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.

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.

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.

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.

Eigenstate Entanglement: Crossover from the Ground State to Volume Laws.

For the typical quantum many-body systems that obey the eigenstate thermalization hypothesis (ETH), we argue that the entanglement entropy of (almost) all energy eigenstates is described by a single crossover function. The ETH implies that the crossover functions can be deduced from subsystem entropies of thermal ensembles and have universal properties. These functions capture the full crossover from the ground-state entanglement regime at low energies and small subsystem size (area or log-area law) to the extensive volume-law regime at high energies or large subsystem size. For critical one-dimensional systems, a universal scaling function follows from conformal field theory and can be adapted for nonlinear dispersions. We use it to also deduce the crossover scaling function for Fermi liquids in d>1 dimensions. The analytical results are complemented by numerics for large noninteracting systems of fermions in d≤3 dimensions and have also been confirmed for bosonic systems and nonintegrable spin chains.

Effects of Percutaneous Neuromuscular Electrical Stimulation for Neck Pain in Patients With Cervical Spondylosis.

CONTEXT: Cervical spondylosis (CS) is a very common, age-related, chronic, disc-degeneration condition. Alternative medicine has been widely used to treat neck pain in CS. However, no randomized controlled trials have focused on the effects and safety of percutaneous neuromuscular electrical stimulation (PNMES) for neck-pain relief in patients with CS. OBJECTIVE: The study aimed to evaluate the effects and safety of PNMES for treating neck pain in patients with cervical spondylosis (CS). DESIGN: The research team designed a two-arm, double-blinded, randomized, sham-controlled trial. SETTING: The study was conducted at the People's Hospital of Yan'an in Yan'an, China. PARTICIPANTS: Participants were 124 patients with neck pain from CS at the hospital. INTERVENTION: Participants were randomly divided into an intervention group and a control group in a ratio of 1:1. The intervention group received PNMES (PNMES group), and the control group received sham PNMES for 30 minutes daily 3 times weekly, for 12 weeks. OUTCOME MEASURES: The outcome measures included: (1) a visual analog scale (VAS), (2) a test of cervical range of motion (ROM), and (3) the neck disability index (NDI) score. All outcome measurements were measured immediately postintervention and in a follow-up at 4 weeks postintervention. In addition, AEs were also recorded duration the period of treatment. RESULTS: Immediately postintervention and at the follow-up, the PNMES group exhibited decreases in the mean VAS (P < .01) and NDI score (P < .01) that were significantly greater than those of the control group. Additionally, the increase in the mean ROM was significantly higher in the PNMES group than that in the control group, both immediately postintervention and at the follow-up (P < .01). No AEs were found in either group. CONCLUSIONS: The results of this study have demonstrated that PNMES is more effective than sham PNMES for neck-pain relief in patients with CS.

Unfavourable treatment outcomes in tuberculosis patients with different vitamin D status and blood glucose levels in a programme setting in China.

OBJECTIVE: Tuberculosis (TB) treatment success rates are high in China, but there are still a considerable number of cases who have unfavourable treatment outcomes (UTO). We aimed to determine the proportion of TB patients with UTO and to assess whether baseline characteristics that included glycaemic status [normal fasting blood glucose (FBG), transient hyperglycaemia and diabetes mellitus (DM)] and vitamin D status were associated with UTO. METHOD: Prospective cohort study conducted between November 2015 and July 2016 at six clinics within routine TB services in Jilin province, where persons with TB were consecutively recruited. Data analysis was performed using the chi-squared test and multivariate logistic regression. RESULTS: Of the 306 recruited TB patients, 96 (31.4%) had smear-positive pulmonary TB, 187 (61.1%) had smear-negative pulmonary TB and 23 (7.5%) had extrapulmonary TB (EPTB). Of these, 95 (31.1%) had normal blood glucose, 83 (27.1%) had transient hyperglycaemia and 128 (41.8%) had DM. 227 (74.2%) patients had vitamin D deficiency/severe deficiency. There were 125 (40.8%) patients with UTO of whom the majority were lost to follow-up (57.6%) or not evaluated (28.8%). UTO was significantly associated with smear-negative pulmonary TB (P = 0.009), EPTB (P < 0.001) and DM (P = 0.007). CONCLUSION: The proportion of TB patients with UTO increased with smear-negative pulmonary TB, EPTB and DM. TB programmes need to pay more attention to these issues and ensure intensive patient support to those at risk and early detection of DM.

