Endoplasmic reticulum stress-related genes as prognostic and immunogenic biomarkers in prostate cancer.

BACKGROUND: The metastasis and aggressive nature of prostate cancer (PCa) has become a major malignancy related threat that concerns men's health. The efficacy of immune monotherapy against PCa is questionable due to its lymphocyte-suppressive nature. METHOD: Endoplasmic reticulum stress- (ERS-) and PCa-prognosis-related genes were obtained from the Molecular Signatures Database and the Cancer Genome Atlas database. The expression, prognosis and immune infiltration values of key genes were explored by "survival R package", "rms", "xCELL algorithm", and univariate-multivariate Cox and LASSO regression analyses. The "consensus cluster plus R package" was used for cluster analysis. RESULT: As ERS-related genes, ERLIN2 and CDK5RAP3 showed significant expressional, prognostic and clinic-pathologic values. They were defined as the key genes significantly correlated with immune infiltration and response. The nomogram was constructed with T-stage and primary treatment outcome, and the risk-prognostic model was constructed in the following way: Riskscore = (- 0.1918) * ERLIN2 + (0.5254) * CDK5RAP3. Subsequently, prognostic subgroups based on key genes classified the high-risk group as a pro-cancer subgroup that had lower mutation rates of critical genes (SPOP and MUC16), multiple low-expression immune-relevant molecules, and differences in macrophages (M1 and M2) expressions. Finally, ERLIN2 as an anti-oncogene and CDK5RAP3 as a pro-oncogene were further confirmed by cell phenotype assays and immunohistochemistry. CONCLUSION: We identified ERLIN2 and CDK5RAP3 as ERS-related genes with important prognostic and immunologic values, and classified patients between high- and low-risk subgroups, which provided new prognostic markers, immunotherapeutic targets, and basis for prognostic assessments.

Derivation and Validation of a Risk Score for Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BACKGROUND: Compared with methicillin sensitive Staphylococcus aureus (MSSA), the prognosis of patients with methicillin resistant Staphylococcus aureus (MRSA) bloodstream infection is poor. Therefore, the construction of MRSA and MSSA identification model has certain value for the selection of antibiotics and treatment outcome control. This study aimed to derive and validate a simple risk prediction model for MRSA bloodstream infection in Chinese patients. METHODS: Three hundred and thirty-five patients with Staphylococcus aureus (S. aureus) bloodstream infection were retrospectively analyzed and divided into three groups. The first group was used for the risk score derivation (n = 163), the second group was used for internal validation (n = 80), and the third group was used for external validation (n = 92). According to the odds ratio (OR) obtained from multivariate logistic regression, the risk prediction model for MRSA bloodstream infection was established, and the prediction efficiency of the model in three cohorts were evaluated. RESULTS: Hospital stay before BSI ≥ 7 days, hospital acquired BSI, infection source ≥ 2 sites, indwelling gastric tube before BSI and carbapenems used before BSI and after admission were independent influencing factors of MRSA in the derivation group, the above influencing factors were scored 3, 5, 4, 3, and 3, respectively. The derivation, internal and external validation groups showed adequate discrimination (the AUCs were 0.788, 0.780, and 0.742, respectively) and good calibration (H-L tests were χ2 = 3.896, p = 0.306; χ2 = 4.221, p = 0.298; and χ2 = 3.974, p = 0.352, respectively). The risk scores were further divided into very low-risk (score 0 - 3), low-risk (score 4 - 7), high-risk (score 8 - 12), and very high-risk (score ≥ 13) layers. CONCLUSIONS: The simple risk score model for predicting MRSA bloodstream infection has good predictive effect, high predictive accuracy, and good clinical applicability, which can help clinicians choose sensitive antibiotics and reduce the adverse prognosis of patients.

YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6.

BACKGROUND: Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines. METHODS: Tissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid-liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment. RESULTS: YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors. CONCLUSIONS: Phase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer-promoter interactions, thereby increasing PCa progression.

2D SiP2/h-BN for a Gate-Controlled Phototransistor with Ultrahigh Sensitivity.

