A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Biological characteristics and metabolic phenotypes of different anastomosis groups of Rhizoctonia solani strains.

BACKGROUND: Rhizoctonia solani is an important plant pathogen worldwide, and causes serious tobacco target spot in tobacco in the last five years. This research studied the biological characteristics of four different anastomosis groups strains (AG-3, AG-5, AG-6, AG-1-IB) of R. solani from tobacco. Using metabolic phenotype technology analyzed the metabolic phenotype differences of these strains. RESULTS: The results showed that the suitable temperature for mycelial growth of four anastomosis group strains were from 20 to 30oC, and for sclerotia formation were from 20 to 25oC. Under different lighting conditions, R. solani AG-6 strains produced the most sclerotium, followed by R. solani AG-3, R. solani AG-5 and R. solani AG-1-IB. All strains had strong oligotrophic survivability, and can grow on water agar medium without any nitrutions. They exhibited three types of sclerotia distribution form, including dispersed type (R. solani AG-5 and AG-6), peripheral type (R. solani AG-1-IB), and central type (R. solani AG-3). They all presented different pathogenicities in tobacco leaves, with the most virulent was noted by R. solani AG-6, followed by R. solani AG-5 and AG-1-IB, finally was R. solani AG-3. R. solani AG-1-IB strains firstly present symptom after inoculation. Metabolic fingerprints of four anastomosis groups were different to each other. R. solani AG-3, AG-6, AG-5 and AG-1-IB strains efficiently metabolized 88, 94, 71 and 92 carbon substrates, respectively. Nitrogen substrates of amino acids and peptides were the significant utilization patterns for R. solani AG-3. R. solani AG-3 and AG-6 showed a large range of adaptabilities and were still able to metabolize substrates in the presence of the osmolytes, including up to 8% sodium lactate. Four anastomosis groups all showed active metabolism in environments with pH values from 4 to 6 and exhibited decarboxylase activities. CONCLUSIONS: The biological characteristics of different anastomosis group strains varies, and there were significant differences in the metabolic phenotype characteristics of different anastomosis group strains towards carbon source, nitrogen source, pH, and osmotic pressure.

Tuning the Electrolyte and Interphasial Chemistry for All-Climate Sodium-ion Batteries.

Sodium-ion batteries (SIBs) present a promising avenue for next-generation grid-scale energy storage. However, realizing all-climate SIBs operating across a wide temperature range remains a challenge due to the poor electrolyte conductivity and instable electrode interphases at extreme temperatures. Here, we propose a comprehensively balanced electrolyte by pairing carbonates with a low-freezing-point and low-polarity ethyl propionate solvent which enhances ion diffusion and Na+-desolvation kinetics at sub-zero temperatures. Furthermore, the electrolyte leverages a combinatorial borate- and nitrile-based additive strategy to facilitate uniform and inorganic-rich electrode interphases, ensuring excellent rate performance and cycle stability over a wide temperature range from -45 °C to 60 °C. Notably, the Na||sodium vanadyl phosphate cell delivers a remarkable capacity of 105 mAh g-1 with a high rate of 2 C at -25 °C. In addition, the cells exhibit excellent cycling stability over a wide temperature range, maintaining a high capacity retention of 84.7 % over 3,000 cycles at 60 °C and of 95.1 % at -25 °C over 500 cycles. The full cell also exhibits impressive cycling performance over a wide temperature range. This study highlights the critical role of electrolyte and interphase engineering for enabling SIBs that function optimally under diverse and extreme climatic environments.

SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report.

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.

Influence of Electronic Modulation of Phenanthroline-Derived Ligands on Separation of Lanthanides and Actinides.

