Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P ＜ 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P＜ 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.

BACKGROUND:Existing studies have made significant progress in PIWI-interacting RNAs(piRNAs)against osteoporosis,but the specific targets and related mechanisms by which piRNAs exert their functions remain to be explored.OBJECTIVE:To investigate the effects and downstream mechanisms of piR-7472 on the differentiation of mouse osteoblasts(MC3T3-E1 cells).METHODS:(1)Twelve C57/BL6J mice were randomly divided into a sham-operated and an ovariectomized group,with six mice in each group.Changes in bone mass and the expression of piR-7472 were detected using Micro-CT and RT-qPCR,respectively,at 8 weeks after surgery.(2)MC3T3-E1 cells were divided into NC mimics group,piR-7472 mimics group,NC inhibitor group,and piR-7472 inhibitor group.The mRNA expression of piR-7472,osteopontin,type I collagen,Runt-related transcription factor 2,and potassium voltage-gated channel modifier subfamily F member 1 were detected by RT-qPCR after 7 days of osteogenic induction.The protein expression of osteopontin,Runt-related transcription factor 2,bone morphogenetic protein 2,and potassium voltage-gated channel modifier subfamily F member 1(KCNF1)was detected using western blot assay.The expression of alkaline phosphatase was detected by alkaline phosphatase staining after 14 days of osteogenic induction,and the number of mineralized nodules was detected by alizarin red staining after 21 days of induction.Whether piR-7472 could bind to KCNF1 was observed by the dual luciferase reporter gene assay.RESULTS AND CONCLUSION:(1)Bone mineral density,bone volume fraction,bone trabecular thickness,bone trabecular number were significantly decreased and bone trabecular separation was significantly increased in ovariectomized mice,and piR-7472 in bone tissue was significantly down-regulated in osteoporotic mice.(2)Compared with the NC group,the mRNA expression of osteopontin,type I collagen,and Runt-related transcription factor 2 were significantly increased,the protein expression of osteopontin,Runt-related transcription factor 2,and bone morphogenetic protein 2 were significantly elevated,and the levels of mineralized deposition and alkaline phosphatase were increased in the piR-7472 mimics group.Compared with the NC inhibitor group,the mRNA expression of osteopontin,type I collagen,and Runt-related transcription factor 2 was significantly downregulated,the protein expression of osteopontin,Runt-related transcription factor 2,and bone morphogenetic protein 2 were significantly decreased,and the levels of mineralized deposition and alkaline phosphatase were reduced in the piR-7472 inhibitor group.(3)piR-7472 was found to interact with the potassium voltage-gated channel modifier subfamily F member 1 as predicted by the miRanda database.The dual luciferase reporter gene assay revealed that piR-7472 mimics could bind to and promote the expression of KCNF1.To conclude,piR-7472 can promote osteogenic differentiation of osteogenic precursor cells MC3T3-E1,and its mechanism of action may be achieved by promoting the expression of KCNF1.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes mellitus,and it has become the main cause of chronic kidney disease and end stage renal disease.Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress,improving renal tissue damage,restoring renal function.This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine,so as to provide reference for clinical drug application,basic research and new drug research and development of DKD.

Objective:To systematically evaluate the qualitative study on HIV pre-exposure prophylaxis (PrEP) medication experience among men who have sex with men (MSM) .Methods:China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, Embase, CINAHL, Cochrane Library, and PsycINFO were searched. The search period was from database establishment to February 1, 2024. The methodological quality of the included literature was evaluated according to the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The integrative synthesis was used to integrate the findings.Results:A total of 11 articles were included, and 36 findings were distilled into eight new categories, which were synthesized to form three integrated findings (perceived PrEP medication benefits by MSM, perceived barriers to PrEP medication by MSM, and multidimensional adaptations to enhance the PrEP medication experience in MSM) .Conclusions:Healthcare providers should pay close attention to the PrEP medication experience of MSM, identify medication challenges promptly, and focus on assisting them with self-adaptation to improve the PrEP medication experience and increase PrEP medication adherence in MSM.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Objective:To investigate the anti-leukemic effects and resistance mechanisms of venetoclax in acute myeloid leukemia (AML). Genomic, transcriptomic, and clinical data from AML patients who underwent venetoclax drug sensitivity testing were downloaded from the Beat AML database. Correlation analysis was performed between these data and venetoclax sensitivity outcomes. Differentially expressed genes (DEGs) associated with venetoclax sensitivity were identified from transcriptomic data and subsequently validated using GEO database transcriptomic results and in vitro experiments (including Western blot). Functional enrichment analyses (KEGG and GSEA), transcription factor enrichment analysis (KnockTF), and data from public databases were employed to further investigate key genes and pathways influencing drug sensitivity.Results:After filtering the Beat AML cohort, data from 52 patient samples with available in vitro venetoclax sensitivity results were included for analysis. Patients with FLT3 mutations exhibited greater sensitivity to venetoclax compared to those with FLT3 wild-type. Correlation analysis between clinical information and drug sensitivity data indicated that higher peripheral blood tumor burden was associated with increased sensitivity to venetoclax. Transcriptomic analysis and in vitro experiments confirmed that venetoclax inhibits the FLT3-related signaling pathway, including downregulation of FLT3 expression and reduced phosphorylation of its downstream targets AKT and STAT5. KEGG pathway and KnockTF transcription factor enrichment analyses indicated that venetoclax resistance was associated with increased transcriptional activity of FOXM1 and STAT3. Moreover, high expression of FOXM1 and STAT3 correlated with shorter overall survival in patients.Conclusion:Venetoclax can inhibit the activation of FLT3-related signaling pathways. The activation of STAT3 and FOXM1 transcription factors is a potential key mechanism contributing to venetoclax resistance in AML.

