Effects of Continuous Quality Improvement on Complication Rate and Treatment Outcome of Extremely Premature Infants.

Background: Extremely premature infants (EPIs) are those less than 32 weeks of gestational age. Preterm birth is the leading cause of neonatal death and poor prognosis, accounting for 25% of neonatal deaths, with extremely premature births accounting for 50% of all premature deaths. Continuous quality improvement (CQI) improves patient outcomes by changing and optimizing clinical practice including increasing participation of neonatologists in prenatal consultation, maintenance of normal body temperature in preterm infants, early use of pulmonary surfactant, reduction of mechanical ventilation time and intensive breastfeeding to reduce clinically avoidable adverse events. Objective: The risk of death and disability is high for very preterm infants, with a mortality rate of 30-50% and a risk of at least 20-50% for survivors. This study aimed to investigate the effect of CQI on the incidence of complications and treatment outcomes in very preterm infants. Design: This was a retrospective study. Setting: This study was conducted in the Maternal and Child Health Hospital of Hubei Province. Participants: A total of 140 EPIs born in our hospital and transferred to the neonatal intensive care unit between August 1, 2020, and July 31, 2022, were enrolled. The EPIs were divided into two groups: before improvement (n=79, 56.4%) and after improvement (n=61, 43.6%) according to the week of birth, and the gestational age ranged from 26 weeks to 26 weeks 6 days into the 26 weeks group. Interventions: From August 2021, the hospital implemented the CQI method, which included neonatologists' participation in consultations before birth, the care of a professionally trained resuscitation team after birth, and the introduction of transport heating tanks and ventilators during transport. Primary Outcome Measures: (1) Apgar score (2) body weight (3) duration of invasive ventilation (4) length of stay (5) treatment expense (6) incidence of complications and (7) survival rate of EPIs. Results: The application of CQI methods resulted in significant improvements in body weight (1305 g vs 1404 g) and duration of invasive ventilation (4.64 d vs 7.40 d) in EPIs (P = .036 and P = .040), reduced the time of invasive mechanical ventilation decreased significantly, from 7.4 days to 4.64 days (P < .01), increased the median temperature of newborn infants (36.2°C vs 35.7°C) (P = 0), increased the proportion of newborn infants with a temperature greater than 36°C (67.2% vs 35.4%) (P < .001), reduced the incidence of complications in EPIs (32.79% vs 45.57%) (P < .05). Conclusion: The application of the CQI approach significantly increases the body temperature, improves the incidence of complications of EPIs, and is conducive to the survival of EPIs. Our study may provide a clinical reference for management of EPIs.

Gemcitabine enhances pharmacokinetic exposure of the major components of Danggui Buxue Decoction in rat via the promotion of intestinal permeability and down-regulation of CYP3A for combination treatment of non-small cell lung cancer.

CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.

Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma.

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.

Nano-selenium controlled cadmium accumulation and improved photosynthesis in indica rice cultivated in lead and cadmium combined paddy soils.

Selenium nanoparticles (Se NPs) are less toxic and more biocompatible than selenite or selenate. However, studies involving spraying with Se NPs for reducing accumulation of cadmium (Cd) and lead (Pb) in rice grains have been rarely reported as yet. Herein, indica rice seedlings cultivated in Cd+Pb-spiked paddy soils (denoted as positive control) were sprayed with Se NPs sols for four times from tillering to booting stage. Compared to positive control, 50-100 µmol/L Se NPs downregulated Cd transporters-related genes such as OsLCT1, OsHMA2 and OsCCX2 in leaves and OsLCT1, OsPCR1 and OsCCX2 genes in node I at filling stage. Meanwhile, Se-binding protein 1 was distinctly elevated, involving the repression of Cd and Pb transportation to rice grains. Se NPs also differentially improved RuBP carboxylase and chlorophylls especially some key genes and proteins involving photosynthetic system. Besides, 25-50 µmol/L Se NPs diminished reactive oxygen species overproduction from NADPH oxidases whereas boosted glutathione peroxidase, reducing protein carbonylation in rice seedlings. However, the antioxidant isozymes and oxidatively modified proteins were slightly rebounded at 100 µmol/L. Se contents were noticeably elevated and confirmed to exist as selenomethionine in the rice grains following all the treatments by Se NPs. Thus, the optimal dosage of Se NPs for foliar application is 50 µmol/L, which significantly decreased Cd accumulation, improved photosynthesis and Se enrichment whereas caused no distinct reduction of Pb in the grains. Thus, an appropriate dosage of Se NPs can be conducted to decrease Cd accumulation, improve photosynthesis, and organic Se contents in rice grains.

Atorvastatin Targets the Islet Mevalonate Pathway to Dysregulate mTOR Signaling and Reduce ß-Cell Functional Mass.