The solvent extraction, complexing ability, and basicity of tetradentate N-donor 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-1,10-phenanthroline (CyMe4-BT- Phen) and its derivatives functionalized by Br, hydroxyphenyl, nitryl were discussed and compared. It was demonstrated that four BTPhen ligands are able to selectively extract Am(lll) over Eu(lll). It was notable that the distribution ratio of 5-nitryl-CyMe4-BTPhen for Eu(lll) was suppressed under 0.02, which was much lower compared to DEu(lll) = 1 by CyMe4-BTPhen. The analysis of the effect of the substituent on the affinity to lanthanides was conducted by UV/vis and fluorescence spectroscopic titration. The stability constants of various ligands with Eu(lll) were obtained by fitting titration curve. Additionally, the basicity of various ligands was determined to be 3.1 ± 0.1, 2.3 ± 0.2, 0.9 ± 0.2, 0.5 ± 0.1 by NMR in the media of CD3OD with the addition of DClO4. The basicity of ligands follows the order of L1 > L2 > L3 > L4, indicating the tendency of protonation decreases with the electron-withdrawing ability increase.

Circ_ROBO2/miR-149 Axis Promotes the Proliferation and Migration of Human Aortic Smooth Muscle Cells by Activating NF-κB Signaling.

Atherosclerosis is the leading global cause of mortality. The occurrence of coronary artery disease (CAD) is regulated by a diversity of pathways, including circRNAs. However, the potential mechanisms of circRNAs in CAD remain unclear. Here, qRT-PCR was used to examine the expressions of miR-149 and circ_ROBO2. Their influences on cell proliferation, migration, and apoptosis were measured by CCK-8, trans-well, and flow cytometry assays, respectively. The protein levels of p-IκBα and NF-κB p65 were examined using western blot. The molecular interactions were validated using dual luciferase reporter and RNA pull-down assays. The expression patterns of circ_ROBO2 and miR-149 in CAD patients and PDGF-BB-treated human aortic smooth muscle cells (HASMCs) were upregulated and downregulated, respectively. Knockdown of circ_ROBO2 could markedly inhibit the capabilities of proliferation and migration, enhance the apoptotic rate, and suppress NF-κB signaling in PDGF-BB-treated HASMCs. Mechanistically, circ_ROBO2 acted as a sponge of miR-149 to activate TRAF6/NF-κB signaling. Rescue studies demonstrated that neither silencing miR-149 nor activation of NF-κB signaling obviously abolished the biological roles of circ_ROBO2 knockdown in PDGF-BB treated-HASMCs. This discovery elucidated a functional mechanism of circ_ROBO2 in CAD, suggesting that circRNAs serve a vital role in the progression of CAD.

Application of Restriction Site-Associated DNA Sequencing (RAD-Seq) for Copy Number Variation and Triploidy Detection in Human.

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value.

Preparation, characterization and in vitro-in vivo evaluation of bortezomib supermolecular aggregation nanovehicles.

BACKGROUNDS: Intolerable toxicity and unsatisfactory therapeutic effects are still big problems retarding the use of chemotherapy against cancer. Nano-drug delivery system promised a lot in increasing the patients' compliance and therapeutic efficacy. As a unique nano-carrier, supermolecular aggregation nanovehicle has attracted increasing interests due to the following advantages: announcing drug loading efficacy, pronouncing in vivo performance and simplified production process. METHODS: In this study, the supermolecular aggregation nanovehicle of bortezomib (BTZ) was prepared to treat breast cancer. RESULTS: Although many supermolecular nanovehicles are inclined to disintegrate due to the weak intermolecular interactions among the components, the BTZ supermolecules are satisfying stable. To shed light on the reasons behind this, the forces driving the formation of the nanovehicles were detailed investigated. In other words, the interactions among BTZ and other two components were studied to characterize the nanovehicles and ensure its stability. CONCLUSIONS: Due to the promising tumor targeting ability of the BTZ nanovehicles, the supermolecule displayed promising tumor curing effects and negligible systemic toxicity.

A new prenylated coumarin and a new anthranilamide derivative from Evodia lepta.

