Contribution of crosstalk of mesothelial and tumoral epithelial cells in pleural metastasis of lung cancer.

Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen (EPGN)-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Conclusions: Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.

CCR2+TREM-1+ monocytes promote natural killer T cell dysfunction contributing towards HBV disease progression.

Natural killer T (NKT) cells are amongst the most important innate immune cells against hepatitis B virus (HBV) infection. Moreover, previous studies have shown that HBV infection induced TREM-1+ expression in monocyte and secretion of inflammatory cytokines. Thus, this prompted us to elucidate the role of TREM-1+ monocytes in regulating the function of iNKT cells. Ninety patients and 20 healthy participants were enrolled in the study. The percentage and phenotype of iNKT cells and TREM-1+ monocytes were measured in the peripheral blood of healthy controls (HC), patients with chronic HBV infection (CHB), HBV-related liver cirrhosis (LC), and HBV-related acute-on-chronic liver failure (ACLF) via flow cytometry. Moreover, co-culture experiments with iNKT cells and TREM-1 overexpressing THP-1 cells were performed to determine the role of TREM-1 in the regulation of NKT cell function. We observed that the percentage of iNKT cells and CD4-iNKT cells gradually decreased, whereas the percentage of CCR2+TREM-1+ monocytes increased with the progression of the disease. In addition, activation of the TREM-1 signaling pathway induced the secretion of inflammatory cytokines leading to pyroptosis of iNKT cells and secretion of IL-17 contributing towards disease progression. Therefore, this study suggests that blocking the activation of TREM-1 in monocytes could promote the elimination of HBV by inhibiting pyroptosis of iNKT cells and restoring their function. However, further studies are required to validate these results that would help in developing new treatment strategies for patients with HBV infections.

A preliminary study on the reference intervals of serum tumor marker in apparently healthy elderly population in southwestern China using real-world data.

BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. CONCLUSION: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Freeze-Thaw Damage Characteristics of Concrete Based on Compressive Mechanical Properties and Acoustic Parameters.

Concrete is a versatile material widely used in modern construction. However, concrete is also subject to freeze-thaw damage, which can significantly reduce its mechanical properties and lead to premature failure. Therefore, the objective of this study was to assess the laboratory performance and freeze-thaw damage characteristics of a common mix proportion of concrete based on compressive mechanical tests and acoustic technologies. Freeze-thaw damage characteristics of the concrete were evaluated via compressive mechanical testing, mass loss analysis, and ultrasonic pulse velocity testing. Acoustic emission (AE) technology was utilized to assess the damage development status of the concrete. The outcomes indicated that the relationships between cumulative mass loss, compressive strength, and ultrasonic wave velocity and freeze-thaw cycles during the freezing-thawing process follow a parabola fitting pattern. As the freeze-thaw damage degree increased, the surface presented a trend of "smooth intact surface" to "surface with dense pores" to "cement mortar peeling" to "coarse aggregates exposed on a large area". Therefore, there was a rapid decrease in the mass loss after a certain number of freeze-thaw cycles. According to the three stages divided by the stress-AE parameter curve, the linear growth stage shortens, the damage accumulation stage increases, and the failure stage appears earlier with the increase in freeze-thaw cycles. In conclusion, the application of a comprehensive understanding of freeze-thaw damage characteristics of concrete based on compressive properties and acoustic parameters would enhance the evaluation of the performance degradation and damage status for concrete structures.

The complete chloroplast genome sequence of Thladiantha nudiflora Hemsl. ex F.B.Forbes & Hemsl. 1887 (Cucurbitaceae).

Thladiantha nudiflora Hemsl. ex F.B.Forbes & Hemsl. 1887 (Cucurbitaceae) has been widely known as a traditional medicine plant. In this study, we sequenced, assembled, and annotated the complete chloroplast genome of T. nudiflora. The chloroplast genome of T. nudiflora is 156,824 base pair (bp) in length, containing a large single-copy region of 86,566 bp and a small single-copy region of 18,070 bp, separated by a pair of inverted repeats of 26,094 bp. The chloroplast genome contains 132 genes, including 87 protein-coding, 37 transfer RNA, and eight ribosomal RNA genes. Phylogenetic analysis of the chloroplast genome revealed that species of the genus Thladiantha were clustered together in the phylogenetic trees. This study will not only shed light on T. nudiflora's evolutionary position but also provide valuable chloroplast genomic information for future studies into the origins and diversification of the genus Thladiantha and the Cucurbitaceae family.

