Benefit from Almonertinib after Osimertinib treat EGFR 19 exon deletion NSCLC induced Severe rash: a case report.

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been recommended as a first-line treatment of EGFR-positive non-small cell lung cancer (NSCLC). Skin rash is one of the most common side effects of osimertinib, and can have an impact on patients' quality of life and follow-up. However, there are few reports on the safety and efficacy of switching therapy with osimertinib and the other three generations of TKIs. In this paper, we present a case of NSCLC with an EGFR exon 19 deletion (19del) and MET gene amplification who developed a severe rash after 2 months of treatment with osimertinib that did not recur after switching to replacement therapy with aumonertinib. Our findings indicate that aumonertinib is as effective as osimertinib in treating EGFR19del, while also exhibiting a lower occurrence of adverse skin reactions. This may result in an improved quality of life for patients.

Insight into the plant-associated bacterial interactions: Role for plant arsenic extraction and carbon fixation.

This study investigated the interactions between rhizosphere and endosphere bacteria during phytoextraction and how the interactions affect arsenic (As) extraction and carbon (C) fixation of plants. Pot experiments, high-throughput sequencing, metabonomics, and network analysis were integrated. Results showed that positive correlations dominated the interconnections within modules (>95 %), among modules (100 %), and among keystone taxa (>72 %) in the bacterial networks of plant rhizosphere, root endosphere, and shoot endosphere. This confirmed that cooperative interactions occurred between bacteria in the rhizosphere and endosphere during phytoextraction. Modules and keystone taxa positively correlating with plant As extraction and C fixation were identified, indicating that modules and keystone taxa promoted plant As extraction and C fixation simultaneously. This is mainly because modules and keystone taxa in plant rhizosphere, root endosphere, and shoot endosphere carried arsenate reduction and C fixation genes. Meanwhile, they up-regulated the significant metabolites related to plant As tolerance. Additionally, shoot C fixation increased peroxidase activity and biomass thereby facilitating plant As extraction was confirmed. This study revealed the mechanisms of plant-associated bacterial interactions contributing to plant As extraction and C fixation. More importantly, this study provided a new angle of view that phytoextraction can be applied to achieve multiple environmental goals, such as simultaneous soil remediation and C neutrality.

Encrypted information reading technology at the micro/nano scale based on surface plasma-driven reactions.

The plasma exciton induced photocatalytic reaction has considerable potential in terms of controllability and selectivity. In this paper, with the advantage of Raman fingerprinting, the localized photocatalytic reaction driven by surface plasmons is realized by the writing and reading process of encrypted information at the micro/nano scale. A layer of probe molecules (4-nitrobenzenethiol, 4-NBT) was assembled on a gold nanoporous array grown on porous anodic aluminium oxide (AAO) membranes. The focused Raman spot is manipulated in a two-dimensional micro/nano manipulation technique to control the movement of the spot at an excitation wavelength of 633 nm. Probe molecules within the spot trajectory will undergo a photocatalytic reaction to produce p,p'-dimercaptoazobenzene (DMAB) molecules, thereby writing the specific information required. The use of Raman mapping to image the characteristic peaks of formed DMAB under excitation light with a longer wavelength of 785 nm enables the readout of 2D micro/nano cryptograms. Combined with finite-difference time-domain (FDTD) simulations, it was found that the presence of a large number of regularly arranged hot spots on the surface of the array is the key to achieving the efficient photocatalytic reaction. This study enables real-time, lossless recording/reading of encrypted information with the aid of 2D Raman technology. This would be a very interesting research area with broad application in confidential information storage.

Plasmon-driven photocatalytic reaction based on gold microsphere array.

