OBJECTIVE To compare the efficacy and safety of vedolizumab （VDZ） versus infliximab （IFX） in biologic-naive（Bio-naive） patients with moderate-to-severe active ulcerative colitis （UC）， and to analyze the factors influencing efficacy. METHODS Clinical data were retrospectively collected from Bio-naive patients with moderate-to-severe active UC who received treatment in the Department of Gastroenterology at Shanxi Provincial People’s Hospital from June 2023 to June 2024. Based on the type of biologic agent administered， the patients were divided into the IFX group （41 cases） and the VDZ group （30 cases）. Patients in the two groups received IFX （5 mg/kg） or VDZ （300 mg） for induction and maintenance of remission therapy. The two groups were compared regarding modified Mayo score， serological indicators （hemoglobin， albumin， platelet count， erythrocyte sedimentation rate， C-reactive protein）， combined medication， efficacy-related indexes （clinical response rate/remission rate， and endoscopic response rate/remission rate）， and the occurrence of adverse drug reactions （ADR）. Based on Logistic regression model， univariate and multivariate analyses were conducted to identify potential factors influencing clinical remission at week 14 and endoscopic remission at week 38. RESULTS There were no statistically significant differences in clinical response rate/remission rate， or endoscopic response rate/remission rate between the two groups at weeks 14 and 38 （ P ＞0.05）. However， at week 14 of treatment， the proportion of patients using concomitant corticosteroids in VDZ group was 26.67%， significantly higher than the 7.50% in IFX group （ P ＜0.05）. There was no statistical significance in the overall incidence of ADR between the two groups （ P ＞0.05）； all ADRs in the IFX group were grade 3 and led to treatment discontinuation （6 cases）， whereas ADR in the VDZ group was grade 2 and did not interrupt therapy （1 case）. Univariate and multivariate regression analyses revealed that disease type （relapsing） was significantly associated with clinical remission at week 14 of treatment， and a history of smoking was significantly associated with endoscopic remission at week 38 of treatment （the odds ratios were 0.08 for both， with 95% confidence intervals of 0.01-0.77 and 0.01-0.91 respectively， P ＜0.05）. CONCLUSIONS For Bio-naive patients with moderate-to-severe active UC， VDZ and IFX demonstrate comparable efficacy in inducing and maintaining clinical remission and promoting mucosal healing， as well as overall safety. Although IFX can achieve faster control of inflammation in the early stage of the disease， it causes more severe ADR. Disease type （relapsing） and smoking history are identified as independent negative predictors for short-term clinical remission and long-term endoscopic remission， respectively.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Objective To investigate the effects and underlying mechanisms of down-regulating m6A demethylase fat mass and obesity-associated protein(FTO)on proplatelet formation in the MEG-01 megakaryocytic cells.Methods ①MEG-01 cells were treated with 1 nmol/L phorbol myristate acetate(PMA)(treatment group)or DMSO(control group)for 72 h.FTO expression was measured by Western blotting and RT-qPCR.② MEG-01 cells were infected with targeted FTO shRNA(knockdown group,sh-FTO)or negative control shRNA(negative control group,sh-NC)viruses.FTO knockdown group and negative control group MEG-1 cells were treated with 1 nmol/L PMA for 72 h,and the protein and mRNA expression levels of FTO were detected by Western blotting and RT-qPCR.Cell cycle,viability and apoptosis were assessed by propidium iodide(PI)DNA staining,CCK-8 assay and Annexin V-FITC/PI double staining and TUNEL staining.The expression of cleaved Caspase-3 protein was determine by Western blotting.Megakaryocyte maturation was assessed by CD41/CD61 staining.Proplatelet formation was observed under bright field and detected by CD61 immunofluorescence assay.The expression of apoptosis-related molecules(Caspase3,BAD,BAK1,BCL2 and MCL1)was detected by RT-qPCR,and the protein change of BCL2 was further verified by Western blotting.The dataset was screened out from the gene expression omnibus(GEO)database,and then analyzed with University of California,Santa Cruz(UCSC)genome browser to compare the methylation sequencing peaks on BCL2 mRNA,and m6A methylated RNA immunoprecipitation(m6A-RIP)was used to assess the m6A methylation levels of BCL2 target gene mRNAs in MEG-01 megakaryocytes.Then,the changes in the m6A methylation enrichment level of BCL2 mRNA were observed between the sh-NC group and the sh-FTO group.mRNA stability and ribosome profiling assays were performed to assess translational efficiency of target genes.Results ①PMA treatment upregulated the expression of FTO at protein(P＜0.05)and mRNA(P＜0.01)levels.② FTO shRNA resulted in reduced FTO expression at both mRNA and protein levels(P＜0.01).Compared to the negative control group,the FTO knockdown group showed more cells arrested at the G1/S phase[(60.80±1.29)%vs(72.13±1.18)%,P＜0.01],significantly reduced cell viability[(1.17±0.03)%vs(0.69±0.05)%,P＜0.01],increased Annexin V-FITC/PI positive cells[(12.87±0.83)%vs(17.45±1.58)%,P＜0.01],more TUNEL positive cells[(1.03±0.27)%vs(17.49±9.91)%,P＜0.01],enhanced protein level of cleaved Caspase-3(P＜0.01),decreased proportion of CD41/CD61 positive cells[(51.63±1.13)%vs(34.08±0.53)%,P＜0.01],and less proplatelet formation in MEG-01 megakaryocytes[(26.49±6.73)%vs(13.31±5.97)%,P＜0.01].③Compared to sh-NC group,the FTO knockdown group had significantly decreased protein and mRNA expression of anti-apoptotic molecule BCL2(P＜0.01).UCSC GEO sequencing data revealed there were m6A methylation modification sites on BCL2 mRNA,which was verified through m6A-RIP experiment in MEG-01 megakaryocytes.Compared with GAPDH mRNA,BCL2 mRNA exhibited a significantly enriched m6A signal(P＜0.01).Compared to sh-NC group,a significant increase in m6A methylation modification was observed on BCL2 mRNA.BCL2 mRNA stability was significantly decreased,and its translation efficiency significantly was decreased(P＜0.01).Conclusion m6 A demethylase FTO rgulates BCL2 mRNA stability and translation efficiency,thereby promoting proplatelet formation in MEG-01 megakaryocytes.

