Establishment of potential reference measurement procedure and reference materials for EML4-ALK fusion variants measurement.

Echinoderm microtubule-associated protein 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene detection is of great significance in personalized tumor treatment. With the development of EML4-ALK fusion variants detection, it is necessary to establish traceability to ensure the consistency and comparability of its detection results in clinical practice. The establishment of traceability relies on SI traceable reference materials (RMs) and potential reference measurement procedures (RMPs). In this study, a potential RMP for the quantitative detection of V1 and V3 fusion mutations and the reference type (ALK-ref, including wild type, V1 and V3 mutant type) based on reverse transcription dPCR (RT-dPCR) and EML4-ALK fusion gene RMs were established. The proposed potential RMP has high specificity, good inter-laboratory reproducibility (CV < 7.3%) and good linear relationship (0.92 < slope < 1.06, R2 ≧ 0.99). The limit of detection (LoD) of V1, V3, and ALK-ref are 2 copies/reaction, 2 copies/reaction, and 1 copy/reaction, respectively. Interlaboratory studies using the EML4-ALK RMs and potential RMP showed that participating laboratories can produce consistent copy concentrations of fusion variant and ALK-ref as well as the ratio of EML4-ALK/ALK-ref. The established potential RMP with high specificity and accuracy can be used to characterize the EML4-ALK RMs, and the potential RMP and RM are useful to establish the traceability of EML4-ALK fusion measurement to improve the comparability and consistency in clinical tests.

Establishment of genomic RNA reference materials for BCR-ABL1 P210 measurement.

Quantitation of BCR-ABL1 with the quantitative reverse transcriptase polymerase chain reaction (RT-PCR) is very important in monitoring chronic myeloid leukemia (CML), which relies on an RNA reference material. A genomic RNA reference material (RM) containing the BCR-ABL1 P210 fusion mutation was developed, and an absolute quantitative method based on one-step reverse transcription digital PCR (RT-dPCR) was established for characterizing the RM. The proposed dPCR method demonstrates high accuracy and excellent analytical sensitivity, as shown by the linear relationship (0.94 < slope < 1.04, R2≧0.99) between the measured and nominal values of b2a2, b3a2, and ABL1-ref within the dynamic range (104-101 copies/reaction). Homogeneity and stability assessment based on dPCR indicated that the RM was homogeneous and stable for 24 months at -80 °C. The RM was used to evaluate inter-laboratory reproducibility in eight different laboratories, demonstrating that participating laboratories could consistently produce copy concentrations of b3a2 and ABL1-ref, as well as the BCR-ABL1/ABL1 ratio (CV < 2.0%). This work suggests that the RM can be employed in establishing metrological traceability for detecting mutations in the BCR-ABL1 fusion gene, as well as in quality control for testing laboratories.

Effect of different shock conditions on mesenteric hemodynamics.

BACKGROUND: Reduced effective circulating blood volume and impaired peripheral tissue perfusion play an important role in the pathophysiology of shock. However, there have been no studies examining the relationship between Doppler ultrasound of the superior mesenteric artery (SMA) under different shock conditions. METHODS: We evaluated a total of 85 patients, including 63 patients with different types of shock and 22 in the control group. we included patients who were diagnosed with shock upon admission or developed shock during their hospital stay. At the same time, patients with stable hemodynamics, no use of vasoactive drugs and normal lactate levels were used as a control group. We collected SMA Doppler ultrasound parameters, including Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Resistance Index (RI), pulsatility index (PI), Time-Averaged Mean Velocity (TAMV), and Blood Flow (BF). RESULTS: In the cardiac shock group, SMA PSV, TAMV, and BF were lower compared to the other groups. There was no significant difference in SMA RI and PI between the different types of shock groups, but both were significantly lower than the control group. Cardiac index (CI) is correlated with SMA PSV (r = 0.487, P = 0.000) and TAMV (r = 0.538, P = 0.000), whereas SVRI is not correlated with SMA RI and PI. Lactate levels was correlation with SMA RI (r = -0.307, P = 0.000) and PI (r = -0.287, P = 0.000). The area under the ROC curve of SMA RI and PI to predict hyperlactatemia was 0.85[0.78-0.91] and 0.83[0.76-0.90]. CONCLUSIONS: The velocity parameters of SMA Doppler ultrasound such as TAMV and PSV can reflect cardiac function. The measurements of SMA RI and PI are correlated with lactate levels, having a positive predictive value for hyperlactatemia and provide guidance for fluid resuscitation in patients with shock in the future.