Plasma-driven photocatalytic reactions have great research value in the fields of energy utilization, environmental pollution treatment and micro-nano information encryption. In most cases, the substrates used to study photocatalytic reactions are dispersed and disordered, which leads to poor signal reproducibility and makes it difficult to realize applications in the field of quantitative analysis. In this paper, two different sizes of polystyrene (PS) microspheres were used as templates to prepare gold microsphere arrays (Au MA) with homogeneous particle size and regular arrangement. The p-Aminothiophenol (PATP) was selected as the probe molecule to systematically investigate the photocatalytic reaction on Au MA, and the dependence of the photocatalytic reaction on the particle size of the spheres was discussed. It was found that the smaller size of Au MA has higher catalytic activity. In addition, using conventional gold films as a comparison, no significant photocatalytic reaction was found under the same experimental conditions. The reason is the existence of strong surface plasma "hot spots" in the interstices of the particles on the surface of the Au MA, which promotes the reaction. The above experimental results are of theoretical and practical significance for the in-depth study of the photocatalytic effect of micro-nano array catalytic substrates.

LncRNA UCA1 promotes SOX12 expression in breast cancer by regulating m6A modification of miR-375 by METTL14 through DNA methylation.

Breast cancer, a multifactorial disease, represents one of the leading causes of cancer-related morbidity and mortality in women. This study set out to elucidate the underlying mechanism by which lncRNA UCA1 affects the m6A modification of miR-375 by mediating the DNA methylation of METTL14 and then altering SOX12 expression in breast cancer. First, the expression patterns of lncRNA UCA1, miR-375, and apoptosis-related factors were quantitated by means of RT-qPCR and western blot analysis. In addition, the proliferation, invasion, and apoptosis of cells were detected using CCK-8, Transwell, and flow cytometry, respectively. RIP was performed to further uncover the interaction of lncRNA UCA1 and DNA methyltransferases, and MSP was employed for METTL14 promoter region methylation. The DNA methyltransferase enrichment in the METTL14 promoter region was measured by ChIP. The targeting relationship between miR-375 and SOX12 was confirmed by bioinformatics analysis and dual-luciferase report assay. Lastly, the aforementioned mechanism was also verified using tumor xenograft in vivo. It was found the elevated lncRNA UCA1 expression levels serve as a risk factor of poor prognosis in breast cancer. Meanwhile, silencing lncRNA UCA1 could inhibit the proliferation and invasion, but promote apoptosis of breast cancer cells by reducing the DNA methylation of METTL14 and augmenting its expression. Furthermore, METTL14 was observed to mediate the low miR-375 expression through m6A modification, leading to increased SOX12 expression levels in breast cancer. Altogether, findings obtained in our study indicated that silencing lncRNA UCA1 curbed the progression of breast cancer through the METTL14-miR-375-SOX12 axis.

Plasmon-driven photocatalytic properties based on the surface of gold nanostar particles.

Surface plasmon resonance (SPR) generated in gold nanoparticles can induce the conversion of p-Aminothiophenol (PATP) molecules into p,p'-dimercaptoazobenzene (DMAB) molecules by coupling reaction under the action of excitation light. Molecular detection of samples by surface enhanced Raman spectroscopy (SERS) techniques allows the study of their plasma-driven photocatalytic reaction processes. In this study, we used gold nanostars (GNS) as the substrate to study its catalytic performance and sensitivity. On this basis, catalytic substrates of gold nanospheres (GNPs) were prepared for comparison. The catalytic reactions of PATP molecules on each of the above two substrates were systematically investigated under 633 nm laser irradiation. The reduction process was subsequently observed by introducing NaBH4 solution. The results show that photocatalytic reactions can be achieved on both substrates under laser excitation at the same wavelength. However, the catalytic and reduction reaction rates on GNSs as a substrate are much faster than those of GNPs. This phenomenon may be due to the abundant nano-branched microstructures on the surface of GNSs, which will generate more and stronger local surface plasma hot spots under the irradiation of excitation light. In order to test the above hypothesis, the surface electromagnetic field distribution of two nanostructures was numerically simulated using the finite-difference time domain (FDTD) method. It is found that the star-like nanostructures not only have the same inter-particle hot spot system as the spherical nanostructures, but also have a large number of high-intensity single-particle hot spot systems arising from the abundance of branched nanostructures on their own surfaces. Compared with the spherical nanostructures, they are characterized by a dual hot spot system, which accelerates the photocatalytic reaction rate. The above experiments are of some reference significance for the in-depth study of multi-branched nanostructures and surface plasma distribution properties and their applications.

