RFID Adaptive Parallel Response Collision Tree Algorithm Based on Lock-Bit.

This paper proposes the Lock-Position-Based RFID Adaptive Parallel Collision Tree (LAPCT) algorithm to address the issues of excessive time slots required in the identification process of collision tree algorithms for multiple tags and the high communication complexity between the reader and multiple tags. The LAPCT algorithm adopts a single-query multiple-response mechanism and dynamically divides the response sub-cycle numbers in the identification cycle based on an adaptive strategy. It uses Manchester encoding to lock collision positions and generate a common query prefix, effectively reducing the number of reader queries. This reduction in queries decreases the total number of required time slots and transmitted bits during the reader-tag communication process, thereby improving the efficiency of multiple tag recognition. Theoretical and simulation experiments demonstrate that compared to similar algorithms, the LAPCT algorithm achieves a maximum reduction of 37% in total time slots required, a maximum improvement of 30% in recognition efficiency, and a maximum reduction of 90% in communication complexity. Furthermore, with an increase in the number of tags, the performance advantages of the LAPCT algorithm become more pronounced, making it suitable for large-scale tag scenarios.

Joint Optimization of Multi-User Partial Offloading Strategy and Resource Allocation Strategy in D2D-Enabled MEC.

With the emergence of more and more computing-intensive and latency-sensitive applications, insufficient computing power and energy of user devices has become a common phenomenon. Mobile edge computing (MEC) is an effective solution to this phenomenon. MEC improves task execution efficiency by offloading some tasks to edge servers for execution. In this paper, we consider a device-to-device technology (D2D)-enabled MEC network communication model, and study the subtask offloading strategy and the transmitting power allocation strategy of users. The objective function is to minimize the weighted sum of the average completion delay and average energy consumption of users, which is a mixed integer nonlinear problem. We first propose an enhanced particle swarm optimization algorithm (EPSO) to optimize the transmit power allocation strategy. Then, we utilize the Genetic Algorithm (GA) to optimize the subtask offloading strategy. Finally, we propose an alternate optimization algorithm (EPSO-GA) to jointly optimize the transmit power allocation strategy and the subtask offloading strategy. The simulation results show that the EPSO-GA outperforms other comparative algorithms in terms of the average completion delay, average energy consumption, and average cost. In addition, no matter how the weight coefficients of delay and energy consumption change, the average cost of the EPSO-GA is the least.

Improved efficiency of urine cell image segmentation using droplet microfluidics technology.

Recent advances in the recognition of biological samples using machine vision have made this technology increasingly important in research and detection. Image segmentation is an important step in this process. This study focuses on how to reduce the interference factors such as the overlap between different types (or within the same type) of urine cells according to microfluidics and improve the machine vision segmentation accuracy for cell images. In this study, we demonstrate that the platform can realize this hypothesis using urine cell image segmentation as an example application. We first discuss the reported urine cell droplet microfluidic chip system, which can realize the test conditions in which urine cells are encapsulated in the droplet and isolated from salt crystallization and/or bacteria and other urine-formed elements. Then, based on the analysis conditions set in the aforementioned experiment, the proportions of red blood cells, white blood cells, and squamous epithelial cells covered by various formed elements in the total urine cells in the same urine sample are measured. We simultaneously analyze the percentage of urine cells covered by salt crystallization and the incidence of overlapping between urine cells. Finally, the Otsu algorithm is used to segment the urine cell images encapsulated by the droplet and the urine cell images not encapsulated by the droplet, and the Dice, Jaccard, precision, and recall values are calculated. The results suggest that the method of encapsulating single cells based on droplets can improve the image segmentation effect without optimizing the algorithm.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

Influences of Probe's Morphology for Metal Ion Detection Based on Light-Addressable Potentiometric Sensors.