Multifunctional Superamphiphobic Coating Based on Fluorinated TiO2 toward Effective Anti-Corrosion.

The application of superamphiphobic coatings improves the surface's ability to repel fluids, thereby greatly enhancing its various functions, including anti-fouling, anti-corrosion, anti-icing, anti-bacterial, and self-cleaning properties. This maximizes the material's potential for industrial applications. This work utilized the agglomeration phenomenon exhibited by nano-spherical titanium dioxide (TiO2) particles to fabricate 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFDTES) modified TiO2 (TiO2@fluoroPOS) fillers with low surface energy. This was achieved through the in-situ formation of protective armor on the surface of the agglomerates using the sol-gel method and fluorination modification. Polyvinylidene fluoride-tetrafluoropropylene (PVDF-HFP) and TiO2@fluoroPOS fillers were combined using a spraying technique to prepare P/TiO2@fluoroPOS coatings with superamphiphobicity. Relying on the abundance of papillae, micropores, and other tiny spaces on the surface, the coating can capture a stable air film and reject a variety of liquids. When the coatings were immersed in solutions of 2 mol/L HCl, NaCl, and NaOH for a duration of 12 h, they retained their exceptional superamphiphobic properties. Owing to the combined influence of the armor structure and the organic binder, the coating exhibited good liquid repellency during water jetting and sandpaper abrasion tests. Furthermore, the coating has shown exceptional efficacy in terms of its ability to be anti-icing, anti-waxing, and self-cleaning.

The CRISPR-Cas13a Gemini System for noncontiguous target RNA activation.

Simultaneous multi-target detection and multi-site gene editing are two key factors restricting the development of disease diagnostic and treatment technologies. Despite numerous explorations on the source, classification, functional features, crystal structure, applications and engineering of CRISPR-Cas13a, all reports use the contiguous target RNA activation paradigm that only enables single-target detection in vitro and one-site gene editing in vivo. Here we propose a noncontiguous target RNA activation paradigm of Cas13a and establish a CRISPR-Cas13a Gemini System composed of two Cas13a:crRNA binary complexes, which can provide rapid, simultaneous, highly specific and sensitive detection of two RNAs in a single readout, as well as parallel dual transgene knockdown. CRISPR-Cas13a Gemini System are demonstrated in the detection of two miRNAs (miR-155 and miR-375) for breast cancer diagnosis and two small RNAs (EBER-1 and EBER-2) for Epstein-Barr virus diagnosis using multiple diagnostic platforms, including fluorescence and colorimetric-based lateral flow systems. We also show that CRISPR-Cas13a Gemini System can knockdown two foreign genes (EGFP and mCherry transcripts) in mammalian cells simultaneously. These findings suggest the potential of highly effective and simultaneous detection of multiple biomarkers and gene editing of multiple sites.

A dual amplification-based CRISPR/Cas12a biosensor for sensitive detection of miRNA in prostate cancer.

MicroRNA (miRNA) has gained significant attention as a potential biomarker for cancer clinics, and there is an urgent need for developing sensing strategies with high selectivity, sensitivity, and low background. In vitro diagnosis based on Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-Associated protein (CRISPR/Cas) technology could simplify the detection procedure, improve sensitivity and selectivity, and has broad application prospects as the next-generation molecular diagnosis technology. We propose a novel dual signal amplification strategy, called CENTER, which integrates the CRISPR/Cas12a system, an entropy-driven DNA signaling network, and strand displacement amplification to achieve ultrasensitive detection of miR-141, a potential marker for prostate cancer. The experimental results demonstrate that CENTER can distinguish single nucleotide mutations, and the strategy exhibits a good linear calibration curve ranging from 100 aM to 1 pM. Due to dual signal amplification, the detection limit is as low as 34 aM. We proposed a method for identifying miR-141 expressed in human serum and successfully distinguished between prostate cancer patients (n = 20) and healthy individuals (n = 15) with an impressive accuracy of 94%. Overall, CENTER shows great promise for the detection of miRNA.

