Integration of network pharmacology and experimental verifications reveals the Bian-Se-Tong mixture can alleviate constipation in STC rats by reducing apoptosis of Cajal cells via activating PI3K-Akt signaling pathway.

Bian-Se-Tong mixture (BSTM) is an optimized formulation based on the classical prescription "Zhizhu pill", which is widely used in the clinical treatment of slow-transit constipation (STC). The potential molecular mechanism of BSTM therapy for STC was investigated by network pharmacology prediction combined with animal experiments. The active components of BSTM were screened via the TCMSP platform. The GeneCards, OMIM and DrugBank databases were used to search for STC targets. With the help of the Biogenet tool, a protein interaction network between drugs and disease targets was constructed, and the intersection network of the two was extracted to obtain the key targets of BSTM in the treatment of STC. GO and KEGG enrichment analyses of key targets were carried out with Metascape. Loperamide hydrochloride was used to establish an STC rat model, and the key targets and related pathways were preliminarily verified. The important signaling pathways included the PI3K-Akt, MAPK, IL-17, cAMP, and cell cycle signaling pathways. The experimental results showed that BSTM treatment increased the body weight of STC rats and increased the fecal particle number, fecal water content and intestinal carbon ink promotion rate within 24 h. Further pathological changes in the colon of the rats were also observed. In-depth mechanistic studies have shown that BSTM can significantly reduce the apoptosis of intestinal Cajal cells, downregulate the expression of Bax and c-Caspase 3, upregulate the expression of Bcl-2 and c-kit, and promote the phosphorylation of AKT. The results showed that BSTM can significantly relieve constipation in STC rats via a mechanism related to activating the PI3K-Akt signaling pathway and improving Cajal cell apoptosis.

Prognostic value of tumor­associated CD177+ neutrophils in lung adenocarcinoma.

The aim of the present study was to detect CD177+ neutrophils in tumor tissues and analyze their association with the clinical characteristics and prognosis of patients with lung adenocarcinoma (LUAD). Immunohistochemistry was used to detect CD177+ neutrophils in tumors and adjacent tissues of 16 patients with LUAD who underwent curative surgical resection. A total of 120 patients with LUAD were recruited, and their clinical data were collected; survival follow-up was performed. CD177+ neutrophils in tumor tissues were detected via immunohistochemistry, and the association between CD177+ neutrophils and clinical characteristics was analyzed. The density of CD177+ neutrophils in tumor tissues and adjacent tissues of patients with LUAD was analyzed using t-test, and the association between CD177+ neutrophils and clinical characteristics was analyzed through the Chi-square test. Survival was calculated using the Kaplan-Meier survival rate curve. Finally, the association between these indicators and the survival of LUAD patients was evaluated using Cox regression analysis. CD177+ neutrophil infiltration was significantly higher in LUAD tumor tissues, and the high density of CD177+ neutrophils was associated with the clinical characteristics of TNM stage, tumor differentiation and poor progression-free and overall survival in LUAD. In conclusion, tumor-associated CD177+ neutrophils associated with malignant progression and poor prognosis may be independent and unfavorable prognostic biomarkers for LUAD.

Ginkgolides with anti-PAF activity from Ginkgo biloba L.

Four undescribed ginkgolides, including two rare sesquiterpene ginkgolides (compounds 1 and 2) and two diterpenoid ginkgolides (compounds 3 and 4), were isolated from Ginkgo biloba L. The structures of these four ginkgolides were identified based on extensive spectroscopic analysis, DP4+ probability analysis and X-ray diffraction. Compounds 1 and 2 exhibited excellent antiplatelet aggregation activities with IC50 values of 1.20 ± 0.25 and 4.11 ± 0.34 µM, respectively.

Xiebai San alleviates acute lung injury by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating multiple metabolisms.

