Objective To investigate the current distribution and predict the future suitable habitats of Haemaphysalis longicornis in Nanjing City, so as to provide insights into control and early warning of ticks and management of tick-borne diseases in Nanjing City. Methods The electronic map of Nanjing City was obtained from the National Platform for Common GeoSpatial Information Services. The distribution of H. longicornis and the longitude and latitude of distribution points from 2022 to 2024 were obtained from centers for disease control and prevention across each district in Nanjing City. Climatic and environmental variable data in Nanjing City were captured from the Worldclim database. Initially, 19 bioclimatic variables in this database were selected, including annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the warmest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter. The elevation and normalized difference vegetation index were obtained from Data Sharing Platform of the Center for Resources and Environmental Sciences, Chinese Academy of Sciences. Then, the distribution points of H. longicornis, elevation, vegetation index and 19 bioclimatic variables were loaded into the software MaxEnt 3.4.4 to evaluate and screen out the variables with a contribution rate of 1% and higher. ArcGIS 10.8.1 software was used to extract the elevation, vegetation index and 19 bioclimatic variables of the distribution points of H. longicornis for a correlation analysis. If the absolute value of the correlation coefficient was 0.8 and higher, the variable with the higher contribution was retained. The 2050 dataset of the BCCCSM2-MR atmospheric circulation model in the coupled model intercomparison project phase 6 (CMIP6) were obtained from the Worldclim database as climate data for 2050. Screened H. longicornis species data and environmental and climate data were loaded into the maximum entropy (MaxEnt) model with the software MaxEnt 3.4.4 for training and validation, and then, all data generated from the model were imported into the software ArcGIS 10.8.1 to generate raster data and yield the map pertaining to the distribution of H. longicornis risk in Nanjing City. The accuracy of the model was evaluated with a receiver operating characteristic (ROC) curve, and the predictive effect of the model was assessed with area under the ROC curve (AUC). The suitable habitats of H. longicornis were classified in Nanjing City with the software ArcGIS 10.8.1, and the areas of distribution of suitable habitats in various categories were recorded to create the map of current H. longicornis suitable habitats classification in Nanjing City. The climatic and geographic information data in 2050 were employed as future environmental and climatic factors, and current environmental and climatic factors and current H. longicornis distribution data were additionally used to predict the future suitable habitats of H. longicornis in Nanjing City. In addition, the contributions of environmental and climatic factors to distribution of suitable habitats of H. longicornis was evaluated with the Jackknife method in Nanjing City. Results A total of 10 environmental and climatic variables were screened for analysis of the suitability of H. longicornis in Nanjing City based on correlation analyses and contributions of the MaxEnt model, including annual mean temperature, precipitation of the warmest quarter, vegetation index, precipitation of the wettest month, temperature annual range, annual precipitation, mean temperature of the warmest quarter, elevation, mean temperature of the wettest quarter, and maximum temperature of the warmest month, and annual mean temperature (34.8%), precipitation of the warmest quarter (17.3%), vegetation index (13.1%), and precipitation of the wettest month (10.8%) contributed relatively highly to the distribution of suitable habitats of H. longicornis in Nanjing City. The mean AUC of the ROC curve was 0.810 ± 0.055 for 10 repeated modeling results of the MaxEnt model, indicating high predictive performance of the model. The potential distribution areas of H. longicornis were predicted to be mainly located in Luhe District, Pukou District, Jiangning District, Lishui District, and Gaochun District in Nanjing City with the MaxEnt model. Under current climatic conditions, the area of potential suitable habitats of H. longicornis was 4 182.42 km² in Nanjing City, including 1 252.94 km² highly suitable habitats, which accounted for 19.00% of the total area of Nanjing City. Under the climate scenario in 2050, the area of potential suitable habitats of H. longicornis was projected to increase to 5 467.58 km² in Nanjing City, accounting for 82.95% of the total area of the city, and these habitats were mainly