Adjuvant chemotherapy for lymph node positive esophageal squamous cell cancer: The prediction role of low mean platelet volume

BackgroundThis study aimed to examine whether MPV is a useful prognostic marker and investigated whether MPV is a risk factor that helps identify patients with locally advanced-stage ESCC who will most likely benefit from adjuvant chemotherapy.MethodsPatients (n =1690) with histologically confirmed ESCC were diagnosed with locally advanced stage (pT3-4N0M0 and pT1-4N+M0) at Sichuan Cancer Hospital from 2009 to 2017. Clinicopathological factors and platelet-related values were tested for their associations with survival using univariate and multivariate Cox regression analyses. The optimal cut-off value for continuous variables was determined using the ‘maxstat’ R package. The KM curve continuous variable analysis was performed to identify the optimal cut-off value for MPV. Cumulative survival rates were determined using the Kaplan–Meier estimator and compared using the log-rank test. The survival analysis was performed using the ‘survival’ R package. All statistical analyses were performed using R software 4.1.3 (https://www.r-project.org/), and a two-sided p-value <0.05 was considered to indicate statistical significance.ResultsMultivariate analysis indicated that low MPV was an important risk factor for overall survival in locally advanced ESCC, independent of classic clinicopathological factors. The optimal cut-off value of MPV (11.8 fL) was used to stratify high-risk patients. Patients with low mean platelet volumes had a worse prognosis than those with larger platelet volumes, according to Kaplan–Meier analysis and the log-rank test. Patients diagnosed with a pathological lymph node-positive stage with a low MPV (≤11.8 fL) benefited from postoperative chemotherapy, but not those with a high-level MPV (>11.8 fL).ConclusionMPV served as an independent predictor of prognosis of locally advanced-stage ESCC and predicted a survival benefit conferred by postoperative adjuvant chemotherapy in lymph node-positive ESCC

Portacaval anastomosis-induced hyperammonemia does not lead to oxidative stress

Ammonia is neurotoxic and believed to play a major role in the pathogenesis of hepatic encephalopathy (HE). It has been demonstrated, in vitro and in vivo, that acute and high ammonia treatment induces oxidative stress. Reactive oxygen species (ROS) are highly reactive and can lead to oxidization of proteins resulting in protein damage. The present study was aimed to assess oxidative status of proteins in plasma and brain (frontal cortex) of rats with 4-week portacaval anastomosis (PCA). Markers of oxidative stress, 4-hydroxy-2-nonenal (HNE) and carbonylation were evaluated by immunoblotting in plasma and frontal cortex. Western blot analysis did not demonstrate a significant difference in either HNE-linked or carbonyl derivatives on proteins between PCA and sham-operated control rats in both plasma and frontal cortex. The present study suggests PCA-induced hyperammonemia does not lead to systemic or central oxidative stress.CIHR-MOP-8283

Optimal Design of Bus Stop Locations Integrating Continuum Approximation and Discrete Models

Although transit stop location problem has been extensively studied, the two main categories of modeling methodologies, i.e., discrete models and continuum approximation (CA) ones, seem have little intersection. Both have strengths and weaknesses, respectively. This study intends to integrate them by taking the advantage of CA models’ parsimonious property and discrete models’ fine consideration of practical conditions. In doing so, we first employ the state-of-the-art CA models to yield the optimal design, which serves as the input to the next discrete model. Then, the stop location problem is formulated into a multivariable nonlinear minimization problem with a given number of stop location variables and location constraint. The interior-point algorithm is presented to find the optimal design that is ready for implementation. In numerical studies, the proposed model is applied to a variety of scenarios with respect to demand levels, spatial heterogeneity, and route length. The results demonstrate the consistent advantage of the proposed model in all scenarios as against its counterparts, i.e., two existing recipes that convert CA model-based solution into real design of stop locations. Lastly, a case study is presented using real data and practical constraints for the adjustment of a bus route in Chengdu (China). System cost saving of 15.79% is observed by before-and-after comparison. Document type: Articl

Novel sulfamoylamino-containing cephalosporin derivatives, and their in vitro antibacterial properties

Purpose: To prepare and develop new antibacterial agents with novel molecular structures. Method: A series of novel sulfamoylamino-containing cephalosporin derivatives were synthesized. The in vitro antibacterial effects of the derivatives against Gram-positive bacteria (S. aureus, S. pneumonia and S. epidermidis), and Gram-negative bacteria (E. coli, P. aeruginosa, and K. pneumonia) were investigated. Results: Compounds 13a and 13b exhibited excellent antibacterial effects against all the Gram-positive and Gram-negative bacteria tested, when compared with other cephalosporin derivatives. Conclusion: Of these new cephalosporin derivatives, compounds 13a and 13b show the most potent antibacterial activity and would need to be further investigated

