Objective : To explore the effects of microRNA-155 (miR-155) on apoptosis of chronic myeloid leukemia ( CML) cells，and the influence of miRNA-155 regulating the expression of heat shock proteins ( HSP) 27， HSP60，HSP70． Methods : Reverse transcription-quantitative real-time PCR ( RT-qPCR) was used to detect the expression levels of miR-155 in CML-resistant imatinib (IM) cell line K562-G and CML cell line K562 ．K562-G cells were infected with the lentivirus carrying miR-155 or the negative control lentivirus ，and they were named miR-155 group and control group．The effect of miR-155 on the proliferation of drug-resistant cells was detected by cell counting kit-8 ( CCK-8) method. RT-qPCR and Western blot were used to detect the effect of miR-155 on the expression of heat shock proteins HSP27，HSP60，HSP70．Flow cytometry was used to detect the percentage of cell apoptosis in miR-155 group and control group. Results : ompared with K562 cells，miR-155 showed low expres- sion in K562-G cells (P ＜0. 05) ．The proliferation of miR-155 group cells decreased significantly from the 36th hour (P＜0. 05) ．Compared with the control group，in the miR-155 group，HSP60 and HSP70 increased (P < 0. 05) ，while HSP27 decreased (P＜0. 01) ．The apoptosis rate of miR-155 group was higher than that of control group (P＜0. 05) ． Conclusion miR-155 promotes the apoptosis of chronic myeloid leukemia cells，increases the expression of HSP60 and HSP70，and decreases the expression of HSP27 .

Objective: To understand the social adaptation in the association between attitude towards parents with academic anxiety among middle school students in Chongqing, so as to provide a basis and thinking method for theoretical framework of family education and youth development. Methods: Convenient and clustering sampling method was used to select 34 097 middle school students aged 13-18 years during September to November 2023. All the participants were investigated with self designed questionnaire, Social Adaptability Scale and Mental Health Test. The mediating effect of social adaptability in the relationship between students attitudes towards their parents academic anxiety was evaluated by using Logistic regression analysis and structural equation model. Results: The proportion of high school students in Chongqing with academic anxiety was 48.80%. Academic anxiety differed significantly by sex, academic grade, attitude towards parents, and social adaptability ( χ 2=948.45, 173.92, 537.51, 4 770.04, P < 0.01). The results of Logistic regression analysis showed that positive attitudes towards parents were positively correlated with moderate academic anxiety ( OR=1.13, 95%CI =1.08-1.18) and high academic anxiety ( OR=1.14, 95%CI =1.09-1.19) ( P < 0.05 ). The results of the mediation effect analysis showed that positive attitude of middle school students towards their parents negatively predicted academic anxiety ( β= -0.12 , P <0.01), but when social adaptation ability was used as a control variable, the original negative relationship between the positive attitude towards parents and academic anxiety of middle school students changed ( β=0.02, P <0.01), and social adaptation ability played a masking effect in the relationship. The social adaptation ability of middle school students played a mediating role in the relationship between their positive attitudes towards their parents and academic anxiety, with a mediating effect of -0.63. Conclusions The attitude of middle school students towards their parents will directly affect academic anxiety, and also have an indirect impact on academic anxiety through social adaptability, but there is a cover effect. Pay more attention to family education and actively focus on students social adaptability can contribute to improve the mental health level of adolescents.

Objective To investigate the relationship between polymorphism of resistin(RETN)gene and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients in middle and high altitude areas.Methods A total of 400 patients with T2DM in Qinghai area were recruited and divided into simple T2DM group(T2DM,n=200)and T2DM combined with MAFLD group(T2DM+ MAFLD,n=200)according to liver ultrasonography.Healthy individuals confirmed by physical examination were selected as the normal control group(NC,n=180).Plasma resistin levels were measured by ELISA.The polymorphism of RETN-420C/G and +299G/A genes were detected by PCR sequencing.Results By comparing the polymorphism of RETN-420C/G gene in each group,it was found that the frequencies of G/G genotype and G allele frequency in T2DM+MAFLD group were higher than those in NC group and T2DM group(P<0.05),while the frequencies of C/C genotype and C allele frequency were lower than those in NC group and T2DM group(P<0.05).The risk of MAFLD increased by 1.571,2.126 and 1.537 times respectively in T2DM patients with C/G,G/G genotype and G allele.Logistic regression analysis showed that G/G genotype was a risk factor for MAFLD in T2DM patients.By comparing the polymorphism of RETN+299G/A gene in each group,it was found that A allele frequency in T2DM+MAFLD group was higher than that in NC group and T2DM group,while G allele frequency was lower than that in NC group and T2DM group(P<0.05).The allele A increased the risk of MAFLD in T2DM patients by 1.432 times compared to allele G.Conclusion RETN gene-420C/G locus G/G genotype increases the risk of T2DM combined with MAFLD in middle and high altitudeareas.

