Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

Background Volatile organic compounds (VOCs) in exhaled breath are closely associated with respiratory diseases and are linked to various metabolic reactions in the human body. A quantitative analytical method can provide technical support for studying VOCs related to various diseases. Objective To establish a thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method for the determination of 27 VOCs in exhaled breath. Methods VOCs in exhaled breath were collected using a Bio-VOC sampler and enriched with Tenax TA thermal desorption tubes before TD-GC-MS analysis. Standards were collected using thermal desorption tubes and optimized for thermal desorption conditions as well as chromatographic and mass spectrometric conditions: The separation of the 27 VOCs was achieved by an optimized temperature program, the improvement of sensitivity by optimizing quantitative ions, and the increase of VOCs desorption efficiency by optimizing thermal desorption time and temperature. Limit of detection, limit of quantification, accuracy, precision, and stability of the proposed method were investigated by spiking with a blank gas bag, and exhaled breath samples from 20 healthy individuals were collected for an application study of the proposed method. Results The thermal desorption temperature was 280 ℃, and desorption time was 6 min. A VF-624ms chromatographic column was selected for the separation of target substances. The initial temperature of heating program was 35 ℃, maintained for 1 min, and then increased to 100 ℃ at a heating rate of 3 ℃·min⁻¹ for 1 min, followed by increasing to 210 ℃ at a heating rate of 28 ℃·min⁻¹ for 5 min. A quantitative analysis was conducted with a single ion monitoring (SIM) mode. Under these conditions, the 27 VOCs showed good linear relationships in their respective concentration ranges and the correlation coefficients were higher than 0.9990. The limits of detection of the method were in the range of 0.01-0.13 nmol·mol⁻¹, the limits of quantification were in the range of 0.02-0.44 nmol·mol⁻¹, and the spiked recoveries were in the range of 80.1%-120.5%, with intra-batch and inter-batch precision ≤ 18.8% and 17.9% respectively. All substances can be stored at room temperature (23-28 °C) for 7 d and at 4 °C for 14 d. The proposed method was applied to exhaled breath samples from 20 subjects with detection rates≥ 80% (except for trans-2-pentene and decane) and a concentration range of 0.00-465.50 nmol·mol⁻¹. Conclusion The established TD-GC-MS method for quantification of VOCs in exhaled breath is characterized by high sensitivity and good accuracy, and is suitable for quantitative determination of VOCs in exhaled breath, which can provide technical support for the study of exhaled breath VOCs.

The composition and concentration of volatile organic compounds (VOCs) in exhaled breath are closely related to human health and the analysis of VOCs by collecting human exhaled breath has been widely used in disease surveillance research. This article reviewed the collection, enrichment, and detection methods of exhaled VOCs, which can provide a reference for selecting appropriate technology for follow-up research. The exhaled breath collection devices mainly include sampling bags for mixed exhaled breath and biological volatile organic compound (Bio-VOC) samplers for alveolar air. The pre-enrichment equipment included thermal desorption (TD), solid-phase microextraction device (SPME), and needle trap device (NTD). The detection methods of exhaled VOCs include gas chromatography-mass spectrometry (GC-MS), proton transfer reaction mass spectrometry (PTR-MS), selective ion flow tube mass spectrometry (SIFT-MS), and electronic nose. At present, the collection and enrichment technology of exhaled breath is not mature yet, and its influence on the results of detection is lack of evaluation. In the future, the research on collection and enrichment technology of exhaled breath should be strengthened to further promote the application of exhaled breath in disease surveillance research.

ObjectiveTo investigate the relative content changes of differential metabolites and reducing sugars during the processing process of Rehmanniae Radix Praeparata （RRP） processed with Amomi Fructus （AF） and Citri Reticulatae Pericarpium （CRP）， and to lay the foundation for revealing the processing principle of this characteristic variety. MethodThe samples of the 0-54 h processing process of RRP processed with AF and CRP were taken as the research object， and their secondary metabolites were detected by ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. The 0.1% formic acid aqueous solution （A）-acetonitrile （B） was used as the mobile phase for gradient elution （0-1 min， 1%-3%B； 1-10 min， 3%-9%B； 10-15 min， 9%-12%B； 15-22 min， 12%-18%B； 22-31 min， 18%-24%B； 31-35 min， 24%-100%B； 35-36 min， 100%-5%B； 36-40 min， 5%-1%B； 40-45 min， 1%B）， column temperature was 40 ℃， injection volume was 3 μL， flow rate was 0.3 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in the negative ion mode， the scanning range was m/z 50-1 250. Data analysis was carried out using PeakView 1.2 software， and the chemical composition of RRP processed with AF and CRP was identified by combining the literature information and chemical composition databases. The MS data were normalized by MarkerView 1.2， and then the multivariate statistical analysis was applied to screen the differential metabolites， and the changes of the relative contents of the differential metabolites with different processing times was analyzed， finally， correlation analysis was performed between the differential metabolites， the change of the reducing sugar content was combined to determine the most suitable processing time of RRP processed with AF and CRP. ResultA total of 121 compounds were identified from RRP processed with AF and CRP at different processing times， and 12 differential metabolites were screened out by multivariate statistical analysis， including catalpol， hesperidin， isoacteoside， acteoside， narirutin， echinacoside， isomartynoside， decaffeoylacteoside， 6-O-E-feruloylajugol， dihydroxy-7-O-neohesperidin， jionoside D， and rehmapicroside. With the prolongation of processing time， the relative contents of these 12 differential metabolites and reducing sugars changed slightly at 52-54 h. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents of RRP processed with AF and CRP at different processing times， and the suitable processing time of 52-54 h is determined according to the content changes of different metabolites and reducing sugars， which provides a basis for revealing the scientific connotation of the processing principle of this variety.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

