Risk Factors of the Occurrence and Treatment Failure of Refractory Peritoneal Dialysis-Associated Peritonitis: A Single-Center Retrospective Study From China.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of refractory peritoneal dialysis (PD)-associated peritonitis as well as the risk factors of its occurrence and treatment failure. METHODS: A single-center retrospective cohort study was conducted among 519 patients undergoing PD from January 2007 to October 2021. According to the International Society for Peritoneal Dialysis guidelines, all episodes occurred in our center were divided into two groups: refractory and nonrefractory. Demographic, biochemical, and pathogenic bacteria and treatment outcome data were collected. RESULTS: During the 15-year period, 282 episodes of peritonitis occurred in 166 patients undergoing PD. The refractory rate was 34.0% (96/282). Gram-positive organisms were the leading cause of peritonitis (47.9%); however, gram-negative organisms were predominant in refractory peritonitis (34.4%, p = 0.002). Multiple logistic regression revealed that gram-negative organism-based peritonitis, longer PD duration, and female sex were the significant independent predictors of refractory peritonitis. Among 96 refractory episodes, white blood cell (WBC) count, dialysate WBC on Day 3, and PD duration ≥5 years were the independent risk factors of treatment failure. CONCLUSIONS: Gram-negative organism-based peritonitis, longer PD duration, and female sex were the independent risk factors of refractory peritonitis. Refractory peritonitis with higher WBC count, higher dialysate WBC on Day 3, and PD duration ≥5 years increased treatment failure risk and required immediate PD catheter removal. The timely identification of refractory peritonitis with high risk of treatment failure as well as timely PD catheter removal is important.

Effect of different dialysis duration on the prognosis of peritoneal dialysis-associated peritonitis: a single-center, retrospective study.

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis is a serious complication observed in peritoneal dialysis patients. Herein, we investigated the clinical characteristics and treatment outcomes of PD peritonitis in patients with different PD durations. METHODS: All peritonitis episodes from January 2007 to December 2020 at Peking University People's hospital PD center were retrospectively analyzed and divided into the long-dialysis duration (≥60 months, LDD) and short-dialysis duration (<60 months, SDD) groups. Clinical characteristics and outcomes were compared between these groups. The risk factors for treatment failure were analyzed using a logistic regression model. RESULTS: During 14 years, 156 patients had 267 peritonitis episodes. There were 83 (31.1%) peritonitis episodes in the LDD group and 184 (68.9%) in the SDD group. No statistical difference was noted in peritonitis causes and the composition of causative pathogens between the two groups. The hospitalization, treatment failure, and transfer-to-hemodialysis rates, and peritonitis-related mortality were significantly higher in the LDD group than in the SDD group (all p < .05). Logistic regression analysis revealed that PD duration was an independent risk factor for PD-associated hospitalization, treatment failure and peritonitis-related death (p < .05). The receiver operating characteristic curve analysis results showed that when the cutoff value of PD duration was 5.5 years, the sensitivity of predicting PD peritonitis treatment failure was 51.1%, specificity was 78.8%, and the area under the curve was 0.679 (95% confidence interval: 0.594-0.765, p < .001). CONCLUSIONS: PD duration is an independent risk factor for poor prognosis in PD peritonitis. Careful and active attention should be paid to the prevention of peritonitis in PD patients with long PD duration.

Enhanced Adsorption and Separation of Xenon over Krypton via an Unsaturated Calcium Center in a Metal-Organic Framework.

Krypton (Kr) and xenon (Xe) are nowadays widely applied in technical and industrial fields. Separating and collecting highly pure Xe from nuclear facilities are necessary and urgent. However, the technology is limited due to the inert nature of Xe and other interferential factors. In this work, a calcium-based metal-organic framework, Ca-SINAP-1, which comprises a three-dimensional microporous framework with a suitable pore width, was researched for xenon and krypton separation through both experimental and theoretical methods. Ca-SINAP-1, synthesized in solvothermal and gamma ray conditions, features accessible open-metal sites, exhibits a high Xe/Kr selectivity of 10.32, and owns a Xe adsorption capacity of 2.87 mmol/g at room temperature (1.0 bar). Particularly, its excellent chemical stability (from pH 2 to 13) and thermal stability (up to 550 °C), as well as radiation-resistance (up to 400 kGy ß irradiations), render this material a promising candidate for radioactive inert gases treatment.

Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides from Ligustrum robustum (Roxb.) Blume by AMPK-SREBP-1c pathway in hamsters fed a high-fat diet.

The aim of this study was to evaluate the hypolipidemic effect and mechanisms of total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) in hamsters fed a high-fat diet and to discover bioactive components in HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6 g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days in hamsters. We found that in hamsters fed a high-fat diet, LRTPG effectively reduced the concentrations of plasma triglycerides (TG), free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and hepatic TG and total cholesterol. And the compounds acteoside, ligupurpuroside A, ligupurpuroside C, and ligupurpuroside D significantly inhibited lipid accumulation in HepG2 cell at the concentration of 50 µmol/L. Mechanism research demonstrated that LRTPG increased the levels of phospho-AMP-activated protein kinase and phospho-sterol regulatory element binding protein-1c in liver, further to suppress the downstream lipogenic genes as stearoyl-CoA desaturase 1, glycerol-3-phosphate acyltransferase, 1-acylglycerol-3-phosphate O-acyltransferase 2, and diacylglycerol acyltransferase 2. In addition, LRTPG increased the hydrolysis of circulating TG by up-regulating lipoprotein lipase activities. These results indicate that LRTPG prevents hyperlipidemia via activation of hepatic AMP-activated protein kinase-sterol regulatory element binding protein-1c pathway.

Size and morphology control over MOF-74 crystals.

Precise control of the size and morphology of metal-organic framework (MOF) crystals is challenging yet critical for the expansion of the application potential of MOF materials. This work presents a detailed investigation of the impact of various synthetic conditions such as reactant ratio, acidity, capping agent, reaction solution (H2O, ethanol and DMF) etc. on the size and morphology of Mg-MOF-74, a classical MOF with record high CO2 uptake capacity. By varying these fabrication parameters and modulators, the morphology and size of crystals can be precisely tuned in the nanometer to micrometer range. Particularly, the nanosized flaky Mg-MOF-74 crystals with an aspect ratio of ∼0.5 were synthesized for the first time by varying the amount of water. The MOF-74 crystals with different size and morphologies are good candidates for more advanced applications favored by crystal size and morphology control.

Short-term peritoneal rest reduces peritoneal solute transport rate and increases ultrafiltration in high/high average transport peritoneal dialysis patients: a crossover randomized controlled trial.

Background: The peritoneal solute transport rate (PSTR) tends to increase over time in some patients undergoing peritoneal dialysis (PD), potentially leading to ultrafiltration (UF) failure. Previous case reports have shown a significant decrease in PSTR and subsequent recovery of UF after discontinuing PD for a while. Therefore, we conducted a randomized controlled crossover study to evaluate the impact of short-term peritoneal rest on PSTR. Methods: The study involved 14 continuous ambulatory peritoneal dialysis (CAPD) patients with high/high-average transport rate. Two groups were randomly assigned different treatment sequences: one group underwent daily intermittent peritoneal dialysis (IPD) for 4 weeks followed by CAPD, while the other group initially received CAPD treatment for 4 weeks and then switched to IPD. Peritoneal equilibration tests were performed before and after each treatment to evaluate PSTR and paired t-tests were used to compare the changes. Volume load, serum potassium and other clinical indicators were monitored at the same time. Results: Short-term peritoneal rest (daily IPD) significantly reduced PSTR, with a decrease in the dialysate:plasma creatinine ratio from 0.71 ± 0.05 to 0.65 ± 0.07 (P < .001). Additionally, ultrafiltration significantly increased from 210 ± 165 ml to 407 ± 209 ml (P = .001). But there were no significant changes in interleukin-6 and vascular endothelial growth factor of PD effluent. No serious adverse events such as hypotension or hyperkalaemia occurred. Conclusions: In PD patients with high and high-average transport, a 4-week period of short-term peritoneal rest by switching from CAPD to IPD (without long dwell) can lead to reductions in PSTR and increases in UF volumes, while maintaining clinical safety.

