Metabolomic biomarkers for benign conditions and malignant ovarian cancer: Advancing early diagnosis.

BACKGROUND: Ovarian cancer (OC) is a major global cause of death among gynecological cancers, with a high mortality rate. Early diagnosis, distinguishing between benign conditions and early malignant OC forms, is vital for successful treatment. This research investigates serum metabolites to find diagnostic biomarkers for early OC identification. METHODS: Metabolomic profiles derived from the serum of 60 patients with benign conditions and 60 patients with malignant OC were examined using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Comparative analysis revealed differential metabolites linked to OC, aiding biomarker identification for early-diagnosis of OC via machine learning features. The predictive ability of these biomarkers was evaluated against the traditional biomarker, cancer antigen 125 (CA125). RESULTS: 84 differential metabolites were identified, including 2-Thiothiazolidine-4-carboxylic acid (TTCA), Methionyl-Cysteine, and Citrulline that could serve as potential biomarkers to identify benign conditions and malignant OC. In the diagnosis of early-stage OC, the area under the curve (AUC) for Citrulline was 0.847 (95 % Confidence Interval (CI): 0.719-0.974), compared to 0.770 (95 % CI: 0.596-0.944) for TTCA, and 0.754 for Methionine-Cysteine (95 % CI: 0.589-0.919). These metabolites demonstrate a superior diagnostic capability relative to CA125, which has an AUC of 0.689 (95 % CI: 0.448-0.931). Among these biomarkers, Citrulline stands out as the most promising. Additionally, in the diagnosis of benign conditions and malignant OC, using logistic regression to combine potential biomarkers with CA125 has an AUC of 0.987 (95 % CI: 0.9708-1) has been proven to be more effective than relying solely on the traditional biomarker CA125 with an AUC of 0.933 (95 % CI: 0.870-0.996). Furthermore, among all the differential metabolites, lipid metabolites dominate, significantly impacting glycerophospholipid metabolism pathway. CONCLUSION: The discovered serum metabolite biomarkers demonstrate excellent diagnostic performance for distinguishing between benign conditions and malignant OC and for early diagnosis of malignant OC.

Development and validation of a model and nomogram for breast cancer diagnosis based on quantitative analysis of serum disease-specific haptoglobin N-glycosylation.

BACKGROUND: A better diagnostic marker is in need to distinguish breast cancer from suspicious breast lesions. The abnormal glycosylation of haptoglobin has been documented to assist cancer diagnosis. This study aims to evaluate disease-specific haptoglobin (DSHp)-ß N-glycosylation as a potential biomarker for breast cancer diagnosis. METHODS: DSHp-ß chains of 497 patients with suspicious breast lesions who underwent breast surgery were separated from serum immunoinflammatory-related protein complexes. DSHp-ß N-glycosylation was quantified by mass spectrometric analysis. After missing data imputation and propensity score matching, patients were randomly assigned to the training set (n = 269) and validation set (n = 113). Logistic regression analysis was employed in model and nomogram construction. The diagnostic performance was analyzed with receiver operating characteristic and calibration curves. RESULTS: 95 N-glycopeptides at glycosylation sites N207/N211, N241, and N184 were identified in 235 patients with benign breast diseases and 262 patients with breast cancer. DSHp-ß N-tetrafucosyl and hexafucosyl were significantly increased in breast cancer compared with benign diseases (p < 0.001 and p = 0.001, respectively). The new diagnostic model and nomogram included GN2F2, G6N3F6, GN2FS at N184, G-N&G2S2, G2&G3NFS, G2N3F, GN3 at N207/N211, CEA, CA153, and could reliably distinguish breast cancer from benign diseases. For the training set, validation set, and training and validation sets, the area under the curves (AUCs) were 0.80 (95% CI: 0.75-0.86, specificity: 87%, sensitivity: 62%), 0.77 (95% CI:0.69-0.86, specificity: 75%, sensitivity: 69%), and 0.80 (95% CI:0.76-0.84, specificity: 77%, sensitivity: 68%), respectively. CEA, CA153, and their combination yielded AUCs of 0.62 (95% CI: 0.56-0.67, specificity: 29%, sensitivity: 90%), 0.65 (95% CI: 0.60-0.71, specificity: 74%, sensitivity: 51%), and 0.67 (95% CI: 0.62-0.73, specificity: 60%, sensitivity: 68%), respectively. CONCLUSIONS: The combination of DSHp-ß N-glycopeptides, CEA, and CA153 might be a better serologic marker to differentiate between breast cancer and benign breast diseases. The dysregulated N-glycosylation of serum DSHp-ß could provide insights into breast tumorigenesis.

