Objective: To investigate prevalence of hepatitis E virus (HEV) infection among voluntary blood donors in Dalian and provide evidence for enhancing blood screening strategies. Methods: A total of 3 277 blood donor samples collected between December 2023 and February 2024 at Dalian Blood Center underwent routine blood screening (ALT, HBsAg, anti-HCV, HIV Ag/Ab, anti-TP, and HBV/HCV/HIV NAT). Subsequently, HEV antigen (Ag) was detected using chemiluminescence immunoassay (CLIA). HEV-Ag reactive samples were further tested for HEV RNA, IgM and IgG antibodies. Blood donors with repeated reactive HEV Ag results were followed up to clarify the status of infection. Results: Among the 3 277 blood donor samples, 6 (0.18%) were repeatedly reactive for HEV Ag. However, supplemental testing for HEV RNA, anti-HEV IgM, and anti-HEV IgG on these samples yielded non-reactive results. One of these six blood donors was successfully followed up. On day 218 after the initial detection of HEV Ag reactivity, HEV Ag, HEV RNA, HEV IgM and IgG antibody were found to be non-reactive. Conclusion: The reaction rate for HEV antigen screening among voluntary blood donors in Dalian is low. CLIA method for detecting HEV antigen is easy to operate and cost-effective, but demonstrates some false reactivity. Improving the specificity of the assay and combining it with nucleic acid testing (NAT) would be valuable for implementing a selective HEV screening strategy for blood donors.

Fucoxanthin is a pigment found in plants and animals such as algae， marine plankton and aquatic shellfish， and holds significant potential for development in the pharmaceutical field. This review introduces the anti-inflammatory， antioxidant， anticancer， anti-obesity， and other pharmacological effects of fucoxanthin， as well as recent advances in drug design research. It was found that fucoxanthin can exert anti-inflammatory and antioxidant effects through mechanisms such as activating AMP- activated protein kinase related signaling pathways， regulating the expression of inflammatory factors， altering microbial stability， thereby improving conditions such as metabolic associated fatty liver disease and colitis. It can exert selective antitumor effects through multi-target synergistic actions； and it was also found that it can exert anti-obesity effects by regulating the intestinal microbiota. Its characteristic functional groups （such as hydroxyl and epoxy groups） possess target specificity and reversible inhibitory properties， making it a suitable template for guiding the design and development of novel drugs， thereby providing new insights for breaking through the limitations of traditional drug design.

Objective To investigate the effect of curcumin regulating miR-142-5p targeting pleckstrin homology domain containing family A member 3(PLEKHA3)on proliferation,migration and apoptosis of adrenocortical carcinoma cells.Methods Adrenal cortical cancer cells were divided into NC group(normal culture),NC+60 μmol·L-1 curcumin(60 μmol·L-1 curcumin),NC+60 μmol·L-1curcumin+miR-142-5p group(60 μmol·L-1 curcumin and transfected with miR-142-5p mimic),NC+60 μmol·L-1 curcumin+miR-142-5p+PLEKHA3 group(60 μmol·L-1 curcumin and transfected with miR-142-5p mimic+PLEKHA3).Cell proliferation and migration abilities were detected by cell counting kit-8(CCK-8)and Transwell assays.Expression levels of apoptosis-related proteins were detected by Western blotting.At the animal level,a nude mouse model of human adrenal cortical tumor SW-13 cell transplantation was established and divided into control group and 15,30,45,60 μmol·L-1curcumin groups to verify the anti-adrenal cortical carcinoma effect of curcumin in vivo.Results The cell migration numbers in NC group,NC+60 μmol·L-1 curcumin group,NC+60 μmol·L-1+miR-142-5p group and NC+60 μmol·L-1+miR-142-5p+PLEKHA3 group were 135.76±17.42,37.11±10.08,98.31±14.88 and 24.39±5.28;the apoptosis rates were(3.27±0.11)％,(68.80±4.64)％,(25.47±2.39)％and(78.29±5.47)％;the protein expression levels of B-cell lymphoma 2(Bel-2)were 1.00±0.13,0.59±0.11,0.97±0.09 and 0.31±0.06;the protein expression levels of Bel-2 associated X protein were 1.00±0.08,1.38±0.11,0.69±0.05 and 1.93±0.18;there were statistically significant differences between NC group and NC+60 μmol·L-1 group(P＜0.05,P＜0.01).At the animal level,the volumes of the xenograft tumors in control group and 15,30,45 and 60 μmol·L-1 curcumin groups were(1 653.02±435.93),(1 148.77±327.18),(1 054.21±286.06),(996.89±257.62)and(670.64±157.32)mm3;the weights of the xenograft tumors were(1.00±0.17),(0.82±0.09),(0.76±0.12),(0.68±0.13)and(0.44±0.11)g,there were statistically significant differences between 15,30,45 and 60 μmol·L-1curcumin groups and control group(P＜0.05,P＜0.01).Conclusion Curcumin exerts anti-adrenal cortical cancer effects both in vitro and in vivo,may inhibit the proliferation and migration of adrenal cortical cancer cells and promote their apoptosis by regulating the miR-142-5p/PLEKHA3 signaling pathway.This provides a new potential target for the treatment of adrenal cortical cancer.

BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.

Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

Exploring the action targets (groups) of traditional Chinese medicine (TCM) is an important proposition to promote the innovation and development of TCM, but it has attracted a lot of attention as to whether it is related to the efficacy or the disease. Our team found that the metabolomic signature molecules in the development of diabetes mellitus (DM) were significantly associated with the clinical efficacy of Yuquan Pill through a large clinical sample study. Taking this as a clue, our team intends to expand the information on the omics features of DM development, and discover the key targets (groups) and their lead compounds for the hypoglycemic effect of Yuquan Pill. The project includes: ① Based on the retrospective clinical trials, using omics technology integrated with generative artificial intelligence, mining the characteristic information of proteome and microbiome, forming driving factors together with metabolome characteristic molecules, and characterizing the molecular trajectories of diabetes evolution and their interference by Yuquan Pill; ② Taking the evolving molecular trajectories as a link and pointer, using anthropomorphic modeling and molecular biology techniques such as chemical proteomics to discover the key targets (groups) of Yuquan Pill's hypoglycemic effect, with the prospective clinical samples for validation; ③ Evaluate the overall response of key targets (groups) using graph neural network technology, and search for drug-derived/endogenous lead compounds with proven clinical pathologies and clear mechanisms of action, so as to provide a new paradigm and technology for the discovery of complex active ingredient targets (groups) of TCM that are related to their clinical efficacy, as well as for the discovery of innovative medicines.

Objective:To investigate the imaging quality of CBCT under different exposure parameters and the relationship between subjective and objective evaluation.Methods:CBCT scanners of 6 different suppliers[3D Accuitomo(Morita),i-mCAT(Kavo),5G(NewTom),Smart3D(Beijing Langshi),DCT Pro(Vatech),Vgi(NewTom)]were used to scan the spatial resolution models and head simulators under typical exposure conditions(different device with different tube voltage and current for exposure).The visibility of SedentexCT IQ phantom and anatomical structures generated by different CBCT scanners were compared.For objective evaluation,7 professional evaluators scored CBCT imaging qualities.For subjective evaluation,the resolution(LP/mm)of the images were com-pared among the devices.Results:No significant difference was found by 7 evaluators either intra or inter of the teams.By objective e-valuation,the score of NewTom 5G was 2,that of i-CAT was 5 and that of the others was 4.By subjective evaluation,the LP/mm of i-CAT was 1.8,that of Smart3D was 2.0 and that of the others was 1.0-1.7.The subjective evaluation of image quality obtained un-der different tube voltages and tube currents were significantly different.Conclusion:The subjective and objective evaluations of image quality are approximately consistent.The difference of the subjective image quality may be produced by the different tube voltage and current for exposure.