BACKGROUND: Acute lung injury (ALI) often leads to serious respiratory diseases with high incidence rates and mortality. For centuries, Xiebai San (XBS) has been a classical traditional Chinese medicine (TCM) about respiratory illness such as pneumonia in children. However, the related mechanism of XBS against ALI remains indistinct. PURPOSE: To reveal specific targets of XBS in lipopolysaccharide (LPS)-induced ALI mice using integrated pharmacology. STUDY DESIGN: The integrated method was to expound mechanism and targets of XBS inhibited ALI. METHODS: The primary components in XBS were identified by ultra high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS). The potential drug targets were established using network pharmacology. The anti-ALI effect of XBS was evaluated in mice. Additionally, therapeutic targets were screened by integrating metabolome and transcriptome and verified in lung tissue. RESULTS: In total, 163 chemical components were identified in XBS, and a network of "3 drugs-18 components-86 targets" for XBS against ALI was constructed. In ALI mice, XBS alleviated lung inflammation by decreasing permeation and expression of neutrophils, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF), serum, and lung tissue. Next, the transcriptome of lung tissue was analyzed and enriched, indicating the importance of mitogen-activated protein kinase (MAPK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and others, which was consistent with network pharmacology prediction. Also, western blotting and immunohistochemistry results showed that XBS was against ALI mainly by inhibiting extracellular signal regulated kinase (ERK) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. In addition, the metabolome of lung tissue revealed that XBS mainly regulated pathways involved in arachidonic acid, glycerophospholipid, and tryptophan metabolisms. The expression levels of leukotriene, phosphatidylcholine, kynurenine, and others were also verified. CONCLUSION: XBS alleviated inflammation of ALI by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating arachidonic acid, glycerophospholipid, and tryptophan metabolisms. This study will guide clinical precision medicine and promote modernization of XBS.

Metabolomic analysis revealed the edible and extended-application potential of specific Polygonum multiflorum tissues.

The diverse applications of various tissues of Polygonum Multiflorum (PM) encompass the use of its leaf and bud as tea and vegetables, as well as the utilization of its expanded root tubers and caulis as medicinal substances. However, previous studies in the field of metabolomics have primarily focused on the medicinal properties of PM. In order to investigate the potential for broader applications of other tissues within PM, a metabolomic analysis was conducted for the first time using UPLC-Q-TOF-MS/MS on 15 fresh PM tissues. A total of 231 compounds, including newly discovered compounds such as torosachrysone and dihydro-trihydroxystilbene acid derivatives, were identified within PM. Through clustering analysis, the PM tissues were categorized into edible and medicinal parts, with edible tissues exhibiting higher levels of phenolic acids, organic acids, and flavonoids, while the accumulation of quinones, dianthrones, stilbenes, and xanthones was observed in medicinal tissues. Comparative analysis demonstrated the potential application of discarded tissues, such as unexpanded root tuber (an industrial alternative to expanded root tuber) and young caulis (with edible potential). Moreover, the quantification of representative metabolites indicated that flowers and buds contained significant amounts of flavonoids or phenolic acids, suggesting their potential as functional food. Additionally, the edible portion of PM exhibited a high content of quercitrin, ranging from 0.59 to 10.37 mg/g. These findings serve as a valuable point of reference for the expanded utilization of PM tissues, thereby mitigating resource waste in this plant.

Circ_UBAP2 exacerbates proliferation and metastasis of OS via targeting miR-665/miR-370-3p/HMGA1 axis.

