OBJECTIVE To investigate the improvement mechanism of hyperoside （HYP） on non-alcoholic fatty liver disease （NAFLD）. METHODS Male C57BL/6 mice were randomly divided into normal （NFD） group， model （HFD） group and HYP group， with 8 mice in each group. Except for NFD group， the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model； HYP group was simultaneously given HYP 100 mg/kg intragastrically every day， for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication； the histopathological changes and lipid accumulation in the liver were observed， and the contents of triglyceride （TAG） in liver tissue and serum contents of TAG， aspartate transaminase （AST） and alanine transaminase （ALT） were measured； LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis， and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α （PPARα） were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group， model group， HYP low-concentration group （50 μmol/L）， HYP high-concentration group （100 μmol/L）， HYP low-concentration+GW6471 （PPARαinhibitor） group， and HYP high-concentration+GW6471 group. Except for normal control group， the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed， and the TAG content was detected. RESULTS Compared with HFD group， HYP group exhibited significant reductions in liver fat vacuoles， lipid accumulation， liver weight， and TAG content in liver tissue， as well as serum contents of ALT， AST and TAG （P＜0.05）. Additionally， the expression of PPARα protein in liver tissue was significantly increased （P＜0.05）， and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG， diacylglycerol and other lipids in the liver. Compared with model group， cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups （P＜0.05）； GW6471 could significantly reverse the improvement effect of HYP on above indicators （P＜0.05）. CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice， and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

Objective:To screen differentially expressed circular RNA (circRNA) in rat articular chondrocyte injury induced by T-2 toxin, and explore the mechanism of cartilage injury.Methods:Twenty-four SD rats (males, body weight 60 - 80 g) were randomly divided into T-2 toxin group (administrated T-2 toxin 100 ng·g -1·d -1 by gavage) and control group (administrated equal amounts of deionized water by gavage) using a random number table method, 12 rats in each group. After 4 weeks of intervention, the articular cartilage was collected for transcriptome sequencing. Deseq2 software [ P < 0.05 and |log 2(fold change)| > 1, fold change was the multiple of differential expression] was used to identify differentially expressed circRNA. Based on the competing endogenous RNAs (ceRNA) hypothesis, the miRanda software was used to predict the microRNA (miRNA, miR) binding sites of differentially expressed circRNA, and Cytoscape 3.10.0 software was used to plot the circRNA-miRNA interaction network. MiRWalk 3.0, MiRDB, and miRTarBase softwares were used to predict downstream target genes, and Cytoscape 3.10.0 software was used to map the circRNA-miRNA-mRNA interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the biological functions and enrichment pathways of target genes. Results:A total of 19 differentially expressed circRNAs were screened (including 10 upregulated and 9 downregulated). A total of 1 320 miRNAs binding sites and 16 target genes were predicted. Target gene enrichment analysis revealed significant enrichment of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathway ( P < 0.05). Tumour necrosis factor receptor-associated factor 6 (Traf6) and interleukin-1 receptor-associated kinase 1 (Irak1) were enriched in the MAPK and NF-κB signaling pathways, with corresponding miRNA and circRNA of miR-146a-5p and chr2: 94716330|94720889. Conclusion:Nineteen differentially expressed circRNAs in rat articular chondrocyte injury are successfully screened, and chr2: 94716330|94720889 may regulate the MAPK and NF-κB signaling pathways through the miR-146a-5p/Traf6/Irak1 axis, inducing articular chondrocyte injury.

Purpose To explore the clinicopathological features,diagnosis and differential diagnosis of large B-cell lym-phoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 8 cases of LBCL-IRF4r were collect,hematoxy-lin-eosin and immunohistochemical of EnVision two-step stains,in situ hybridization and FISH was used to study the histology,immunotypes and molecular genetic characteristics.The rele-vant literatures were reviewed.Results Among 8 cases of LBCL-IRF4r,the male to female ratio was 1.67:1,with age range 10-53 years(mean 25.8 years).Five cases occurred in tonsils,2 cases in nasopharynx and 1 cases in inguinal lymph node.Microscopically,the tumors presented with a purely follic-ular,purely diffuse or a combined follicular and diffuse architec-ture.The tumor cells were typical centroblasts and less frequent-ly medium-sized blastic cells with smaller nucleoli,apoptosis and nuclear fragmentation were easily seen.Immunophenotypi-cally,the tumor cells of the eight cases of LBCL-IRF4r diffuse strongly expressed CD20(8/8),PAX5(2/2),CD79a(3/3),BCL6(8/8)and MUM-1(8/8),mostly expressed CD10(7/8),partially expressed BCL2(5/8)and CD5(4/8),and did not express Cyclin D1,CD23 and CD30.The percentage of Ki67 index ranged from 70％to 95％.EBER in situ hybridiza-tion was negative in all cases.IRF4 rearrangements were detec-ted in all cases(8/8).BCL6 rearrangements were detected in one case(1/2).MYC(0/4)and BCL2(0/3)rearrangements were not detected in all cases.Conclusion LBCL-IRF4r is more common in children and adolescents with characteristic IG::IRF4 rearrangement and a good prognosis,which needs to be differentiated from other types of large B-cell lymphoma.