Two-dimensional (2D) materials are extremely attractive for the construction of highly sensitive photodetectors due to their unique electronic and optical properties. However, developing 2D photodetectors with ultrahigh sensitivity for extremely low-light-level detection is still a challenge owing to the limitation of high dark current and low detectivity. Herein, a gate-controlled phototransistor based on 2D SiP2/hexagonal boron nitride (h-BN) was rationally designed and demonstrated ultrahigh sensitivity for the first time. With a back-gate device geometry, the SiP2/h-BN phototransistor exhibits an ultrahigh detectivity of 3.4 × 1013 Jones, which is one of the highest values among 2D material-based photodetectors. In addition, the phototransistor also shows a gate tunable responsivity of ≤43.5 A/W at a gate voltage of 30 V due to the photogating effect. The ultrahigh sensitivity of the SiP2-based phototransistor is attributed to the extremely low dark current suppressed by the phototransistor configuration and the improved photocurrent by using h-BN as a substrate to reduce charge scattering. This work provides a facile strategy for improving the detectivity of photodetectors and validates the great potential of 2D SiP2 phototransistors for ultrasensitive optoelectronic applications.

Identification and validation of RB1 as an immune-related prognostic signature based on tumor mutation burdens in bladder cancer.

Bladder cancer (BCa) is one of the most common malignant tumors in the urinary system. Developing effective prognostic gene and exploring the immune cells that affect the prognosis of tumor are required. Full transcriptome data ( n = 433), clinical information ( n = 581) and mutation sequencing ( n = 412) were obtained from The Cancer Genome Atlas and independent mutation sequencing data of 101 samples were acquired from International Cancer Genome Consortium. Statistical processing was conducted using R packages. Gene biologically functional research was performed with gene set enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes database. Twenty-two types of immune cell infiltration were assessed and calculated in 398 samples of BCa. Furthermore, the expression of immune-related prognostic signature was verified. The relationship between prognostic gene and immune cells was explored preliminarily. Tumor mutation burdens of mutant-type groups were higher than wild-type groups of 19 genes, except for FGFR3 and CREBBP. Kaplan-Meier analysis showed that high frequency of retinoblastomal 1 (RB1) mutation led to poor prognosis of BCa patients and was an independent prognostic factor ( P = 0.004; HR = 1.776). Proportions and correlation of 22 types of immune cells in 433 samples were determined. We found that RB1 expression decreased in BCa validated through quantitative PCR and immunohistochemistry. In addition, regulatory T cells (Tregs) were detected as a negatively correlated type of immune cell to mutation of RB1, whereas fluorescence costaining showed that Foxp3 expression of Tregs infiltration was negatively related to the expression of RB1. Mutation of RB1 can be identified as an independent prognostic predictor of BCa, and it may suppress the infiltration of Tregs in BCa tissues, increasing the incidence of tumor immune escape.

Development of genomic instability-associated long non-coding RNA signature: A prognostic risk model of clear cell renal cell carcinoma.

Purpose: Renal clear cell carcinoma (ccRCC) is the most lethal of all pathological subtypes of renal cell carcinoma (RCC). Genomic instability was recently reported to be related to the occurrence and development of kidney cancer. The biological roles of long non-coding RNAs (lncRNAs) in tumorigenesis have been increasingly valued, and various lncRNAs were found to be oncogenes or cancer suppressors. Herein, we identified a novel genomic instability-associated lncRNA (GILncs) model for ccRCC patients to predict the overall survival (OS). Methods: The Cancer Genome Atlas (TCGA) database was utilized to obtain full transcriptome data, somatic mutation profiles, and clinical characteristics. The differentially expressed lncRNAs between the genome-unstable-like group (GU) and the genome-stable-like group (GS) were defined as GILncs, with |logFC| > 1 and an adjusted p-value< 0.05 for a false discovery rate. All samples were allocated into GU-like or GS-like types based on the expression of GILncs observed using hierarchical cluster analyses. A genomic instability-associated lncRNA signature (GILncSig) was constructed using parameters of the included lncRNAs. Quantitative real-time PCR analysis was used to detect the in vitro expression of the included lncRNAs. Validation of the risk model was performed by the log-rank test, time-dependent receiver operating characteristic (ROC) curves analysis, and multivariate Cox regression analysis. Results: Forty-six lncRNAs were identified as GILncs. LINC00460, AL139351.1, and AC156455.1 were employed for GILncSig calculation based on the results of Cox analysis. GILncSig was confirmed as an independent predictor for OS of ccRCC patients. Additionally, it presented a higher efficiency and accuracy than other RCC prognostic models reported before. Conclusion: GILncSig score was qualified as a critical indicator, independent of other clinical factors, for prognostic prediction of ccRCC patients.