″Boundarics in biomedicine″(or″Biomedical boundarics″)is an emerging frontier interdisciplinary subject that focuses on addressing key scientific issues related to the formation,identification,and evolution of biological boundaries within living organisms.In this field,the study of tumor boundaries is of particular importance.Imaging tumor boundaries not only helps to reveal the molecular mechanisms of tumor boundary evolution and interaction with the microenvironment,tumor invasion and metastasis,but is also crucial for clinical tumor diagnosis,treatment decision-making,efficacy monitoring and prognosis evaluation.Molecular probes,as functional substances that enhance imaging signals,play a crucial role in tumor boundary recognition.In this article,the basic concepts and research significance of boundarics in biomedicine and tumor boundarics in biomedicine were summarized firstly.Then a comprehensive review of the research progress in tumor boundary imaging molecular probes was provided,covering areas such as magnetic imaging,optical imaging,acoustic imaging,nuclear imaging,and multimodal imaging.The strategies to regulate the sensitivity,specificity,and safety of molecular probes through chemical structure modifications,conjugation with targeting ligands,and tumor microenvironment-responsive designs were emphasized.Finally,the research trends of molecular probes for tumor boundary imaging were analyzed,and the challenges faced in this field and the future research directions were discussed.

As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

AIM:This study aims to investigate whether a specific synbiotic,consisting of Bifidobacterium longum subspecies BB536 and fructooligosaccharides,can inhibit colon tumorigenesis by modulating gut flora composi-tion.METHODS:Six-week-old male ApcMin/+mice were randomly divided into control group and synbiotic-treated group,with 8 mice in each group.The mice in synbiotic-treated group received daily gavage of 1×109 CFU/kg of Bifidobacterium longum BB536 and 2 g/kg of fructooligosaccharides,while those in control group were gavaged with sterile water for 10 weeks.The number and size of colon tumors were assessed and compared between the 2 groups.Colon tissue sections were evaluated using hematoxylin-eosin staining,Alcian blue staining,and immunohistochemistry assays.The bacterial compo-sition in the colon was analyzed via 16S rDNA sequencing,and differentially expressed genes were examined through tran-scriptome sequencing and RT-qPCR.RESULTS:The synbiotic treatment significantly enhanced bacterial diversity and increased the relative abundance of Bifidobacterium in the colon(P<0.01).Additionally,the number and size of colon tu-mors were both significantly reduced in the synbiotic-treated mice(P<0.01),along with decreased expression of Ki-67(P<0.01).Concurrently,the number of goblet cells and the expression of epithelial tight junction proteins(ZO-1 and occlu-din)were up-regulated(P<0.05).CONCLUSION:Supplementation with this synbiotic effectively modulated gut flora composition and suppressed colon tumorigenesis in ApcMin/+mice.

This study examines the effects of zearalenone(ZEA)on the survival and function of lu-teinized granulosa cells,and studies the role of activating transcription factor 6(ATF6)in regula-ting apoptosis and functional abnormalities of luteinized granulosa cells induced by ZEA.An in vitro model of luteinized granulosa cells was utilized to examine the effects of ZEA treatment on apoptosis,hormone secretion,and the expression of relevant proteins.Furthermore,the expression of ATF6 was manipulated using siRNA to elucidate its regulatory function in the ZEA-induced damage of luteinized granulosa cells in mice.Our findings revealed that ZEA inhibited the activity of luteinized granulosa cells and reduced the secretion of estradiol(E2)and progesterone(P4)in a dose-dependent manner.The expression levels of p-IRE1,ATF6 and StAR in both low(20 pmol/L)and high(40 μmol/L)ZEA groups were significantly increased after 24 h(P＜0.05).GRP78 had no significant change at low concentration treatment(P＞0.05),but significantly increased at high concentration treatment(P＜0.05).Similarly,ATF4 and p-EIF2α had no significant change at low concentration treatment(P＞0.05),but significantly decreased at high concentration treat-ment(P＜0.05).HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).After 48 h of treatment,ATF6 and GRP78 were significantly increased in both low and high concentration treatments(P＜0.05).p-IRE1 was significantly de-creased at low concentration treatment(P＜0.05),but remained unchanged at high concentration treatment(P＞0.05).ATF4,p-EIF2α,HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).St AR was significantly increased in both low and high concentration treatments(P＜0.05).Interference with the expression of ATF6 could sig-nificantly reduce the apoptosis induced by low concentration group(P＜0.05),and enhanced the hormone secretion in both high and low concentration groups(P＜0.05).In conclusion,ZEA can cause damage to luteinized granulosa cells and activate ATF6 signaling pathway.Interference with ATF6 can alleviate apoptosis and hormone secretion disturbance induced by low concentration ZEA,but has limited effect on damage caused by high concentration ZEA.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.