Effect of TiC Content on Microstructure and Wear Performance of 17-4PH Stainless Steel Composites Manufactured by Indirect Metal 3D Printing.

In order to improve the performance of 17-4PH under wear conditions (e.g., gears, etc.) and reduce the cost of metal additive manufacturing, TiC needs to be added to 17-4PH to improve its wear resistance. Micron-sized TiC-reinforced 17-4PH stainless steel composites with different contents (0-15 wt%) have been prepared by fused filament fabrication 3D printing for the first time. The effects of TiC content on the structure and properties of composites were studied by XRD, SEM, and sliding wear. The obtained results show that the microstructure of TiC-reinforced 17-4PH stainless steel composites mainly consists of austenite. With the increase in TiC content, the grain size is obviously refined, and the average grain size decreases from 65.58 µm to 19.41 µm. The relative densities of the composites are maintained above 95% with the addition of TiC. The interfaces between TiC particles and the 17-4PH matrix are metallurgical bonds. The hardness of the composites increases and then decreases with increasing TiC content, and the maximum hardness (434 HV) is obtained after adding 10 wt.% of TiC content. The wear rate of the composites was reduced from 2.191 × 10-5 mm3 /(N‧m) to 0.509 × 10-5 mm3 /(N‧m), which is a 3.3-fold increase in wear resistance. The COF value declines with the addition of TiC. The reasons for the significant improvement in the composites' performance are fine grain strengthening, solid solution strengthening, and second phase strengthening. The wear mechanisms are mainly abrasive and adhesive wear. Compared to the 10 wt% TiC composites, the 15 wt% TiC composites show limited improvement in wear resistance due to more microcracks and TiC agglomeration.

Characterization of the aerosol vertical distributions and their impacts on warm clouds based on multi-year ARM observations.

Aerosol vertical distribution plays a crucial role in cloud development and thus precipitation since both aerosol indirect and semi-direct effects significantly depend on the relative position of aerosol layer in reference to cloud, but its precise influence on cloud remains unclear. In this study, we integrated multi-year Raman Lidar measurements of aerosol vertical profiles from the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) facility with available Value-Added Products of cloud features to characterize aerosol vertical distributions and their impacts on warm clouds over the continental and marine ARM atmospheric observatories, i.e., Southern Great Plains (SGP) and Eastern North Atlantic (ENA). A unimodal seasonal distribution of aerosol optical depths (AODs) with a peak in summer is found at upper boundary layer over SGP, while a bimodal distribution is observed at ENA for the AODs at lower levels with a major winter-spring maximum. The diurnal mean of upper-level AOD at SGP shows a maximum in the early evening. According to the relative positions of aerosol layers to clouds we further identify three primary types of aerosol vertical distribution, including Random, Decreasing, and Bottom. It is found that the impacts of aerosols on cloud may or may not vary with aerosol vertical distribution depending on environmental conditions, as reflected by the wide variations of the relations between AOD and cloud properties. For example, as AOD increases, the liquid water paths (LWPs) tend to be reduced at SGP but enhanced at ENA. The relations of cloud droplet effective radius with AOD largely depend on aerosol vertical distributions, particularly showing positive values in the Random type under low-LWP condition (<50 g m-2). The distinct features of aerosol-cloud interactions in relation to aerosol vertical distribution are likely attributed to the continental-marine contrast in thermodynamic environments and aerosol conditions between SGP and ENA.

Effect of Deposition Temperature on Long-Term Residual Stress Evolution of Au Films.

To increase the residual stress stability of Au films while reducing the residual stress level, the effect of deposition temperature on long-term residual stress evolution of Au films under different conditions were studied. Au films with a thickness of 360 nm were deposited using e-beam evaporation on fused silica under different temperatures. Observations and comparisons were made of the microstructures of Au films deposited under different temperatures. Results showed that by increasing the deposition temperature, a more compact microstructure of Au film was obtained, which was manifested in increased grain size and reduced grain-boundary voids. After deposition, a combined process consisting of natural placement and 80 °C thermal holding was conducted on the Au films, and the residual stresses were monitored using the curvature-based technique. Results showed that the initial tensile residual stress of the as-deposited film decreased with the deposition temperature. The Au films with higher deposition temperatures showed better residual stress stability, maintaining low stress levels in the subsequent long-term combination of natural placement and thermal holding. The mechanism was discussed based on the differences in microstructure. Comparisons were made between post-deposition annealing and increased deposition temperature.

