Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

In recent years,the global prevalence of myopia has remained high,seriously endangering the eye health of adolescents.A large number of studies have confirmed that orthokeratology lens can control or delay the progression of my-opia and reduce the incidence of fundus lesions in high myopia.Although the efficacy of myopia control with orthokeratolo-gy has been widely recognized,its exact mechanism of action is still unclear,and there are many hypotheses.This paper re-views the role of factors such as accommodation,defocus,choroidal thickness,high-order aberrations and biomechanics in myopia control with orthokeratology,and explores how these factors jointly affect the development of myopia.

Objective To investigate and elucidate the effect of trigonelline(TRG)on the ARPE-19 ferroptosis sig-naling pathway under hypoxia conditions.Methods ARPE-19 cells were routinely cultured and intervened with different concentrations of TRG.According to the optimal concentration(40 mg·L-1)of TRG determined for ARPE-19 interven-tion,the cells were divided into an NC group(routinely cultured for 24 h),a CoCl2 group(treated with 150 mmol·L-1 CoCl2 for 24 h),a Fer-1 group(treated at first with 1 μmol·L-1 Fer-1 for 12 h and then with 150 mumol·L-1 CoCl2 for 12 h),and a TRG group(treated at first with 40 mg·L-1 TRG for 24 h and then with 150 mmol·L-1 CoCl2 for 24 h).The levels of glutathione(GSH),malondialdehyde(MDA)and Fe2+ions in each group of cells were evaluated by detectionkits.The levels of reactive oxygen species(ROS)in each group of cells were detected by flow cytometry.Western blot was used to analyze the expression levels of hypoxia-induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)in each group of cells.The expression levels of VEGF and ACSL4 proteins in each group of cells were measured by immunofluorescence staining.Results The ROS levels in TRG and Fer-1 groups were significantly lower than those in the CoCl2 group(t=27.91,31.61;both P＜0.01).The change trend of MDA and Fe2+levels was the same with that of ROS levels in each group.Com-pared with those in the CoCl2 group,the GSH levels were increased significantly(t=15.95,12.76;both P＜0.01)and the relative expression levels of HIF-1α and VEGF proteins were decreased significantly in Fer-1 and TRG groups(all P＜0.01).The CoCl2 group had higher ACSL4 levels and lower GPX4 levels than the NC group(t=31.05,13.18;both P＜0.01).Fer-1 and TRG groups had lower ACSL4 expression levels and higher GPX4 expression levels than the CoCl2 group(all P＜0.01).The results of immunofluorescence staining showed that the expression levels of VEGF and ACSL4 proteins in the CoCl2 group were higher than those in the NC group.The expression levels of VEGF and ACSL4 proteins in Fer-1 and TRG groups were lower than those in the CoCl2 group.Conclusion TRG protects ARPE-19 cells from hypoxia-induced oxidative stress damage by inhibiting ferroptosis.

Objective The data related to adverse drug reaction of trastuzumab deruxtecan(T-DXd)were mined to provide references for its clinical management and adverse event handling.Methods Based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database,the data reported from the post-marketing period of T-DXd until the fourth quarter of 2024 were extracted.The proportion imbalance method,specifically the reporting odds ratio(ROR)method,was used to mine and analyze the data related to adverse events of T-DXd.Results A total of 13 134 cases of adverse events related to T-DXd were obtained from the FAERS database.Gastrointestinal disorders were the most common,with 2348 adverse reaction signals,accounting for 17.88％.The most frequent adverse reactions were nausea(n=809),interstitial lung disease(n=732),and fatigue(n=579).The one with the highest ROR value was Listeriosis gastroenteritis(ROR=1228.74).The highest number of deaths were from interstitial lung disease(226),pneumonitis(90),and nausea(67).Conclusion By mining data on real-world adverse drug reaction related to T-DXd,suggests that pulmonary function,cardiac function,complete blood count and other parameters should be closely monitored during treatment for early diagnosis and treatment of corresponding complications.