Carbon ion (12C6+) irradiation induces the expression of Klrk1 in lung cancer and optimizes the tumor microenvironment based on the NKG2D/NKG2D-Ls pathway.

With the identification of "negative immune regulation" defects in the immune system and the continuous improvement of immunotherapy, natural killer cells (NK) have received more attention, especially as tools in combined immunotherapy. Carbon ions (12C6+) have become the ideal radiation for combined immunotherapy due to their significant radiobiological advantages and synergistic effects. The purpose of this study was to explore the NK cell-mediated cytotoxicity pathway and related mechanisms in lung cancer induced by carbon ion irradiation. KLRK1, which specifically encodes the NKG2D receptor, was significantly correlated with the prognosis, clinical stage, functional status of NK cells, and the immune microenvironment of lung cancer, as shown by bioinformatics analysis. Based on RNA-seq data of Lewis lung cancer in C57BL/6 mice, carbon ion irradiation was found to significantly induce Klrk1 gene expression and activate the NKG2D/NKG2D-Ls pathway. The Treg inhibition pathway combined with carbon ion radiotherapy could significantly increase the infiltration and function of NK cells in the tumor microenvironment of lung cancer and prolong the survival time of C57BL/6 mice. In conclusion, carbon ions have significant radiobiological advantages, especially under conditions of combined immunotherapy. Carbon ions combined with Treg inhibitors can significantly improve the infiltration and functional status of NK cells.

The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis.

BACKGROUND: Previous studies have revealed the key functions of N6-methyladenosine (m6A) modification in breast cancer (BC). MALAT1 as a highly m6A modified lncRNA associated with cancer development and metastasis, but the functional relevance of m6A methyltransferase and MALAT1 in BC is still unknown. Here, our study investigated the effects of the novel m6A methyltransferase METTL3 on epithelial-mesenchymal transition (EMT) in BC via the MALAT1/miR-26b/HMGA2 axis. METHODS: Firstly, we collected clinical BC samples and cultured BC cells, and detected mRNA and protein levels in the human samples and human cell lines by RT-qPCR and Western blot, respectively. Then, the binding of MALAT1 and miR-26b and the targeting relationship between miR-26b and HMGA2 were examined by dual-luciferase assay. Moreover, the binding of MALAT1 and miR-26b was tested by RNA pull down and RNA immunoprecipitation (RIP) assays. Methylated-RNA immunoprecipitation (Me-RIP) was used to detect the m6A modification level of MALAT1. The interaction of METTL3 and MALAT1 was detected by photoactivatable ribonucleoside-crosslinking immunoprecipitation (PAR-CLIP). Finally, effects on invasion and migration were detected by Transwell. RESULTS: In BC, the level of miR-26b was consistently low, while the levels of METTL3, MALAT1 and HMGA2 were high. Further experiments showed that METTL3 up-regulated MALAT1 expression by modulating the m6A modification of MALAT1, and that MALAT1 could promote the expression of HMGA2 by sponging miR-26b. In BC cells, we found that silencing METTL3 could inhibit EMT and tumor cell invasion by suppressing MALAT1. Furthermore, MALAT1 mediated miR-26b to target HMGA2 and promote EMT, migration, and invasion. In summary, METTL3 promoted tumorigenesis of BC via the MALAT1/miR-26b/HMGA2 axis. CONCLUSIONS: Silencing METTL3 down-regulate MALAT1 and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.

Irradiation-Induced Changes in the Immunogenicity of Lung Cancer Cell Lines: Based on Comparison of X-rays and Carbon Ions.