Artificial ovaries constructed from biodegradable chitin-based hydrogels with the ability to restore ovarian endocrine function and alleviate osteoporosis in ovariectomized mice.

BACKGROUND: Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix. METHODS: In vitro, follicles isolated from 10-12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10-12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination. RESULTS: The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P < 0.05), and the follicle recovery rate was significantly higher in CTP hydrogels (28%) than in ALG hydrogels (17.2%) (P < 0.05). After two weeks of transplantation, OVX mice implanted with CTP grafts exhibited normal steroid hormone levels, which were maintained until week eight. After 10 weeks of transplantation, CTP grafts effectively ameliorated bone loss and atrophy of the reproductive organs, as well as prevented the increase in body weight and rectal temperature in OVX mice, which were superior to those elicited by ALG grafts. CONCLUSIONS: Our study is the first to demonstrate that CTP hydrogels support follicles longer than ALG hydrogels in vitro and in vivo. The results highlight the clinical potential of AO constructed using CTP hydrogels in the treatment of menopausal symptoms.

Synthesis of Monodispersed Hollow Mesoporous Organosilica and Silica Nanoparticles with Controllable Shell Thickness Using Soft and Hard Templates.

Hollow mesoporous nanoparticles with controllable size (less than 100 nm) are desired as drug-delivery carriers. Herein, we report the synthesis of monodispersed hollow mesoporous organosilica (HMOS) and hollow mesoporous silica (HMS) nanoparticles using soft and hard templating methods. HMOS shells, with 1,2-bis(triethoxysilyl)ethane (BTEE) as the precursor and hexadecyltrimethylammonium bromide and sodium dodecyl sulfate (SDS) as the soft templates, were formed on monodispersed silica nanoparticles (SNPs), which were used as the hard templates. HMOS and HMS nanoparticles were obtained by removing the SNPs after three rounds of ammonia dialysis. The hollow size of HMOS can be tuned by changing the size of the SNPs. By using SNPs with a size of 36.5 nm, hollow spaces of approximately 20 nm connected the surface through narrow pores (<5 nm). Mesopores of approximately 12 nm were formed by the surfactant micelles. Additionally, the interparticle space in HMOS and HMS was approximately 12 nm. The shell thicknesses of HMOS and HMS could be tuned in the range of 5-9 nm by changing the BTEE amount. Moreover, the amount of surfactant used varied the porous structure. The HMOS with a thickness of 5 nm exhibited a Brunauer-Emmett-Teller (BET) surface area of 268 m2/g and a total pore volume of 1.14 cm3/g. Meanwhile, HMS demonstrated a BET surface area of 553 m2/g and a total pore volume of 1.82 cm3/g while maintaining a hollow structure. HMOS displayed a high loading capacity for ibuprofen (3009 mg/g), and its drug release system showed a sustained-release property. Therefore, the HMOS preparation using hard and soft templates proposed herein can control the hollow size and shell thickness for drug-delivery applications.

Evaluation of p16/Ki-67 dual-stain as triage test for high-risk HPV-positive women: A hospital-based cross-sectional study.