N-glycosylation of disease-specific haptoglobin for the early screening of diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. EXPERIMENTAL DESIGN: Serum disease-specific haptoglobin-ß (Hp-ß) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry. RESULTS: Fucosylation of Hp-ß was significantly increased and sialylation of Hp-ß was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-ß was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. CONCLUSION: Changes in Hp-ß glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.

Polyurea-magnetic hierarchical porous composites for profiling of anionic metabolites.

Combining powerful adsorption capacity, simple preparation, rapid separation as well as superior stability and recyclability, a polyurea-magnetic hierarchical porous composite has been prepared. It demonstrates efficient physisorption for anionic metabolites in less than one minute and is promising for application to the analysis of a broad range of anionic metabolites in complex matrices.

Case Report: Exploration of changes in serum immunoinflammation-related protein complexes of patients with metastatic breast cancer.

Patients with advanced breast cancer are difficult to treat and have poor prognosis. At present, the commonly used methods to monitor the disease progression of breast cancer are imaging examinations such as breast ultrasound, mammography and peripheral blood tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). However, none of them can detect tumor progression at an early stage. Serum immunoinflammation-related protein complexes (IIRPCs) showed potential to indicate cancer progression. Therefore, we attempted to monitor the level of IIRPCs in peripheral blood of patients with metastatic breast cancer and compare it with patients' treatment and disease progression, and here we performed case reports of two of them.

Serum disease-specific IgG Fc glycosylation as potential biomarkers for nonproliferative diabetic retinopathy using mass spectrometry.

OBJECTIVE: To explore the potential of serum disease-specific immunoglobulin G (DSIgG) glycosylation as a biomarker for the diagnosis of nonproliferative diabetic retinopathy (NPDR). METHODS: A total of 387 consecutive diabetic patients presenting in an eye clinic without proliferative diabetic retinopathy (DR) were included and divided into those with nondiabetic retinopathy (NDR) (n = 181) and NPDR (n = 206) groups. Serum was collected from all patients for DSIgG separation. The enriched glycopeptides of the tryptic digests of DSIgG were detected using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients were randomly divided into discovery and validation sets (1:1). The differences in glycopeptide ratios between the groups were compared by using Student's t-test or the Mann-Whitney U test. The predictive ability of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: DSIgG1 G1FN/G0FN, G2N/G2, G2FN/G2N and DSIgG2 G1F/G0F, G1FN/G0FN, G2N/G1N, G2S/G2 were significantly different between NDR and NPDR patients (p < 0.05) in both the discovery and validation sets. The prediction model that was built comprising the seven glycopeptide ratios showed good NPDR prediction performance with an AUC of 0.85 in the discovery set and 0.87 in the validation set. CONCLUSION: DSIgG Fc N-glycosylation ratios were associated with NPDR and can be used as potential biomarkers for the early diagnosis of DR.

Profiling of Amino Metabolites in Biological Samples without Protein Precipitation Using a Solid-Phase-Supported Phenyl Isothiocyanate-Based Chemoselective Probe.