Objective To analyze the influencing factors of peritoneal dialysis associated peritonitis(PDAP)and the distribution characteristics of pathogenic bacteria.Methods The clinical data of 257 patients who underwent peritoneal dialysis(PD)and regular follow-up in Meizhou People's Hospital from January 2012 to October 2022 were retrospectively analyzed.According to the occurrence of PDAP,the patients were divided into the PDAP group(n=102)and the non-PDAP group(n=155).The exhaled liquid(5-10 mL)was extracted with a sterile syringe,and the pathogen was identified by blood culture method.General data such as gender,age,primary disease,education level,whether complicated with hypertension/diabetes/cardiovascular diseases,whether keeping pets or poultry,body mass index(BMI)and dialysis duration were collected.Fasting elbow venous blood was drawn in the morning of the next day after diagnosis,the levels of hemoglobin(Hb),albumin(ALB),serum potassium,serum phosphorus,and serum calcium were detected.The estimated glomerular filtration rate(eGFR)and urea clearance index(UCI)were recorded.Multivariate logistic regression was used to analyze the risk factors of PDAP in PD patients.Results There were 217 cases of PDAP in 102 patients with PDAP,and 124 cases(57.14％)were positive for pathogen culture.A total of 127 pathogenic bacteria were isolated,including 84 Gram-positive strains(66.14％),39 Gram-negative strains(30.71％)and 4 Fungi strains(3.15％).Among the 84 strains of Gram-positive bacteria,there were 25 strains of staphylococcus epidermidis(29.76％),17 strains of staphylococcus aureus(20.24％),12 strains of staphylo-coccus haemolyticus(14.29％),8 strains of staphylococcus warneri(9.52％),10 strains of streptococcus salivarius(11.90％),5 strains of streptococcus sanguis(5.95％),and 7 other strains(8.33％).Among the 39 strains of Gram-nega-tive bacteria,there were 20 strains of escherichia coli(51.28％),6 strains of pseudomonas aeruginosa(15.38％),6 strains of acinetobacter baumannii(15.38％),5 strains of klebsiella pneumoniae(12.82％),and 2 strains of enterobacter cloacae(5.13％).Among the 4 strains of Fungi,there were 3 strains of near-smooth candida(75.00％)and 1 strain of candida glabrata(25.00％).There was no significant difference in gender,age,primary disease,education level,BMI,and the propor-tion of comorbidities with hypertension,diabetes and cardiovascular diseases between the PDAP and non-PDAP groups(P＞0.05).The proportion of patients keeping pets or poultry in the PDAP group was higher than that in the non-PDAP group,and the dialysis duration was longer than that in the non-PDAP group(P＜0.05).There was no significant difference in serum phosphorus,serum calcium,eGFR and UCI between the PDAP and non-PDAP groups(P＞0.05).The levels of Hb,ALB and serum potassium in the PDAP group were significantly lower than those in the non-PDAP group(P＜0.05).Logistic regression analysis showed that keeping pets or poultry and long dialysis duration were risk factors for PDAP in PD patients(P＜0.05).High Hb and ALB levels were protective factors for PDAP in PD patients(P＜0.05).There was no correlation between serum potassium and PDAP in PD patients(P＞0.05).Conclusion Gram-positive bacteria are the main pathogenic bacteria of PDAP,among which staphylococcus epidermidis is the predominant one.Keeping pets or poultry and long dialysis duration are risk factors for PDAP,while high Hb and ALB levels are protective factors for PDAP in PD patients.

The online and offline hybrid teaching model of evidence-based medicine (EBM) is currently in the stage of development. Previous teaching focused on the teaching process in the classroom, and did not organically combine all the course contents before, during, and after class. The BOPPPS model can be used to establish coherence and integrity in the EBM teaching process. Considering the discipline characteristics and teaching objectives of EBM, this study initially explored and designed a BOPPPS-based online and offline hybrid teaching model. Taking the "diagnostic evidence" module as an example, the teaching implementation details were introduced. A pre-designed questionnaire was used to conduct baseline survey and follow-up survey on students before and after class to evaluate the teaching model and effect. The surveys showed that half of the students (77/154) preferred the new online and offline hybrid teaching model of EBM. The students found that all aspects of BOPPPS teaching were generally acceptable and satisfactory. Compared with before teaching, the students' proficiency in EBM was significantly improved after the teaching ( P<0.001), particularly in their ability to retrieve literature and evaluate the quality of evidence, which is of great significance for expanding their knowledge and clinical thinking.