BACKGROUND: Most human papillomavirus (HPV)-positive women recover from infections and do not develop cervical intraepithelial neoplasia (CIN) and cervical cancer. Additional triage approaches are needed to reduce unnecessary colposcopy referrals. The aim of this study is to determine the high-risk HPV prevalence in a hospital-based population and to evaluate the performance of p16/Ki-67 dual-stain test for the triage of high-risk HPV-positive women to detect precursor lesions and cervical cancer compared with the ThinPrep cytologic test (TCT). METHODS: In a hospital-based population, 100,801 women were provided with a primary HPV DNA test and only women with high-risk HPV infections were triaged using TCT and p16/Ki-67 dual-stain test. CIN2 or worse (≥CIN2) or CIN3 or worse (≥CIN3) were defined as the clinical end points. RESULTS: The p16/Ki-67 dual-stain indicated a statistically significant higher sensitivity (82.8% vs. 66.7%%), specificity (51.6% vs. 44.4%), positive predictive value (33.2% vs. 25.8%), negative predictive value (91.2% vs. 82.1%), and accuracy (58.6% vs. 49.4%) compared with TCT examination within ≥CIN2 cases. Similar patterns were observed for the ≥CIN3 end point. CONCLUSIONS: Our study demonstrated that p16/Ki-67 dual-stain test could achieve better performance compared with TCT examination for ≥CIN2 or ≥ CIN3 detection, representing a promising approach as a specific and efficient triage strategy for high-risk HPV-positive women.

DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome-mediated cell-cell communication.

The involvement of DEAD-box helicase 55 (DDX55) in oncogenesis has been suggested, but its biological role in hepatocellular carcinoma (HCC) remains unknown. The present study verified the upregulation of DDX55 in HCC tissues compared with non-tumor controls. DDX55 displayed the highest prognostic values among the DEAD-box protein family for recurrence-free survival and overall survival of HCC patients. In addition, the effects of DDX55 in the promotion of HCC cell proliferation, migration, and invasion were determined ex vivo and in vivo. Mechanistically, we revealed that DDX55 could interact with BRD4 to form a transcriptional regulatory complex that positively regulated PIK3CA transcription. Following that, ß-catenin signaling was activated in a PI3K/Akt/GSK-3ß dependent manner, thus inducing cell cycle progression and epithelial-mesenchymal transition. Intriguingly, both DDX55 mRNA and protein were identified in the exosomes derived from HCC cells. Exosomal DDX55 was implicated in intercellular communication between HCC cells with high or low DDX55 levels and between HCC cells and endothelial cells, thereby promoting the malignant phenotype of HCC cells and angiogenesis. In conclusion, DDX55 may be a valuable prognostic biomarker and therapeutic target in HCC.

Antifibrotic activities of Scutellariae Radix extracts and flavonoids: Comparative proteomics reveals distinct and shared mechanisms.

BACKGROUND: Scutellariae Radix (SR), the root of Scutellaria baicalensis Georgi, and SR flavonoids have antifibrotic activities. It remains obscure, however, amongst SR aqueous extract (SRA), SR methanolic extract (SRM) and five major SR flavonoids (baicalein, baicalin, wogonoside, wogonin and oroxyloside), which ones are the most promising antifibrotics and what their mechanisms are. PURPOSE: To compare the antifibrotic activities of SR extracts and flavonoids, and the proteomic signatures of selected SR extract and flavonoid, versus IN1130 phosphate, an antifibrotic positive control (abbreviated as IN1130), in TGF-ß1-induced in vitro model of fibrosis in NRK-49F renal fibroblasts. METHODS: Isobaric labelling-based mass spectrometry was used for proteomic studies. Differentially expressed proteins were further analyzed using Gene Ontology annotation enrichment, protein-protein interaction network analysis and pathway analysis. Selected proteins of interest were validated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Baicalein was the SR flavonoid with the best efficacy-toxicity ratio. SRM contained 8-fold more flavonoids and was more potently antifibrotic than SRA. Proteomic analysis of cells treated by TGF-ß1, with or without baicalein (40 and 80 µM), SRM (40 and 80 µg/ml) and IN1130 (1 µM) suggested that baicalein, SRM and IN1130 all repressed TGF-ß1-induced ribosomal proteins in cell lysates, while baicalein and SRM, but not IN1130, regulated the intracellular lysosome pathway; secretomic analysis suggested that 40 and 80 µg/ml SRM and 80 µM baicalein, but not IN1130 and 40 µM baicalein increased ribosomal proteins in conditioned media, whereas only baicalein regulated the lysosome pathway. ELISA verified secretomic findings that baicalein, SRM and IN1130 repressed TGF-ß1-induced PAI-1 (Serpine1), Plod2, Ctgf (Ccn2), Ccl2 and Ccl7; baicalein and IN1130, but not SRM, reversed TGF-ß1-induced Cyr61 (Ccn1) and Tsku; only baicalein reversed TGF-ß1 repression of Mmp3; only IN1130 reversed TGF-ß1-repressed Nov (Ccn3). ELISA validated cell-lysate proteomic findings that baicalein, SRM and IN1130 all reversed TGF-ß1-induced Enpp1; only IN1130 reversed TGF-ß1-induced Impdh2 and Sqstm1 and TGF-ß1-repressed Aldh3a1. Baicalein and SRM induced Ccdc80, while only baicalein induced Tfrc. CONCLUSION: Baicalein, SRM and IN1130 repress TGF-ß1-induced fibrogenesis in renal fibroblasts by regulating overlapping protein targets and biological pathways. Our findings offer a comprehensive view of shared, drug- and dose-specific pharmacological and toxicological mechanisms and provide a valuable resource for further research and development of more efficacious and safer antifibrotics.

