Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Different animals in Xinjiang carry Escherichia coli O157:H7(E.coli O157:H7),but the connection between these strains is not clear.This study aims to understand the evolutionary sub-group of E.coli O157:H7,the distribution of the dominant genetic lineage,the biofilm formation ability,the carriage of mobile genetic elements and their drug resistance profile.E.coli O157:H7 was identified by PCR.Multilocus sequence typing(MLST)protocol was used for E.coli O157 to detect ST type,plasmid replicon and integron genes.Biofilm formation ability was determined by crystal violet microplate,and Kirby-Bauer was used to detect drug resistance.The results showed that 46.7％(7/15)of E.coli O157:H7 belongs to Group A,53.3％(8/15)of E.coli O157:H7 be-longs to Group E.Sheep source were mainly prevalent in Group A(4/6).Cattle sources are mainly Group E(6/7).A total of six ST types were detected:ST11(8/15),ST-206(1/15),ST-6126(3/15),ST-1640(1/15),ST-178(1/15),ST-4550(1/15).Two strains had a moderate biofilm-form-ing capacity,two strains had a weak biofilm-forming capacity,10 strains have no biofilm-forming capacity.All were multidrug-resistant strains,with complete resistance to lincomycin,oxacillin,clindamycin,vancomycin,midemycin and cefthiophene,and 88％-94％resistance to poly-myxin B,ampicillin,penicillin G and erythromycin,they are highly drug resistant.The five resist-ance genes detected were acrA(66.66％,10/15),tolC(73.33％,11/15),qurS(13.33％,2/15),floR and qurA(6.67％,1/15).Four plasm id replicons were detected,they were IncP(66.66％,10/15),IncFrepB(86.67％,13/15),IncFIA(6.67％,1/15),IncFIB(66.66％,10/15).Two class Ⅰ integrons were detected and they were ISCR1(33.33％,5/15),ISECP1(20％,3/15).The re-sults showed that E.coli O157:H7 in Xinjiang was predominantly prevalent in Group A and Group E.Sheep sources were predominantly prevalent in Group A,and cattle sources were predominantly prevalent in Group E.The ST types were widely distributed,with ST11 types being the predomi-nant type,the biofilm-forming ability was weak,and the resistance was strong,all of them were multi-drug-resistant strains,and the resistance genes were mainly externally excreted from the pumps,and the resistance genes had more spreading elements.

Objective:To establish a model of reactive Th17 cells proliferation induced by collagen type Ⅱ(C Ⅱ)in vitro and investigate its influencing factors.Methods:The splenic lymphocytes of normal and CIA mice were isolated and divided into groups.They were given inactivated or non-inactivated C Ⅱ or different concentrations of IL-23(2,10,50 ng/mL),or IL-23p19 antibody.Culturing for 60 hours,the ratio of CD4+RORγt+Th17 cells was detected by flow cytometry.Then,the results obtained are ana lyzed,and the corresponding conclusions are drawn.Results:After 60 hours of culture in vitro,the ratio of Th 17 cells stimulated by inactivated or non-inactivated C Ⅱ in normal mouse spleen lymphocytes was significantly lower than that before culture,and the ratio of Th17 cells not stimulated by C Ⅱ in CIA mouse spleen lymphocytes was also significantly lower than that before culture,while the ratio of Th17 cells stimulated by inactivated C Ⅱ or non-inactivated C Ⅱ in CIA mouse spleen lymphocytes was significantly higher than that before culture,and there was a significant difference compared with the CIA control group(P＜0.05).However,there was no statistical difference in the ratio of Th17 cells between the two groups without inactivated C Ⅱ and inactivated C Ⅱ(P=0.44).After the analysis of the data obtained from the study,it was further concluded that different concentrations of IL-23 did not affect the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro,but after adding IL-23p19 antibody neutralization reagent,the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro decreased significantly,with a statistical difference compared with the blank control group(P＜0.01).Conclusions:This study established an in vitro Th17 cell proliferation model induced by type Ⅱ collagen,exploring the effects of IL-23 and collagen activity on Th17 cell proliferation.The results showed that CⅡ stimulation significantly promoted Th17 cell proliferation in CIA mice,with both active and inactivated CⅡ inducing proliferation.IL-23 was found to be essential for the maintenance of Th17 cells,although its direct proliferative effect was limited.These findings provide new experimental evidence and theoretical support for the mechanism research of rheumatic diseases and IL-23/IL-17 pathway-targeted therapies,with important implications for immune regulation and drug development.

BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression

Objective:To construct the sphingosine kinase 1(SPHK1)overexpression lentiviral vector,and to establish the SKOV3 lentiviral stable transfection cell line.Methods:According to the SPHK1 data information provided by the National Center for Biotechnology Information(NCBI)database,the primers were designed and synthesized,the target gene was amplified,and connected to the GV492 plasmid treated with Bam HⅠ and AgeⅠ restriction enzymes to construct the SPHK1 overexpression lentiviral vector;the positive clones were selected for PCR and sequencing identification;the lentiviral plasmid and the lentiviral packaging auxiliary plasmid were co-transfected into the HEK-293T cells for packaging and titer determination;according to the measured optimal multiplicity of infection(MOI)of 10,the corresponding lentiviral amounts in various groups were transfected into the SKOV3 cells,and the SKOV3 cells were divided into blank group(without treatment),GV492 control group(GV492 control lentivirus infected SKOV3 cells),and GV492-SPHK1 overexpression group(GV492-SPHK1 overexpression lentivirus infected SKOV3 cells,ov-SPHK1 group);the optimal concentration of 2 mg·L-1 puromycin was used to screen the stably transfected SKOV3 cell line;after 48 h,the medium was changed and replaced with 1 mg·L-1 puromycin for screening for 14 d;the morphology and fluorescence expression of the cells were observed under fluorescence microscope;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of SPHK1 mRNA in the SKOV3 cells in various groups;Western blotting method was used to detect the expression level of SPHK1 protein in the SKOV3 cells in various groups.Results:The PCR sequencing results showed that the gene sequence of the SPHK1 overexpression lentiviral vector was completely consistent with the target sequence,and the SPHK1 overexpression lentiviral vector was successfully constructed;the titer determination results showed that the lentiviral titers in GV492 control group and ov-SPHK1 group were 5×1011 and 8×1011 TU·L?1,respectively;the SKOV3 cells in GV492 control group and ov-SPHK1 group were in good state and showed strong fluorescence expression,suggesting that the SKOV3 stable transfection cell line overexpressing SPHK1 was successfully established;the RT-qPCR results showed that compared with blank group and GV492 control group,the expression level of SPHK1 mRNA in the SKOV3 cells in ov-SPHK1 group was significantly increased(P<0.01);the Western blotting results showed that compared with blank group and GV492 control group,the expression level of SPHK1 protein in the SKOV3 cells in ov-SPHK1 group was significantly increased(P<0.01).Conclusion:The SPHK1 overexpression lentiviral vector is successfully constructed,and the SKOV3 stable transfection cell line is established.

Objective:To investigate the levels and clinical significances of miRNA-155-5p (miR-155-5p) and hypoxia inducible factor-1α (HIF-1α) in the bone marrow of patients with acute myeloid leukemia (AML)-M 5. Methods:A cross sectional study was conducted. The bone marrow samples were collected from 32 AML-M 5 patients who were admitted to the First Affiliated Hospital of Hebei North University from November 2023 to December 2024, and the bone marrow samples collected from 11 patients with megaloblastic anemia from November 2023 to May 2025 were used as controls. Reverse transcription real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to determine relative expression of miR-155-5p at the transcription level in bone marrow mononuclear cells, and enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of HIF-1α protein in bone marrow supernatant. The levels of miR-155-5p and HIF-1α in bone marrow were compared between AML patients and control group, as well as among AML patients with different prognostic risks. Spearman method was used to analyze the relationship between miR-155-5p level and HIF-1α level in bone marrow of AML patients and their levels with bone marrow and peripheral blood cell indicators. Results:Among the 32 AML-M 5 patients, 20 patients (62.5%) were male and 12 patients (37.5%) were female, with a median age [ M ( Q1, Q3)] of 63 (51, 70) years; according to the clinical response criteria recommended by the European Leukemia Network (ELN) in 2022, there were 12 cases (37.5%) of complete response (CR) and 8 cases (25.0%) of non-complete response (NCR); according to the risk stratification criteria recommended by ELN in 2022, there were 8 cases (25.0%) with good prognosis, 13 cases (40.6%) with moderate prognosis and 11 cases (34.4%) with poor prognosis. In the control group, there were 5 males and 6 females, with a median age of 68 (63, 72) years. There was no statistically significant difference in gender and age between the two groups (both P > 0.05). The transcription level relative expression of miR-155-5p in the bone marrow mononuclear cells of AML-M 5 patients [5.13 (2.83, 8.84) vs. 0.87 (0.56, 1.69)] and the concentration of HIF-1α protein in the bone marrow supernatant of AML-M 5 patients [(116±32) pg/ml vs. (58±22) pg/ml] were higher than those in the control group, and the differences were statistically significant (both P < 0.001). The relative expression of miR-155-5p at the transcription level in the initial diagnosis group and NCR group and the concentration of HIF-1α in the initial diagnosis group, NCR group and CR group were higher than those in the control group (all P < 0.01), the relative expression of miR-155-5p at the transcription level in the CR group was higher than that in the control group, but the difference was not statistically significant ( P > 0.05); the relative expression of miR-155-5p at the transcription level in the newly diagnosis group was higher than that in the CR group, and the difference was statistically significant ( P < 0.01). However, there was no statistically significant difference between the newly diagnosis group and the NCR group or between the NCR group and the CR group (all P > 0.05). The concentration of HIF-1α in the newly diagnosis group and NCR group was higher than that in the CR group, and the differences were statistically significant (both P < 0.05). However, there was no statistically significant difference between the newly diagnosis group and the NCR group ( P > 0.05). There was no statistically significant difference in the relative expression of miR-155-5p at the transcription level and HIF-1α concentration in bone marrow among AML-M 5 patients with poor prognosis, moderate prognosis and good prognosis (both P > 0.05). The level of miR-155-5p in the bone marrow of AML-M 5 patients was positively correlated with the level of HIF-1α ( r = 0.446, P = 0.010); the level of miR-155-5p in bone marrow was positively correlated with the proportion of bone marrow primitive cells ( r = 0.583, P < 0.001), peripheral blood leukocyte count ( r = 0.464, P = 0.008), peripheral blood monocyte count ( r = 0.464, P = 0.007), and peripheral blood monocyte-to-leukocyte ratio ( r = 0.457, P = 0.009). The concentration of HIF-1α in the bone marrow of AML-M 5 patients was positively correlated with the proportion of bone marrow primitive cells ( r = 0.568, P = 0.001) and peripheral blood mononuclear cells-to-white blood cells ratio ( r = 0.375, P = 0.034), but not with peripheral blood white blood cell count ( r = 0.159, P = 0.385) or peripheral blood mononuclear cell count ( r = 0.300, P = 0.095). Conclusions:The levels of miR-155-5p and HIF-1α in the bone marrow of AML-M 5 patients are relatively high, and the levels of both are lower in patients with remission. However, the levels of both may not be related to the risk of prognosis. The levels of miR-155-5p and HIF-1α in the bone marrow of AML-M 5 patients are positively correlated, and their levels are also positively correlated with major hematological indicators in the bone marrow and peripheral blood.