Expression mapping of GREM1 and functional contribution of its secreting cells in the brain using transgenic mouse models.

GREMLIN1 (GREM1) is a secreted protein that antagonizes bone morphogenetic proteins (BMPs). While abnormal GREM1 expression has been reported to cause behavioral defects in postpartum mice, the spatial and cellular distribution of GREM1 in the brain and the influence of the GREM1-secreting cells on brain function and behavior remain unclear. To address this, we designed a genetic cassette incorporating a 3×Flag-TeV-HA-T2A-tdTomato sequence, resulting in the creation of a novel Grem1Tag mouse model, expressing an epitope tag (3×Flag-TeV-HA-T2A) followed by a fluorescent reporter (tdTomato) under the control of the endogenous Grem1 promoter. This design facilitated precise tracking of the cell origin and distribution of GREM1 in the brain using tdTomato and Flag (or HA) markers, respectively. We confirmed that the Grem1Tag mouse exhibited normal motor, cognitive, and social behaviors at postnatal 60 days (P60), compared with C57BL/6J controls. Through immunofluorescence staining, we comprehensively mapped the distribution of GREM1-secreting cells across the central nervous system. Pervasive GREM1 expression was observed in the cerebral cortex (Cx), medulla, pons, and cerebellum, with the highest levels in the Cx region. Notably, within the Cx, GREM1 was predominantly secreted by excitatory neurons, particularly those expressing calcium/calmodulin-dependent protein kinase II alpha (Camk2a), while inhibitory neurons (parvalbumin-positive, PV+) and glial cells (oligodendrocytes, astrocytes, and microglia) showed little or no GREM1 expression. To delineate the functional significance of GREM1-secreting cells, a selective ablation at P42 using a diphtheria toxin A (DTA) system resulted in increased anxiety-like behavior and impaired memory in mice. Altogether, our study harnessing the Grem1Tag mouse model reveals the spatial and cellular localization of GREM1 in the mouse brain, shedding light on the involvement of GREM1-secreting cells in modulating brain function and behavior. Our Grem1Tag mouse serves as a valuable tool for further exploring the precise role of GREM1 in brain development and disease.

Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma.

OBJECTIVE: To investigate the relationship between pro-gastrin-releasing peptide (ProGRP) and the clinical characteristics of patients with medullary thyroid carcinoma (MTC) and the value of ProGRP in surgical treatment monitoring. PATIENTS AND METHODS: A total of 347 patients with MTC and non-MTC malignant and benign thyroid diseases were enrolled. The concentrations of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), calcitonin (CT), and ProGRP were determined by Elecsys® assays. The NSE, CEA, CT, and ProGRP levels in different thyroid disease groups were compared, and ProGRP levels in different clinicopathological feature groups pre and postoperatively were further compared. RESULTS: The CT, CEA, NSE, and ProGRP levels were upregulated in the MTC group compared to those in the non-MTC malignant and benign thyroid disease groups. The area under the receiver operating characteristic curve (AUC) of ProGRP for the diagnosis of MTC was 0.832(0.787-0.871), similar to that of CT and CEA. The sensitivity and specificity were 71.4% and 92.7%, respectively, and the optimal cut-off value was 61.8 pg/mL. The AUC of ProGRP combined with CT or CEA for the diagnosis of MTC was 0.933 (0.900-0.958) and 0.922 (0.886-0.949), respectively, which were higher than those of a single index. ProGRP levels were higher in patients with lymph nodes and distant metastases than in patients without metastases. The postoperative level of ProGRP was lower than that before treatment. CONCLUSION: ProGRP is comparable to CEA and CT as an MTC biomarker with broad prospects. It has potential application value in the progression of MTC assessment and the evaluation of surgical intervention effects.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells.

OBJECTIVE: To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action. METHODS: This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 ß (IL-1 ß), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively. RESULTS: GSE reduced the secretion of TNF-α, IL-1 ß and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 ß, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05). CONCLUSION: GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Conditional empirical wavelet transform with modified ratio of cyclic content for bearing fault diagnosis.