Amino metabolites are essential for life activities and can be used clinically as biomarkers for disease diagnosis and treatment. Solid-phase-supported chemoselective probes can simplify sample handling and enhance detection sensitivity. However, the low efficiency and complicated preparation of traditional probes limit their further application. In this work, a novel solid-phase-supported probe Fe3O4-SiO2-polymers-phenyl isothiocyanate (FSP-PITC) was developed by immobilizing phenyl isothiocyanate on magnetic beads with disulfide as an orthogonal cleavage site, which can couple amino metabolites directly regardless of whether proteins and other matrixes were removed. After purification, the targeted metabolites were released by dithiothreitol and detected by high-resolution mass spectrometry. The simplified processing steps shorten the analysis time, and the introduction of polymers results in a 100-1000-fold increase in probe capacity. With high stability and specificity, FSP-PITC pretreatment allows accurate qualitative and quantitative (R2 > 0.99) analysis, facilitating the detection of metabolites in subfemtomole quantities. Using this strategy, 4158 metabolite signals were detected in negative ion mode. Among them, 352 amino metabolites including human cells (226), serum (227), and mouse samples (274) were searched from the Human Metabolome Database. These metabolites participate in metabolic pathways of amino acids, biogenic amine, and the urea cycle. All these results indicate that FSP-PITC is a promising probe for novel metabolite discovery and high-throughput screening.

Disease-Specific haptoglobin N-Glycosylation in inflammatory disorders between cancers and benign diseases of 3 types of female internal genital organs.

BACKGROUND: N-glycosylation of the haptoglobin is closely related to pathological states. This study aims to evaluate the association of glycosylation of disease-specific Hp (DSHp) ß chain with different pathological states of the cervix, uterus, and ovary to explore differences in their inflammatory responses and to screen potential biomarkers to distinguish cancer from benign diseases. METHODS: DSHp-ß chains of 1956 patients with cancers and benign diseases located in the cervix, uterus, and ovary organs were separated from serum immunoinflammatory-related protein complexes (IIRPCs). The N-glycopeptides from DSHp-ß chains were detected using mass spectrometry, followed by an analysis of machine learning algorithms. RESULTS: 55 N-glycopeptides at N207/N211, 19 at N241, and 21 at N184 glycosylation sites of DSHp for each sample were identified. Fucosylation and sialylation of DSHp in cervix, uterus, and ovary cancer were significantly increased compared to their corresponding benign diseases (p < 0.001). The cervix diagnostic model, a combination of G2N3F, G4NFS, G7N2F2S5, GS-N&GS-N, G2N2&G4N3FS, G7N2F2S5, G2S2&G-N, and GN2F&G2F at N207/N211 sites, G3NFS2 and G3NFS at N241site, G9N2S, G6N3F6, G4N3F5S, G4N3F4S2, and G6N3F4S at N184 site), has shown a good diagnostic capability to distinguish cancer from benign diseases, with the area under curve (AUC) of 0.912. The uterus diagnostic model including G4NFS, G2S2&G2S2, G3N2S2, GG5N2F5, G2&G3NFS, and G5N2F3S3 at N207/N211 sites, and G2NF3S2 at N184 site, with an AUC of 0.731. The ovary diagnostic model including G2N3F, GF2S-N &G2F3S2, G2S&G2, and G2S&G3NS at N207/N211 sites; G2S and G3NFS at N241 site, G6N3F4S at N184 site, with an AUC of 0.747. CONCLUSIONS: These findings provide insights into differences in organ-specific inflammatory responses of DSHp for different pathological states among the organs of the cervix, uterus, and ovary.

Facile synthesis of amino-functionalized magnetic materials for efficient enrichment of anionic metabolites from biological samples.