The sensing mechanism of binding Hg(2+) into thymine-thymine (T-T) mismatched base pairs was introduced into a light-addressable potentiometric sensor (LAPS) with anti-Hg(2+) aptamer as the sensing units. Three kinds of T-rich single-strand DNA (ssDNA) chains with different spacer lengths, from 0 to 12 -CH2 groups, were designed to investigate surface charge and morphological effects on the LAPS' output. First, by comparing the responding of LAPS modified with three kinds of ssDNA, it was found that the best performance for Hg(2+) sensing was exhibited by the probe without -CH2 groups. The detection limit of Hg(2+) ion was 1 ppt under the optimal condition. Second, the cooperative effects of surface charge and morphology on the output were observed by the controlled experiments. The two effects were the negative charge balanced by metal cations and the morphological changing caused by the formation of T-Hg(2+)-T structure. In conclusion, not only the influences of the aptamer probe's morphology and surface charge was investigated on the platform of LAPS, but also sensing Hg(2+) ions was achieved for the first time by the presented aptamer LAPS.

Preparation and catalytic activity of poly(N-vinyl-2-pyrrolidone)-protected Au nanoparticles for the aerobic oxidation of glucose.

PVP-protected Au nanoparticles (NPs) for the aerobic oxidation of glucose were prepared by using NaBH4 reduction method. The effects of processing parameters such as Au3+ ion concentration, reaction temperature, ratio of NaBH4 or PVP to Au3+, and solvent composition on their particle sizes and catalytic activities were studied in detail and the synthesis conditions optimized. As-prepared Au NPs possessed a FCC structure, with an average size varying from about 100 to 2.6 nm depending on their preparation conditions. The size changes affected their catalytic activities in the aerobic oxidation of glucose. The Au NPs with the average size of 2.6 nm prepared under the optimal conditions showed a high instantaneous catalytic activity as well as a high long-time stability. Based on the kinetic study on the glucose oxidation over the PVP-protected Au NPs, the corresponding apparent activation energy was determined as 82 kJ mol(-1).

Deletion of Luzp2 Does Not Cause Hearing Loss in Mice.

Deafness is the prevailing sensory impairment among humans, impacting every aspect of one's existence. Half of congenital deafness cases are attributed to genetic factors. Studies have shown that Luzp2 is expressed in hair cells (HCs) and supporting cells of the inner ear, but its specific role in hearing remains unclear. To determine the importance of Luzp2 in auditory function, we generated mice deficient in Luzp2. Our results revealed that Luzp2 has predominant expression within the HCs and pillar cells. However, the loss of Luzp2 did not result in any changes in auditory threshold. HCs or synapse number and HC stereocilia morphology in Luzp2 knockout mice did not show any notable distinctions. This was the first study of the role of Luzp2 in hearing in mice, and our results provide important guidance for the screening of deafness genes.

High levels of bcl-2 protein expression do not correlate with genetic abnormalities but predict worse prognosis in patients with lymphoblastic lymphoma.

We aimed to investigate bcl-2, bcl-6, and c-myc rearrangements in patients with lymphoblastic lymphoma (LBL), especially focus on the correlation of protein expression with genetic abnormalities. Moreover, their prognostic significance was further analyzed in LBL. Protein expression and genetic abnormalities of bcl-2, bcl-6, and c-myc were investigated in microarrayed tumors from 33 cases of T cell LBL and eight cases of B cell lineage. Immunohistochemical (IHC) staining was performed to evaluate protein expression, including bcl-2, bcl-6, c-myc, TdT, CD1α, CD34, Ki-67, PAX-5, CD2, CD3, CD4, CD8, and CD20. Genetic abnormalities of bcl-2, bcl-6, and c-myc were detected by dual color fluorescence in situ hybridization (FISH). Bcl-2 protein was positive in 51.2 % (21/41) of the patients, bcl-6 protein in 7.3 % (three out of 41), and c-myc protein in 78.0 % (32/41). Bcl-2 breakpoint was found in two cases by FISH analysis. There was no evidence of bcl-6 or c-myc rearrangement in patients with LBL. However, both gene gain and loss events occurred in bcl-2, bcl-6, and c-myc. A univariate analysis showed that stage III or IV, elevated lactate dehydrogenase (LDH), and positivity for bcl-2 protein were associated with shorter survival (p<0.05). Enhanced protein expression and detectable genetic abnormalities of bcl-2, bcl-6, and c-myc were observed in patients with LBL. No statistical correlation was found between IHC results and cytogenetic findings. Stage III or IV, elevated LDH, and positivity for bcl-2 protein were identified as adverse prognostic factors. The patients with more adverse factors would have increasingly worse prognosis.