Background Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides that have been used in various pest management regimens worldwide as alternatives to conventional insecticides. Recently, several studies have indicated that humans are widely exposed to NEOs, but limited is known about the levels and associated health risks of NEOs exposure among children. Objective To estimate exposure levels of four kinds of NEOs in urine samples among 5-year-old children from Laizhou Wan, Shandong Province, and to evaluate health risks of single and cumulative exposure to NEOs among children in this area. Methods A total of 205 children who participated in the 5-year-old follow-up in Laizhou Wan Birth Cohort (LWBC) were included. Urinary concentrations of four NEOs [imidacloprid (IMI), acetamiprid (ACE), clothianidin (CLO), and thiamethoxam (THM)] were measured by high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Based on the detected NEOs concentrations, estimated daily intake (EDI) was calculated, and the health risk of exposure to single NEO was assessed using hazard quotient (HQ, risk threshold=1). A relative potency factor (RPF) approach was used to standardize the concentrations of the four NEOs by IMI to calculate their cumulative concentrations. Then, the health risk of cumulative exposure to the four NEOs was further evaluated based on the HQ method. Results The detection rates of the four NEOs in the 5-year-old children were all above 90%, and their median creatinine-adjusted urinary concentrations were in the order from high to low as follows: CLO (1.373 μg·g⁻¹) > THM (0.628 μg·g⁻¹) > IMI (0.310 μg·g⁻¹) > ACE (0.073 μg·g⁻¹). Of the four NEOs, the median EDI of IMI was 0.035 µg·kg⁻¹·d⁻¹, higher than those of CLO (0.032 µg·kg⁻¹·d⁻¹), THM (0.012 µg·kg⁻¹·d⁻¹), and ACE (0.002 µg·kg⁻¹·d⁻¹). The maximum HQ values of IMI, CLO, THM, and ACE were 0.168, 0.152, 0.055, and 0.022, respectively, which were all far lower than the risk threshold of 1. The median concentration of cumulative exposure to the four NEOs standardized by IMI was 21.241 μg·g⁻¹, and its median EDI was 2.370 µg·kg⁻¹·d⁻¹. The maximum HQ of cumulative exposure to the four NEOs was only 0.694, which also did not exceed the risk threshold of 1. Conclusion NEOs exposure is common among the 5-year-old children in Laizhou Wan, Shandong. Although there is no obvious health risk associated with single and cumulative exposure to NEOs in the children in this area, their exposure levels of NEOs are higher than those in some foreign areas. The adverse health effects of long-term exposure to low dose of NEOs deserve our extensive attention.

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

Objective:To develop a grading prediction model of traumatic hemorrhage volume based on deep learning and assist in predicting traumatic hemorrhage volume.Methods:A retrospective observational study was conducted based on the experimental data of pig gunshot wounds in the time-effect assessment database for experiments on war-traumatized animals constructed by the General Hospital of the Chinese People's Liberation Army. The hemorrhage volume data of the study population were extracted, and the animals were divided into 0-300 mL, 301-600 mL, and > 600 mL groups according to the hemorrhage volume. Using vital signs indexes as the predictive variables and hemorrhage volume grading as the outcome variable, trauma hemorrhage volume grading prediction models were developed based on four traditional machine learning and ten deep learning methods. Using laboratory test indexes as predictive variables and hemorrhage volume grading as outcome variables, trauma hemorrhage volume grading prediction models were developed based on the above fourteen methods. The effect of the two groups of models was evaluated by accuracy and area under the receiver operator characteristic curve (AUC), and the optimal models in the two groups were mixed to obtain hybrid model 1. Feature selection was conducted according to the genetic algorithm, and hybrid model 2 was constructed according to the best feature combination. Finally, hybrid model 2 was deployed in the animal experiment database system.Results:Ninety-six traumatic animals in the database were enrolled, including 27 pigs in the 0-300 mL group, 40 in the 301-600 mL group, and 29 in the > 600 mL group. Among the fourteen models based on vital signs indexes, fully convolutional network (FCN) model was the best [accuracy: 60.0%, AUC and 95% confidence interval (95% CI) was 0.699 (0.671-0.727)]. Among the fourteen models based on laboratory test indexes, recurrent neural network (RNN) model was the best [accuracy: 68.9%, AUC (95% CI) was 0.845 (0.829-0.860)]. After mixing the FCN and RNN models, the hybrid model 1, namely RNN-FCN model was obtained, and the performance of the model was improved [accuracy: 74.2%, AUC (95% CI) was 0.847 (0.833-0.862)]. Feature selection was carried out by genetic algorithm, and the hybrid model 2, namely RNN-FCN* model, was constructed according to the selected feature combination, which further improved the model performance [accuracy: 80.5%, AUC (95% CI) was 0.880 (0.868-0.893)]. The hybrid model 2 contained ten indexes, including mean arterial pressure (MAP), hematocrit (HCT), platelet count (PLT), lactic acid, arterial partial pressure of carbon dioxide (PaCO 2), Total CO 2, blood sodium, anion gap (AG), fibrinogen (FIB), international normalized ratio (INR). Finally, the RNN-FCN* model was deployed in the database system, which realized automatic, continuous, efficient, intelligent, and grading prediction of hemorrhage volume in traumatic animals. Conclusion:Based on deep learning, a grading prediction model of traumatic hemorrhage volume was developed and deployed in the information system to realize the intelligent grading prediction of traumatic animal hemorrhage volume.