The analysis of biological samples is often affected by the background matrix. Proper sample preparation is a critical step in the analytical procedure for complex samples. In this study, a simple and efficient enrichment strategy based on Amino-functionalized Polymer-Magnetic MicroParticles (NH2-PMMPs) with coral-like porous structures was developed to enable the detection of 320 anionic metabolites, providing detailed coverage of phosphorylation metabolism. Among them, 102 polar phosphate metabolites including nucleotides, cyclic nucleotides, sugar nucleotides, phosphate sugars, and phosphates, were enriched and identified from serum, tissues, and cells. Furthermore, the detection of 34 previously unknown polar phosphate metabolites in serum samples demonstrates the advantages of this efficient enrichment method for mass spectrometric analysis. The limit of detections (LODs) were between 0.02 and 4 nmol/L for most anionic metabolites and its high sensitivity enabled the detection of 36 polar anion metabolites from 10 cell equivalent samples. This study has provided a promising tool for the efficient enrichment and analysis of anionic metabolites in biological samples with high sensitivity and broad coverage, facilitating the knowledge of the phosphorylation processes of life.

Diagnostic potential of site-specific serotransferrin N-glycosylation in discriminating different liver diseases.

BACKGROUND: Altered glycosylation modulates the structure and function of disease-related proteins. The associations between serotransferrin (STF) N-glycosylation and liver diseases (LDs) have been revealed. However, how intact N-glycopeptides vary among different types of liver diseases remains unclear. METHODS: Intact STF N-glycopeptides from patients with chronic liver disease (CLD, n = 92), primary liver cancer (PLC, n = 123), metastatic liver cancer (MLC, n = 57), and healthy controls (HCs, n = 59) were determined using high-resolution mass spectrometry. RESULTS: Significant changes were displayed in STF glycosylation among 4 groups. The LD screening model, including Asn432 G1S/G2S, Asn432 G2S/G2S2, and Asn630 G2NS2/G2FNS2, was constructed to differentiate LDs from HCs, with a AUC of 0.92. The liver cancer (LC) diagnostic model, a combination of Asn432 G1-N/G1S-N, Asn432 G1/G2, Asn432 G2FS/G2FS2, and Asn630 G1S-N /G1S, showed good performance in discriminating LC from CLD (AUC = 0.93). Moreover, AFP-negative LC patients (93 %) were successfully predicted by the LC diagnostic model. Furthermore, the MLC triage model, composed of Asn432 G1/G2, Asn432 G3F/G3FS, Asn630 G2/G2S, Asn630 G2S2/G2NS2, and Asn630 G3FS/G3FS2, yielded an AUC of 0.98 between PLC and MLC. CONCLUSIONS: STF N-glycosylation is a potential biomarker for the accurate classification of different LDs.

Intra-Individual Variation in Disease-Specific IgG Fc Glycoform Ratios to Monitor the Disease Progression of Lung Cancer.

Aberrant protein glycosylation is an active pathological alteration related to the progression of cancers. The speed of progression varies among individuals, increasing the difficulties of prognosis assessment. Hence, evaluating variation in glycosylation using patients themselves as their own controls is a potential way to reduce the impact of individual differences on progression monitoring. Here, following a longitudinal follow-up study involving 125 lung cancer (LC) patients with progressive disease, we isolated disease-specific IgG from serum using polyacrylamide gel electrophoresis, obtained IgG glycoform ratios using mass spectrometry, and then set a fold-change cutoff of 1.5 to utilize the intra-individual variation in IgG glycosylation to monitor PD. We found that the serial monitoring of 15 types of glycoform ratios provided an effective way for monitoring LC progression. Over 1.5-fold changes in glycoform ratios relative to the first observed value were detected in 117 of 125 LC patients (93.6%). Our established method predicted LC progression 55.8 (IQR 31.1-90.1) weeks earlier than imaging examination did. In summary, intra-individual variation in IgG glycoform ratios is useful to monitor LC progression, expanding our knowledge about the relationship between IgG glycosylation and cancer prognosis. The raw data files are available via the ProteomeXchange Consortium with the identifier PXD037541.

Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

Polyurea-Modified Magnetic Particles with Versatile Probes for Chemoselective Capture of Carbonyl Metabolites and Biomarker Discovery.

