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.

ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan （XJW）-containing serum interfering with endothelial-mesenchymal transition （EMT） in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW （4 g·kg^-1） to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum （4 g·kg^-1） according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group， β-catenin intervention/overexpression group， intervention/overexpression blank + XJW group， and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and active-Caspase-3］ and EMT-related proteins （E-cadherin， N-cadherin， and vimentin）. Real-time polymerase chain reaction （Real-time PCR） was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group， the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates （P<0.05， P<0.01）， elevated protein levels of Bax， active Caspase-3， and E-cadherin （P<0.05， P<0.01）， and decreased protein levels of Bcl-2 and Vimentin （P<0.05， P<0.01）. β-catenin mRNA expression was reduced in the β-catenin intervention group （P<0.05， 0.63 ± 0.15） and the intervention blank + XJW group （P<0.05， 0.79 ± 0.33）. Compared with the β-catenin intervention group， the β-catenin intervention + XJW group exhibited an increased apoptosis rate （P<0.01）， elevated Bax and active Caspase-3 protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and Vimentin protein levels （P<0.05）. β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group （P<0.01， 0.22 ± 0.08）. Compared with the intervention blank + XJW group， the β-catenin intervention + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax， active Caspase-3， and E-cadherin protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and vimentin protein levels （P<0.05， P<0.01）. β-catenin mRNA expression was also reduced （P<0.05）. Overexpression experiment results showed that compared with the overexpression blank group， the β-catenin overexpression group exhibited a reduced apoptosis rate （P<0.01）， while the overexpression blank + XJW group showed an increased apoptosis rate （P<0.05）. In the β-catenin overexpression and β-catenin overexpression + XJW groups， Bax and E-cadherin protein levels decreased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels increased （P<0.05）. In the overexpression blank + XJW group， Bax and E-cadherin levels increased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels decreased （P<0.05， P<0.01）. β-catenin mRNA expression increased in the β-catenin overexpression group （P<0.01， 7.26 ± 1.03） but decreased in the overexpression blank + XJW group （P<0.05， 0.73 ± 0.14）. Compared with the β-catenin overexpression group， the β-catenin overexpression + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax and E-cadherin levels （P<0.05）， and decreased N-cadherin and vimentin levels （P<0.05）. β-catenin mRNA expression was reduced （P<0.05， 4.65 ± 1.02）. Compared with the overexpression blank + XJW group， the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate （P<0.01）， decreased Bax and E-cadherin levels （P<0.01）， and increased Bcl-2， N-cadherin， and Vimentin levels （P<0.05）. β-catenin mRNA expression increased （P<0.01）. ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT， which is associated with the regulation of the Wnt/β-catenin pathway.

ObjectiveTo establish a mouse model of hypoxic pulmonary hypertension (HPH) through intermittent hypoxia induction, and to develop a comprehensive and reliable evaluation system for the HPH model, thereby providing experimental evidence for mechanistic studies and translational applications related to this disease. MethodsTwenty-four male specific pathogen-free (SPF) BALB/c mice were randomly divided into a control group and a model group, with 12 mice per group. Mice in the model group were placed in a hypobaric oxygen chamber control system to establish the HPH model, whereas mice in the control group received no intervention. After 28 days of modeling, a comprehensive evaluation of the pathophysiological characteristics of both groups was performed using a general condition scoring scale, echocardiography, hemodynamic measurements, blood gas analysis, hematological tests, organ coefficient determination, histopathological examination, and enzyme-linked immunosorbent assay (ELISA). In addition, correlation analyses were conducted among echocardiographic parameters, the contents of endothelin‑1 (ET‑1) and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) in lung tissue, and other measured indices. ResultsWith prolonged modeling duration time, body weight, water intake, and activity level of mice in the model group were significantly decreased compared with the control group (P<0.05). Echocardiography showed that, compared with the control group, the model group exhibited increased right ventricular dimensions (P<0.01), right ventricular anterior wall thickening (P<0.01), and widened main pulmonary artery diameter (P<0.01), whereas the peak systolic velocity across the pulmonary valve, tricuspid annular plane systolic excursion, and peak systolic velocity of the tricuspid annulus were significantly decreased (P<0.001); tricuspid regurgitation was observed in some model animals. Hemodynamic results revealed that right ventricular systolic pressure was elevated in the model group compared with the control group (P<0.001). Blood gas analysis showed that pH, partial pressure of oxygen, oxygen saturation, actual bicarbonate, and total carbon dioxide were all decreased in the model group compared with the control group (P<0.01). Hematological indices demonstrated that lymphocyte counts (P<0.05) and reticulocyte counts (P<0.001) were decreased in the model group compared with the control group. Compared with the control group, the organ coefficients of heart and lung in the model group were significantly increased (P<0.05 and P<0.001). Pathological examination revealed that the right ventricular hypertrophy index was significantly increased in the model group (P<0.001), with varying degrees of damage to the right ventricle, pulmonary artery, and pulmonary vessels; both the pulmonary artery wall thickness percentage and the pulmonary wall area percentage were significantly elevated (P<0.001). ELISA results showed that the levels of ET‑1 and NT‑proBNP in lung tissues were significantly increased in the model group compared with the control group (P<0.05 and P<0.001, respectively). Correlation analysis indicated that some echocardiographic parameters were highly correlated with multiple indices in the development of HPH (P<0.05). ConclusionEchocardiography can accurately assess a series of hemodynamic changes in HPH, including right ventricular structural, functional impairment, and pulmonary hypertension. Laboratory tests not only help verify whether the model has been successfully established, but also provide deeper insights into the pathogenesis of HPH, evaluate the effects of interventions, and offer scientific evidence for clinical outcomes. Pathological examination can further confirm the alterations in pulmonary vascular remodeling and increased right heart load. This multimodal analysis provides a reliable animal model and evaluation paradigm for both basic and translational research on HPH, and is of great significance for exploring disease mechanisms and developing precision therapeutic strategies.