Current status and perspectives of non-coding RNA and phase separation interactions.

Phase separation refers to a phenomenon in which different components of a cell collide and fuse with each other to form droplets such that some components are encapsulated within the droplet and some are blocked outside. It is prevalent in eukaryotic cells and is closely related to genome assembly and transcriptional regulation, enabling multiple biological functions. With the development of high-throughput sequencing technologies, several non-coding RNAs (ncRNAs) have been shown to play an important role in epigenetic regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional levels. In addition, some ncRNAs are involved in the formation of membraneless organelles (MLOs), the regulation of genomic stability and stress response through phase separation. Notably, phase separation can also affect the biogenesis, processing and maturation of ncRNAs. This review summarizes recent discoveries related to the relationship between ncRNAs and phase separation, providing new perspectives to guide future interventions.

The effect of Alzheimer's disease risk factors on brain aging in normal Chineses: Cognitive aging and cognitive reserve.

Aging has been recognized as a major driving force of the Alzheimer's disease's (AD) progression, however, the relationship between brain aging and AD is still unclear. There is also a lack of studies investigating the influence of AD risk factors on brain aging in cognitively normal people. Here, the "Brain Age Gap Estimation" (BrainAGE) framework was applied to investigate the effects of AD risk factors on individual brain aging. Across a total of 165 cognitively normal elderly subjects, although no significant difference was observed in the BrainAGE scores among the three groups, AD risk dose (i.e., the number of AD risk factors) is tend to associated with an increased BrainAGE scores (high-risk > middle risk > low risk). Female exhibited more advanced brain aging (P = 0.004), and higher education years were associated with preserved brain aging (P < 0.001). APOE-ɛ4 (P = 0.846) and family history (FH) of dementia (P = 0.209) did not increase BrainAGE scores. When comparing 52 aMCI patients with 38 cognitively normal controls from ADNI dataset, aMCI patients showed significantly increased BrainAGE scores. BrainAGE scores were negatively correlated with CSF Aß42 levels in the aMCI group (r = -0.275, P = 0.048). With an accuracy of 68.9%, BrainAGE outperformed APOE-ɛ4 and hippocampus gray matter volume (GMV) in predicting aMCI. In conclusion, AD is independently associated with structural changes in the brain that reflect advanced aging. Potentially, BrainAGE combined with APOE-ɛ4 and hippocampus GMV could be used as a pre-screening tool in early-stage AD.

Curative Effect and Survival Assessment Comparing Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin and Cisplatin as Neoadjuvant Therapy for Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Neoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes than radical cystectomy or a cisplatin-based regimen. In the present study, we aimed to compare the two most commonly used cisplatin-based neoadjuvant chemotherapies, gemcitabine plus cisplatin and methotrexate plus vinblastine plus doxorubicin plus cisplatin, by summarizing and analyzing clinical data and outcomes of published research. METHODS: We searched for qualified studies that compared these two types of neoadjuvant chemotherapy, including 4 randomized controlled trials and 14 retrospective studies. Data and information on pathological responses and long-term survival studies were extracted and analyzed separately. RESULTS: A total of 18 studies with 3116 patients were selected from 1188 studies, which contained data on pathological complete response, pathological partial response, and overall survival. In contrast to the results of previous studies, there was no significant difference in pathological complete response (odds ratio, 0.97; 95% confidence interval, 0.81-1.15), pathological partial response (odds ratio, 0.85; 95% confidence interval, 0.72-1.14), and overall survival (hazard ratio, 0.99; 95% confidence interval, 0.83-1.17) between GC and MVAC in this meta-analysis. CONCLUSION: No significant differences were observed between GC and MVAC in the muscle-invasive bladder cancer treatment due to the similar curative effect and parallel long survival outcomes due to the similar curative effect and parallel long survival outcomes. The priority selection of GC or MVAC in the clinic should be guided by further investigation, and the clinical standard strategy still counts on the results of more randomized controlled trials in the future.