Objective:Distribution and antibiotic resistance of pathogen isolated from children with intra-abdominal infection (IAI) associated sepsis in the intensive care unit (ICU) were analyzed to provide a reference for the empirical anti-infective treatment of IAI in children.Methods:We retrospectively analyzed the data of 116 children with culture-positive IAI-associated sepsis admitted to Children's Hospital of Zhejiang University School of Medicine from January 2019 to December 2021. Clinical isolation and drug resistance analysis were conducted based on different years of onset, locations of onset, and primary diseases.Results:A total of 186 strains of pathogens causing children with IAI-associated sepsis in ICU were collected. The distribution and antibiotic resistance of pathogen were as follows: the percentages of gram-positive bacteria, gram-negative bacteria, and fungi were 53.2%, 40.9%, and 5.9%, respectively; the top four strains were Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, accounting for 57.0% of all isolates; Enterococcus faecium(19.9%) and Enterococcus faecalis (10.2%) were the dominating gram-positive bacteria; Escherichia coli (13.4%) and Klebsiella pneumoniae (13.4%) were more common gram-negative bacteria; Fungi were dominated by Candida albicans (3.8%).Fifty-seven strains of gram-positive bacteria were detected in 61 children with infectious diseases, mainly Enterococcus faecium (28 strains). There were 53 gram-negative strains, mainly Klebsiella pneumoniae (21 strains). Thirty-two strains of gram-positive bacteria were detected in 40 children with digestive tract malformation, and Enterococcus faecalis (six strains) were the most common. There were 14 gram-negative strains, mainly Escherichia coli (six strains). In 13 children with malignant tumors of digestive system, nine strains of gram-positive bacteria were cultured, and Enterococcus faecium (four strains) was the most common. There were eight gram-negative strains, mainly Escherichia coli (four strains).In the 46 community-acquired IAI patients,30 gram-positive isolates were cultured,mainly including Enterococcus faecium (12 strains), Staphylococcus epidermidis (seven strains), and Viridans streptococci (six strains); Forty gram-negative isolates mainly contained Escherichia coli (16 strains), Klebsiella pneumoniae (14 strains), and Enterobacter cloacae (five strains). In the 70 hospital-associated IAI patients, 69 gram-positive isolates such as Enterococcus faecium (25 strains), Enterococcus faecalis (17 strains), Enterococcus gallinarum (eight strains), and Staphylococcus aureus (seven strains) were cultured;Tirty-six gram-negative isolates were dominated by Klebsiella pneumoniae (11 strains), Escherichia coli (nine strains), Pseudomonas aeruginosa (four strains), and Acinetobacter baumannii (four strains). The mixed infection rate of clinical pathogens was up to 46.6%, and the overall resistance rate was 43.4%, in which gram-negative bacteria had high sensitivity to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, and tigecycline.The detection rates of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum β-lactamases were 36.0% and 24.6%, respectively, with 100% sensitivity to tigecycline. Gram-positive bacteria showed 100% sensitivity to vancomycin, linezolid, and tigecycline. Conclusion:Pathogen isolated from children with IAI-associated sepsis in ICU were dominated by Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis,respectively. Before confirmation of pathogenic bacteria, antibacterial agents can be selected according to the infection type. It is important to note that a single broad-spectrum antibacterial agent or combination medication can be considered the initial empirical choice due to the large variety of pathogens, high rates of mixed infections, and high overall resistance.

Objective To investigate the best evidence application of exercise prescription in patients with chronic heart failure in clinical practice and evaluate its effectiveness.Methods The best evidence of exercise prescription for patients with chronic heart failure was summarized,and the evidence-based practice plan was developed,and it was implemented in the cardiology department of a tertiary hospital in Zhejiang Province from August to October,2022.Nurses'exercise prescription knowledge-attitude-practice level,implementation rate of review indicators,the length of hospital stay,exercise endurance,daily living ability and grip strength of both groups before and after the intervention were compared.Results After the application of the best evidence,the score of knowledge dimension was(9.34±0.98)points;the score of attitude dimension was(63.29±1.37)points;the score of practice dimension was(25.49±1.51)points,which were statistically significant compared with the scores before the application of evidence(P<0.05).After the application of the best evidence,the implementation rate of 16 review indicators was higher than that before the application of evidence(P<0.001).The length of hospital stay in the evidence application group was shorter than that in the baseline examination group(Z=-2.610,P<0.001).After intervention,the exercise endurance,daily living ability and grip strength of patients in the evidence application group were improved compared with the baseline review group,and the difference was statistically significant(P<0.05).Conclusion After the application of the best evidence of exercise prescription in patients with chronic heart failure,it can improve the level of knowledge,attitude and practice of nurses on exercise prescription,standardize the compliance of nurses'exercise prescription,reduce the number of days in the hospital,and improve patients'exercise endurance,daily living ability and grip strength.

