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This study is a prospective study to explore the therapeutic effect of endoscopic purse-string sutures in high-risk peptic ulcer hemorrhage. We prospectively collected and analyzed data from July 2018 to December 2020 from patients in Jinshan hospital, Fudan University, who underwent emergency endoscopy for acute severe high-risk non-variceal upper gastrointestinal hemorrhage (NVUGIB) and were treated with endoscopic purse-string sutures. We included 38 patients whose median age was 64 years (interquartile range: 57.2 − 71.2 years). All patients were high risk gastric ulcer larger than 1 cm, including Forrest Ia (n = 4, 10.5%), Forrest Ib (n = 13, 34.2%) and Forrest IIa (n = 21, 55.3%). All patients were treated with endoscopic purse-string sutures. The clinical success rate reached 89.5%. Three patients suffered from rebleeding within seven days, and were treated with surgery or arterial embolization, respectively, all of which successfully stopped bleeding. One patient died of myocardial infarction. All other patients were followed up for 30 days without bleeding. We conclude that endoscopic purse-string sutures seem to be safe and effective in the treatment of patients at high risk of ulcer bleeding. [ABSTRACT FROM AUTHOR]

In this paper, we consider the equilibrium excess-of-loss reinsurance and investment problem for both an insurer and a reinsurer. The risk process of the insurer is described by a classical Cramér-Lundberg (C-L) risk model and the insurer can purchase excess-of-loss reinsurance from the reinsurer. Both the insurer and the reinsurer are allowed to invest in a financial market consisting of a risk-free asset and two risky assets. The market price of risk depends on a Markovian, affine-form and square-root stochastic factor process. Dynamic mean-variance criterion is considered in this paper. We aim to maximize the weighted sum of the insurer's and the reinsurer's objectives with different risk averse coefficients. By solving the corresponding extended Hamilton-Jacobi-Bellman (HJB) equations, we derive the equilibrium reinsurance and investment strategies and the corresponding equilibrium value function. Finally, the economic implications of our findings are illustrated. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii has become a major healthcare threat that causes nosocomial infections, especially in critically ill patients. The spread of carbapenem-resistant A. baumannii (CRAB) strains has long been a clinical concern. It is important to study the epidemiology and virulence characteristics of different CRAB isolates in order to tailor infection prevention and antibiotic prescribing. In this study, a total of 71 CRAB isolates were collected in the hospital, and clinical characteristics of infections were analyzed. The genomic characteristics and phylogenetic relationships were elucidated based on genome sequencing and analysis. The isolates were assigned to three sequence types (STs, Pasteur) and nine capsular polysaccharide (KL) types, among which ST2/KL22 was the most prevalent CRAB in the hospital. Even though all the ST2/KL22 isolates contained the same reported virulence genes, one specific clade of ST2/KL22 showed more pathogenic in mouse infection model. Complete genomic analysis revealed differences at the oprD locus between the low- and high-virulent isolates. More specifically, a premature stop codon in the low-virulence strains resulted in truncated OprD expression. By evaluating pathogenicity in C57BL/6 J mice, knock-out of oprD in high-virulent isolate resulted in virulence attenuation, and complementing the avirulent strain with full-length oprD from high-virulent isolate enhanced virulence of the former. The oprD gene may be associated with the enhanced virulence of the specific ST2/KL22 clone, which provides a potential molecular marker for screening the hypervirulent A. baumannii strains. [ABSTRACT FROM AUTHOR]

Service has become an important factor that affects insurance holders' purchase behaviors, competition and even the survival of insurers. This paper introduces value-added service into the optimal investment problem between two competing insurers, one provides value-added service while the other does not. The surplus processes of the two insurers are assumed to follow classical Cramér-Lundberg (C-L) model. Both of the two insurers are allowed to invest in a risk-free asset and two different risky assets, respectively. Dynamic mean-variance criterion is considered in this paper. Each insurer wants to maximize the expectation of the difference between her terminal wealth and that of her competitor, and to minimize the variance of the difference between her terminal wealth and that of her competitor. By solving the corresponding extended Hamilton-Jacobi-Bellman (HJB) equations, we derive the equilibrium service level, investment strategies and the corresponding equilibrium value functions. In addition, some special cases of our model are provided. Finally, the economic implications of our findings are illustrated. It is interesting to find that for the insurer with value-added service, the equilibrium value function in the case of providing value-added service is larger than that without value-added service under some given assumptions. [ABSTRACT FROM AUTHOR]