Playing a great role in human physiologies and pathologies, carbonyl metabolites are intimately associated with a variety of diseases, though the effective analysis method of them remains a challenge. A hydrazide-terminated polyurea-modified magnetic particle (HPMP) with versatile probes is developed to address this issue. The capture ability of HPMPs for carbonyl metabolite is more than 1200 µmol g-1 , which is increased by 4 orders of magnitude via the introduction of polyurea. With a broad linear range of over 4 orders of magnitude, remarkably improved sensitivity, and limit of detection at attomole quantities, HPMPs are applied in relative quantification of more than 1500 carbonyl metabolites in 113 human serum samples with high throughput and high coverage. The combined indicators of these metabolites demonstrates a great diagnostic accuracy for distinguishing between health and disease subjects as well as differentiating the patients with benign lung disease and lung cancer. Combining powerful capture ability, low-cost preparation, and convenient operation, the HPMPs demonstrate extensive application in biomarker discovery and the detailed study of the biochemical landscape.

Coral-like Magnetic Particles for Chemoselective Extraction of Anionic Metabolites.

To date, advanced chemical biology tools for chemoselective extraction of metabolites are limited. In this study, unique coral-like polymer particles were synthesized via high concentrations of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS), which are usually used as condensation agents. The polymers can wrap or adhere Fe3O4 nanoparticles (Fe3O4-NPs) to form polymer magnetic microparticles (PMMPs). With abundant NHS-activated moieties on their surface, the coral-like PMMPs could be modified by cystamine for the chemoselective extraction of phosphate/carboxylate anion metabolites from complex biological samples. Finally, 97 metabolites including nucleotides, phosphates, phosphate sugars, carboxylate sugars, and organic acids were extracted and identified from serum, tissues, and cells. These metabolites are involved in four major metabolic pathways including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, and nucleotide metabolism. This study has provided a cost-effective and easy-to-implement preparation of PMMPs with a robust chemoselective extraction ability and versatile applications.

Small molecules as potential biomarkers of early gastric cancer: A mass spectrometry imaging approach.

BACKGROUND AND AIMS: Early detection of gastric cancer is an effective way to decrease the associated mortality. Efficient methods are needed to provide more sensitive biomarkers for detection of early gastric cancer (EGC). MATERIALS AND METHODS: We performed liquid extraction-electrosonic spray ionization mass spectrometry imaging and immunofluorescent staining of enzymes related to lipid synthesis on cancerous and paracancerous tissues obtained from six EGC patients and investigated the serum lipid profiles. Areas under the receiver operating characteristic curves were used to determine the diagnostic accuracy of putative biomarkers. RESULTS: Five lipids detected in the positive ion mode and seven in negative ion mode displayed higher relative intensities in the cancerous than the paracancerous tissues. Seven lipids detected in the positive ion mode and seven in the negative ion mode displayed lower relative intensities in the cancerous than the paracancerous regions. Phosphatidylcholine (34:3) and phosphatidylcholine (36:1) showed higher relative intensities in the cancerous than in the paracancerous tissues and showed higher relative intensities in the serum of EGC patients than healthy controls. Phosphatidylcholine (32:0) showed lower relative intensities in the cancerous than in the paracancerous tissues and lower relative intensities in the serum of EGC patients than healthy controls. The areas under the receiver operating characteristic curves of serum phosphatidylcholine (32:0) and phosphatidylcholine (34:3) for identifying EGC patients were 1.000 and 0.978, respectively. CONCLUSIONS: Regions associated with EGC showed different lipid distributions and enzyme expression from the paracancerous regions. Serum Phosphatidylcholine (32:0) and phosphatidylcholine (34:3) are potential biomarkers for discriminating between EGC patients and healthy controls.

Panax notoginseng Alleviates Sepsis-Induced Acute Kidney Injury by Reducing Inflammation in Rats.

