Objective To analyze the effect of fisetin against venous thrombosis in rats.Methods Seventy SD rats were randomly divided into the following groups:sham-operation group,model group,fisetin 45 mg/kg,15 mg/kg,5 mg/kg groups,and aspirin group(47 mg/kg).The corresponding medication was administered by gavage once a day consecutively(the sham-operation group and the model group were given 0.5％carboxymethyl cellulose sodium solution with 10 mL/kg,respectively)for 7 consecutive days.One hour after the last administration,the rats were anesthetized,the lower part of the intersection of inferior vena cava and left renal vein was ligated with silk thread(no ligation in the sham-operation group),and the abdominal wall was sutured.Two hours later,the abdominal cavity was reopened,the other venous branches 1.5 cm away from the ligation site were closed with the artery clamp,and blood was collected from the abdominal aorta.The anticoagulant ratio of 3.8％sodium citrate∶whole blood was 1∶9.The venous thrombus 1 cm down from the ligation point of the intersection of inferior vena cava and left renal vein was cut and the thrombus was separated.The residual blood was dried with filter paper,weighed and recorded.Plasma was taken after anticoagulant blood centrifugation.The levels of plasma antithrombin-Ⅲ(AT-Ⅲ),protease C(PC),plasminogen(PLG),and plasminogen activator inhibitor(PAI-1)were detected by ELISA kits.Results Compared with the model group,the weight of thrombus in fisetin 45 mg/kg group and aspirin 47 mg/kg group decreased(P＜0.01).The content of AT-Ⅲ in three fisetin groups increased(all P＜0.05).The content of PC in fisetin 45 mg/kg increased(P＜0.05).The content of PLG and PAI-1 in fisetin 45 mg/kg group decreased(both P＜0.05).Conclusion Fisetin has the effect against venous thrombosis in vivo,and the effect is related to the upregulation of AT-Ⅲ and PC and the downregulation of PLG and PAI-1.

In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

A target screening methodology was developed for detection of 63 kinds of chemical hazards substances,including 17 kinds of flame retardants,14 kinds of perfluorinated compounds,15 kinds of phthalate esters,5 kinds of fluorescent whitening agents and 12 kinds of ultraviolet absorbers,in various types of face masks using ultra high performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry based on an in-house database and mass spectral library.And the quantification was achieved using the external standard method.The results showed that the linear correlation coefficient(r)of all compounds was greater than 0.99,the limits of detection(LODs)ranged from 3.3 to 26.7 μg/kg(S/N=3),the limits of quantification(LOQs)ranged from 10.0 to 80.0 μg/kg(S/N=10),the average recoveries(n=6)were 72.3%-102.6%,and the relative standard deviations(RSDs)were 0.8%-9.9%.The validation of the screening results from both the database and mass spectral library was conducted,and benzophenone and dibutyl phthalate were detected from three positive samples.The human health exposure assessment of the inhalation exposure doses based on the relevant exposure models showed that the contents of benzophenone and dibutyl phthalate were within the recommended reference doses.The method represented a valuable technical reference for ensuring the quality and safety of face mask products and protecting consumer health.

Objective To explore the evidence,urinary biomarkers,and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis(IgAV).Methods Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry,followed by Reactome pathway analysis.Protein-protein interaction(PPI)network analysis was conducted using STRING and Cytoscape software.In the validation cohort,15 healthy children and 25 children with IgAV were included,and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay.Results A total of 772 differential proteins were identified between the IgAV group and the control group,with 768 upregulated and 4 downregulated.Reactome pathway enrichment results showed that neutrophil degranulation,platelet activation,and hemostasis pathways were involved in the pathogenesis of IgAV.Among the differential proteins,macrophage migration inhibitory factor(MIF)played a significant role in neutrophil degranulation and hemostasis,while thrombin was a key protein in platelet activation and hemostasis pathways.PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses,and these interactions involved MIF.Validation results showed that compared to healthy children,children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels(P<0.05).Conclusions Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors.Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

Objective:To investigate the characteristics of thalassemia gene types in children in Liuzhou,Guangxi.Methods:A total of 822 children suspected thalassemia aged from 1 day to 14 years who were admitted to our hospital from January 2019 to April 2022 were collected.Gap-PCR and PCR combined with reverse dot blot hybridization were used to detect α-and β-thalassemia genes.Results:Among 822 children,561 thalassemia carriers were detected,with a detection rate of 68.25％.Among them,303 cases were detected with α-thalassemia,and the most common genotype was--SEA/αα(163 cases),followed by-α3.7/αα(37 cases)and αcsα/αα(26 cases),44 cases with HbH disease.240 cases were detected with β-thalassemia,with a detection rate of 29.20％,and the most common genotype was βCD41-42/β N(112 cases),followed by βCD17/βN(75 cases)and βIVS-Ⅱ-654/β N(11 cases),11 cases with moderate to severe β-thalassemia.18 cases were detected with α β-thalassemia,with a detection rate of 2.19％,and--SEA/αα complex βCD41-42/βN was the most common genotype(4 cases).In Zhuang and Han populations,the detection ratio of-α3.7α/αα in α-thalassemia was the same(both 12.50％).While,the other main types such as--SEA/αα,αCSα/αα and-α4.2α/αα had certain differences.In β-thalassemia,CD41-42 and CD17 were the main genotypes detected in Han and Zhuang.Conclusion:In Liuzhou of Guangxi autonomous region,α-thalassemia is the main type in children,with a detection rate of 68.25％,and--SEA/αα is the most common genotype in mild thalassemia,followed by βCD41-42/βN.The detection rate of moderate to severe α-and β-thalassemia is relatively high.There are certain differences in the distribution of thalassemia among different ethnic groups.

Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.

Apoptosis is a process of programmed cell death,which has the function of maintaining skin balance.In psoriasis,the disturbance of apoptosis is characterized by abnormal prolif-eration of keratinocytes.Traditional Chinese medicine(TCM)has a regulatory effect on keratinocyte apoptosis,which can in-hibit the excessive proliferation of psoriasis epidermis,promote normal epidermal differentiation,and maintain epidermal homeo-stasis.It has the advantages of fewer adverse reactions and multi-targets.Therefore,this article summarizes and analyzes the specific mechanism of various active ingredients of TCM to in-duce the apoptosis of psoriasis keratinocytes by interfering with related factors and signaling pathways,hoping to provide a refer-ence for the treatment of psoriasis with TCM.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Aim To study the protective effect of eplerenone on the contralateral kidney in pregnant rats with chronic kidney disease (CKD) and its mechanism. Methods Female Wistar rats were randomly divided into sham-operation group, sham-operation pregnancy group, model group and eplerenone group. The rats in the model group and eplenone group had ligation unilateral ureter, and the rats in the eplenone group were treated with 100 mg • kg

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC) compared with the general population. Currently the molecular mechanism of CRC occurrence in the context of IBD is not clear. The inflammation-atypical hyperplasia-cancer process has been widely accepted. Toll-like receptor 4(TLR4) is a key receptor for pathogen recognition and immune activation, and plays a crucial role in inflammatory and carcinogenic transformation of IBD. Therefore, this paper reviews the epidemiology of colitis-associated colorectal cancer (CAC) and the main mechanisms of TLR4 in the development of IBD to CAC, which will help to further understand the carcinogenesis of IBD, detect and better describe CAC at an earlier stage, and provide more effective prevention and treatment for CAC.