The direct and indirect competitive fluorescence-linked immunosorbent assay (FLISA and icFLISA) incorporating quantum dots (QDs) for the detection of fleroxacin (FLE) was established for the first time in this study. The monoclonal antibody specific for FLE was successfully conjugated with QDs after purification by the caprylic acid-ammonium sulphate method. The limits of detection of FLISA and icFLISA were 0.012 ng/mL and 0.006 ng/mL, respectively; IC50 were 0.32 ng/mL and 0.19 ng/mL; and the detection ranges were 0.012–24.490 ng/mL and 0.006–16.210 ng/mL. The recovery was 93.8%-112.4% and the coefficient of variation was below 11.75%. The fabricated FLISA and icFLISA are cost-effective, high sensitive and can be an alternative method in the detection of FLE residues. [ABSTRACT FROM AUTHOR]

Cell cycle progression is precisely regulated by diverse extrinsic and intrinsic cellular factors. Understanding the underlying mechanisms of cell cycle regulation is essential to address how normal development and tissue homeostasis are achieved. Here, we present a novel cell cycle regulator Caliban (Clbn), the Drosophila ortholog of human Serologically defined colon cancer antigen 1 (SDCCAG1) gene. We show that ionizing radiation induces expression of clbn, and over-expression of clbn blocks G1-to-S cell cycle transition in Drosophila, while flies loss of clbn have defective S phase checkpoint in response to irradiation. Mechanistically, induced expression of clbn suppressed E2F1 activity and down-regulates the DNA replication and expression of its downstream target cyclin E, a key regulator of G1-to-S transition. Meanwhile, clbn over-expression leads to upregulation of the CDK inhibitor Dacapo (Dap), and upregulated Dap is decreased when e2f1 is over-expressed. Furthermore, expression of clbn is down-regulated in cells with e2f1 over-expression or rbf1 knockdown, indicating that Clbn and E2F1 act antagonistically in mediating G1-to-S transition. Thus we provide genetic evidence that Clbn works together with E2F1 in regulating cell cycle progression, and Clbn is required for S phase cell cycle checkpoint in response to DNA damage. [ABSTRACT FROM AUTHOR]

Biocatalysts have been increasingly used in the synthesis of fine chemicals and medicinal compounds due to significant advances in enzyme discovery and engineering. To mimic the synergistic effects of cascade reactions catalyzed by multiple enzymes in nature, researchers have been developing artificial tandem enzymatic reactions in vivo by harnessing synthetic biology and metabolic engineering tools. There is also growing interest in the development of one-pot tandem enzymatic or chemo-enzymatic processes in vitro due to their neat and concise catalytic systems and product purification procedures. In this review, we will briefly summarize the strategies of designing and optimizing in vitro tandem catalytic reactions, highlight a few representative examples, and discuss the future trend in this field. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From thein vivoresults, scopolamine intranasal administration can avoid hepatic first-pass effect. Tmaxplasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8–70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery. [ABSTRACT FROM AUTHOR]

Background: Adenosine A2A receptor antagonist istradefylline 20 mg/day has been approved this year for manufacturing and market in Japan. Therefore, we did this meta-analysis to systematically evaluate the clinical applicability of 40 mg/day as augmentation to levodopa in patients with Parkinson's disease (PD). Method: Randomized controlled trials (RCT) that compared istradefylline with placebo for short-course treatment of PD in adults were systematically reviewed up to November 2013. Outcome measurements were daily off time and unified Parkinson's disease rating scale (UPDRS) Part III score (on state). Random-effect model was used. Result: Data were obtained from four RCTs. In these RCTs, 405 patients received istradefylline 20 mg/day and 420 patients received 40 mg/day. The pooled weighted mean difference was 0.17 with 95% confidence interval (CI) 5 [-20.23, 0.56] on daily off time and 0.70 with 95% CI 5 [-20.89, 2.29] on UPDRS Part III score (on state). The adverse events analysis showed that 20 and 40 mg/day had comparable acceptability. Heterogeneity was not existed. Conclusion: These results indicate that istradefylline 40 mg/day as augmentation shows potential promise on clinical applicability, and is worthy of further study. Limited by the number of included RCTs, future studies are needed to verify and support this conclusion, and assess the long-term effect of istradefylline, the effect of istradefylline as monotherapy and other dose of istradefylline. [ABSTRACT FROM AUTHOR]