Circ_UBAP2 is extensively engaged in regulating the development of various malignancies, containing osteosarcoma (OS). However, its biological significance and function are not fully understood. In this study, we found that circ_UBAP2 and HMGA1 levels were up-regulated, and miR-370-3p and miR-665 expressions were decreased in osteosarcoma tissues. Inhibition of circ_UBAP2 or HMGA1 expression in OS cells, cell viability, invasion and migration abilitities were notably hindered, and cell apoptosis abilities were increased. Bioinformatics analysis predicted that miR-665 and miR-370-3p were the downstream targets of circ_UBAP2, and the dual luciferase experiment demonstrated the correlation between them. In addition, inhibition of miR-665 and miR-370-3p expression could significantly reverse the impact of knocking down circ_UBAP2 on OS cells. HMGA1 was discovered to become the downstream target of both miR-665 and miR-370-3p. It was shown that over-expression of miR-665 or miR-370-3p notably stimulated the cell growth, invasion, and migration of osteosarcoma cells, while hindered cell apoptosis. Nevertheless, this effect could be reversed by concurrent over-expression of HMGA1. Our data strongly prove that circ_UBAP2 makes a vital impact on promoting the proliferation, invasion as well as migration of osteosarcoma cells via down-regulating the level of miR-665 and miR-370-3p, and later up-regulating the level of HMGA1. In conclusion, circ_UBAP2 is upregulated in osteosarcoma, and it competitively adsorbs miR-370-3p and miR-665, resulting in up-regulation of HMGA1, thus promoting OS development.

ASPSCR-1 and Sirt-5 alleviate Clonorchis liver fluke rCsNOSIP-induced oxidative stress, proliferation, and migration in cholangiocarcinoma cells.

BACKGROUND: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma. It has been well known that NO from chronic inflammation responses are thought to be a major component of the damage and ultimate carcinogenesis ESPs such as nitric oxide synthase interacting protein (NOSIP) are thought to enhance the damage. The objective of this study was to identify the protein candidates interact with recombinant CsNOSIP (rCsNOSIP) and explore their role involved in CCA development or progression. METHODS: We applied HuProt microarray containing 21,000 probe sets for a systematic identification of rCsNOSIP-binding proteins and grouped binding hits by gene function. Pull-down assays were used to confirm the interaction of rCsNOSIP with alveolar soft part sarcoma (ASPSCR-1) and sirtuins 5 (Sirt-5). ASPSCR-1/Sirt-5 over-expression and siRNA knockdown experiments were employed for obtain of ASPSCR-1/Sirt-5 high or low expression (ASP-oe/Sirt5-oe or ASP-si/Sirt5-si) cholangiocarcinoma cell line (CCLP-1) cells. Nitric oxide (NO) and reactive oxygen species assay (ROS) as well as cell proliferation and wound-healing assays were performed to observe the effect of rCsNOSIP on ASP-oe/Sirt5-oe or ASP-si/Sirt5-si CCLP-1 cells. RESULTS: Seventy candidate proteins protein "hits" were detected as rCsNOSIP-binding proteins by HuProt microarray and bioinformatics analysis. Pull down assay showed that ASPSCR-1 and Sirt-5 could interact with rCsNOSIP. In addition, endotoxin-free-rCsNOSIP could increase the production of NO and ROS and promote the migration of CCLP-1 cells, while its effect on enhancing cell proliferation was not significant. Furthermore, ROS/NO production, proliferation, or migration were increased in ASP-si or Sirt5-si CCLP-1 cells but decreased in Asp-oe or Sirt5-oe CCLP-1 cells when stimulated with rCsNOSIP. CONCLUSIONS: Our findings suggest that CsNOSIP as a component of CsESPs might promote the development and invasion of CCA and Sirt5/ ASPSCR1 as host molecules might play a novel protective role against adverse stimulus during C. sinensis infection. This work supports the idea that CsESPs induce the occurrence and progression of CCA through ROS/RNS-induced oxidative and nitrative DNA damage.

Two pyrrole acids isolated from Phyllanthus emblica L. and their bioactivities.

An undescribed pyrrole acid, 1-(4'-methoxy-4'-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.

Identification of Two Novel Carbapenemase-Encoding Hybrid Plasmids Harboring blaNDM-5 and blaKPC-2 in a Clinical ST11-KL47 Klebsiella pneumoniae.