Background: Sepsis is defined as a host inflammatory response to infection that can result in end-organ dysfunction. One of the most common consequences of sepsis is acute kidney injury (AKI). Panax notoginseng powder (PNP) has been previously reported to protect against overactive inflammation process. However, the potential effect of PNP on septic AKI is poorly described. The current study was conducted to investigate the protective effects of PNP in septic AKI rats. Methods: A model of septic AKI was established on male SD rats by using the cecal ligation and puncture procedure. PNP was administrated by gavage after the cecal ligation and puncture (CLP) procedure, and the mice were sacrificed at 6, 12, and 72 h after induction of sepsis. The serum and kidney samples were collected and assayed for biochemical tests, histopathological staining, inflammation, and apoptosis-related gene/protein expression. In addition, 15 rats in each group were used to calculate the 7-day survival rate. Results: CLP-induced kidney injury was observed by the histopathological score, which markedly was attenuated by PNP treatment. Consistently, PNP intervention significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in CLP-induced sepsis rats. The CLP procedure also triggered proinflammatory cytokine production and increased the expression of various inflammation-related proteins in the kidneys. However, PNP inhibited the renal expression of IL-18, IL-1ß, TNF-α, and IL-6 to substantially improve inflammatory response. Mechanistically, CLP induced the increase of the NF-κB p65 level in the injured kidneys, while PNP notably inhibited the corresponding protein expression. Conclusion: PNP attenuated kidney inflammation to protect against CLP-induced septic AKI in rats via inhibiting the NF-κB signaling pathway.

Serum immunoinflammatory-related protein complexes as personalized biomarkers for monitoring disease progression and response to treatment in lung cancer patients.

BACKGROUND: Although routine surveillance to detect lung cancer recurrence with clinical imaging is recommended, early detection of disease progression has a major role in avoiding over-treatment. METHODS: Here, serum immunoinflammatory-related protein complexes (IIRPCs) of a series of 1331 serum samples collected from 119 patients during the follow-up period were isolated using native-PAGE and then their levels were quantified. The associations of representative IIRPCs levels at their beginning, maximum, and minimum and the ratios of the maximum or minimum to the beginning IIRPCs levels with clinical characteristics were statistically analyzed. RESULTS: The statistical results indicate that patients with these ratios below the first quantiles of the minimum ratios had shorter progressive-free survival (PFS) and the follow-up time points for 108 of 113 patients with over 1.5-fold change in IIRPCs level relative to the beginning level as the beginning time point of humoral immune response has a median lead time of 61.9 weeks (IQR, 30.9-105.3) relative to progressive disease(PD) detected using clinical imaging. CONCLUSIONS: These findings suggest that changes in IIRPCs levels may be early-warning signals of disease progression and response to treatment for lung cancer patients.

Profiling of amines in biological samples using polythioester-functionalized magnetic nanoprobe.

Introduction: The metabolic balance of amines is closely related to human health. It remains a great challenge to analyze amines with high-throughput and high-coverage. Methods: Polythioester-functionalized magnetic nanoprobes (PMPs) have been prepared under mild conditions and applied in chemoselective capture of amides. With the introduction of polythioester, PMPs demonstrate remarkably increased capture efficiency, leading to the dramatically improved sensitivity of mass spectrometry detection. Results: The analysis method with PMPs treatment has been applied in rapid detection of more than 100 amines in lung adenocarcinoma cell lines, mouse organ tissues, and 103 human serum samples with high-throughput and high-coverage. Statistical analysis shows that arginine biosynthesis differed between lung adenocarcinoma cell lines. Discussion: Phenylalanine, tyrosine and tryptophan biosynthesis differed between tissues. The combination indicators demonstrate a great diagnostic accuracy for distinguishing between health and lung disease subjects as well as differentiating the patients with benign lung disease and lung cancer. With powerful capture ability, low-cost preparation, and convenient separation, the PMPs demonstrate promising application in the intensive study of metabolic pathways and early diagnosis of disease.high-throughput and high-coverage. Here, polythioester-functionalized magnetic nanoprobes (PMPs) have been prepared under mild conditions and applied in chemoselective capture of amides. With the introduction of polythioester, PMPs demonstrate remarkably increased capture efficiency, leading to the dramatically improved sensitivity of mass spectrometry detection. The analysis method with PMPs treatment has been applied in rapid detection of more than 100 amines in lung adenocarcinoma cell lines, mouse organ tissues, and 103 human serum samples with high-throughput and high-coverage. Statistical analysis shows that arginine biosynthesis differed between lung adenocarcinoma cell lines. Phenylalanine, tyrosine and tryptophan biosynthesis differed between tissues. The combination indicators demonstrate a great diagnostic accuracy for distinguishing between health and lung disease subjects as well as differentiating the patients with benign lung disease and lung cancer. With powerful capture ability, low-cost preparation, and convenient separation, the PMPs demonstrate promising application in the intensive study of metabolic pathways and early diagnosis of disease.