A new prenylated coumarin (1) and a new anthranilamide derivative (2) were isolated from the aerial parts of Evodia lepta. Compound 2 represents the first anthranilamide derivative from the Evodia genus. Their structures were elucidated by spectroscopic data analysis (MS, UV, IR, and NMR). Compound 1 exhibited certain inhibition on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages with an IC50 value of 37.96 ± 1.7 µM.

Two new naphthoate derivatives from Morinda officinalis.

Two new naphthoate derivatives, including a symmetrical dimer (1) and a monomer (2), were separated from the roots of Morinda officinalis var. hirsuta. Their structures were characterized on the basis of spectroscopic means especially MS and NMR methods. Biological evaluations revealed that the two compounds did not show inhibition against both cholinesterases AChE and BChE, while the dimer (1) did exhibit moderate growth inhibitory activity toward one human osteosarcoma cell line U2OS with an IC50 value of 18.5 ± 1.1 µM.

Long noncoding RNA MEG3 prevents vascular endothelial cell senescence by impairing miR-128-dependent Girdin downregulation.

Long noncoding RNAs (lncRNAs) are commonly associated with various biological functions, in which the function of lncRNA maternally expressed gene 3 (MEG3) has been identified in various cancers. Strikingly, an association between MEG3 with microRNAs (miRNAs), mRNAs, and proteins has been reported. This study investigates the role of MEG3 in vascular endothelial cell (VEC) senescence. Expression of Girdin and miR-128 was monitored in the blood vessel samples of young and old mice/healthy volunteers, along with the measurement of human umbilical vein endothelial cells (HUVECs). The relationship between MEG3/Girdin and miR-128 was determined and verified. Loss- and gain-of-function approaches were applied to analyze the regulatory effects of MEG3 on platelet phagocytosis and lipoprotein oxidation of HUVEC membrane. In addition, the effect of MEG3 on HUVEC senescence was evaluated by detection of the reactive oxygen species, telomerase activity, and telomere length. To further analyze the MEG3-mediated regulatory mechanism, miR-128 upregulation and inhibition were introduced into the HUVECs. Downregulated Girdin and upregulated miR-128 were found in the blood vessels of old individuals and old mice, as well as in senescent HUVECs. MEG3 downregulation was found to be capable of inhibiting Girdin but enhancing miR-128 expression. It was also indicated to inhibit platelet phagocytosis and reduce telomerase activity and telomere length, while enhancing lipoprotein oxidation and reactive oxygen species production, which ultimately contributed in preventing and protecting HUEVCs from senescence. These findings provide evidence supporting that MEG3 leads to miR-128 downregulation and Girdin upregulation, which promotes platelet phagocytosis, thus protecting VECs from senescence.

Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells.

316: F1006-F1015, 2019. First published March 6, 2019; doi: 10.1152/ajprenal.00413.2018 .-Experimental studies have shown that pharmacological activation of calcium-sensing receptor (CaSR) attenuates renal fibrosis in some animal models beyond modification of bone and mineral homeostasis; however, its underlying mechanisms remain largely unknown. Since excessive collagen deposition is the key feature of fibrosis, the present study aimed to examine whether CaSR was involved in the regulation of collagen expression in rats with adenine diet-induced renal fibrosis and in profibrotic transforming growth factor (TGF)-ß1-treated renal proximal tubular epithelial cells (PTECs). The results showed that the CaSR agonist cinacalcet significantly attenuated renal collagen accumulation and tubular injury in adenine diet-fed rats. Additionally, the in vitro experiment showed that profibrotic TGF-ß1 significantly increased the expression of collagen and decreased CaSR expression at the mRNA and protein levels in a concentration- and time-dependent manner. Furthermore, the CaSR CRISPR activation plasmid and cinacalcet partially abrogated the upregulation of collagen induced by TGF-ß1 treatment. Blockade of CaSR by the CRISPR/Cas9 KO plasmid or the pharmacological antagonist Calhex231 further enhanced TGF-ß1-induced collagen expression. Mechanistic experiments found that Smad2 phosphorylation and Snail expression were markedly increased in PTECs treated with TGF-ß1, whereas the CaSR CRISPR activation plasmid and cinacalcet substantially suppressed this induction. In summary, this study provides evidence for a direct renal tubular epithelial protective effect of CaSR activation in renal fibrosis, possibly through suppression of collagen expression in PTECs.

Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice.

BACKGROUND: Chronic gastritis has been demonstrated to be a key cause of gastric cancer (GC), and control of gastric inflammation is regarded as an effective treatment for the clinical prevention of gastric carcinogenesis. However, there remains an unmet need to identify the dominant regulators of gastric oncogenesis-associated inflammation in vivo. METHODS: The mouse model for the study of inflammation-associated GC was induced by Benzo[a]pyrene (BaP) intragastric administration in Bcl6b-/- and wildtype mice on a C57BL/6 background. 5-Aza-2'-deoxycytidine (5-Aza), the demethylation drug, was intraperitoneally injected to restore Bcl6b expression. Human GC tissue array was used to analyse patient survival based on BCL6B and CD3 protein expression. RESULTS: Bcl6b was gradually downregulated by its own promoter hypermethylation in parallel to an increasing inflammatory response during the progression of BaP-induced gastric carcinogenesis in mice. Moreover, knockout of Bcl6b dramatically worsened the severity of gastric cancer and aggravated the inflammatory response in the BaP-induced mice GC model. Re-activation of Bcl6b by 5-Aza impeded inflammatory amplification and BaP-induced GC development, prolonging survival time in wildtype mice, whereas no notable curative effect occurred in Bcl6b-/- mice with 5-Aza treatment. Finally, significant negative correlations were detected between the mRNA levels of BCL6B and inflammatory cytokines in human GC tissues; patients harbouring BCL6B-negetive and severe-inflammation GC tumours were found to exhibit the shortest survival time. CONCLUSIONS: Epigenetic inactivation of Bcl6b promotes gastric cancer through amplification of the gastric inflammatory response in vivo and offers a new approach for GC treatment and regenerative medicine.

Cp*Co(III)-Catalyzed Dearomative [3 + 2] Spiroannulation of 2-Alkenylphenols with Ynamides via C-H Activation.

An oxidative [3 + 2] C-H spiroannulation reaction of 2-alkenylphenols with ynamides has been developed toward the synthesis of spiro[4,5]decane derivatives. This dearomative reaction employs earth-abundant cobalt as the metal catalyst and occurs under rather mild reaction conditions (room temperature). The use of ynamides confers unique reactivity and exclusive regioselectivity. The products bearing an all-carbon quaternary stereogenic center were constructed in generally good yields with good functional group tolerance being observed. Experimental mechanistic studies were conducted, and a possible reaction mechanism is proposed.

Quantum Hall Effect in Electron-Doped Black Phosphorus Field-Effect Transistors.

The advent of black phosphorus field-effect transistors (FETs) has brought new possibilities in the study of two-dimensional (2D) electron systems. In a black phosphorus FET, the gate induces highly anisotropic 2D electron and hole gases. Although the 2D hole gas in black phosphorus has reached high carrier mobilities that led to the observation of the integer quantum Hall effect, the improvement in the sample quality of the 2D electron gas (2DEG) has however been only moderate; quantum Hall effect remained elusive. Here, we obtain high quality black phosphorus 2DEG by defining the 2DEG region with a prepatterned graphite local gate. The graphite local gate screens the impurity potential in the 2DEG. More importantly, it electrostatically defines the edge of the 2DEG, which facilitates the formation of well-defined edge channels in the quantum Hall regime. The improvements enable us to observe precisely quantized Hall plateaus in electron-doped black phosphorus FET. Magneto-transport measurements under high magnetic fields further revealed a large effective mass and an enhanced Landé g-factor, which points to strong electron-electron interaction in black phosphorus 2DEG. Such strong interaction may lead to exotic many-body quantum states in the fractional quantum Hall regime.