concentrated in Luhe District, Pukou District, Jiangning District, Lishui District, and Gaochun District. The areas of suitable habitats of H. longicornis at various categories were predicted to vary greatly in 2050, and the area of highly suitable habitats of H. longicornis was projected to increase to 2 378.82 km², accounting for 36.08% of the total area of Nanjing City. Based on jackknife tests and contributions of environmental and climatic variables, 6 dominant environmental and climatic factors were screened, including annual mean temperature (34.8% contribution), precipitation of the warmest quarter (17.3% contribution), vegetation index (13.1% contribution), precipitation of the wettest month (10.8% contribution), temperature annual range (5.4% contribution), and mean temperature of the warmest quarter (5.0% contribution), with cumulative contributions of 86.4%. Conclusion The distribution of H. longicornis is strongly associated with vegetation, temperature and precipitation in Nanjing City. Future climate change may lead to an expansion of the distribution area of H. longicornis in Nanjing City.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Purpose To investigate the correlation between molecular typing of urothelial carcinoma(UC)and its clinicopathologic features and prognosis,in order to explore the prognostic markers and therapeutic targets for UC.Methods 115 patients with UC were retrospectively analyzed.Immunohistochemical markers GATA-3,CK20,CK5/6 and CD44 were used for molecular typing of UC(luminal-like type,basal-like type and null).Correlations between molecular typing and clinicopathological features were analyzed using the Chi-square test and Fisher precise test.Sur-vival analysis was performed using the Kaplan-Meier test and Log-rank test.Results The expression of GATA-3 and CK20 was negatively correlated with the clinical stage of UC,while the expression of CD44 was positively correlated with the clinical stage of UC(both P＜0.05).CK20 was a marker of good prognosis(P=0.03).The proportion of clinically advanced UC with basal-like type was significantly higher than that of luminal-like type(78.4％vs 53.4％,P=0.033).Among the histologic variants,UC with neuroendocrine differentiation(100％),sarcomatoid carcinoma(80.0％)and squamous differentiation(77.8％)were basal-like type.All plasmacytoid and lymphoepithelioma-like types,as well as 81.8％of micropapillary UC.Among the null phenotypes,the differential variant predominated(66.7％).Compared with the luminal-like type,although the prognosis of basal-like UC was worse,there was no sta-tistically significant difference(P＞0.05).Conclusion Patients with CK20-expressing UC had a significantly better prognosis.The main histologic variants types of basal-like type and coelomofacial type are different.Molecular typing of UC using immunohistochemical markers is suggestive of clinical staging and prognosis of patients.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7％reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.

Objective To investigate the impact of eccentric placement for various types of artificial aortic valves on downstream flow dynamics.Methods A physiological pulsatile circulation simulation system was employed and particle image velocimetry(PIV)was utilized to analyze the downstream flow field variations for bioprosthetic and mechanical valves under two placement conditions:centralized placement(0 mm)and eccentric placement(1 mm).Hemodynamic parameters such as velocity,vorticity,and viscous shear stress were assessed to evaluate the flow field characteristics.Results By analyzing the flow field variations at four characteristic time points,namely,early systole,acceleration phase,peak systole,and deceleration phase,a significant difference in flow field distribution between bioprosthetic and mechanical valves was observed.The bioprosthetic valve exhibited a centrally symmetric jet with a higher flow velocity,whereas the mechanical valve displayed a three-jet structure with a lower central flow velocity.Under eccentric placement,the blood flow in the aortic sinus region was sluggish,with a reduction in average velocity,hindering the formation and maintenance of vortices.During the peak systolic phase,the maximum viscous shear stresses in the sinus region for the bioprosthetic and mechanical valves were 0.45 and 0.67 Pa,respectively,approaching the threshold for endothelial cell damage.Conclusions Eccentric placement of both mechanical and bioprosthetic valves resulted in reduced sinus blood flow velocity and diminished viscous shear stress,creating favorable conditions for thrombus formation.In clinical practice,careful attention should be given to the placement of valve replacement to prevent eccentric placement.