Primary Surgical Management of Laryngeal Neuroendocrine Neoplasms: A Single Institution Case Series.

Objective: Laryngeal neuroendocrine neoplasms (NENs) are rare diseases. A single institution retrospective study was done of the outcome of patients with laryngeal NENs who undergo primary surgery as the first treatment modality. Methods: Retrospective analysis of medical records of patients with laryngeal NENs between 2009 and 2018. Cases were classified by applying the 2022 World Health organization Classification of Head and Neck Tumors (5th edition). Results: Six patients were eligible at our tertiary center: 1 large cell neuroendocrine carcinoma (NEC), 3 small cell NEC, 1 neuroendocrine tumor grade 1, and 1 neuroendocrine tumor grade 2. All admitted patients received upfront surgeries, including 3 transoral CO2 laser surgeries and 3 total laryngectomies with or without elective neck dissection. Four patients underwent subsequent chemoradiotherapy. Although 3 patients had recurrent disease and distal metastasis, the overall survival was generally improved. Conclusion: According to our institutional experience, upfront surgery in the first-line setting of a multi-modality approach with adjuvant chemoradiotherapy plays a very important role in managing laryngeal NECs, and may confer additional survival benefit in some patients of the large cell carcinoma subgroup.

Advances in nerve guidance conduits for peripheral nerve repair and regeneration.

Peripheral nerve injury (PNI) can cause partial or total motor and sensory nerve function, leading to physical disability and nerve pain that severely affects patients' quality of life. Autologous nerve transplantation is currently the clinically recognized gold standard, but due to its inherent limitations, researchers have been searching for alternative treatments. Nerve guidance conduits (NGCs) have attracted much attention as a favorable alternative to promote the repair and regeneration of damaged peripheral nerves. In this review, we provide an overview of the anatomy of peripheral nerves, peripheral nerve injury and repair, and current treatment methods. Importantly, different design strategies of NGCs used for the treatment of PNI and their applications in PNI repair are highlighted. Finally, an outlook on the future development and challenges of NGCs is presented.

A Cell Component-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma Based on the Tumor Microenvironment.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with a high mortality rate. The tumor microenvironment (TME) is composed of numerous noncancerous cells that contribute to tumorigenesis and prediction of therapeutic effects. In this study, we aimed to develop a cell component-related prognostic model based on TME. We screened cell component enrichments from samples in The Cancer Genome Atlas (TCGA) HNSCC cohort using the xCell algorithm. Univariate Cox and multivariate Cox regression analyses were performed to establish an optimal independent risk model. The prognostic value of the model was further validated using Gene Expression Omnibus datasets. We found that patients in the low-risk group had a better outcome and activated immunity and may benefit more from the immune checkpoint inhibitor therapy. We also explored microRNAs (miRNAs) that may regulate these identified cell components, and 11 miRNA expression levels influenced the overall survival time. Moreover, their target mRNAs were differentially expressed in TCGA cohort and enriched in pathways of cell cycle pathways, extracellular matrix receptor interaction, human papillomavirus infection, and cancer. In summary, our cell component-related signature was a promising prognostic biomarker that provides new insights into the predictive value of nontumor components in the TME.

Tumor microenvironment features decipher the outperformance of neoadjuvant immunochemotherapy over chemotherapy in resectable non-small cell lung cancer.