Background: Emergence of blaKPC and blaNDM co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co-producing KPC and NDMs carbapenemases in Henan. Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime-avibactam and tetracycline. K9 carried two different plasmids that contained blaNDM-5 and blaKPC-2. Both plasmids were shown to be novel hybrid plasmids and IS26 played an important role in generation of two plasmids. Gene blaKPC-2 was flanked by the NTEKPC-Ib-like genetic structure (IS26-ΔTn3-ISKpn8-blaKPC-2-ISKpn6-IS26) and was located on a conjugative IncFII/R/N type hybrid plasmid. Conclusion: The resistance gene blaNDM-5 located on a region organized as IS26-blaNDM-5-ble-trpF-dsbD-ISCR1-sul1-aadA2-dfrA12-IntI1-IS26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread.

[Improvement of high-quality evaluation criteria of Chinese patent medicines based on whole process control].

Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.

The Prognostic Value of Procalcitonin Clearance and Procalcitonin to Albumin Ratio in Sepsis Patients.

BACKGROUND: The goal was to investigate the prognostic value of serum procalcitonin (PCT), procalcitonin clearance (PCTc), and procalcitonin/albumin (PCT/ALB) in patients with sepsis. METHODS: We conducted a retrospective study on 128 adult patients with sepsis in the Department of Intensive Care Unit (ICU) and in the Department Infectious Disease in the Affiliated Cancer Hospital of Zhengzhou University. We observed PCT, ALB, arterial blood gas analysis (ABGs) and other main indicators of patients within 5 days after admittance from June 2020 to June 2021. The acute physiological function and chronic health status system II (APACHE II) scores, sepsis related organ failure assessment (SOFA) scores, procalcitonin clearance and PCT/ALB ratio were calculated, respectively. SPSS 22.0 and Graph pad 6.0 statistical software were used for statistical analysis. RESULTS: The septic shock group had higher PCT, lower ALB, higher PCT/ALB ratio and higher APACHE II score than the sepsis group (p = 0.01733, p = 0.0142, p = 0.0030, p = 0.0061, respectively). The 28 day mortality group had lower ALB value, higher PCT/ALB ratio and higher APACHE II score than the survival group (p = 0.0105, p = 0.0345, p = 0.0152, respectively). The PCTc-day3 and PCTc-day5 were both significantly higher in patients who survived than in the 28 day mortality group (p = 0.0159, p = 0.0042, respectively). The AUC of PCT/ ALB for predicted the septic shock was 0.8966 (95% CI: 0.8370 to 0.9562, p < 0.0001), and the cutoff value, sensitivity and specificity was 0.87, 81.25%, and 85.19%, respectively. The AUC of PCT/ALB for the predicted 28 day mortality was 0.8353 (95% CI: 0.7534 to 0.9171, p < 0.0001), and the cutoff value, sensitivity and specificity was 0.83, 70.83% and 92.59%, respectively. CONCLUSIONS: The PCT/ALB ratio was an important indicator for predicting septic shock and 28 day mortality in sepsis patients compared to PCT or ALB alone.

Corylin ameliorates chronic ulcerative colitis via regulating the gut-brain axis and promoting 5-hydroxytryptophan production in the colon.