[Hsa_circ_0005221 promotes prostate cancer progression through the miR-339-5p/STAT5a pathway].

OBJECTIVE: To investigate the molecular mechanism of hsa_circ_0005221 regulating the progression of PCa through the miR-339-5p/STAT5a pathway. METHODS: Localizations of hsa_circ_0005221 and miR-339-5p in cells were detected by nuclear-cytoplasmic isolation. MiRNA-339-5p was selected as the target miRNA bound to hsa_circ_0005221 by RNA pull-down assay. The binding site of the luciferase reporter gene was predicted by software and the binding capability of miR-339-5p validated by luciferase assay. The expression of hsa_circ_0005221 in the prostatic epithelial and PCa cells was determined by qPCR. The hsa_circ_0005221-overexpressed plasmid and siRNA were transfected into the PCa cells for measurement of their proliferation, invasion and migration abilities and the levels of epithelial-mesenchymal transformation (EMT) and apoptosis. After knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics and miR-339-5p inhibitor, the proliferation, invasion and migration abilities of the DU145 and LNCaP cells were detected, and so were the levels of the EMT signature protein, STAT5a and cell apoptosis. RESULTS: The expression of hsa_circ_0005221 was significantly higher in the PCa than in the prostatic epithelial cells. Nuclear-cytoplasmic isolation experiments showed that hsa_circ_0005221 and miR-339-5p were mainly located in the cytoplasm. The proliferation, invasion and migration abilities and EMT were decreased and the apoptosis increased in the DU145 and LNCaP cells with knockdown of hsa_circ_0005221, which was just the reverse in those with overexpressed hsa_circ_0005221. Among the top 5 miRNAs predicted by software, miR-339-5p, miR-17 and miR-520h were shown by pull-down assay to be bound to hsa_circ_0005221, with most obvious changes in miR-339-5p when hsa_circ_0005221 knocked down or overexpressed. Luciferase reporter gene assay showed the binding of hsa_circ_0005221 to miR-339-5p. Knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics into the DU145 and LNCaP cells significantly reduced the proliferation, invasion and migration abilities of the cells and the N-cad level, increased their apoptosis and E-cad level, and up-regulated the expression of STAT5a, while overexpression of hsa_circ_0005221 and transfection of miR-339-5p mimics induced just the opposite effects. CONCLUSIONS: Hsa_circ_0005221 enhances the progression of prostate cancer through the miR-339-5p/STAT5a pathway.

High Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Are Associated With Sarcopenia Risk in Hospitalized Renal Cell Carcinoma Patients.

PURPOSE: This study aimed i) to identify the best cutoff points of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) that predict sarcopenia and ii) to illustrate the association between sarcopenia risk and NLR or PLR in renal cell carcinoma (RCC) patients undergoing laparoscopic partial or radical nephrectomy. METHODS: A total of 343 RCC patients who underwent laparoscopic partial or radical nephrectomy between 2014 and 2019 were enrolled in our study. Sarcopenia was assessed by lumbar skeletal muscle index (SMI). Receiver operating characteristic (ROC) curve was used to identify the best cutoff point of NLR or PLR to predict sarcopenia risk. Univariate and multivariate logistic regression and dose-response analysis curves of restricted cubic spline function were conducted to assess the relationship between sarcopenia and NLR or PLR. RESULTS: The best cutoff points of NLR >2.88 or PLR >135.63 were confirmed by the ROC curve to predict sarcopenia risk. Dose-response curves showed that the risk of sarcopenia increased with raising NLR and PLR. Patients with NLR >2.88 or PLR >135.63 had a higher sarcopenia risk than those in the NLR ≤2.8 or PLR ≤135.63 group, respectively. By adjusting for all variables, we found that patients with NLR >2.88 and PLR >135.63 had 149% and 85% higher risk to develop sarcopenia, respectively, than those with NLR ≤2.8 (aOR = 2.49; 95% CI = 1.56-3.98; p < 0.001) or PLR ≤135.63 (aOR = 1.85; 95% CI = 1.16-2.95; p = 0.010). CONCLUSION: In RCC patients receiving laparoscopic partial or radical nephrectomy, NLR and PLR, which were biomarkers of systemic inflammation, were associated with sarcopenia risk.

