Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 patients with lung cancer under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progression-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T-cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20,000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted natural killer (NK) cells and decreased CD8+ T-cell and NK-cell populations in patients with MET amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3'-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET. SIGNIFICANCE: We suggest that the combination of MET inhibitor together with ICB will overcome ICB resistance induced by MET amplification. Our report reveals much-needed information that will benefit the treatment of patients with primary MET amplification or EGFR-tyrosine kinase inhibitor resistant-related MET amplification.This article is highlighted in the In This Issue feature, p. 2659.
Poly (ADP-ribose) polymerase 1/2 (PARP1/2) can catalyze the poly (ADP ribose) (PAR) substrate protein modification and play an important role in the regulation of DNA damage repair, cell death and transcriptional activity. The PARP inhibitor olaparib (AZD2281) can be used as a sensitizer of radiotherapy and chemotherapy in the cancer treatment. Through establishment of biological fluorescent labeled 4T1 ectopic breast tumor model, we found that olaparib exhibited a poor effect on 4T1 breast cancer alone. However, in the combination with Taxol, olaparib significantly increased the anti-tumor effect of Taxol, and reduced the PAR levels of the tumor tissues. Importantly, olaparib did not amplify the toxicity of chemotherapy drugs. This study suggests that olaparib is a representative of the PARP inhibitor that can enhance Taxol’s antitumor effect in the 4T1 ectopic breast tumor model, which sets the foundation for future study of the mechanism of olaparib action.
Objective
To investigate the effect of comprehensive nursing intervention and evaluate its role in the entire clinical course of in the treatment of children with severe burns.
Methods
A total of 60 children with 1-5 years old with clinical diagnosis of severe burns were randomly divided into experimental group and control group by random digits table method, 30 cases in each group. The control group received routine burn care. The experimental group received comprehensive nursing interventions on the basis of routine burn care and the intervention time covered the entire course of treatment. During hospitalization, the recovery and family social system were evaluated by anxiety scales and social support scales combined with the cure rate and hospitalization of children.
Results
Before intervention, the score of Anxiety Rating Scale was high in both groups of families, while Social Support Scale was lower, the difference was not statistically significant between the two groups (P>0.05). After intervention, the score of Anxiety Rating Scale and was Social Support Scale were (52.31±7.81), (31.52±5.48)points in the experimental group, and (62.51±6.52), (23.62±5.62) points in the control group, and there were significant differences (t=5.491 3, 5.512 5, P<0.01). The length of stay was (18.34±3.58) d in the experimental group, and (21.82±4.23) d in the control group, and there was significant difference(t=3.439 6, P<0.05). The cure rate was 93.33% (28/30) in the experimental group, and 56.67%(17/30) in the control group, and there was significant difference(χ2=10.755 6, P<0.05).
Conclusions
The comprehensive nursing intervention can provide comprehensive refinement of the overall care in children and their families, promote physical and psychological rehabilitation of children with severe burns, and repair their family and social support systems. The comprehensive nursing intervention has far-reaching implications for the rehabilitation of children with severe burns.
Key words:
Comprehensive nursing intervention; Children with severe burns; Anxiety Rating Scale; Social Support Scale
Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 μg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.
Glioma is one of the most common malignant tumors affecting the central nervous system. We screened active drugs from 12 classes to provide experimental data for the study of human glioma. Serum-free suspension clone formation was used to induce the formation of glioma stem‑like cells (GSLCs) from U251 cells. We screened active drugs from 12 classes and observed their effects on the number of tumor balls. The results revealed that serum‑free suspension clone formation successfully induced the formation of GSLCs. Six active drugs [curcumin, chrysin, apigenin, luteolin, casticin and 8-bromo-7-methoxychrysin (BrMChR)] were identified by MTT assay. The drugs that affected the number of tumor balls were curcumin, luteolin, casticin and BrMChR (all P<0.05). The GSLCs were obtained by serum‑free clone suspension formation and exhibited the features of cancer stem cells.
To determine the expression of EGFR of lung cancer tissues and its clinical significance.The expression of EGFR was detected in 95 primary lung cancer tissues and their para-cancerous lung tissues and 39 benign pulmonary lesion tissues as control by immunohistochemical method.The positive rate of EGFR expression was 87. 9 %(80/ 91) in non2small cell lung cancer (NSCLC) and 10. 3 %(4/ 39) in benign pulmonary tissues , but was 0 % in 4 small cell lung cancer. The positive rate was 63. 7 %(58/ 91) in the para-cancerous tissues from 0 to 3. 0 cm outside the tumors ,12. 1 %(11/ 91) from 3. 0 to 6. 0cm outside the tumors.The positive rate of EGFR expression in lung cancer tissues was significantly higher than that in benign pulmonary tissues. Determinatation of EGFR expression might be useful to differentiate malignant from benign lesion of the lung.
The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (P<0.05) and improve renal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.
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