Improved urine DNA methylation panel for early bladder cancer detection.

BACKGROUND: Bladder cancer is one of the most common malignancies but the corresponding diagnostic methods are either invasive or limited in specificity and/or sensitivity. This study aimed to develop a urine-based methylation panel for bladder cancer detection by improving published panels and validate performance of the new panel with clinical samples. METHODS: Related researches were reviewed and 19 potential panels were selected. RRBS was performed on a cohort with 45 samples to reassess these panels and a new panel inherited best markers was developed. The new panel was applied with qMSP platform to 33 samples from the RRBS cohort and the results were compared to those of RRBS. Lastly, another larger cohort with 207 samples was used to validate new panel performance with qMSP. RESULTS: Three biomarkers (PCDH17, POU4F2 and PENK) were selected to construct a new panel P3. P3 panel achieved 100% specificity and 71% sensitivity with RRBS in corresponding cohort and then showed a better performance of 100% specificity and 84% sensitivity with qMSP platforms in a balanced cohort. When validated with 207-sample cohort, P3 with qMSP showed a performance of 97% specificity and 87% sensitivity which was modestly improved compared to the panels it derided from. CONCLUSIONS: Overall, the P3 panel achieved relatively high sensitivity and accuracy in bladder cancer detection.

Urinary metabolomics for discovering metabolic biomarkers of bladder cancer by UPLC-MS.

Bladder cancer (BC) is one of the most frequent cancer in the world, and its incidence is rising worldwide, especially in developed countries. Urine metabolomics is a powerful approach to discover potential biomarkers for cancer diagnosis. In this study, we applied an ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) method to profile the metabolites in urine from 29 bladder cancer patients and 15 healthy controls. The differential metabolites were extracted and analyzed by univariate and multivariate analysis methods. Together, 19 metabolites were discovered as differently expressed biomarkers in the two groups, which mainly related to the pathways of phenylacetate metabolism, propanoate metabolism, fatty acid metabolism, pyruvate metabolism, arginine and proline metabolism, glycine and serine metabolism, and bile acid biosynthesis. In addition, a subset of 11 metabolites of those 19 ones were further filtered as potential biomarkers for BC diagnosis by using logistic regression model. The results revealed that the area under the curve (AUC) value, sensitivity and specificity of receiving operator characteristic (ROC) curve were 0.983, 95.3% and 100%, respectively, indicating an excellent discrimination power for BC patients from healthy controls. It was the first time to reveal the potential diagnostic markers of BC by metabolomics, and this will provide a new sight for exploring the biomarkers of the other disease in the future work.

Development and Validation of a Novel Circulating miRNA-Based Diagnostic Score for Early Detection of Hepatocellular Carcinoma.