Empirical wavelet transform (EWT) is usually employed to segment Fourier spectrum for fault diagnosis. However, the original empirical segmentation approach may be easily affected by noise. In this paper, several conditions and a modified ratio of cyclic content are then proposed to help establish proper spectrum segments and to improve fault diagnosis. The proposed conditions include a pre-whitening process to reduce discrete frequency noise, a threshold to avoid white frequency noise, an additional boundary for the last considered maximum, distance requirement for consecutive local maxima, as well as one iteration of finding local extremums. Finally, the proposed method is compared with EWT and fast kurtogram methods in three case studies. The results indicate that the proposed method can provide more favorable diagnosis results.

Changes in lung cancer-related serum tumor markers in patients with chronic kidney disease and determination of upper reference limit.

Aims: To investigate the changes in lung cancer-related serum tumor markers in patients with chronic kidney disease (CKD) and determine the upper reference limit for patients with different stages. Methods: Included inpatients diagnosed with CKD who did not receive dialysis temporarily in our hospital from March to September 2020. Changes in serum CA125, HE4, CYFRA21-1, SCCA, NSE and ProGRP in CKD patients were analyzed. The non-parametric method was used to estimate the upper reference limit of the above indicators in patients with CKD stages 2-5. Results: The serum levels of HE4, CYFRA21-1, SCCA, and ProGRP in the CKD group were significantly higher than those in the healthy control group; CA125 and NSE levels were not statistically different. The false positives of SCC, CYFRA21-1, ProGRP, and HE4 increased significantly with the CKD stage. Still, NSE and CA125 did not show a significant increasing trend. Both HE4 and ProGRP have independent upper reference limits from CKD2 to CKD5 stage, namely 220.8 pmol/l and 101.4 pg/ml in the CKD2 stage, 496.7 pmol/l and 168.63 pg/ml in CKD3 stage, 4592.4 pmol/l and 272.8 pmol/l for CKD4 stage, CKD5 stage was 4778.2 pmol/l and 491.6 pmol/l. Conclusion: This study preliminarily determined the upper reference limits of Lung cancer-related tumor markers in patients with different CKD stages and provided laboratory support for the rational use and interpretation of Lung cancer-related tumor markers in special populations.

Targeting the differentiation of astrocytes by Bilobalide in the treatment of Parkinson's disease model.

Background: The etiology of Parkinson's disease (PD), a chronic and progressive neurodegenerative disease, is multifactorial but not fully unknown. Until now, no drug has been proven to have neuroprotective or neuroregenerative effects in patients with PD.Objectives: To observe the therapeutic potential of Bilobalide (BB), a constituent of ginkgo biloba, in MPTP-induced PD model, and explore its possible mechanisms of action.Material and Methods: Mice were randomly divided into three groups: healthy group, MPTP group and MPTP + BB group. PD-related phenotypes were induced by intraperitoneal injection of MPTP into male C57BL/6 mice, and BB (40 mg/kg/day) was intraperitoneally given for 7 consecutive days at the end of modeling. The injection of saline was set up as the control in a similar manner.Results: BB induced M2 polarization of microglia, accompanied by inhibition of neuroinflammation in the brain. Simultaneously, BB promoted the expression of BDNF in astrocytes and neurons, and expression of GDNF in neurons. Most interestingly, BB enhanced the formation of GFAP+ astrocytes expressing nestin, Brn2 and Ki67, as well as the transformation of GFAP+ astrocytes expressing tyrosine hydroxylase around subventricular zone, providing experimental evidence that BB could promote the conversion of astrocytes into TH+ dopamine neurons in vivo and in vitro.Conclusions: These results suggest the natural product BB may utilize multiple pathways to modify degenerative process of TH+ neurons, revealing an exciting opportunity for novel neuroprotective therapeutics. However, its multi-target and important mechanisms need to be further explored.

Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population.