Objective To investigate the forensic toxicological characteristics associated with etomidate abuse.Methods Blood and urine samples from six cases of etomidate abuse were quantitatively analyzed for etomidate and its metabolite etomidate acid.Relevant literature on etomidate abuse and poisoning was reviewed to summarize the pharmacological and toxicological effects of etomidate and case data.Results In the cases examined,the blood concentrations of etomidate and its metabolite,etomidate acid,were relatively low,ranging from 1.97～187.61 ng/mL and 12.29～316.31 ng/mL,respectively.Urine samples offered a broader detection window,with etomidate concentrations ranging from 1.65 to 700.89 ng/mL and etomidate acid concentrations from 295.26～214 483.52 ng/mL.Notably,in a sexual assault case,the victims's blood concentration of etomidate acid dropped below 6.98 ng/mL eight hours post-ingestion,while urinary concentration was still above 59 449.02 ng/mL.Conclusion Abuse of electronic cigarettes containing etomidate can result in severe overdoses.Given that etomidate is rapidly metabolized in vivo,it is essential to collect and analyze biological samples promptly,with a particular emphasis on detecting its metabolite,etomidate acid.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

Objective:To investigate the feasibility and value of nomogram based on base line clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) characteristics for pretreatment predicting the depth of myometrial invasion and tumor grade of endometrioid endometrial carcinoma (EEC).Methods:Preoperative baseline clinical characteristics and DCE-MRI characteristics of 194 EEC patients were prospectively collected at Obstetrics and Gynecology Hospital, Fudan University from October 2020 to January 2022 and used as a training set. Univariate analysis was conducted to compare baseline clinical characteristics and DCE-MRI quantitative parameters [including tumor volume, and mean, median, and standard deviation of volume transfer constant (K trans), rate constant (K ep), extravascular extracellular volume fraction (V e), and initial area under the enhancement curve (iAUC)] between patients with deep myometrial invasion (DMI) and those with superficial myometrial invasion (SMI), as well as between high-grade and low-grade EEC. Multivariate logistics regression analysis was used to identify independent predictors for the construction of nomogram. An independent external testing set comprising 127 EEC patients was retrospectively collected from Zhongshan Hospital, Fudan University and Zhongshan Hospital, Fudan University (Xiamen Branch). The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used for evaluating the model′s predictive performance and clinical net benefit, respectively. Results:(1) The depth of myometrial invasion: univariate analysis showed that in the training set, the EEC patients with DMI differed significantly from those with SMI in clinical characteristics including higher proportion of postmenopausal state and overweight [body mass index (BMI)≥25 kg/m2], and abnormal levels of serum cancer antigen (CA) 125, CA 199, and human epididymis protein 4 (HE4), and in DCE-MRI quantitative parameters including tumor volume, and median, mean, and standard deviation of K trans, median of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, CA 199, tumor volume, and mean of iAUC were independent predictors of the depth of myometrial invasion, and constructed the nomogram (recorded as Nomogram_1), achieving an AUC of 0.861 (95% CI: 0.803-0.919) in the training set. In the independent external testing set, the AUC was 0.876 (95% CI: 0.815-0.938), with corresponding sensitivity of 82.0%, specificity of 80.7%, accuracy of 81.1%, positive predictive value (PPV) of 65.3%, and negative predictive value (NPV) of 91.0% for predicting DMI. (2) The EEC grade: univariate analysis showed that in the training set, high-grade EEC patients differed significantly from low-grade EEC in clinical characteristics including patient′s age, the proportion of postmenopausal state and overweight, and abnormal levels of serum CA 125, and in DCE-MRI quantitative parameters including tumor volume, median, mean, and standard deviation of K trans, median and mean of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, tumor volume, and median of V e emerged as independent predictors of EEC grade, and constructed the nomogram (recorded as Nomogram_2), achieving an AUC of 0.845 (95% CI: 0.786-0.893) in the training set. While in the external testing set, the AUC was 0.819 (95% CI: 0.744-0.894), with corresponding sensitivity of 72.4%, specificity of 72.4%, accuracy of 72.4%, PPV of 43.8%, and NPV of 89.9% for predicting high-grade EEC. (3) The DCA curves demonstrated that both Nomogram_1 and Nomogram_2 yielded obvious positive clinical net benefits across a wide range of threshold probabilities. Conclusion:The nomogram based on pretreatment clinical and DCE-MRI characteristics has the potential to noninvasive predict the depth of myometrial invasion and grade of EEC, providing valuable reference information for clinical management decision-making.

Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P＜0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285～5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031～1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P＞0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.