress inhibitor TUDCA (50 mg/kg) for 7 days. The effects of metformin and resveratrol on ROS production, mitochondrial fission, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation and apoptosis were observed. RESULTS: Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1α and eIF2α in the adipose tissue. As a result from suppressing TXNIP/NLRP3 inflammasome activation, metformin and resveratrol inhibited inflammation and reduced cell apoptosis in adipose tissue or adipocytes exposed to high glucose. CONCLUSION: Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult.

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