High Hydrogen Isotope Separation Efficiency: Graphene or Catalyst?

Single-layer graphene has been demonstrated to be a high-efficiency hydrogen isotope sieving membrane in the electrochemical hydrogen pumping system. In this work, we transferred this membrane to proton exchange membrane water electrolysis (PEMWE), which has wide industrial applications. Two membrane electrode assemblies with decorated Pt and ink-coated Pt were investigated. The graphene with the decorated Pt scheme acquired the reported highest proton-to-tritium separation factor of 19.50 in PEMWE. However, rather than graphene, the decorated catalyst was demonstrated to be responsible for this remarkable separation efficiency. Previous studies from Geim's group underestimated the enhanced separation efficiency of decorated Pt over ink-coated Pt, resulting in an exaggerated separation efficiency for graphene. The behavior of proton transfer with hydrogen isotope separation through graphene was interpreted by a serial-parallel circuit model, which suggested that hydrogen isotope separation occurs at defect sites. The limited separation efficiency for graphene was also well understood by a density functional theory (DFT) calculation using an SW 55-77 model and the transition state theory for the kinetic isotope effect. This research provides a thorough understanding of proton transfer with hydrogen isotope separation through graphene.

A comparison of coupled microeconomic and mental health devastating alterations between low-income and affluent countries afflicted with COVID-19.

BACKGROUND: The exponential increase in the rate of individuals' affliction by SARS-CoV-2 (COVID-19) has put extreme strains on health care systems worldwide and has sparked fears of an impending economic recession and mental turmoil. OBJECTIVE: The review discusses the impact of COVID-19 on medical crises in two sections, focusing on the evidence presented from both neuropathological and epidemiological perspectives. First, this paper outlines how countries have implemented containment and appraises its effect on the microeconomy. Second, it highlights how government support for the economic crisis caused by COVID-19 depends on the size of a country's economy. Third, it attempts to explain how COVID-19 has affected business by explicitly evaluating each industry divided into primary, secondary, and tertiary sectors. Finally, we assert an extended discussion on the challenges and post-pandemic outlook. METHODS: Peer-reviewed studies from inception until 2021 were searched in the Google scholar, PubMed, and Scopus databases. RESULTS: Through the imposition of restrictions and lockdown measures to contain the COVID-19 pandemic spread, besides arising a broad array of mental health concerns, a drastic drop in liquidity and significant spillover effect across almost all the global economic system has ensued. CONCLUSION: The COVID-19 implication on socioeconomic issues and mental wellbeing, as the most devastating sequelae of the current pandemic, is of great importance to curb the infection and deprive post-pandemic sequelae, demanding prompt actions.

A microporous Ce-based MOF with the octahedron cage for highly selective adsorption towards xenon over krypton.

The collection of high-purity noble gases with recyclable nuclides provides substantial economic benefits and minimizes the risk of environmental pollution, which is a future development tendency for nuclear industries. Here, Ce-SINAP-1, with its radiation-resistance (up to 20 kGy of γ-ray irradiation) and suitable pore channels for the separation of noble gases (Ar, Kr and Xe), was synthesized. Ce-SINAP-1 exhibited the selective adsorption of Xe (2.02 mmol g-1) over Kr (0.67 mmol g-1) and Ar (0.27 mmol g-1) at 293 K (1 bar) with a Henry's selectivity of 8.24 (Xe/Kr), and an ideal adsorbed solution theory selectivity of 14.9 (Xe : Kr 20 : 80). The result of the dynamic breakthrough experiment also indicates a good separation for Xe/Kr with Ar.