BACKGROUND: Chronic ulcerative colitis (UC) is a lifelong disease, patients with chronic UC have a high prevalence of common mental disorders. The increasing interest in the role of gut-brain axis is seen in inflammatory bowel diseases. PURPOSE: Corylin is a representative flavonoid compound isolated from the Psoraleae Fructus. This study aimed to identify the effects and mechanism of corylin on the inflammation interactions and 5-HT synthesis between the gut and brain in chronic UC. METHODS: Dextran sulfate sodium (DSS) induced chronic UC mouse model was established to assess the therapeutic effect of corylin on chronic UC symptoms. The expression of inflammatory cytokines was detected in the colon and brain. The expression of tight junction (TJ) proteins of intestinal mucosal barrier and blood-brain barrier (BBB) and the ionized calcium-binding adaptor molecule 1 (Iba1) in the hippocampus were determined by western blotting and immunofluorescence staining. In addition, several tryptophan (Trp) metabolites and related neurotransmitters in faeces, colon, serum, and brain were detected by UPLC-MS/MS. The interaction between corylin and 5-hydroxytryptophan decarboxylase (5-HTPDC) was performed by molecular docking and surface plasmon resonance (SPR). Finally, the changes of gut microbiota composition were analyzed by 16S rRNA sequencing. RESULTS: Corylin significantly alleviated colitis symptoms and inhibited inflammatory response in the colon and brain of DSS-induced chronic UC mice. The TJ proteins of intestinal mucosal barrier and BBB were improved and the expression of Iba1 in the hippocampus was normalized after corylin treatment. In addition, corylin treatment increased the expression of neurotransmitters in the brain, especially 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP), but the expression of 5-HT in the colon was inhibited. Further study firstly proved that corylin could bind to the 5-HTDPC, and then inhibit the expression of 5-HTDPC and VB6, resulting in the 5-HT reduction and 5-HTP accumulation in the colon. Moreover, the intake of corylin transformed the diversity and composition of intestinal microbiota, Bacteroides, Escherichia-Shigella, and Turicibacter were decreased but Dubosiella, Enterorhabdus, and Candidatus_Stoquefichus were increased. CONCLUSION: Corylin administration ameliorated DSS-induced colitis and inhibited intestinal inflammation and neuroinflammation via regulating the inflammation interactions across gut-brain axis and increasing 5-HTP generation in the colon.

Flavonoids dimers from the fruits of Psoralea corylifolia and their cytotoxicity against MCF-7 cells.

Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

Establishment and validation of a novel prognostic model for non-virus-related hepatocellular carcinoma.

OBJECTIVE: The incidence of non-virus-related hepatocellular carcinoma (NV-HCC) in hepatocellular carcinoma (HCC) is steadily increasing. The aim of this study was to establish a prognostic model to evaluate the overall survival (OS) of NV-HCC patients. METHODS: Overall, 261 patients with NV-HCC were enrolled in this study. A prognostic model was developed by using LASSO-Cox regression analysis. The prognostic power was appraised by the concordance index (C-index), and the time-dependent receiver operating characteristic curve (TD-ROC). Kaplan-Meier (K-M) survival analysis was used to evaluate the predictive ability in the respective subgroups stratified by the prognostic model risk score. A nomogram for survival prediction was established by integrating the prognostic model, TNM stage, and treatment. RESULTS: According to the LASSO-Cox regression results, the number of nodules, lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), alkaline phosphatase (ALP), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (SLR) and C-reactive protein (CRP) were included for prognostic model construction. The C-index of the prognostic model was 0.759 (95% CI 0.723-0.797) in the development cohort and 0.796 (95% CI 0.737-0.855) in the validation cohort, and its predictive ability was better than TNM stage and treatment. The TD-ROC showed similar results. K-M survival analysis showed that NV-HCC patients with low risk scores had a better prognosis (P < 0.05). A nomogram based on the prognostic model, TNM stage, and treatment was constructed with sufficient discriminatory power with C-indexes of 0.78 and 0.85 in the development and validation cohort, respectively. CONCLUSION: For NV-HCC, this prognostic model could predict an OS benefit for patients, which may assist clinicians in designing individualized therapeutic strategies.

Dynamic process and mechanism of crude oil release from silty intertidal sediment under different influencing factors.