Increasing the immunogenicity of tumors is considered to be an effective means to improve the synergistic immune effect of radiotherapy. Carbon ions have become ideal radiation for combined immunotherapy due to their particular radiobiological advantages. However, the difference in time and dose of immunogenic changes induced by Carbon ions and X-rays has not yet been fully clarified. To further explore the immunogenicity differences between carbon ions and X-rays induced by radiation in different "time windows" and "dose windows." In this study, we used principal component analysis (PCA) to screen out the marker genes from the single-cell RNA-sequencing (scRNA-seq) of CD8+ T cells and constructed a protein-protein interaction (PPI) network. Also, ELISA was used to test the exposure levels of HMGB1, IL-10, and TGF-ß under different "time windows" and "dose windows" of irradiation with X-rays and carbon ions for A549, H520, and Lewis Lung Carcinoma (LLC) cell lines. The results demonstrated that different marker genes were involved in different processes of immune effect. HMGB1 was significantly enriched in the activated state, while the immunosuppressive factors TGF-ß and IL-10 were mainly enriched in the non-functional state. Both X-rays and Carbon ions promoted the exposure of HMGB1, IL-10, and TGF-ß in a time-dependent manner. X-rays but not Carbon ions increased the HMGB1 exposure level in a dose-dependent manner. Besides, compared with X-rays, carbon ions increased the exposure of HMGB1 while relatively reduced the exposure levels of immunosuppressive factors IL-10 and TGF-ß. Therefore, we speculate that Carbon ions may be more advantageous than conventional X-rays in inducing immune effects.

Accuracy of intercellular adhesion molecule-1 for diagnosing sepsis: A systematic review and meta-analysis protocol.

BACKGROUND: Sepsis is a complex and life-threatening systemic disease. A positive blood culture is the criterion standard of diagnosis for sepsis; however, it does not produce results for 24 to 72 hours. Besides, the clinical manifestations of sepsis are variable and nonspecific. Therefore, a new diagnostic biomarker for diagnosis of sepsis should be developed. The present study aims to assess the diagnostic value of intercellular adhesion molecule-1 (ICAM-1) in individuals with sepsis. METHODS: The literature will be searched in PubMed, EMBASE, the Cochrane Library, and Web of Science databases from the inception of each database up to June 2019. The methodological quality of eligible study will be assessed by Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2). Stata 15.1 software (version 15.1, Stata Corporation) will be used to calculate the pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, pooled diagnostic odds ratio, pre-test probability, post-test probability, and summary receiver-operating characteristic curve for diagnostic value of ICAM-1. The I statistic will be used to test heterogeneity. Subgroup analysis will be used to explore the source of inconsistency. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system will be used to assess the certainty of evidence. This study will be conducted fully following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of diagnostic test accuracy. RESULTS AND CONCLUSIONS: Our study will detect the potential of ICAM-1 for diagnosing the patients with sepsis and the results will be submitted to a peer-reviewed journal. DISCUSSION: The evidence will indicate that ICAM-1 is a valuable biomarker for detecting sepsis. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required.

MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1.

BACKGROUND: Accumulating studies have identified that microRNAs (miRNAs) are novel regulators acting as tumor suppressors or oncogenes in tumor progression. The aim of the study is to investigate the functional roles of miR-138-5p in breast cancer (BC) cells and explore the underlying mechanisms by identifying its target gene. METHODS AND RESULTS: Our results first showed that miR-138-5p expression was remarkably decreased in BC tissues and cells using quantitative real-time PCR analysis. Forced expression of miR-138-5p significantly suppressed cell migration and invasion ability of BC using transwell assay. Moreover, miR-138-5p overexpression suppressed cell epithelial-mesenchymal transition (EMT) phenomenon of BC by upregulating E-cadherin expression, but downregulating N-cadherin and Vimentin expression. More importantly, rhomboid domain-containing protein 1 (RHBDD1) was predicted as the direct target of miR-138-5p by TargetScan and miRanda, which was subsequently confirmed by luciferase reporter assay in BC cells. RHBDD1 was up-regulated in BC tissues and negatively correlated with miR-138-5p expression. Furthermore, forced expression of miR-138-5p could down-regulate the expression of RHBDD1, but overexpression of RHBDD1 reversed the suppressive effects of miR-138-5p in BC cell migration, invasion and EMT. CONCLUSIONS: Our findings revealed the tumor-suppressive role of miR-138-5p in regulating BC migration by targeting RHBDD1, suggesting that miR-138-5p negatively regulating EMT might be a therapeutic target in BC.