[Effects of long-term oral administration of ß-blocker on septic myocardial injury and prognosis].

OBJECTIVE: To investigate the effect of long-term oral administration of ß-blocker on septic myocardial injury and prognosis. METHODS: A retrospective study was conducted. Patients who were admitted to the emergency intensive care unit (EICU) and intensive care unit (ICU) of Tongde Hospital of Zhejiang Province from January 2015 to June 2020 were enrolled. A total of 289 patients who met the criteria of myocardial injury induced by sepsis were included in the analysis. Among them, 187 patients who had never taken ß-blocker within 3 months before diagnosis were divided in the non-ß-blocker group, and 102 patients who took ß-blocker daily for more than 3 months before diagnosis were in the ß-blocker group. The physiological and biochemical characteristics were compared between the two groups, including heart rate, mean arterial pressure (MAP) at the time of diagnosis, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), MB isoenzyme of creatine kinase (CK-MB), blood lactic acid (Lac), central venous oxygen saturation (ScvO2), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of diagnosis, left ventricular ejection fraction (LVEF), early and late mitral orifice diastolic peak flow velocity ratio (E/A), utilization rate of vasoactive drugs during hospitalization and 28-day mortality. RESULTS: The heart rate in the ß-blocker group at the time of diagnosis was significantly lower than that in the non-ß-blocker group (bpm: 107±8 vs. 110±7, P < 0.01), and the levels of cTnI and BNP within 24 hours of diagnosis were significantly lower than those in the non-ß-blocker group [cTnI (µg/L): 0.191 (0.220) vs. 0.291 (0.300), BNP (ng/L): 627 (133) vs. 690 (201), both P < 0.05]. However, there were no significant differences in MAP, CK-MB, Lac, ScvO2, SOFA score, APACHE II score, LVEF, E/A, vasoactive drug utilization rate, and 28-day mortality between the ß-blocker and non-ß-blocker groups [MAP (mmHg, 1 mmHg = 0.133 kPa): 70.6±3.9 vs. 69.9±3.8, CK-MB (µg/L): 4.24 (3.33) vs. 4.32 (3.13), Lac (mmol/L): 3.50 (1.80) vs. 3.50 (1.90), ScvO2: 0.729±0.032 vs. 0.735±0.041, SOFA score: 7.74±2.34 vs. 7.25±2.23, APACHE II score: 17.19±5.13 vs. 18.27±6.12, LVEF: 0.567±0.058 vs. 0.557±0.051, E/A: 0.71 (0.20) vs. 0.69 (0.20), vasoactive drug utilization rate: 60.8% (62/102) vs. 56.7% (106/187), 28-day mortality: 23.5% (24/102) vs. 25.7% (48/187), all P > 0.05]. CONCLUSIONS: Long-term oral administration of ß-blocker reduce myocardial injury in septic patients, and has no effect on disease severity and prognosis.