Under tidal scouring, residual petroleum in the intertidal sediment after oil spills could release again, causing secondary pollution in the marine ecosystem. The current study aimed to investigate the dynamic process and principles of crude oil release from silty intertidal sediment under different influencing factors and screened for the key factors. In this paper, the fitting equations and correlation between the release amount and various factors were explored through the single-factor and orthogonal experiments. Then, the key influencing factors were selected for multi-factor fitting of the release amount. The results showed that the oil release amount rose with the increase in oil concentration, oscillation frequency, and release time, but decreased with an increase in salinity. As the pH decreased, the oil release amount increased. The relationship between release amount and concentration/oscillation frequency can be equipped by the polynomial equation, and the average R2 was 0.95 and 0.84, respectively. The release amount can be fitted by the Lagergren pseudo-second-order kinetic equation with time, with the average R2 0.89. The pH was negatively correlated with the release amount in the fresh contaminated sediment but positively correlated with the weathered one. The correlation between each factor and oil release amount was ranked (from large to small) as oil concentration, oscillation frequency, salinity, time, and pH. At last, a polynomial equation can be fitted between the key influencing factors (oil concentration and oscillation frequency) and the release amount. The results can provide a theoretical basis for predicting the secondary pollution owing to the oil re-release from intertidal sediment.

Practical application of European biological variation combined with Westgard Sigma Rules in internal quality control.

OBJECTIVES: Westgard Sigma Rules is a statistical tool available for quality control. Biological variation (BV) can be used to set analytical performance specifications (APS). The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) regularly updates BV data. However, few studies have used robust BV data to determine quality goals and design a quality control strategy for tumor markers. The aim of this study was to derive APS for tumor markers from EFLM BV data and apply Westgard Sigma Rules to establish internal quality control (IQC) rules. METHODS: Precision was calculated from IQC data, and bias was obtained from the relative deviation of the External quality assurance scheme (EQAS) group mean values and laboratory-measured values. Total allowable error (TEa) was derived using EFLM BV data. After calculating sigma metrics, the IQC strategy for each tumor marker was determined according to Westgard Sigma Rules. RESULTS: Sigma metrics achieved for each analyte varied with the level of TEa. Most of these tumor markers except neuron-specific enolase reached 3σ or better based on TEamin. With TEades and TEaopt set as the quality goals, almost all analytes had sigma values below 3. Set TEamin as quality goal, each analyte matched IQC muti rules and numbers of control measurements according to sigma values. CONCLUSIONS: Quality goals from the EFLM BV database and Westgard Sigma Rules can be used to develop IQC strategy for tumor markers.

[Biotransformation of psoralenoside and isopsoralenoside in Psoraleae Fructus incubated with human intestinal bacteria flora in vitro].

Absorption is crucial to the resultant efficacy of oral drugs where the intestinal bacteria flora functions as one of the first-pass effects.The present study investigated the biotransformation of psoralenoside and isopsoralenoside in Chinese medicine Psoraleae Fructus(the dried fruit of Psoralea corylifolia) with the internationally recognized human intestinal bacteria flora model in vitro.Pso-ralenoside and isopsoralenoside were anaerobically incubated with human intestinal bacteria flora at 37 ℃, respectively, and biotransformation products were analyzed and identified using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) and comparison with reference standards.The main biotransformation products of psoralenoside were psoralen and a small amount of 6,7-furano-hydrocoumaric acid, and the main biotransformation products of isopsoralenoside were isopsoralen and a small amount of 5,6-furano-hydrocoumaric acid.

Recognition and Classification of Ship Images Based on SMS-PCNN Model.

In the field of ship image recognition and classification, traditional algorithms lack attention to the differences between the grain of ship images. The differences in the hull structure of different categories of ships are reflected in the coarse-grain, whereas the differences in the ship equipment and superstructures of different ships of the same category are reflected in the fine-grain. To extract the ship features of different scales, the multi-scale paralleling CNN oriented on ships images (SMS-PCNN) model is proposed in this paper. This model has three characteristics. (1) Extracting image features of different sizes by parallelizing convolutional branches with different receptive fields. (2) The number of channels of the model is adjusted two times to extract features and eliminate redundant information. (3) The residual connection network is used to extend the network depth and mitigate the gradient disappearance. In this paper, we collected open-source images on the Internet to form an experimental dataset and conduct performance tests. The results show that the SMS-PCNN model proposed in this paper achieves 84.79% accuracy on the dataset, which is better than the existing four state-of-the-art approaches. By the ablation experiments, the effectiveness of the optimization tricks used in the model is verified.