This study evaluated the efficacy of neoadjuvant immunochemotherapy (Io+Chemo) versus chemotherapy alone (Chemo) in resectable non-small cell lung cancer (NSCLC) in a real-world setting. The association of tumor immune microenvironment (TIME) with pathologic response to different neoadjuvant therapies was also explored.Stage I-III NSCLC patients who received Io+Chemo or Chemo alone followed by surgery were included in the study. Tumor tissues collected during surgery were subjected to TIME evaluation using multiplex immunohistochemistry to measure immune cell subsets, including T cells, B cells, NK cells, and macrophages. Fifty-five patients were included, including 24 treated with neoadjuvant Io+Chemo and 31 with Chemo alone. Io+Chemo induced significantly higher major pathologic response (MPR) (75.0% vs. 38.7%, P = 0.0133) and numerically better pathologic complete response (pCR) (33.3% vs. 12.9%, P = 0.1013) than Chemo. Compared with tumors with Chemo, tumors with Io+Chemo demonstrated a significantly higher ratio of M1 macrophage density in the tumor to that in the stroma (P = 0.0446), more abundant CD8+ cells in the stroma (P = 0.0335), and fewer PD-L1+CD68+ cells in both tumor and stroma. pCR/MPR patients displayed significantly higher density of CD3+, CD3+CD4+, CD20+, CD56 bright cell subsets and more tertiary lymphoid structures and significantly lower density of PD-L1+CD68+ and CD3+CD4+Foxp3+cells in the tumor or stroma. This study favored neoadjuvant Io+Chemo over Chemo and revealed the TIME features underlying the outperformance of Io+Chemo over Chemo.

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). METHODS: The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. RESULTS: M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. CONCLUSIONS: METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.

Circulating tumor DNA predicts neoadjuvant immunotherapy efficacy and recurrence-free survival in surgical non-small cell lung cancer patients.

Background: There is currently a lack of effective biomarkers to evaluate efficacy of neoadjuvant therapy (NAT) for resectable non-small cell lung cancer (NSCLC) patients. Circulating tumor DNA (ctDNA) has been investigated as a non-invasive tool for the assessment of tumor burden and minimal residual disease (MRD). The utility of ctDNA profiling in reflecting NAT efficacy, however, has not been confirmed. This study explored the association of ctDNA change with treatment response to NAT and recurrence-free survival (RFS) after surgery. Methods: Eligible patients with stage IB-IIIA NSCLC were retrospectively included if they had received neoadjuvant immunotherapy combined with chemotherapy (IO+Chemo), dual immunotherapy (IO+IO), or chemotherapy alone (Chemo). We conducted ctDNA profiling before and after NAT, after surgery, and during follow-ups using an ultra-deep lung cancer-specific MRD (LC-MRD) sequencing panel. Results: A total of 22 patients who received NAT followed by surgery between August 2018 and July 2019 were included in this study. The major pathological response (MPR) rates were 58.33% (7/12) in the IO+Chemo group, 25.00% (1/4) in the IO+IO group, and 16.67% (1/6) in the Chemo group. The ctDNA dynamics during NAT were highly concordant with pathologic response, demonstrating 100% sensitivity and 83.33% specificity, for an overall accuracy of 91.67%. Pre-surgery detectable ctDNA (after NAT) trended to correlate with inferior RFS [hazard ratio (HR), 7.41; 95% confidence interval (CI): 0.91-60.22, log-rank P=0.03]. At 3-8 days after surgery, ctDNA was detectable in 31.8% of patients and was an independent risk factor for recurrence (HR, 5.37; 95% CI: 1.27-22.67; log-rank P=0.01). The presence of ctDNA at 3 months after surgery showed 83% sensitivity and 90% specificity for predicting relapse (C-index, 0.79; 95% CI: 0.62-0.95). During disease monitoring after surgery, molecular recurrence by means of ctDNA preceded radiographic relapse, with a median time of 6.83 months. Conclusions: This study investigated the potential of ctDNA in evaluating NAT efficacy in NSCLC, implying the high concordance between ctDNA and pathological response. We also set out the prognostic value of perioperative ctDNA in predicting recurrence.

Thrombocytopenia Is Associated with COVID-19 Severity and Outcome: An Updated Meta-Analysis of 5637 Patients with Multiple Outcomes.