Statins are cholesterol-lowering agents that increase the incidence of diabetes and impair glucose tolerance via their detrimental effects on nonhepatic tissues, such as pancreatic islets, but the underlying mechanism has not been determined. In atorvastatin (ator)-treated high-fat diet-fed mice, we found reduced pancreatic ß-cell size and ß-cell mass, fewer mature insulin granules, and reduced insulin secretion and glucose tolerance. Transcriptome profiling of primary pancreatic islets showed that ator inhibited the expression of pancreatic transcription factor, mechanistic target of rapamycin (mTOR) signaling, and small G protein (sGP) genes. Supplementation of the mevalonate pathway intermediate geranylgeranyl pyrophosphate (GGPP), which is produced by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, significantly restored the attenuated mTOR activity, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) expression, and ß-cell function after ator, lovastatin, rosuvastatin, and fluvastatin treatment; this effect was potentially mediated by sGP prenylation. Rab5a, the sGP in pancreatic islets most affected by ator treatment, was found to positively regulate mTOR signaling and ß-cell function. Rab5a knockdown mimicked the effect of ator treatment on ß-cells. Thus, ator impairs ß-cell function by regulating sGPs, for example, Rab5a, which subsequently attenuates islet mTOR signaling and reduces functional ß-cell mass. GGPP supplementation could constitute a new approach for preventing statin-induced hyperglycemia.

Danggui Buxue Decoction Sensitizes the Response of Non-Small-Cell Lung Cancer to Gemcitabine via Regulating Deoxycytidine Kinase and P-glycoprotein.

This study aimed to investigate whether the anti-tumor effect of gemcitabine (GEM) in non-small-cell lung cancer (NSCLC) treatment was affected by Danggui Buxue decoction (DBD), and explore the potential mechanisms. The combined use of GEM and DBD showed an enhanced tumor growth inhibition effect in a murine Lewis lung carcinoma (LLC) model. LC-MS/MS results showed that the pharmacokinetic behaviors of a GEM active metabolite, gemcitabine triphosphate (dFdCTP), were found to be altered remarkably in the peripheral blood mononuclear cells (PBMC) of DBD co-administration rats. In addition, after co-administration of DBD with GEM, Western Blot and qPCR results confirmed that the expression of deoxycytidine kinase (dCK) in tumor tissues of LLC-bearing mice were markedly increased. DBD co-administration also reversed the upregulation of P-glycoprotein (P-gp) in tumor tissues induced by GEM. Moreover, DBD could notably up-regulate the IL-12p70 and GM-CSF expression in mice serum, suggesting potential immunomodulatory activities in tumor-bearing mice. Meanwhile, DBD inhibited the P-gp efflux activity in A549 cells. Therefore, the regulation of dCK and P-gp played important roles in the alternation of GEM pharmacokinetics and the enhancement of the anti-tumor effect of GEM. DBD being a potential dCK promoter could work as an adjuvant agent to boost the anticancer effect of GEM.

Effects of traditional Chinese medicine Fu Zheng decoction on the immunological function and clinical prognosis of the elderly patients with pneumonia.

Pneumonia is one of the most serious infectious diseases for elderly people who have impaired organ functions and are more susceptible to infection. Elderly patients having pneumonia often need long-term hospitalization, leading to declined quality of life, and increase of financial burden to the society and their family. Therefore, studies on novel therapeutic strategies and the clinical prognosis of the pneumonia patients are imperative. In the present study, we found that the Chinese herbal medicine Fu Zheng decoction had great immunomodulatory effects during the recovery period of elderly pneumonia patients. Patients treated with combined treatment of Fu Zheng decoction and antibiotic had a faster decline of temperature and a more significant decrease of C reactive protein and inflammatory factors level, and it is easier for them to cough off phlegm, compared with the antibiotic only treatment. Furthermore, the inflammation absorption and the reduction of NK-cell proportion as well as the inflammatory factors were more remarkable in the patients taken Fu Zheng decoction. Especially, the Fu Zheng decoction treatment could decrease the duration of antibiotic treatment, which may help reduce the side effects of antibiotics. Our study also found that MyD88 might play a role in the immunomodulatory effect of Fu Zheng decoction. Our study provides novel insight for the further development of intravenous injection of Chinese materia medica preparation on the regulation of immune function.

[Effect of water and nitrogen fertilizer coupling on yield and growth of genuine medicinal materials Chuzhou Chrysanthemum morifolium].

OBJECTIVE: To discuss the suitable water and nitrogen management mode in artificial cultivation of Chuzhou Chrysanthemum morifolium. METHODS: According to two factors quadratic regression rotation design experience, pot experiment was conducted. RESULTS: There were remarkable effects of water and nitrogen coupling on inflorescence number, yield and overground part biomass of Chuzhou Chrysanthemum morifolium, and there were significant positive interaction between water and nitrogen. Effects of water on early-term inflorescence yield and overground part biomass of Chuzhou Chrysanthemum morifolium were higher than that of nitrogen fertilizer, but the effect on total inflorescence yield was opposite. CONCLUSION: Considering for the fresh inflorescence yield, the suitable water and nitrogen management mode is to keep 93% of the water holding capacity and nitrogen fertilizer (N) 0.34 g/kg of Chuzhou Chrysanthemum morifolium in pot experiment, and as for the dry inflorescence yield, the suitable water and nitrogen management mode is to keep 75% of the water holding capacity and nitrogen fertilizer (N) 0.2 g/kg.