OBJECTIF: Les taux de succès du traitement de la tuberculose (TB) sont élevés en Chine, mais il existe encore un nombre considérable de cas avec des résultats de traitement défavorables (RTD). Nous avons cherché à déterminer la proportion de patients TB avec un RTD et d'évaluer si les caractéristiques de base comprenant le statut glycémique [glycémie normale à jeun (GJ), hyperglycémie transitoire et diabète sucré (DS)] et le statut en vitamine D étaient associés à un RTD. MÉTHODE: Etude de cohorte prospective réalisée entre novembre 2015 et juillet 2016 dans six cliniques des services anti-TB de routine de la province de Jilin, où des personnes atteintes de TB ont été recrutées consécutivement. L'analyse des données a été réalisée à l'aide du test du chi carré et de la régression logistique multivariée. RÉSULTATS: Sur 306 patients TB recrutés, 96 (31.4%) avaient une TB pulmonaire à frottis positif, 187 (61.1%) avaient une TB pulmonaire à frottis négatif et 23 (7.5%) avaient une TB extra pulmonaire (TBEP). Parmi ceux-ci, 95 (31.1%) avaient une glycémie normale, 83 (27.1%) avaient une hyperglycémie transitoire et 128 (41.8%) avaient un DS. 227 (74.2%) patients avaient une déficience/déficience sévère en vitamine D. Il y avait 125 (40.8%) patients avec un RTD dont la majorité (57.6%) ont été perdus de vue ou ont été non évalués (28.8%). Le RTD était significativement associé à la TB pulmonaire à frottis négatif (p = 0.009), la TBEP (P < 0.001) et le DS (P = 0.007). CONCLUSION: La proportion de patients TB avec un RTD augmentait avec la TB pulmonaire à frottis négatif, la TBEP et le DS. Les programmes anti-TB devraient accorder plus d'attention à ces problèmes et assurer un soutien intensif au patient pour les personnes à risque et une détection précoce du DS.

The therapeutic potential of bilobalide on experimental autoimmune encephalomyelitis (EAE) mice.

Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.

Hydroxyfasudil alleviates demyelination through the inhibition of MOG antibody and microglia activation in cuprizone mouse model.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system characterized by oligodendrocyte loss and progressive neurodegeneration. The cuprizone (CPZ)-induced demyelination is widely used to investigate the demyelination/remyelination. Here, we explored the therapeutic effects of Hydroxyfasudil (HF), an active metabolite of Fasudil, in CPZ model. HF improved behavioral abnormality and reduced myelin damage in the corpus callosum. Splenic atrophy and myelin oligodendrocyte glycoprotein (MOG) antibody were observed in CPZ model, which were partially restored and obviously inhibited by HF, therefore reducing pathogenic binding of MOG antibody to oligodendrocytes. HF inhibited the percentages of CD4+IL-17+ T cells from splenocytes and infiltration of CD4+ T cells and CD68+ macrophages in the brain. HF also declined microglia-mediated neuroinflammation, and promoted the production of astrocyte-derived brain derived neurotrophic factor (BDNF) and regeneration of NG2+ oligodendrocyte precursor cells. These results provide potent evidence for the therapeutic effects of HF in CPZ-induced demyelination.

Therapeutic effect of oligomeric proanthocyanidin in cuprizone-induced demyelination.

NEW FINDINGS: What is the central question of this study? Oligomeric proanthocyanidin has the capacity to alleviate abnormalities in neurological functioning. However, whether oligomeric proanthocyanidin can reduce the progression of demyelination or promote remyelination in demyelinating diseases remains unknown. What is the main finding and its importance? Oligomeric proanthocyanidin can improve cuprizone-induced demyelination by inhibiting immune cell infiltration, reversing overactivated microglia, decreasing the inflammatory cytokines secreted by inflammatory cells and decreasing the production of myelin oligodendrocyte glycoprotein35-55 -specific antibody in the brain. ABSTRACT: Demyelinating diseases of the CNS, including multiple sclerosis, neuromyelitis optica and acute disseminated encephalomylitis, are characterized by recurrent primary demyelination-remyelination and progressive neurodegeneration. In the present study, we investigated the therapeutic effect of oligomeric proanthocyanidin (OPC), the most effective component of grape seed extract, in cuprizone-fed C57BL/6 mice, a classic demyelination-remyelination model. Our results showed that OPC attenuated abnormal behaviour, reduced demyelination and increased expression of myelin basic protein and expression of O4+ oligodendrocytes in the corpus callosum. Oligomeric proanthocyanidin also reduced the numbers of B and T cells, activated microglia in the corpus callosum and inhibited secretion of inflammatory factors. Furthermore, concentrations of myelin oligodendrocyte glycoprotein-specific antibodies were significantly reduced in serum and brain homogenates after OPC treatment. Together, these results demonstrate a potent therapeutic effect for OPC in cuprizone-mediated demyelination and clearly highlight multiple effects of this natural product in attenuating myelin-specific autoantibodies and the inflammatory microenvironment in the brain.

Diagnosis of acute myocardial infarction in patients with renal insufficiency using high-sensitivity troponin T.