[Hamilton-Thorne Integrated Visual Optical System â (IVOSâ ) versus IVOS â ¡ for human sperm analysis].

OBJECTIVE: To compare the computer-assisted sperm analysis (CASA) systems Hamilton-Thorne Integrated Visual Optical System Ⅰ (IVOSⅠ) and IVOS Ⅱ after verifying the performance of the latter so as to ensure the accuracy of the results of analysis. METHODS: Based on the criteria established in the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO 5th Ed), we compared the main semen parameters obtained from IVOSⅠ with those generated by IVOS Ⅱ, and examined the consistency between the results of the two sperm analyzers. RESULTS: The linear relationship of the outlier test, bias estimation and scatter plot and the results of the outlier test of the two systems all met the requirements of comparison analysis and showed an obvious correlativity. The application scope of the results obtained from the apparatus indicated a reasonable value range, with r = 0.988 for sperm concentration, r = 0.975 for sperm progressive motility (PR), and r = 0.981 for total sperm motility. Evaluation of the acceptability of the predicted bias showed that the allowable total error (TEa) to be 6.67% with sperm concentration at 12 × 106 /ml and 2.34% with PR < 31%, their upper limit of the allowable error < 1/2. The results of IVOS Ⅱ conformed to the requirements of the WHO 5th Ed. CONCLUSIONS: The main parameters derived from IVOSⅠ and IVOS Ⅱ are comparable and consistent, indicating that both can be used for the examination of semen samples.

[Molecular Mechanism of Ventilator-associated Lung Injury Based on Keap1/Nfr2/ARE Signaling Pathway].

OBJECTIVE: To explore the molecular mechanism of ventilation induced lung injury (VILI) formation based on Keap1/Nfr2/ARE signaling pathway. METHODS: The VILI model was established by excessive mechanical ventilation in SD rats. HE staining was used to detect the pathological changes of lung tissue in the control group, normal tidal volume (VT) group and large VT group (VT 40 mL/kg). The wet weight of lung tissue was detected in each group. Dry weight (W/D) ratio change; BCA method was used to detect the changes of total protein in bronchoalveolar lavage fluid (BALF) of each group; ELISA was used to detect interleukin-1ß (IL-1ß) and leukocyte in BALF and serum of each group. The content of 8-OHdG in the lung tissue was detected by IL-8 and the content of malondialdehyde (MDA) in the lung tissue was detected by TBA method. The NLRP3, ASC and caspase-1 proteins in macrophages were detected by Western blot. The changes of Keap1 and Nrf2 proteins in lung tissues were detected by RT-PCR. The expressions of SOD mRNA and HO-1 mRNA in lung tissues of each group were detected by RT-PCR. RESULTS: Excessive mechanical ventilation could damage lung tissue, leading to alveolar rupture, inflammatory cell infiltration and erythrocytosis. Compared with the control group and normal VT group, the W/D value, 8-OHdG and MDA content in the large VT group, and total BALF, the contents of IL-1ß and IL-18 in protein, IL-1ß, IL-18 in serum increased significantly ( P<0.05). Compared with the control group and normal VT group, NLRP3, ASC, in macrophage of large VT group, the content of Keap1 protein in caspase-1 protein and lung tissue increased significantly ( P<0.05). The expression of Nrf2 protein, SOD mRNA and HO-1 mRNA in lung tissue decreased significantly. CONCLUSIONS: Large VT ventilation can cause acute inflammatory injury in lung tissue and lead to the occurrence of VILI. Inflammatory bodies of NLRP3 in alveolar macrophages are involved in this process, and the mechanism of NLRP3 inflammatory bodies is caused by hyperventilation in addition to mechanical injury. Decreased Keap1/Nrf2-ARE pathway inhibition and ROS clearance may also cause macrophage production of NLRP3 inflammatory bodies.

Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer.

Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.