Objective:To analyze the risk factors for human cytomegalovirus (HCMV) infection in pediatric recipients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of children who underwent first allo-HSCT were retrospectively analyzed from March 2017 to November 2024. A total of 259 pediatric allo-HSCT recipients were analyzed through comparing HCMV infection group (n=115) and Non-HCMV infection group (n=144). Clinical characteristics were compared, and risk factors for HCMV infection were analyzed using univariate and multivariate logistic regression.Results:The result of univariate analysis showed that adrenoleukodystrophy (ALD), length of hospitalization, duration of antiviral therapy, and bacterial infection were significantly associated with HCMV infection in pediatric allo-HSCT recipients ( P<0.05). The result of multivariate analysis showed that ALD was an independent protective factor against HCMV infection of allo-HSCT recipients ( P<0.05) [OR=0.22, 95% CI: 0.06-0.86], while umbilical cord blood transplantation (UCBT) was an independent risk factor for HCMV infection in allo-HSCT recipients ( P<0.05) [OR=6.13, 95% CI: 1.34-28.04]. When the area under the ROC curve (AUC) for predicting post-transplant relapse based on HCMV viral load was 0.75 (95% CI: 0.55-0.94, P=0.014) and at the cutoff value of 3×10 3 copies/ml, the sensitivity and specificity for predicting relapse were 81.13% and 66.67%, respectively. Conclusions:HCMV infection in pediatric allo-HSCT recipients may lead to longer hospitalization and increased risk of relapse.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective:To investigate the differential impact of ultra-high-resolution photon-counting detector CT (UHR PCD-CT) and energy-integrating detector CT (EID-CT) on image quality and calcified plaque-induced luminal stenosis in coronary CT angiography (CCTA).Methods:This retrospective analysis was conducted on patients who underwent both EID-CT and UHR PCD-CT CCTA at the Geriatric Hospital of Nanjing Medical University between January 2021 and November 2024. A total of 141 patients were included in the study, within 46 patients having scans within a 12-month interval. Image quality of all coronary artery segments was subjectively evaluated. Patients with paired scans (interval≤12 months) were included for calcified plaque analysis. Subjective visualization of calcified plaques evaluated. The blooming artifact was calculated as an objective evaluation index for assessing the calcified plaques. Additionally, the degree of coronary artery lumen stenosis resulting from calcified plaques was assessed, along with the measurement of plaque volume and the Agatston score. Changes in lumen stenosis between the two scans were also evaluated. The Wilcoxon signed-rank test was used to compare the subjective scores of coronary artery image quality and calcified plaques between the two groups, and paired-sample t-tests were used to compare the blooming artifact and lumen stenosis degree. Results:The PCD-CT image quality score was significantly higher than that of EID-CT [PCD-CT : 5 (4,5), EID-CT: 4 (4,5); Z=-21.38, P<0.001]. Compared to EID-CT, PCD-CT reduced the blooming artifact (PCD-CT: 38.88%±9.09%, EID-CT: 50.11%±11.52%; t=-12.97, P<0.001), significantly improving the subjective score for visualization of calcified plaques [PCD-CT: 5 (4,5), EID-CT: 3 (2,3); Z=-9.68, P<0.001], and the measured lumen stenosis was notably lower in PCD-CT(PCD-CT:34.88%±18.20%, EID-CT:45.31%±23.42%; t=-9.93, P<0.001). Among 129 analyzed calcified plaques, luminal stenosis was reduced on PCD-CT in 110 plaques (85.3%) and increased in 19 (14.7%), including 4 plaques that had unclear boundaries with the adjacent lumen in EID-CT CCTA images, making the stenosis difficult to assess. Conclusion:Compared to EID-CT, UHR PCD-CT for CCTA significantly improves coronary artery image quality, provides clearer visualization of calcified plaques and adjacent lumen details, and it can reduce the overestimation of coronary artery caleified plaque stenosis.

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.