This study was designed to explore the correlation between alterations in NLRP3 levels and Th17/Treg imbalance in asthmatic mice undergoing epithelial-mesenchymal transition(EMT).A murine model of asthma was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).Mice were randomly grouped into asthma model group and normal control group.The airway reactivity was detected with non-invasive lung function instrument.Hematoxylin and Eosin(HE)and Masson's trichrome staining were applied to evaluate the histopathological injury of lung tissue and the extent of lung fibrosis;RT-qPCR was applied to detect EMT-related biomarkers(Snail,E-Cadherin,N-Cadherin),the specific transcription factors of T cell subsets(RoRγt,Foxp3)and NLRP3 in lung tissue of mice;Western blot was used to detect the protein expression of E-cadherin,N-Cadherin and NLRP3 in lung tissue of mice.The Th17 and Treg cell populations in the spleen were enumerated via flow cytometry.Furthermore,the expression levels of NLRP3,IL-17 and IL-10 in bronchoalveolar lavage fluid(BALF)were analyzed by Giemsa staining.Compared with the control group,the asthma model group showed higher level of airway resistance,coupled with an obviously decrease in pulmonary ventilation compliance.Pathological alterations in lung tissue were evident,characterized by thickening of the airway epithelium,airway stenosis,infiltration of inflammatory cells,higher expression levels of N-Cadherin and NLRP3 proteins(P<0.05),lower expression level of E-Cadherin(P<0.001)and higher levels of marker genes(Snail and N-Cadherin)in lung tissue.Furthermore,model mice demonstrated higher level of NLRP3 in BALF(P<0.05),higher level of Th17 in spleen,and higher levels of retinoic acid orphan receptor(ROR)-γt mRNA(P<0.05)and Th17-related cytokines(IL-17)(P<0.01).Concurrently,model mice also showed an obviously decrease in the prevalence of Treg cells,Forkhead box Foxp3 mRNA(P<0.001),and Treg-related cytokine IL-10(P<0.05).The results of the Pearson correlation analysis indicated that the level of NLRP3 mRNA was positively correlated the ratio of RoR γt mRNA,but negatively correlated with Foxp3 mRNA in the lung tissue of asthmatic mice.Additionally,NLRP3 in BALF demonstrated a positive correlation with IL-17 and a negative correlation with IL-10.In conclusion,These findings suggest that NLRP3 may trigger bronchial EMT by exacerbating the immune imbalance of Th17/Treg cells.

Objective To investigate the influence of spectral CT monochromatic imaging technique on image quality and liver vol-ume measurement in computed tomography portal venography(CTPV).Methods A total of 120 patients who underwent contrast-enhanced abdominal CT examination were prospectively selected and randomly divided into group A and group B.The group A(n=60)was scanned with conventional parameters such as 120 kVp,Smart mA mode,and image reconstruction of 60％adaptive statistical iterative reconstruction-Veo(ASIR-V);while the group B(n=60)was with instantaneous switching 80/140 kVp,gemstone spectral imaging(GSI)Assist mode,and image reconstruction of 60％ASIR-V.In group B,six subgroups of images from 75 to 50 keV(with 5 keV interval)were recorded as subgroups B1 to B6.On the axial images,the CT values and standard deviation(SD)values of por-tal vein,liver and erector spinae were measured,and then the contrast-to-noise ratio(CNR)of portal vein and liver were calculated.The Liver Segmentation software was used to segment the liver in groups A and B,the liver volumes by automatic segmentation and manual segmentation(golden standard)were recorded,and then the volume difference rate was calculated.The overall image quality and automatic liver segmentation results were evaluated by two radiologists using a 5-point scale.Results In terms of overall image quality,subgroup B6 achieved the highest score and was superior to group A(P＜0.001).In terms of liver segmentation,subgroup B3 had the highest score and was superior to group A(P＜0.001).With the decrease of keV,the CT values,SD values and CNR of portal vein and liver in group B were gradually increased(P＜0.05),in which subgroup B6 was higher than that in group A(P＜0.001).The volume difference rate initially decreased and then increased with the decrease of keV.Except for subgroups B2 and B3,the differences were statistically significant between other subgroups and group A(P＜O.001),and the subgroup B3 had the lowest volume difference rate.Conclusion Spectral CT monochromatic ima-ging technique has an influence on CTPV image quality and liver volume measurement.The 50 keV images are the best for displaying portal vein,and the automatic liver segmentation volume of 65 keV images is closest to the real liver volume.