Objective To investigate the consistency and diagnostic efficacy of 1.5T and 3.0T MRI in the kidney clear cell likeli-hood score(ccLS)v2.0.Methods A retrospective collection was conducted on the data of 176 pathologically confirmed small renal mass(SRM).Two radiologists independently scored the MRI images using the ccLS v2.0.The Kappa test was used to assess inter-observer consistency,and receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic efficacy.The area under the curve(AUC),sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NP V)were calculated.Results The inter-observer consistency for ccLS v2.0 score was good for 1.5T MRI and excellent for 3.0T MRI(Kappa values were 0.754 and 0.836,respectively).On 1.5T MRI examination,a ccLS≥4 points was identified as the optimal threshold,with AUC of 0.935 and 0.923 for the two radiologists,sensitivities of 92.45％and 88.68％,and specificities of 88.00％and 92.00％,respec-tively.For 3.0T MRI examination,using the same threshold,the AUC were 0.933 and 0.901,with sensitivities of 91.43％and 90.00％,and specificities of 78.57％and 78.57％for both radiologists.Conclusion The ccLS v2.0 demonstrates good consistency across high and low field intensity MRI,and a threshold of ccLS≥4 pionts provides high diagnostic efficacy for clear cell renal cell carcinoma(ccRCC).

Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

Objective To investigate the value of predicting microsatellite instability(MSI)status in endometrial cancer based on whole-tumor apparent diffusion coefficient(ADC)histogram.Methods The data of 131 endometrial cancer patients who underwent preoperative MRI examination and were confirmed by pathology were retrospectively analyzed.According to the pathological immu-nohistochemical results,they were divided into microsatellite stability(MSS)group(103 cases)and MSI group(28 cases).The whole-tumor volume of interest(VOI)was outlined using ITK-SNAP software,and ADC histogram analysis was performed using uAI Research Portal software.The t-test or Mann-Whitney U-test were used to compare the differences between the two groups,and multifactorial logistic regression analysis was used to screen independent predictors for the above parameters with differences.The area under the curve(AUC),sensitivity and specificity were calculated using the receiver operating characteristic(ROC)curve.Results The ADC histogram parameters that were statistically significant between groups were ADC10th,ADC90th,ADCmaximum,ADCmedian,ADCmean,ADCrange,ADCinterquartile range,ADCuniformity,ADCvariance,ADCenergy,ADCentropy,ADCtotal energy,ADCroot mean square,ADCmean absolute deviation,ADCrobust mean absolute deviation,all the above parameters were significantly smaller in the MSI group than in the MSS group.Further multifactorial logistic regression analysis results showed that ADCmedian[odds ratio(OR)=1.019,P=0.020]and ADCroot mean square(OR=0.977,P=0.005)were independent predictors of the MSI status in endometrial cancer.The results of ROC curve showed that the AUC of ADCmedian and ADCroot mean square for predicting MSI status were 0.699 and 0.731,respectively,and the AUC of combining the two parameters to predict MSI status was 0.760,with a sensitivity of 57.14%and a specificity of 86.41%.Conclusion The parameters of ADCmedian and ADCroot mean square based on whole-tumor ADC histogram can be used to predict the MSI status of endometrial cancer,and the combined use of these two parameters helps to improve the efficacy of predicting MSI.