Objective To investigate the fatigue and workload status among medical students,and to explore the latent profiles of fatigue and workload and their effects on sleep and emotion.Methods A cross-sectional study design with convenience sampling was employed to distribute a comprehensive survey via mixed online and offline modes,and medical college students were enrolled as the subjects for this investigation.The general demographic data,depression,anxiety and stress scale,Pittsburgh sleep quality index,Epworth sleepiness scale,insomnia severity index,National Aeronautics and Space Administration task load index(NASA-TLX)and fatigue scale-14(FS-14)were used to investigate the basic information of the medical students,their emotions(depression,anxiety and stress),sleep(sleep quality,sleepiness and insomnia),workload and fatigue status.Based on latent profile analysis,the types of workload-fatigue profiles and differences in sleep and emotion were analyzed.Results A total of 485 medical students were enrolled,with an average age of(22.07±2.42)years.The total score of the NASA-TLX was 64.44±12.50,and the total score of the FS-14 was 7.90±3.63.Latent profile analysis identified 3 distinct workload-fatigue profiles:low workload-medium fatigue group(12.8％),medium workload-low fatigue group(32.8％),and high workload-high fatigue group(54.4％).Among these,the medium workload-low fatigue group exhibited the highest performance level(all P＜0.05),while the low workload-medium fatigue group showed the lowest effort level and performance level(all P＜0.05).The high workload-high fatigue group showed the highest task-related demand and frustration level(all P＜0.05).Regarding sleep and emotional status,the medium workload-low fatigue group had significantly better outcomes compared to the high workload-high fatigue group and the low workload-medium fatigue group(all P＜0.05).Conclusion Medical students experience a heavy workload and subjective fatigue.It is essential to appropriately adjust their workload,prioritize sleep and emotional well-being,and alleviate fatigue levels,so as to sustain personal physical and mental health.

Objective To compare the application effects of plankton multiplex polymerase chain reac-tion-capillary electrophoresis(PCR-CE),SYBR Green Ⅰ real-time quantitative PCR(qPCR)and microwave digestion-vacuum filtration-automated scanning electron microscopy(MD-VF-Auto SEM)in the diagnosis of drowning.Methods Lung,liver and kidney tissues from 212 drowned corpses and 30 non-drowned corpses were examined respectively by the three drowning-related plankton testing methods,and the detection rates of plankton in each tissue by three methods were compared.Results In drowned corpses,the total detection rates of PCR-CE,qPCR,and MD-VF-Auto SEM were 93.9%,96.2%,and 95.3%,respectively,with no statistically significant difference(P>0.05).The detection rate of lung tissue by MD-VF-Auto SEM(100%)was higher than those of PCR-CE and qPCR(P<0.05),and there was no significant difference in the detection rates of the three methods in liver or kidney tissues(P>0.05).In non-drowning corpses,a small number of diatoms(less than 10 cells/10 g)were detected by MD-VF-Auto SEM method,only in liver and kidney tissues,while the other two methods yielded negative results for all tissues.Conclusion All three methods have good efficacy in the examination of drowned corpses.The MD-VF-Auto SEM method directly observes diatom morpho-logical characteristics through scanning electron microscopy,and the qualitative and quantitative analy-ses are intuitive and accurate.It has great advantages in the examination of difficult degradation samples.The PCR-CE method and qPCR method have a low sample demand(0.5 g),are easy to operate and have short detection time(4-7 h).They are easy to be applied in the grassroots depart-ments and are suitable for the rapid determination of drowned corpses in routin cases.The combina-tion of the two DNA methods with the MD-VF-Auto SEM method can increase the detection rate of plankton,ensuring the reliability of examination results.This combined use is of significant importance in the application of drowning diagnosis.