Epidermal growth factor receptor restoration rescues the fatty liver regeneration in mice

Hepatic steatosis is a common histological finding in obese patients. Even mild steatosis is associated with delayed hepatic regeneration and poor outcomes following liver resection or transplantation. We sought to identify and target molecular pathways that mediate this dysfunction. Lean mice and mice made obese through feeding of a high-fat, hypercaloric diet underwent 70 or 80% hepatectomy. After 70% resection, obese mice demonstrated 100% survival but experienced increased liver injury, reduced energy stores, reduced mitoses, increased necroapoptosis, and delayed recovery of liver mass. Increasing liver resection to 80% was associated with mortality of 40% in lean and 80% in obese mice (P < 0.05). Gene expression profiling showed decreased epidermal growth factor receptor (EGFR) in fatty liver. Meta-analysis of expression studies in mice, rats, and patients also demonstrated reduction of EGFR in fatty liver. In mice, both EGFR and phosphorylated EGFR decreased with increasing percent body fat. Hydrodynamic transfection of EGFR plasmids in mice corrected fatty liver regeneration, reducing liver injury, increasing proliferation, and improving survival after 80% resection. Loss of EGFR expression is rate limiting for liver regeneration in obesity. Therapies directed at increasing EGFR in steatosis might promote liver regeneration and survival following hepatic resection or transplantation

A single-step preparation of carbohydrate functionalized monoliths for separation and trapping of polar compounds

A single-step copolymerization strategy was developed for the preparation of carbohydrate (glucose and maltose) functionalized monoliths using click reaction. Firstly, novel carbohydrate-functionalized methacrylate monomers were synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (alkyne-azide reaction) of terminal alkyne with azide of carbohydrate derivatives. The corresponding carbohydrate functionalized monolithic columns were then prepared through a single-step in-situ copolymerization. The physicochemical properties and performance of the fabricated monolithic columns were evaluated using scanning electron microscopy, Fourier-transform infrared spectroscopy, and nano-liquid chromatography. For the optimized monolithic column, satisfactory column permeability and good separation performance were demonstrated for polar compounds including nucleoside, phenolic compounds and benzoic acid derivatives. The monolithic column is also highly useful for selective and efficient enrichment of glycopeptides from human IgG tryptic digests. This study not only provided a novel hydrophilic column for separation and selective trapping of polar compounds, but also proposed a facile and efficient approach for preparing carbohydrate functionalized monoliths

Systemic oxidative stress is implicated in the pathogenesis of brain edema in rats with chronic liver failure

Chronic liver failure leads to hyperammonemia, a central component in the pathogenesis of hepatic encephalopathy (HE); however, a correlation between blood ammonia levels and HE severity remains controversial. It is believed oxidative stress plays a role in modulating the effects of hyperammonemia. This study aimed to determine the relationship between chronic hyperammonemia, oxidative stress, and brain edema (BE) in two rat models of HE: portacaval anastomosis (PCA) and bile-duct ligation (BDL). Ammonia and reactive oxygen species (ROS) levels, BE, oxidant and antioxidant enzyme activities, as well as lipid peroxidation were assessed both systemically and centrally in these two different animal models. Then, the effects of allopurinol (xanthine oxidase inhibitor, 100mg/kg for 10days) on ROS and BE and the temporal resolution of ammonia, ROS, and BE were evaluated only in BDL rats. Similar arterial and cerebrospinal fluid ammonia levels were found in PCA and BDL rats, both significantly higher compared to their respective sham-operated controls (p<0.05). BE was detected in BDL rats (p<0.05) but not in PCA rats. Evidence of oxidative stress was found systemically but not centrally in BDL rats: increased levels of ROS, increased activity of xanthine oxidase (oxidant enzyme), enhanced oxidative modifications on lipids, as well as decreased antioxidant defense. In PCA rats, a preserved oxidant/antioxidant balance was demonstrated. Treatment with allopurinol in BDL rats attenuated both ROS and BE, suggesting systemic oxidative stress is implicated in the pathogenesis of BE. Analysis of ROS and ammonia temporal resolution in the plasma of BDL rats suggests systemic oxidative stress might be an important "first hit", which, followed by increases in ammonia, leads to BE in chronic liver failure. In conclusion, chronic hyperammonemia and oxidative stress in combination lead to the onset of BE in rats with chronic liver failure.CIHR- MOP-8283

Cellular and Molecular Mechanisms of Hepatic Fibrosis

The occurrence of hepatic fibrosis is a multi-factor involved process. The key is the activation of hepatic stellate cells (HSC). Synthesis of extracellular matrix in the liver cells increases while degradation decreases. This paper reviews the tissue factors and the mechanism closely related to the forming of hepatic fibrosis