Analysis of the molecular characteristics of a blaKPC-2-harbouring untypeable plasmid in Serratia marcescens / Análisis de las características moleculares de un plásmido no tipificable que alberga blaKPC-2 en Serratia marcescens

Introduction: Serratia marcescens has attracted increasing attention worldwide as a neglected opportunistic pathogen of public health concern, especially due to its antimicrobial resistance features, which usually cause nosocomial infections in immunocompromised or critically ill patients. Methods: In our study, four carbapenem-resistant Serratia marcescens (CRSM) clinical isolates were characterized in our hospital from February 2018 to May 2018. The conjugation experiment confirmed the transferability of the carbapenem resistance gene. The types of carbapenem resistance genes were detected by PCR. The homology of the strains was analysed by pulsed field gel electrophoresis (PFGE). The characteristics of the plasmid and environment of carbapenem resistance genes were analysed after whole genome sequencing was performed. Then, we compared the amino acid sequence of the replication initiation protein and constructed a dendrogram by the neighbour-joining method. Results: All four isolates showed carbapenem resistance conferred by a blaKPC-2-harbouring plasmid. They had exactly the same bands confirmed by PFGE and were defined as the homologous strains. The blaKPC-2 genes in all of the isolates were located in a 42,742 bp plasmid, which was located in the core region of antibiotic resistance and was composed of Tn3 family transposons, recombinant enzyme genes, ISKpn6 and ISKpn27. The core region of antibiotic resistance formed a ‘Tn3-ISKpn6-blaKPC-ISKpn27-Tn3’ structure, which was an independent region as a movable element belonging to transposon Tn6296 and its derivatives. The plasmid had a similar skeleton to incX6 plasmids and a similar amino acid sequence to the replication initiation protein. The plasmid was defined as an untypeable blaKPC-2-harbouring plasmid named the ‘IncX6-like’ plasmid. Conclusion: The four CRSM isolates were mainly clonally disseminated with a blaKPC-2-harbouring plasmid in our hospital. The pKPC-2-HENAN1602 plasmid...(AU)

Circular RNA circ_UBAP2 facilitates the progression of osteosarcoma by regulating microRNA miR-637/high-mobility group box (HMGB) 2 axis.

Circular RNA circ_UBAP2 has been reported to be closely associated with various tumors. The present work focused on exploring the roles of circ_UBAP2 and its molecular mechanism in osteosarcoma (OS). Circ_UBAP2, miR-637, and high-mobility group box (HMGB) 2 levels in OS cells and tissues were detected by quantitative real-time polymerase chain reaction. The relationship between miR-637 and circ_UBAP2, as well as between miR-637 and HMGB2, was predicted and examined through bioinformatics analysis and luciferase reporter gene experiments. Moreover, OS cell growth, invasion, migration, and apoptosis were detected using the cell counting kit-8 (CCK-8), Transwell and flow cytometry assays, respectively. HMGB2 protein levels were measured using Western blotting. Xenograft tumor formation assay was also performed. Circ_UBAP2 showed high expression levels in OS tissues and cells, which was directly proportional to metastasis and clinical stage of OS. The overexpression of circ_UBAP2 enhanced the growth, invasion, and migration of OS cells, but suppressed their apoptosis. In contrast, circ_UBAP2 silencing had opposite effects. Furthermore, miR-637 served as a downstream target of circ_UBAP2, which played opposite roles to circ_UBAP2 in OS. More importantly, HMGB2 served as miR-637's downstream target. The xenograft experiments in nude mice also proved that knockdown of circ_UBAP2 could increase miR-637 expression, but decrease HMGB2 expression, thus alleviating OS progression. Mechanistically, circ_UBAP2 exerts a cancer-promoting effect on OS by downregulating miR-637 and upregulating the expression of HMGB2. Circ_UBAP2 plays a promoting role in OS, and the circ_UBAP2/miR-637/HMGB2 axis is involved in OS progression.