OBJECTIVE: To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements. METHODS: Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively. RESULTS: By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT. CONCLUSION The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Translocation, Genetic ; Gene Rearrangement ; Prognosis

Objective To predict the molecular mechanism of Dihuang (Rehmanniae Radix) in the treatment of diabetic nephropathy (DN) complicated with depression based on network pharmacology. Methods The components of Dihuang (Rehmanniae Radix) were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and relevant literature. The component targets were detected by combining the SwissTargetPrediction and PubChem databases. Disease targets were collected from the Therapeutic Target Database (TTD), DisGeNET, and Ensembl databases with “diabetic nephropathy” and “depression” as keywords. The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape 3.7.2. The co-expression genes of the key targets were collected based on the COXPRESdb 7.3. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for potential targets using R language. Target-component docking was verified and evaluated using Discovery Studio 4.5. Results According to the databases and literature reports, Dihuang (Rehmanniae Radix) contained 65 active components, and had 155 related targets for the treatment of DN complicated with depression. PPI screening showed that the key targets included serine/threonine protein kinase 1 (AKT1), signal transducer and activator transcription 3 (STAT3), interleukin 6 (IL-6), mitogen-activated protein kinase 1 (MAPK1), and vascular endothelial growth factor A (VEGFA), etc. GO enrichment analysis mainly involved biological processes, such as lipid metabolism, protein secretion regulation, cell homeostasis, and phosphatidylinositol 3 kinase activity. KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements, insulin resistance (IR), neurotrophin signal path, Toll-like receptor signaling pathway, relaxin signaling pathway, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), etc. Molecular docking showed that the target had high affinity for stachyose, manninotriose, verbascose, nigerose, etc. Conclusion Based on network parmacology, this study preliminarily predict the effects of Dihuang (Rehmanniae Radix) in treating DN complicated with depression by regulating inflammation, glucose metabolism, nution nerve, etc.

Objective:To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People′s Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test.Results:The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome.Conclusion:Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.

Objective: To compare the cytogenetic response detected by conventional banding analysis (CBA) and fluorescence in situ hybridization (FISH) and to explore the correlation between the cytogenetic and molecular response in chronic myeloid leukemia (CML) patients during tyrosine kinase inhibitor (TKI) treatment. Methods: CBA, FISH and real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) methods were performed to detect the cytogenetic and molecular response simultaneously in 504 bone marrow samples from 367 CML patients who received TKI treatment. Results: Among 504 samples, 344 were detected to reach complete cytogenetic response (CCyR) by CBA, while 297 samples reached CCyR by FISH which were considered to carry BCR-ABL positive cells<1%. When the results of CBA, FISH and RQ-PCR were compared in 493 samples at the same time, it showed that in 337 samples with CBA-CCyR, 273 (81.0%) reached FISH-CCyR and 289 (85.8%) were BCR-ABL^IS (International Scale, IS) ≤1% by RQ-PCR, compared to 9.0 (261/290) were BCR-ABL^IS ≤1% among 290 samples with FISH-CCyR. There was no significant difference in the median value of BCR-ABL^IS between samples in CBA-CCyR and FISH-CCyR (0.21% vs 0.13%, z=-1.875, P=0.061) . Furthermore, when the samples were divided into three groups according to BCR-ABL positive cells (0,>0~<1%, 1%~5%) by FISH, the statistical difference was observed, the proportion of samples with BCR-ABL^IS ≤1% in the three groups were 94.1%, 57.6% and 27.7% respectively (χ²=43.499, P<0.001; χ²=9.734, P=0.003) , while the median value of BCR-ABL^IS were 0.10%, 0.64% and 1.80% respectively (z=-5.864, P<0.001; z=-4.787, P<0.001) . Conclusion FISH results were in good concordance with CBA in identify samples in CCyR, FISH was more sensitive and had better correlation with RQ-PCR results than CBA, but how to define FISH-CCyR need further study.

The aim of the study was to investigate the effect of oleic acid(OA)and isosorbide mononitrate(ISMN)on the phase diagrams of glyceryl monooleate(GMO)liquid crystalline systems and release of ISMN from them. Liquid crystalline systems of GMO/H2O, GMO/H2O/ISMN and GMO/H2O/OA were prepared and their phase diagrams were plotted. Investigation of water absorption of GMO and ISMN release profiles shown that the release mechanism of ISMN was diffusion-controlled. Increased drug loading accelerated the release rate. However, the increased loading of OA decreased ISMN release. The result could offer practical basis for drug loading and the selection of additives in GMO liquid crystalline system.