BACKGROUND: The objective of this study was to examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) for acute myocardial infarction (AMI) in patients with renal insufficiency, since this population has a high incidence of non-AMI elevations of hs-cTnT. METHODS: In this prospective study, we enrolled 2249 consecutive patients presenting with chest pain in the emergency department (ED), of whom 19.5% had an estimated glomerular filtration rate (eGFR)cys of <60 mL·min-1 (1.73 m2)-1. Hs-cTnT levels were measured blindly at presentation. RESULTS: Of the patients, 1108 (49.3%) were diagnosed as having AMI [321 with non-ST segment elevation myocardial infarction (NSTEMI)]. In patients whose final diagnosis was not AMI, there was a low but significant correlation between hs-cTnT and renal function [eGFRcys, r=-0.43 (-0.48, -0.38), p<0.001; eGFRcreat, r=-0.33 (-0.38, -0.27), p<0.001]. The area under the curve of the receiver operating characteristic (AUC) for hs-cTnT to diagnose AMI was 0.93 in patients with eGFRcys levels of <30 mL·min-1 (1.73 m2)-1, and AUCs did not vary significantly according to eGFR categories. On the basis of the ROC curve, the optimal threshold value for hs-cTnT was 143.6 ng·L-1 to diagnose AMI in patients with eGFRcys of <30 mL·min-1 (1.73 m2)-1, with a sensitivity of 83% and a specificity of 91%; 54.1 ng·L-1 in patients with eGFRcys between 30 and 59 mL·min-1, with a sensitivity of 90% and a specificity of 87%; 30.0 ng·L-1 in patients with eGFRcys between 60 and 89 mL·min-1, with a sensitivity of 89% and a specificity of 85%; and 20.3 ng·L-1 in patients with eGFRcys ≥90 mL·min-1 (1.73 m2)-1, with a sensitivity of 92% and a specificity of 88%. The same observations were done for the diagnosis of NSTEMI. CONCLUSIONS: Using a higher hs-cTnT cut-off value based on eGFR level is necessary for accurate diagnosis of AMI or NSTEMI in patients with renal insufficiency.

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.

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.

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.

Aptamer-Loop DNA Nanoflower Recognition and Multicolor Fluorescent Carbon Quantum Dots Labeling System for Multitarget Living Cell Imaging.

Visualization of multiple targets in living cells is important for understanding complex biological processes, but it still faces difficulties, such as complex operation, difficulty in multiplexing, and expensive equipment. Here, we developed a nanoplatform integrating a nucleic acid aptamer and DNA nanotechnology for living cell imaging. Aptamer-based recognition probes (RPs) were synthesized through rolling circle amplification, which were further self-assembled into DNA nanoflowers encapsulated by an aptamer loop. The signal probes (SPs) were obtained by conjugation of multicolor emission carbon quantum dots with oligonucleotides complementary to RPs. Through base pairing, RPs and SPs were hybridized to generate aptamer sgc8-, AS1411-, and Apt-based imaging systems. They were used for individual/simultaneous imaging of cellular membrane protein PTK7, nucleolin, and adenosine triphosphate (ATP) molecules. Fluorescence imaging and intensity analysis showed that the living cell imaging system can not only specifically recognize and efficiently bind their respective targets but also provide a 5-10-fold signal amplification. Cell-cycle-dependent distribution of nucleolin and concentration-dependent fluorescence intensity of ATP demonstrated the utility of the system for tracking changes in cellular status. Overall, this system shows the potential to be a simple, low-cost, highly selective, and sensitive living cell imaging platform.

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.

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.

Serum procalcitonin predicts development of acute kidney injury in patients with suspected infection.

BACKGROUND: Procalcitonin (PCT) is an early, sensitive, and accurate marker for diagnosing infection and sepsis. As sepsis and septic shock are dominant causes of acute kidney injury (AKI), we investigated whether PCT is an early predictor of AKI in patients with symptoms of infection. METHODS: Between January 2011 and October 2011, 1361 inpatients in West China Hospital who displayed infection symptoms were enrolled in our study. Levels of PCT, serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC) were determined and participants' renal function was monitored for 3 consecutive days. RESULTS: The rate of AKI occurrence 3 days after enrollment was 14.6%. Higher PCT levels were correlated with higher AKI occurrence rates and higher levels of serum urea, creatinine, and cystatin C (p<0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for PCT was 0.823, making it more predictive (p<0.0001) than SAA, CRP, IL-6, or WBC. The cut-off value of 1.575 ng/mL for PCT had the highest validity for predicting AKI in patients with infection symptoms. The sensitivity, specificity, negative-predictive value (NPV), positive-predictive value (PPV), negative-likelihood ratio (LR-), and positive-likelihood ratio (LR+) for this cut-off value were 61.7%, 84.6%, 93.6%, 37.5%, 0.415, and 4.98, respectively. CONCLUSIONS: PCT can be used as a predictive marker for sepsis-induced acute kidney injury in patients with symptoms of infection.

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.