The Alterations in Methylene Blue/Light-Treated Frozen Plasma Proteins Revealed by Proteomics.

INTRODUCTION: The aim of this study was to investigate the modified proteins in methylene blue/light-treated frozen plasma (MB-FP) compared with fresh frozen plasma (FFP) in order to gain a better application of MB/light-treated plasma in clinic transfusion. METHODS: MB-FP and FFP were collected from Changchun central blood station, and a trichloroacetic acid/acetone precipitation method was used to remove albumin for the enrichment of lower abundance proteins. The plasma protein in MB-FP and FFP were separated using two-dimensional gel electrophoresis (2-DE) and the differentially expressed protein spots were analyzed using mass spectrometry. Finally, the differentially expressed proteins were tested using Western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS: Approximately 14 differentially expressed protein spots were detected in the MB-FP, and FFP was chosen as the control. After 2-DE comparison analysis and mass spectrometry, 8 significantly differentially expressed protein spots were identified, corresponding to 6 different proteins, including complement C1r subcomponent (C1R), inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4), keratin, type II cytoskeletal 1 (KRT1), hemopexin (HPX), fibrinogen gamma chain (FGG), and transthyretin (TTR). Western blot showed no significant difference in the expression level of KRT1 between MB-FP and FFP (p > 0.05). Both Western blot and ELISA indicated that the level of HPX was significantly higher in FFP than in MB-FP (p < 0.05). CONCLUSION: This comparative proteomics study revealed that some significantly modified proteins occur in MB-FP, such as C1R, ITI-H4, KRT1, HPX, FGG, and TTR. Our findings provide more theoretical data for using MB-FP in transfusion medicine. However, the relevance of the data for the transfusion of methylene blue/light-treated plasma remains unclear. The exact modification of these proteins and the effects of these modified proteins on their functions and their effects in clinical plasma infusion need to be further studied.

Development and Verification of a Prostate Cancer Prognostic Signature Based on an Immunogenomic Landscape Analysis.

PURPOSE: Prostate cancer (PCa) has a high incidence among older men. Until now, there are no immunological markers available to predict PCa patients' survival. Therefore, it is necessary to explore the immunological characteristics of PCa. METHODS: First, we retrieved RNA-seq and clinical data of 499 PCa and 52 normal prostate tissue samples from the Cancer Genome Atlas (TCGA). We identified 193 differentially expressed immune-related genes (IRGs) between PCa and normal prostate tissues. Functional enrichment analyses showed that the immune system can participate in PCa initiation. Then, we constructed a correlation network between transcription factors (TFs) and IRGs. We performed univariate and multivariate Cox regression analyses and identified five key prognostic IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1). Finally, a predictive nomogram was established and verified by the C-index. RESULTS: We successfully constructed and validated an immune-related PCa prediction model. The signature could independently predict PCa patients' survival. Results showed that high-immune-risk patients were correlated with advanced stage. We also validated the S100A2 expression in vitro using PCa and normal prostate tissues. We found that higher S100A2 expressions were related to lower biochemical recurrences. Additionally, higher AMH expressions were related to higher Gleason score, lymph node metastasis and positive rate, and tumor stages, and higher ATGR1 expressions were related to lower PSA value. CONCLUSION: Overall, we detected five IRGs (S100A2, NOX1, IGHV7-81, AMH, and AGTR1) that can be used as independent PCa prognostic factors.

Relationship Between Pre-operative Blood Glucose Level and Length of Hospital Stay in Patients With Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy.