Background: The aesthetic facial traits are closely related to life quality and strongly influenced by genetic factors, but the genetic predispositions in the Chinese population remain poorly understood. Methods: A genome-wide association studies (GWAS) and subsequent validations were performed in 26,806 Chinese on five facial traits: widow's peak, unibrow, double eyelid, earlobe attachment, and freckles. Functional annotation was performed based on the expression quantitative trait loci (eQTL) variants, genome-wide polygenic scores (GPSs) were developed to represent the combined polygenic effects, and single nucleotide polymorphism (SNP) heritability was presented to evaluate the contributions of the variants. Results: In total, 21 genetic associations were identified, of which ten were novel: GMDS-AS1 (rs4959669, p = 1.29 × 10-49) and SPRED2 (rs13423753, p = 2.99 × 10-14) for widow's peak, a previously unreported trait; FARSB (rs36015125, p = 1.96 × 10-21) for unibrow; KIF26B (rs7549180, p = 2.41 × 10-15), CASC2 (rs79852633, p = 4.78 × 10-11), RPGRIP1L (rs6499632, p = 9.15 × 10-11), and PAX1 (rs147581439, p = 3.07 × 10-8) for double eyelid; ZFHX3 (rs74030209, p = 9.77 × 10-14) and LINC01107 (rs10211400, p = 6.25 × 10-10) for earlobe attachment; and SPATA33 (rs35415928, p = 1.08 × 10-8) for freckles. Functionally, seven identified SNPs tag the missense variants and six may function as eQTLs. The combined polygenic effect of the associations was represented by GPSs and contributions of the variants were evaluated using SNP heritability. Conclusion: These identifications may facilitate a better understanding of the genetic basis of features in the Chinese population and hopefully inspire further genetic research on facial development.

A Pilot Assessment on the Role of Procalcitonin Dynamic Monitoring in the Early Diagnosis of Infection Post Cardiac Surgery.

Purpose: To evaluate the value of dynamic monitoring of procalcitonin (PCT) as a biomarker for the early diagnosis of postoperative infections in patients undergoing cardiac surgery. Methods: In total, 252 patients who underwent cardiac surgery were retrospectively included. The postoperative patients' PCT level, change value (△PCT), and clearance rate (△PCTc) were compared between the infected and noninfected groups in adult and pediatric patients on postoperative days (PODs) 1, 3, and 5. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic value. Results: Procalcitonin concentration decreased progressively in the noninfected group in adult and pediatric patients; PCT concentration continued to rise until it peaked on POD 3 in the infected group. In adult patients, the AUC of PCT for diagnosis of infection on PODs 1, 3, and 5 were 0.626, 0.817, and 0.806, with the optimal cut-off values of 7.35, 3.63, and 1.73 ng/ml, respectively. The diagnostic efficiency of △PCT3 and △PCT C3 was significantly better than △PCT5 and △PCT C5 , respectively. In pediatric patients, the AUC of PCT for diagnosis of infection on PODs 1, 3, and 5 were 0.677, 0.747, and 0.756, respectively, and the optimal cut-off values were 27.62, 26.15, and 10.20 ng/ml. Conclusion: This study showed that dynamic monitoring of PCT levels could be an effective clinical means to help to discover postoperative infection earlier. The PCT level and its change indicators on POD 3 in adult patients and the PCT level on POD 5 in children can indicate infection.

Tunable microwave-optical entanglement and conversion in multimode electro-opto-mechanics.

We study tunable double-channel microwave-optical (M-O) entanglement and coherent conversion by controlling the quantum interference effect. This is realized in a two-mechanical-mode electro-opto-mechanical (EOM) system, in which two mechanical resonators (MRs) are coupled with each other by phase-dependent phonon-phonon interaction, and link the interaction between the microwave and optical cavity. It's demonstrated that the mechanical coupling between two MRs leads to the interference of two pathways of electro-opto-mechanical interaction, which can generate the tunable double-channel phenomena in comparison with a typical three-mode EOM system. In particular, by tuning of phonon-phonon interaction and couplings between cavities with MRs, we can not only steer the switch from the M-O interaction with a single channel to that of the double-channel, but also modulate the entanglement and conversion characteristics in each channel. Moreover, our scheme can be extended to an N-mechanical-mode EOM system, in which N discrete channels will be observed and controlled. This study opens up prospects for quantum information transduction and storage with a wide bandwidth and multichannel quantum interface.

The neuroprotective effects and transdifferentiation of astrocytes into dopaminergic neurons of Ginkgolide K on Parkinson' disease mice.