The COVID-19 pandemic is persistent worldwide. A prior meta-analysis suggested the association of thrombocytopenia (TCP) with more severe COVID-19 illness and high mortality. Considering newly published studies, we updated the previous meta-analysis to confirm and explain the association of TCP with COVID-19 severity and multiple outcomes. Twenty-four studies with 5637 patients with COVID-19 were included in this study. The weighted incidence of TCP in COVID-19 was 12.4% (95% confidence interval [CI], 7.9%-17.7%). Data synthesis showed that the platelet number was lower in patients with either more severe illness or poor outcomes and even lower in nonsurvivors, with weighted mean differences of -24.56 × 109/L, -22.48 × 109/L, and -49.02 × 109/L, respectively. The meta-analysis of binary outcomes (with and without TCP) indicated the association between TCP and 3-fold enhanced risk of a composite outcome of intensive care unit admission, progression to acute respiratory distress syndrome, and mortality (odds ratio [OR], 3.49; 95% CI, 1.57-7.78). Subgroup analysis by endpoint events suggested TCP to be significantly associated with mortality (OR, 7.37; 95% CI, 2.08-26.14). Overall, the present comprehensive meta-analysis indicated that approximately 12% of hospitalized patients with COVID-19 have TCP, which also represents a sign of more severe illness and poor outcomes.

Potential prognostic markers and significant lncRNA-mRNA co-expression pairs in laryngeal squamous cell carcinoma.

lncRNA-mRNA co-expression pairs and prognostic markers related to the development of laryngeal squamous cell carcinoma (LSCC) were investigated. The lncRNA and mRNA expression data of LSCC in GSE84957 and RNA-seq data of 112 LSCC samples from TCGA database were used. Differentially expressed genes (DEGs) and lncRNAs (DE-lncRNAs) between LSCC and para-cancer tissues were identified. Co-expression analysis of DEGs and DE-lncRNA was conducted. Protein-protein interaction network for co-expressed DEGs of top 25 DE-lncRNA was constructed, followed by survival analysis for key nodes in co-expression network. Finally, expressions of several DE-lncRNAs and DEGs were verified using qRT-PCR. The lncRNA-mRNA network showed that ANKRD20A5P, C21orf15, CYP4F35P, LOC_I2_011146, XLOC_006053, XLOC_I2_003881, and LOC100506027 were highlighted in network. Some DEGs, including FUT7, PADI1, PPL, ARHGAP40, MUC21, and CEACAM1, were co-expressed with above lncRNAs. Survival analysis showed that PLOD1, GLT25D1, and KIF22 were significantly associated with prognosis. qRT-PCR results showed that the expressions of MUC21, CEACAM1, FUT7, PADI1, PPL, ARHGAP40, ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, LOC_I2_011146, and XLOC_006053 were downregulated, whereas the expression of LOC100506027 was upregulated in LSCC tissues. PLOD1, GLT25D1, and KIF22 may be potential prognostic markers in the development of LSCC. C21orf15-MUC21/CEACAM1/FUT7/PADI1/PPL/ARHGAP40 are potential lncRNA-mRNA pairs that play significant roles in the development of LSCC.

High pretreatment platelet-to-lymphocyte ratio is related to poor prognosis in the squamous cell carcinoma of the larynx and hypopharynx in male patients.

BACKGROUND: There were heterogeneous or even conflicting data regarding the ability of platelet-to-lymphocyte ratio (PLR) for predicting the prognosis of laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC). The discrepancies were found to be largely due to the cutoff value of PLR. AIMS: The aims of this study were to rationally select an optimal PLR cutoff value and to analyze the relationship between pretreatment PLR and the prognosis. METHODS: A total of 180 male patients were eligible for this retrospective study. We included another 180 healthy male individuals as controls. The relationship between PLR and age in patients and the controls was determined. The optimal cutoff values of PLR were identified. PLR value was then dichotomized into two categories, and the relationship between PLR and the clinicopathologic parameters were calculated. Kaplan-Meier curves were used to evaluate the overall survival (OS), and the association between PLR and the OS was analyzed. RESULTS: The linear regression analysis showed a positive correlation between age and PLR in the control group, but not the patients. The optimal cutoff value of PLR was 112.5. The high PLR value group of patients exhibited significantly decreased OS. PLR was related to prognosis, as revealed by the univariate Cox regression. CONCLUSION: Patients with LHSCC have abnormal high PLR, and a high pretreatment PLR portends adverse survival.

An immune-related lncRNA signature for the prognosis of pancreatic adenocarcinoma.