Purpose: The aim of this study was to assess the effect of pre-operative blood glucose (POBG) levels on the length of stay (LOS) in patients with renal cell carcinoma (RCC) undergoing laparoscopic nephrectomy. Methods: We collected clinical data on 338 patients with RCC who underwent laparoscopic nephrectomy between 2014 and 2019. Univariate and multivariate logistic regression and dose-response analysis curves of restricted cubic spline function were used to investigate the relationship between POBG and LOS. Results: According to the level of POBG, we divided the patients into three groups: <4.94 mmol/L group, 4.94 to <7.11 mmol/L group, and ≥7.11 mmol/L group. According to the dose-response analysis curves, we found that the adjusted risk of LOS > 2 weeks and LOS > 3 weeks gradually increased with increasing POBG. In addition, we found that among all patients, patients with POBG levels ≥ 7.11 mmol/L had a 115% higher risk of LOS > 2 weeks than patients with POBG levels <4.94 mmol/L [adjusted odds risk (aOR) 2.15; 95% CI 1.11-4.20; p = 0.024] and patients with POBG levels ≥ 7.11 mmol/L had a 129% higher risk of LOS > 3 weeks than patients with POBG levels <4.94 mmol/L (aOR 2.29; 95% CI 1.16-4.52; p = 0.017). Moreover, similar results were observed in the most subgroups analysis. Conclusion: We found that in patients with RCC undergoing laparoscopic nephrectomy, higher POBG levels were significantly associated with prolonged LOS.

Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: a Chinese retrospective cohort study.

BACKGROUND: Relapsing polychondritis (RPC) is a rare autoimmune disease and its early diagnosis remains challenging. Defining the clinical patterns and disease course may help early recognition of RPC. RESULTS: Sixty-six males and 60 females were included in this study. The average age at onset were 47.1 ± 13.8 years and the median follow-up period was 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r = - 0.75, P < 0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%), and patients with Ear pattern and Airway pattern were further divided into limited and systemic form of RPC (27.8% with limited form of Ear pattern and 24.6% with limited form of Airway pattern initially). During follow-up, a minority of patients with Ear pattern and Airway pattern progressed into Overlap pattern, and some Airway-Ear negative pattern patients progressed into Ear pattern. While a large majority of limited RPC patients remained limited form during follow-up, a minority of limited RPC patients progressed into systemic form. Patients with Ear pattern had the highest survival rate and relatively lower inflammatory status. CONCLUSIONS: RPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement. The clinical patterns and presenting forms may evolve during follow-up. Our findings may facilitate early recognition of this rare disease.

Recent Progress of Fiber-Optic Sensors for the Structural Health Monitoring of Civil Infrastructure.

In recent years, with the development of materials science and architectural art, ensuring the safety of modern buildings is the top priority while they are developing toward higher, lighter, and more unique trends. Structural health monitoring (SHM) is currently an extremely effective and vital safeguard measure. Because of the fiber-optic sensor's (FOS) inherent distinctive advantages (such as small size, lightweight, immunity to electromagnetic interference (EMI) and corrosion, and embedding capability), a significant number of innovative sensing systems have been exploited in the civil engineering for SHM used in projects (including buildings, bridges, tunnels, etc.). The purpose of this review article is devoted to presenting a summary of the basic principles of various fiber-optic sensors, classification and principles of FOS, typical and functional fiber-optic sensors (FOSs), and the practical application status of the FOS technology in SHM of civil infrastructure.

Graphene-based ultrasensitive optical microfluidic sensor for the real-time and label-free monitoring of simulated arterial blood flow.