Discovery of an Orally Bioavailable Dual PI3K/mTOR Inhibitor Based on Sulfonyl-Substituted Morpholinopyrimidines.

The discovery and optimization of a series of 2-morpholino-pyrimidine derivatives containing various sulfonyl side chains at the C4 position led to the identification of compound 26 as a potent dual PI3K/mTOR inhibitor. It exhibited high inhibitory activity against PI3Kα/ß/γ/δ (IC50 = 20/376/204/46 nM) and mTOR (IC50 = 189 nM), potent functional suppression of AKT phosphorylation (IC50 = 196 nM), and excellent antiproliferative effects on a panel of cancer cells. Enzymic data and modeling simulation indicate that a cyclopropyl ring on the C4 sulfone chain and a fluorine on the C6 aminopyridyl moiety are responsible for its maintained PI3K activity and enhanced mTOR potency, respectively. Furthermore, compound 26 exhibited higher efficiency in the HT-29 colorectal carcinoma xenograft model at the daily dose of 3.75 and 7.5 mg/kg relative to BKM120 at the dose of 15 and 30 mg/kg.

The Development of Protein Chips for High Throughput Screening (HTS) of Chemically Labeling Small Molecular Drugs.

How to construct protein chips and chemically labeling drug molecules without disrupting structures for HTS is still a challenging area. There are two main obstacles, one is that human multitrans membrane receptors, which are major drug targets, exhibit distinct motifs, and fold structures, and they will collapse unfold without membrane support in vitro; another one is that there still lack effective chemical labeling method for small drugs for detection. Therefore, how to acquire high detecting sensitivity for small molecules and to immobilize membrane protein receptors in native conformation with uniform direction on the chip, need to be solved for drug HTS. This paper reviews drug HTS trends in recent years, proposed a new virion-chip model and a feasible C-H activation method for CY-5 labeling drugs. It is expected to provide a good platform for future drug HTS.

Anti-obesity effect of total phenylpropanoid glycosides from Ligustrum robustum Blume in fatty diet-fed mice via up-regulating leptin.

ETHNOPHARMACOLOGICAL RELEVANCE: In Chinese folk medicine, the leaves of Ligustrum robustum Blume (LR) were commonly used in the treatment of obesity and hyperlipidemia. This study aimed to evaluate the anti-obesity effect and mechanisms of total phenylpropanoid glycosides from Ligustrum robustum Blume (LRTPG) in fatty diet-fed C57BL/6J mice. MATERIALS AND METHODS: C57BL/6J mice were divided randomly into 6 groups, i.e., control, model, positive (Orlistat 0.12g/kg), and LRTPG at three dosages (0.3, 0.6 or 1.2g/kg), respectively. Control mice were fed with standard diet; the others were fed with fatty diet. After 4 weeks׳ modeling, therapy mice were intragastrically administrated with positive drug or LRTPG for 5 weeks, respectively. Pharmacodynamic effects including body weight, fat weight, Lee׳s index, serum lipid levels, morphological changes and adipocyte area ratio were evaluated. The mechanisms were explored as the factors related to lipids metabolism in gene expressions by real-time PCR, and assured as the protein level of differential gene by Western blotting. RESULTS: The anti-obesity effects of LRTPG in all treated mice were shown as decreased body weight, fat mass, Lee׳s index, total cholesterol (TC) level, and adipocyte area. The mechanisms were demonstrated as elevated mRNA and protein levels of adipose leptin, and consequently decreasing mRNA of adipose acyl coenzyme A: diacylglycerol acyltransferase (DGAT) with increasing mRNA of hepatic cholesterol 7α-hydroxylase (CYP7A1), which led to inhibition of triglyceride (TG) synthesis and promotion of cholesterol catabolism. CONCLUSIONS: The anti-obesity effect of LRTPG in fatty diet-fed mice was related to the up-regulation of leptin, which may provide scientific evidence supporting the traditional usage of LR on obesity in China.