[Proximal humeral fractures in children choose different surgical methods].

OBJECTIVE: To observe the therapeutic effect of open reduction Kirschner wire fixation and open reduction external fixation in the treatment of the proximal humeral fractures in children. METHODS: Sixty two patients with proximal humeral fractures had received Kirschner wire fixation and external fixation in our hospital from Oct. 2010 to Aug. 2013 were collected. The Kirschner wire fixation group was 40 cases and the external fixation group 22 cases. Comparison the clinical effects of two groups. RESULTS: Two groups operation time were (40.3 ± 7.2, 62.3 ± 6.7) min, operation amount of bleeding were (28.9 ± 14.5, 71.7 ± 17.5) ml, incision length were (32.4 ± 11.3, 63.3 ± 13.2) cm and postoperative Neer score were (96.8 ± 9.8, 92.3 ± 8.5) respectively. The external fixation group was better than Kirschner wire fixation group in above indexes and the difference was statistical significance (P < 0.05), while it showed no significant difference in hospitalization time, fracture healing time and postoperative complications (P > 0.05). CONCLUSIONS: For the treatment of children with proximal humeral fractures, the open reduction and external fixation have some advantages, such as simple operation, small metaphyseal damage, fixed reliable for early functional exercises and good results for upper extremity functional recovery.

[Outcomes of different operations for distal forearm fractures in children].

OBJECTIVE: To explore the treatment outcomes of plate internal and external fixations for distal forearm fractures in children. METHODS: From July 2010 to September 2013, a total of 89 children were operated for distal forearm ulnar and radial fractures, including plate fixation (n=46) and external fixation (n=43). Two groups were evaluated in terms of operative duration, bleeding volume, length of incision, hospitalization length, fracture healing time, postoperative complications and Berton evaluation criteria. RESULTS: As compared with internal fixation group, external fixation group fare better in operative duration, bleeding volume, operation incision length, fracture healing time and postoperative complications with significant differences (P<0.05). And the hospitalization time had no significant difference (P>0.05). CONCLUSION: Treating distal forearm fractures with external fixation offers the advantages of simpler handling, lesser injury and better postoperative functional recovery in children.

[The design and transposition principles of expanded flap for treatment of cheek skin-soft tissue defect].

OBJECTIVE: To explore an ideal method for repairing the skin-soft tissue defects according to the different anatomical units of cheek, and find reasonable design principles to transfer the expanded flaps. METHODS: According to the location of the defect, we placed 1-3 appropriate expanders nearby, when the flap expanded enough we adopted advanced skin flaps, rotation-advanced skin flaps or transposition skin flaps to repair the defect. In this group of 269 cases, the defects were secondary to hemangioma, various scars, nevus or nevus excision. RESULTS: In all 269 cheek defects, 305 expanded flaps were developed which included 145 rotation-advanced flaps, 121 advanced skin flaps and 39 transposition skin flaps. 52 of them generated complications, including blood circulation disorder of the distal part of flaps, hematoma, infection, injection, lower eyelid ectropion, expander extrusion and capsule contracture. Mostly, these complications didn't affect the final results. CONCLUSIONS: The principles presented in this article are the guidelines to treat the skin-soft tissue defect of check with tissue expansion. The satisfied results come from the reasonable flap designs.