【Objective】 To investigate the diagnostic value of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) specific antibodies IgM and IgG on coronavirus disease 2019 (COVID-19). 【Methods】 1) The test results of SARS-CoV-2 IgM/IgG antibodies and nucleic acid(NAT), which were tested by colloidal gold test and fluorescent quantitative PCR respectively, were collected from 145 febrile outpatients during early March, 2020, named Fever group, in which retrospective analysis and paired chi-square test were performed. 2) 612 cases of SARS-CoV-2 IgM/IgG antibodies test results, which were done on March 5, 2020, were collected. They were named COVID-19 group (Our hospital was provisionally assigned as a specialized hospital for COVID-19, and 1500 COVID-19 patients admitted to our hospital from February 12, 2020 to March 18, 2020). The SARS-CoV-2 IgM/IgG antibodies and NAT were respectively tested on the 30th and the 60th day after the date of discharge. The clinical application values of the antibodies was clarified by statistical analysis. 【Results】 1) In the fever group, the positive rate of SARS-CoV-2 IgM, IgG and IgM+ IgG antibodies were 26.21% (38/145), 54.48% (79/145) and 26.21% (38/145), respectively(P<0.01), and the positive rate of NAT was 4.14% (6/145), which was lower than that of antibody (P<0.01). One (1/145, 0.69%) positive NAT was implicated in initially negative IgM and IgG antibodies samples. 2) In the COVID-19 group, the positive rate of IgM antibody was low (5%) and IgG antibody was high (65%) during 2~14 days after infection, and stably increased during the 15~56 days [IgM 47.68%(277/581) vs IgG 94.15% (547/581) ], then both decreased after 57 days. The positive rates of IgM antibody and IgG antibody were 45.8% (280/612) and 93.1% (570/612) in 612 patients during hospitalization. 15 patients′ data after dischange were not collected as they were later transferred to Huoshenshan Hospital for treatment. The coronavirus NAT results of the rest 597 COVID-19 patients, tested on the 30th and 60th days after the date of discharge, were negative, and the positive rates of IgG antibody and IgM antibody were still ≥80% and ≥40% respectively at the second month after discharge. 【Conclusion】 IgM, IgG antibody against SARS-CoV-2 can be well detected by Colloidal gold method(Innovita), whose positive rate is higher than that of NAT. IgG antibody is produced earlier than IgM, and it keeps high positive rate and persists for a long time. The combination of colloidal gold antibody test and NAT can improve the diagnose rate of COVID-19 and the exclusion of suspected cases.

Partial least square (PLS) combining with Raman spectroscopy was applied to develop predictive models for plasma paclitaxel concentration detection. In this experiment, 312 samples were scanned by Raman spectroscopy. High performance liquid chromatography (HPLC) was applied to determine the paclitaxel concentration in 312 rat plasma samples. Monte Carlo partial least square (MCPLS) method was successfully performed to identify the outliers and the numbers of calibration set. Based on the values of degree of approach ( ), moving window partial least square (MWPLS) was used to choose the suitable preprocessing method, optimum wavelength variables and the number of latent variables. The correlation coefficients between reference values and predictive values in both calibration set ( ) and validation set ( ) of optimum PLS model were 0.933 1 and 0.926 4, respectively. Furthermore, an independent verification test was performed on the prediction model. The results showed that the correlation error of the 20 validation samples was 9.36%±2.03%, which confirmed the well predictive ability of established PLS quantitative analysis model.