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Objective:To investigate the effect of signals mediated by activated CD28 in promoting survival of multiple myeloma(MM)cells and metabolic fitness and its possible mechanism.Methods:The expression of CD28 on 4 MM cell lines(XG2,XG1,RPMI 8226 and U266)was determined by flow cytometry.Two cell lines with the highest or lowest CD28 expression were selected.The proliferation,cell cycle,migration and apoptosis of MM cells in vitro were determined in medium containing high glucose concentration or CD28 agonist monoclonal antibody with different bioassays.shRNA interference assay was used to knock down the expression of CD28 on U266 cells.Then,the effect of activated CD28 on glucose uptake rate and drug resistance in MM cells were analyzed using fluorescent glucose analogues(2-NBDG).The expression of Glut1/4,HkII and Fasn was determined with real time quantitative PCR.Results:Flow cytometry analysis showed that all the four tested MM cell lines expressed CD28 and U266 cells had the highest positive rate.The results of in vitro experiment showed that CD28 activation could significantly up-regulate the expression of Glut4 and HkII,promote MM cell metabolic remodeling,enhance 2-NBDG/glucose uptake,increase energy metabolism,thereby elevating cell proliferation and migration abilities,leading to an increase in the number of cells in S-and G2-phases.Meanwhile,activated CD28 subsequently up-regulated resistance of MM cells to bortezomib or dexamethasone.Conclusion:MM cells express high levels of CD28 abnormally,and activation of CD28 can promote up-regulation of glucose uptake in MM cells,thereby promoting cell proliferation and enhancing drug resistance.

AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR), and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS: A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital, Sun Yat-sen University from 2022 to 2023 were included, including 95 first-diagnosed DR patients and 105 patients without DR, and all patients underwent OCTA examination and a collection of demographics and renal function parameters. After a quality check, automated measurements of the foveal avascular zone area, vessel density(VD), and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS: Using random forest and multivariate Logistic regression methods, we developed a diagnostic model for DR based on 12 variables(age, FBG, SBP, DBP, HbA1c, ALT, ALP, urea/Scr, DM duration, HUA, DN, and CMT). Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window, AUC=0.837 vs 0.819, P=0.03). In the study of DN patients, the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD; outer VD; full VD; outer PD; full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model. Meanwhile, compared with the 3 mm×3 mm window, the microvascular parameters in the 6 mm× 6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.

Objective To systematically analyze novel antibody-drug conjugates(ADCs)associated with breast cancer that cause interstitial lung disease(ILD),providing a reference for the safe clinical use of ADCs.Methods A total of 909 ILD adverse event reports Adverse event reports were collected,extracted from the US Food and Drug Administration Adverse Event Reporting System database.The correlation between trastuzumab deruxtecan(T-DXd),trastuzumab emtansine(T-DM1),and sacituzumab govitecan(SG)with ILD were evaluated using the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods from the disproportionality analysis.Descriptive analysis was performed on the main characteristics of ILD patients(gender,age,time of onset,and outcomes).Results Including 812 for T-DXd,84 for T-DM1,and 13 for SG.The ROR values were 15.97,2.21,and 0.41,respectively,and the PRR values were 15.33,2.19,and 0.41.T-DXd and T-DM1 showed significant correlations with ILD,with the risk signal strength of T-DXd being significantly higher than that of T-DM1.The median time to ILD onset for T-DXd,T-DM1,and SG was 76.0 days,66.0 days,and 53.5 days,respectively.The number of deaths caused by ILD was 265 cases,13 cases,and 1 case,respectively,with the first 180 days after initial administration being a critical monitoring period.Conclusion The risk of ILD induced by different ADC drugs exhibits significant heterogeneity.Clinicians must remain highly vigilant for ILD caused by these agents,emphasizing early diagnosis and treatment to reduce mortality.