Parkinson's disease (PD) is a chronic and progressive movement disorder caused by the selective loss of midbrain dopaminergic neurons of unknown etiology. Up to now, although there is a great development on treatments of PD, cures with neuroprotective or nerve regenerative effects are underway for PD patients. Here we reported neuroprotective effects of Ginkgolide K (GK) when mice were upon acute MPTP exposure, in which GK ameliorated the gait dysfunction and dopaminergic neuron loss. GK exhibits its ability in immunomodulation, including switching microglia to M2 phenotype and decreasing the microglia-mediated inflammation, inhibiting peripheral CD4+IFN-γ+ and CD4+IL-17+ T cells and α-synuclein specific autoantibodies. The expression of neurotrophic factors BDNF, GDNF and NT-3 was promoted with a treatment of GK in MPTP mice brains. Notably, GK enhanced the expression of nestin in GFAP+ astrocytes followed by the transdifferentiation of astrocyte-to-neuron independent on the Wnt signaling although GK induced the expression of Wnt signaling on astrocytes. Based on these results, our work implicates a therapeutic potential of GK for protecting TH+ neurons by multiple and intercellular pathways to modify nerve regeneration in MPTP mice. However, its exactly cellular and molecular mechanisms need to be further explored and confirmed.

Sparsity-Constrained Invariant Risk Minimization for Domain Generalization With Application to Machinery Fault Diagnosis Modeling.

Machine learning has been widely applied to study AI-informed machinery fault diagnosis. This work proposes a sparsity-constrained invariant risk minimization (SCIRM) framework, which develops machine-learning models with better generalization capacities for environmental disturbances in machinery fault diagnosis. The SCIRM is built by innovating the optimization formulation of the recently proposed invariant risk minimization (IRM) and its variants through the integration of sparsity constraints. We prove that if a sparsity measure is differentiable, scale invariant, and semistrictly quasi-convex, the SCIRM can be guaranteed to solve the domain generalization problem based on a few predefined problem settings. We mathematically derive a family of such sparsity measures. A practical process of implementing the SCIRM for machinery fault diagnosis tasks is offered. We first verify our theoretical exploration of the SCIRM by using simulation data. We further compare SCIRM with a set of state-of-the-art methods by using real machinery fault data collected under a variety of working conditions. The computational results confirm that the machinery fault diagnosis model developed by the SCIRM offers a higher generalization capacity and performs better than the other benchmarks across the different testing datasets.

Identification of a Novel 4-gene Diagnostic Model for Atrial Fibrillation Risk Based on Integrated Analysis Across Independent Data Sets.

BACKGROUND: Atrial fibrillation (AF) is the most common persistent arrhythmia and an important factor leading to cardiovascular morbidity and mortality. Several key genes and diagnostic markers have been discovered with the development of advanced modern molecular biology techniques, but the etiology and pathogenesis of AF remained unknown. METHODS: In this study, three-chip-seq data sets and an RNA-seq data set were integrated as a comprehensive network for pathway analysis of the biological functions of related genes in AF, hoping to provide a better understanding of the etiology and pathogenesis of AF. RESULTS: Differential co-expression analysis identified 360 genes with specific expression in AF, and functional enrichment analysis further revealed that these genes were significantly correlated with focal expression (p <0.01), autophagy (p <0.01), and thyroid cancer. In addition, Af-specific proteinprotein interaction (PPI) networks were constructed based on AF-specific expression genes. Network topology analysis identified PLEKHA7, YWHAQ, PPP1CB, WDR1, AKT1, IGF1R, CANX, MAPK1, SRPK2 and SRSF10 genes as hub genes of the networks, and they were considered as potential biomarkers of AF because they were found to participate in the development of AF through Oocyte meiosis and focal expression. Finally, a diagnostic model for AF established with a support vector machine (SVM) demonstrated excellent predictive performance in internal and external data sets (AUC>0.9) and different platform data sets (mean AUC>0.75). CONCLUSION: Finally, a diagnostic model for AF was established, thus showing its potential in the early identification and prediction of AF.

Clinical application of free/total PSA ratio in the diagnosis of prostate cancer in men over 50 years of age with total PSA levels of 2.0-25.0 ng ml-1 in Western China.