AIM:This study utilized CRISPR/Cas9 technology to create Retnlb floxp knock-in mice,followed by the application of the Cre-LoxP recombination system to generate intestinal epithelial-specific Retnlb gene knockout mice(Retnlb-CKO).This model was developed to investigate the pathogenic mechanisms of Retnlb in inflammatory bowel disease.METHODS:Female and male C57BL/6N mice,aged 8 weeks with the Retnlbflox/+genotype,were housed togeth-er for breeding.Offsprings were screened to identify those with the Retnlbflox/flox genotype.These mice were then crossed with Vil1-Cre transgenic mice,which express Cre recombinase specifically in intestinal epithelial cells,resulting in Retnlb-flox/+,Cre+mice.Subsequent crosses between Retnlbflox/+,Cre+mice and Retnlbflox/flox mice produced Retnlbflox/flox,Cre+mice(Retnlb-CKO).Six 8-week-old Retnlbflox/flox,Cre+mice and their littermate Retnlbflox/flox mice were selected for experiments.RT-qPCR and immunohistochemistry were used to assess Retnlb mRNA and protein levels in colonic epithelium.Phenotypic observa-tions included body length,weight,diet,and reproductive capability.Tissue-to-body weight ratios were calculated to ana-lyze growth and development.Intestinal barrier integrity and colonic expression of inflammatory factors were evaluated.RESULTS:The conditional gene knockout mouse model with specific deletion of Retnlb in intestinal epithelial cells was successfully established and validated through genetic identification,mRNA and protein analysis.Compared to Retnlbflox/flox mice,Retnlb-CKO mice exhibited no significant differences in body length,weight,diet,or reproductive capability.There were no differences in the ratios of heart,liver,spleen,lung,kidney,and colon weight to body weight,nor were there morphological differences in various tissues.However,the mRNA expression of tight junction proteins ZO-1,Occlu-din,and Claudin3 in colon tissues of Retnlb-CKO mice was significantly reduced(P<0.01).PAS staining and immunohis-tochemistry revealed a significant decrease in the number of goblet cells and lysozyme-positive cells in the colon tissues of Retnlb-CKO mice(P<0.01).HE staining showed no obvious pathological change in colon tissues of Retnlb-CKO mice.RT-qPCR further demonstrated a significant downregulation of pro-inflammatory factors NLRP3,interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α)in colon tissues(P<0.01),along with significant downregulation of inflamma-tion signaling pathway proteins TLR4,MyD88,and NF-κB(P<0.01).CONCLUSION:A conditional colon epithelial cell Retnlb gene knockout mouse model was successfully constructed and validated.The absence of Retnlb in colon cells led to impaired intestinal barrier function,decreased mRNA expression of pro-inflammatory factors in colon tissue,and downregulation of mRNA expression of inflammatory pathway proteins TLR4,MyD88,and NF-κB.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

Purpose To explore the value of CT large reconstruction matrix 1024×1024 combined with iterative reconstruction algorithm Karl in the diagnosis of pulmonary nodules.Materials and Methods A total of 500 patients who underwent chest CT examination at the First Affiliated Hospital of Dalian Medical University from October 2021 to May 2022 were prospectively collected,and the raw data of CT scans were reconstructed to divide into group A and B.Group A was reconstructed using a conventional 512×512 matrix combined with Karl 5 reconstruction;group B was reconstructed using a large 1 024×1 024 reconstruction matrix combined with different levels of Karl algorithm to obtain four subgroups,including B1(Karl 6),B2(Karl 7),B3(Karl 8)and B4(Karl 9)subgroup.The signal-to-noise ratio was calculated by measuring the CT and standard deviation values of the tracheal lumen above the arch of the aorta(tracheal area)and the avascular area of the upper lobe of the left lung(lung parenchyma).The overall image quality of the lungs in group A and B was evaluated by two physicians.The best image quality subgroup in group B was compared with the lesion display in group A.The diagnostic efficacy was analyzed based on the surgical pathology results.Results In group B,the standard deviation values of trachea and lung parenchyma gradually decreased and the signal-to-noise ratio gradually increased as the Karl grade increased compared with group A(F=675.002-2 020.903,all P<0.05).All subjective scores in group B were significantly higher than those in group A(Z=-15.361--6.465,all P<0.05),and the highest subjective scores were found in group B4.Some solid nodules(≤3 mm)and solid nodules(6.1 mm-≤3 cm)showed no statistically significant difference in clarity(Z=-2.000,-0.378,both P>0.05).Compared with group A,group B4 showed a 12%-100%improvement in nodule clarity.Only pleural depression sign showed the difference was not statistically significant(χ2=2.143,P>0.05).Taking 43 cases of surgical pathology as the gold standard,the diagnostic accuracy of group B4 was 65.12%,which was better than that of group A,which was 41.86%(χ2=4.674,P<0.05).Conclusion The combined application of the large reconstruction matrix and the Karl iteration algorithm results in superior image quality and facilitates the diagnosis of lung nodules.