Highly sensitive, real-time and label-free sensing of liquid flow in microfluidic environments remains challenging. Here, by growing high-quality graphene directly on a glass substrate, we designed a microfluidic-integrated graphene-based flow sensor (GFS) capable of detecting complex, weak, and transient flow velocity and pressure signals in a microfluidic environment. This device was used to study weak and transient liquid flows, especially blood flow, which is closely related to heart and artery functions. By simulating cardiac peristalsis and arterial flow using peristaltic pumps and microfluidic systems, we monitored simulated arterial blood flow. This ultrasensitive graphene-based flow sensor accurately detected a flow velocity limit as low as 0.7 mm/s, a pumping frequency range of 0.04 Hz to 2.5 Hz, and a pressure range from 0.6 kPa to 14 kPa. By measuring the blood flow velocities and pressures, pathological blood flow signals were distinguished and captured by the corresponding flow velocities or pressures, which can reflect vascular occlusion and heart functions. This sensor may be used for the real-time and label-free monitoring of patients' basic vital signs using their blood flow and provide a possible new method for the care of critically ill patients.

Broadband and Ultrasensitive Graphene-Based Mechanical Wave Detector with Nanosecond Response Used for Biological Photoacoustic Imaging.

Achieving broadband and sensitive mechanical wave detection with fast time response remains a great challenge. Here, we exploited the polarization-sensitive absorption characteristics and ultrafast photoelectric response of graphene to construct a broadband and ultrasensitive detector with a nanosecond response for mechanical wave detection. The unprecedented performance of the graphene-based detector allowed us to detect high-frequency mechanical waves over 100 MHz with a detection limit of 0.18 kPa. Moreover, we applied the detector in high-contrast photoacoustic imaging of human hairs and a mouse hindlimb to demonstrate its capability in detection of photoacoustic waves. This device could also find application in other areas such as THz detection and modulation.

Diagnosing relapsing polychondritis remains a common challenge: experience from a Chinese retrospective cohort.

OBJECTIVE: The diagnosis of relapsing polychondritis (RP) is often mistaken or delayed. In this retrospective cohort, we aimed to unveil the causes responsible for such phenomenon, to determine the associated factors, and to compare diagnosis in clinical settings with the current diagnostic criteria. METHOD: Eighty-seven RP patients followed-up by rheumatologists from January 1, 2008, to October 31, 2018, were retrospectively analyzed. RESULTS: A total of 50 male and 37 female patients were included with a mean age of 45.9 ± 14.5 years. Ninety-three percent were initially admitted by non-rheumatologic specialists .Twenty-eight percent were correctly diagnosed, while 72% were misdiagnosed at the first visits, all by non-rheumatologic specialists. Patients admitted by non-rheumatologic specialists had increased odds of misdiagnosis (odds ratio [OR] = 1.3, 95% confidence interval [95% CI] 1.1-1.7, P = 0.000). Fifty-seven (65.5%) patients did not meet with Michet or Damiani criteria, with 16 (18.4%) patients diagnosed as partial RP and 41( 47.1%) patients diagnosed as limited RP. CONCLUSIONS: Incorrect and delayed diagnosis of RP is common in our cohort, and insufficient awareness of the disease in non-rheumatologic specialists at least partially contributes to this. It is imperative to revise the current criteria for early diagnosis.Key Points• Diagnosing relapsing polychondritis (RP) in early stage remains challenging after all these years, especially among non-rheumatologic specialists, indicating the importance of teaching non-rheumatologic specialists to improve their understanding of this rare disease.• Many RP patients did not fully meet with the current criteria, suggesting that revision of the current criteria is imperative for early diagnosis of this rare disease.

Ultrasensitive Optical Detection of Water Pressure in Microfluidics Using Smart Reduced Graphene Oxide Glass.

Despite recent progresses in the field of microfluidics, the effect of liquid pressure on the detection accuracy has been rarely studied. Here, we perform a quantitative analysis of such effect, by utilizing the sensitive optical responses of graphene to the refractive index (RI) change of its surrounding environment. We utilize a reflection coupling configuration by combining the total internal reflection (TIR) and ultrasonic waves. The high-performance graphene is processed on common glasses by using the solution-processable oxidation-reduction method. We find that the RI change of water caused by a pressure as small as 500 Pa generated by the liquid level change in the microfluidics can be measured directly. The detection accuracy and response time limits are approximately 280 Pa and 100 ns, respectively. The Maxwell's boundary conditions, Fresnel's law, and Pascal's law are used in theoretical analyses. This work highlights the importance of liquid pressure in microfluidics and provides guidance in designing and accurate detection of microfluidic devices.