The goal of this study was to investigate the clinical application of free/total prostate-specific antigen (F/T PSA) ratio, considering the new broad serum total PSA (T-PSA) "gray zone" of 2.0-25.0 ng ml-1 in differential diagnosis of prostate cancer (PCa) and benign prostate diseases (BPD) in men over 50 years in Western China. A total of 1655 patients were included, 528 with PCa and 1127 with BPD. Serum T-PSA, free PSA (F-PSA), and F/T PSA ratio were analyzed. Receiver operating characteristic curves were used to assess the efficiency of PSA and F/T PSA ratio. There were 47.4% of cancer patients with T-PSA of 2.0-25.0 ng ml-1. When T-PSA was 2.0-4.0 ng ml-1, 4.0-10.0 ng ml-1, and 10.0-25.0 ng ml-1, the area under the curve (AUC) of F/T PSA ratio was 0.749, 0.769, and 0.761, respectively. The best AUC of F/T PSA ratio was 0.811 when T-PSA was 2.0-25.0 ng ml-1, with a specificity of 0.732, a sensitivity of 0.788, and an optimal cutoff value of 15.5%. The AUC of F/T PSA ratio in different age groups (50-59 years, 60-69 years, 70-79 years, and ≥80 years) was 0.767, 0.806, 0.815, and 0.833, respectively, and the best sensitivity (0.857) and specificity (0.802) were observed in patients over 80 years. The T-PSA trend was in accordance with the Gleason score, tumor node metastasis (TNM) stage, and American Joint Committee on Cancer prognosis group. Therefore, the F/T PSA ratio can facilitate the differential diagnosis of PCa and BPD in the broad T-PSA "gray zone". Serum T-PSA can be a Gleason score and prognostic indicator.

Reference ranges of T lymphocyte subsets by single-platform among healthy population in southwest China.

BACKGROUND: Appropriate reference ranges of T lymphocyte subsets are essential for immune status evaluation of patients with immunological diseases. We aim to establish the age- and sex-related reference intervals of T lymphocyte subsets by single-platform for the southwest China population using the indirect method with the data resulting from 53,822 cases of periodic health examination individuals in the Laboratory Information System (LIS) of West China Hospital from 2018 to 2020. METHODS: We used the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate the outliers, and the nonparametric method to estimate the 95% distribution reference intervals. RESULTS: We initially established the reference ranges of T lymphocyte subsets by single-platform among healthy population in southwest China by indirect method (See text for details). Using the standard normal deviate test (z-test) suggested by Harris and Boyd according to CLSI EP28-A3C, which is more scientific, we found the reference ranges of T lymphocyte subsets should be differentiated by ages and genders since the reference ranges of T lymphocyte subsets by single-platform in different ages and genders are significantly different. CONCLUSIONS: We further demonstrated the absolute count of CD3 + T cell, CD3 + CD4 + T cell, CD3 + CD8 + T cell decreased with aging, which is more marked in men and CD3 + CD8 + T cell count, and the obtained reference intervals were superior to the reference intervals derived from the reagent specification currently in use.

Antibacterial Peptide HHC-36 Sustained-Release Coating Promotes Antibacterial Property of Percutaneous Implant.

Percutaneous implants are widely used in clinical practice. However, infection is the main clinical problem of percutaneous implants. Titanium dioxide nanotubes are suitable for forming coatings on complex surfaces such as implants. HHC-36, a cationic antimicrobial peptide, has been identified to have a strong broad-spectrum antibacterial effect. In the present study, we use poly D,L-lactic acid (PDLLA) and poly lactic-co-glycolic acid (PLGA) coating to build HHC-36 sustained-release system on the surface of titanium dioxide nanotubes. The titanium specimens were anodized coated with HHC-36-PDLLA/PLGA. The morphology and surface elemental distribution of the specimens were evaluated. Besides, results in the present study demonstrated that with antibacterial peptide HHC-36 sustained-release coating, titanium dioxide nanotubes maintain effective drug release for 15 days in vitro, and show significant antibacterial activity. The proliferation of Staphylococcus aureus can be effectively inhibited by PDLLA/PLGA-HHC-36 coated titanium dioxide nanotube. In addition, PDLLA-HHC-36 and PLGA-HHC-36 coating was demonstrated to be biocompatible and antibacterial in vivo. These findings demonstrated that HHC-36 coated titanium nanotube could improve antibacterial potential of percutaneous implants, and indicated a novel and efficient strategy in preventing bacterial infection of percutaneous implants.