Recent evidence suggests that aberrant expression of long non-coding RNA (lncRNA) can drive the initiation and progression of malignancies. However, little is known about the prognostic potential of lncRNA. We aimed at constructing a lncRNA-based signature to improve the prognosis prediction of pancreatic adenocarcinoma (PAAD). The PAAD samples with clinical information were obtained from The Cancer Genome Atlas and International Cancer Genome Consortium. We established an eight-IRlncRNA signature in a training cohort. The prognostic value of eight-IRlncRNA signature was validated in two distinct cohorts when compared to other four prognostic models. We continued to analyze its independence in subgroups by univariate and multivariate Cox regression. We constructed a nomogram for clinicopathologic features and 1-, 3-, and 5-year overall survival performance. Moreover, Gene set enrichment analysis and Gene Set Variation Analysis distinguished the typical functions between high- and low-risk groups. In addition, we further observed the different correlations of immune cell between eight IRlncRNAs. Eight-IRlncRNA signature appears to be a good performer to predict the survival capability of PAAD patients, and the nomogram will enable PAAD patients to be more accurately managed in clinical practice.

Hypoxia-Induced TGFBI as a Serum Biomarker for Laboratory Diagnosis and Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: To explore novel biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC), from the perspective of tumor hypoxia. METHODS: We screened 29 differentially expressed and hypoxia-upregulated genes from the Oncomine database. A total of 12 secretory proteins that interact with hypoxia-inducible factor 1 (HIF-1A) were selected by STRING (protein-protein interaction networks). After excluding enzymes and collagens, insulin-like growth factor-binding protein 3 (IGFBP3), glycoprotein NBM (GPNMB), transforming growth factor-ß-induced (TGFBI), and biglycan (BGN) were detected by sandwich enzyme-linked immunosorbent assay (ELISA) in patients with cancer and healthy control individuals. RESULTS: The serum level of TGFBI was significantly elevated in patients with PDAC, compared with healthy controls; the assay could discriminate among cases of PDAC in different clinical stages. The amount of TGFBI was significantly decreased after treatment. The combination of TGFBI and cancer antigen (CA) 19-9 was more accurate than TGFBI or CA 19-9 alone as diagnostic markers. Also, TGFBI might be used as a prognostic marker according to the PROGgeneV2 Pan Cancer Prognostics Database. CONCLUSIONS: Serum TGFBI, combined with CA 19-9, offers higher diagnostic value than other methods for patients with PDAC. Also, TGFBI might be used as a prognostic marker.

Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression.

The critical roles of oxygen homeostasis in metabolism are indisputable and hypoxic responses are correlated with the pathogenesis of gastrointestinal, pulmonary, renal diseases and cancers. Evaluating tissue hypoxia to predict treatment outcome is challenging, however, due to the lack of rapid, accurate and non-invasive methods. Hypoxia enhances prolyl-4-hydroxylase α1 (P4HA1) expression, which can convert bradykinin (BK) to hydroxyprolyl-BK (Hyp-BK), leading us to hypothesize that circulating Hyp-BK/BK ratios may reflect tissue hypoxia and predict treatment outcomes. Direct quantification of Hyp-BK peptides in serum or plasma by conventional MALDI-TOF MS analysis is technically challenging. In our study, a nanopore-based fractionation and enrichment protocol was utilized to allow the simple workflow for circulating Hyp-BK/BK analysis. Hypoxia is linked to poor prognosis due to its role in promoting pancreatic cancer progression and metastasis. Here we show that P4HA1 expression was increased in pancreatic tumors versus adjacent tissue, associated with poor survival, and corresponded with tumor expression of the hypoxia inducible factor 1α (HIF-1α) and carbonic anhydrase 9 (CA9). Hypoxia-induced P4HA1 expression and BK conversion to Hyp-BK were found to be HIF-1α dependent, pre-treatment serum Hyp-BK/BK ratios corresponded with tissue HIF-1α and P4HA1 expression, and high Hyp-BK/BK levels corresponded with poor response to therapy. These results suggest that pre-treatment circulating Hyp-BK/BK ratios may have value as a non-invasive, surrogate indicator of tissue hypoxia and tumor responses to therapy.