BACKGROUND: With the rise of liquid biopsy in oncology, circulating miRNAs have become one of the most promising noninvasive biomarkers for early detection of hepatocellular carcinoma (HCC). However, a reliable HCC-related circulating miRNA panel and corresponding diagnostic model remain to be explored. METHODS: Five large public datasets related to intact miRNA profiles in the serum or tumors of HCC patients were included and divided into training cohorts (GSE113740 and TCGA-LIHC) and validation cohorts (GSE112264, GSE113486 and GSE106817). Compared with non-cancer controls and high-risk patients, key miRNAs dysregulated in both the serum and tumors of HCC patients were identified by differential expression analysis and overlapping analysis. The corresponding diagnostic model was constructed by LASSO logistic regression and evaluated by receiver operating characteristic curves and a nomogram with calibration plot. RESULTS: A distinctive panel of HCC-related circulating miRNAs, including three upregulated miRNAs (miR-184, miR-532-5p, miR-221-3p) and three downregulated miRNAs (miR-5589-5p, let-7b-3p, miR-26b-3p), were rigorously screened out, all of which displayed significant discriminability between HCC patients and controls (all P < 0.05). In addition, a reliable six-circulating miRNA-based diagnostic score was constructed and displayed robust diagnostic ability for HCC (particularly for early-stage HCC) (AUC = 0.9535, P < 0.05) compared with that of the serum α-fetoprotein test. Importantly, its efficacy was sufficiently validated in three independent datasets (AUC = 0.9780/0.9961/0.9681, all P < 0.05). Furthermore, a visual nomogram based on the diagnostic score was correspondingly established to strengthen its clinical applicability. CONCLUSION: The six-circulating miRNA-based diagnostic score may be a reliable noninvasive biomarker for early-stage HCC screening and dynamic monitoring of postoperative recurrence.

Friend or Foe? The Roles of Antioxidants in Acute Lung Injury.

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various intra- and extra-pulmonary injury factors. The oxidative stress caused by excessive reactive oxygen species (ROS) produced in the lungs plays an important role in the pathogenesis of ALI. ROS is a "double-edged sword", which is widely involved in signal transduction and the life process of cells at a physiological concentration. However, excessive ROS can cause mitochondrial oxidative stress, leading to the occurrence of various diseases. It is well-known that antioxidants can alleviate ALI by scavenging ROS. Nevertheless, more and more studies found that antioxidants have no significant effect on severe organ injury, and may even aggravate organ injury and reduce the survival rate of patients. Our study introduces the application of antioxidants in ALI, and explore the mechanisms of antioxidants failure in various diseases including it.

Treatment of pulmonary infection of extensively drug-resistant Acinetobacter baumannii with intravenous colistin sulfate combined with atomization: a case report.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) pulmonary infection is a serious respiratory system infection. Patients are often very sick and even need to be admitted to the ICU for treatment. In this case report, we presented our treatment experience of one XDRAB pulmonary infection patient. A 71-year-old male patient was admitted to our hospital complaining of "fatigue accompanied by fever for 2 days and shortness of breath for 1 day". The patient's admission diagnosis was as follows: severe pneumonia, acute respiratory distress syndrome, I type respiratory failure, septic shock, cardiac insufficiency, liver insufficiency, and hypertension. Imipenem/cilastatin sodium combined with moxifloxacin were first applied. Then, tigecycline, imipenem/cilastatin and caspofungin were used. The drug sensitivity results suggested that the XDRAB strain of this patient's sputum culture was sensitive to polymyxin only. Thus, colistin sulfate and cefoperazone/sulbactam were applied. The medication process of the patient was monitored. We found that a colistin sulfate intravenous injection combined with aerosol route combined with cefoperazone/sulbactam was effective in the treatment of XDRAB pulmonary infection, and no adverse drug reactions were observed during the treatment. The anti-infection therapy of intravenous colistin sulfate combined with nebulization and cefoperazone/sulbactam could be a good choice for the treatment of XDRAB lung infections.

Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress.

Perimenopause is an important stage of female senescence. Epidemiological investigation has shown that the incidence of cardiovascular disease in premenopausal women is lower than that in men, and the incidence of cardiovascular disease in postmenopausal women is significantly higher than that in men. This phenomenon reveals that estrogen has a definite protective effect on the cardiovascular system. In the cardiovascular system, oxidative stress is considered important in the pathogenesis of atherosclerosis, myocardial dysfunction, cardiac hypertrophy, heart failure, and myocardial ischemia. From the perspective of oxidative stress, estrogen plays a regulatory role in the cardiovascular system through the estrogen receptor, providing strategies for the treatment of menopausal women with cardiovascular diseases.