Breast cancer prevention and treatment have become major issues that urgently need to be addressed in the field of global public health. As a key pathological transitional stage in the progression of breast cancer， preneoplastic breast cancer （PBC） carries a significant risk of clinical transformation. Effective intervention in the progression of PBC is of great clinical significance in preventing the occurrence of breast cancer. Pathological studies have shown that abnormal angiogenesis is a key mechanism driving the transformation of PBC into breast cancer. Vascular endothelial growth factor （VEGF）， as a core regulatory molecule that promotes angiogenesis， plays a pivotal role in this process. The malignant transformation of PBC is closely associated with the abnormal activation of the VEGF-mediated pro-angiogenic network. Although modern medicine has achieved certain therapeutic effects through surgery and endocrine therapy， clinical limitations such as invasiveness， drug resistance， and adverse reactions still exist. Recent studies have demonstrated that the VEGF signaling system mediates the phosphatidylinositol 3-kinase-protein kinase B （PI3K/Akt） signaling pathway and the mitogen-activated protein kinase （MAPK） pathway. In addition， the hypoxia-inducible factor-1α （HIF-1α）/VEGF signaling pathway and the delta-like ligand 4 （DLL4）/Notch receptor 1 （Notch1） signaling pathway， together with other pathways， form a complex regulatory network that plays a central role in angiogenesis during PBC. Traditional Chinese medicine （TCM）， characterized by multi-component synergy， multi-pathway regulation， and high safety， demonstrates significant advantages in inhibiting pathological angiogenesis and blocking PBC progression by targeting the VEGF signaling pathway. From the perspective of VEGF pathway regulation， this paper systematically reviews the latest research progress on TCM in inhibiting angiogenesis and intervening in PBC， and discusses its mechanisms and application value in the early prevention and treatment of PBC， with the aim of providing references for optimizing clinical intervention strategies for PBC.

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.

OBJECTIVE To evaluate the efficacy and safety of second-line treatment regimens for human epidermal growth factor receptor 2 （HER2）-positive advanced gastric cancer.METHODS Phase Ⅲ randomized controlled trials（RCTs） about second-line treatment regimens for HER2-positive advanced gastric cancer patients were retrieved from PubMed， CNKI， and other Chinese and English databases. The search period spanned from the inception to April 1， 2026. After screening the literature， extracting data， and assessing the quality of the included studies， a network meta-analysis was conducted using R 4.3.2 software. Descriptive comparisons of characteristic adverse events （AEs） for each intervention were performed， followed by sensitivity analyses using different effect models to evaluate the robustness of the results.RESULTS A total of 5 RCTs involving 6 intervention regimens were included. Regarding efficacy， compared with trastuzumab emtansine， chemotherapy alone， and lapatinib+paclitaxel， anbenitamab+chemotherapy significantly prolonged patients’ median overall survival （OS） and median progression-free survival （PFS） （ P ＜0.05）. Compared with ramucirumab+paclitaxel and trastuzumab emtansine， trastuzumab deruxtecan also significantly prolonged patients’ median OS and median PFS （ P ＜0.05）. The top two treatment regimens in terms of surface under the cumulative ranking curve （SUCRA） were both anbenitamab+chemotherapy and trastuzumab deruxtecan. In terms of safety， the SUCRA for the incidence of adverse events （AEs） of any grade （41.6%-57.1%） was generally similar across treatments. The SUCRA for the incidence of grade≥3 AEs and serious AEs was lowest for trastuzumab emtansine （19.3%） and chemotherapy alone （25.9%）， respectively. The SUCRA for treatment-related mortality was lowest for anbenitamab+chemotherapy （3.7%）， while the SUCRA for treatment discontinuation due to AEs was lowest for trastuzumab deruxtecan （4.3%）； for both， the SUCRA was highest for lapatinib+paclitaxel （78.3% and 85.6%， respectively）. Regarding characteristic AEs， the incidence of interstitial lung disease/pneumonitis was highest in the trastuzumab deruxtecan group （13.93%）， the incidence of diarrhea was highest in the lapatinib+paclitaxel group （77.10%）， and hypertension was primarily observed in the ramucirumab+paclitaxel group （23.85%）. The results of the sensitivity analysis were consistent with those of the main analysis.CONCLUSIONS For second-line treatment regimens of patients with HER2-positive advanced gastric cancer， both anbenitamab+chemotherapy and trastuzumab deruxtecan demonstrate a trend toward superior OS and PFS benefits； in terms of safety， the incidence rates of AEs of any grade are similar across the intervention groups， but the characteristic profiles of AEs differ significantly among the regimens， requiring close clinical monitoring and comprehensive management throughout treatment.

ObjectiveTo investigate the trends in the disease burden of falls among Chinese children and adolescents from 1990 to 2021, and to inform the development of targeted prevention and control strategies. MethodsData on age-standardized incidence rate, age-standardized mortality rate and age-standardized disability-adjusted life years (DALYs) rate for falls among Chinese children and adolescents under 20 years of age from 1990 to 2021 were systematically extracted from the Global Burden of Disease Study (GBD) 2021 database. The annual percent change (APC) and average annual percent change (AAPC) were calculated to evaluate temporal trends in fall-related disease burden across different age groups and sexes. ResultsFrom 1990 to 2021, the age-standardized incidence rate of falls among Chinese children and adolescents showed a non-linear fluctuation (AAPC=0.08%, P=0.040), while both the age-standardized mortality rate and age-standardized DALYs rate declined (AAPC=-3.66% and -3.09%, both P<0.001). The crude incidence rate decreased in the <5 years old and 5 ‒ <10 years old groups (AAPC=-1.38% and -0.29%, both P<0.001), but increased annually in the 10 ‒ <15 years old and 15 ‒ <20 years old groups (AAPC=0.27% and 0.81%, both P<0.001). The crude mortality rate and crude DALYs rate declined across all four age groups, with the most significant reduction observed in the <5 years old group (AAPC=-5.21%, 95%CI:-5.55%‒ -5.00%; AAPC=-4.98%, 95%CI: -5.20%‒ -4.79%, both P<0.001). For both males and females, the age-standardized incidence rate of falls showed a V-shaped trend (initial decline followed by a subsequent rise). In contrast, the age-standardized mortality rate and age-standardized DALY rate declined in both sexes, with an AAPC of -3.40% and -2.94% for males, and -4.50% and -3.49% for females, respectively (all P<0.001). ConclusionThe overall disease burden of falls among Chinese children and adolescents has been substantially improved; however, the incidence burden remains considerable. Future prevention efforts should be tailored to age- and sex-specific characteristics, with the family as the fundamental care unit in conjunction with high-quality nursing extension services, to establish a closed-loop management model encompassing “early identification, immediate intervention, and continuous follow-up.”

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Due to their unique physicochemical properties, nanomaterials can optimize drug delivery and reshape the tumor microenvironment. Manganese-based nanomaterials are primarily used in tumor immunotherapy for the following purpose, including targeted activating of the cyclic GMP-AMP synthase-stimulator of interferon gene pathway to enhance immunogenicity, utilizating of manganese′s redox properties to regulate the tumor microenvironment, and developing of manganese-based magnetic resonance imaging contrast agents to monitor immune responses in real time. In this review, synthesis methods of manganese-based nanomaterials such as thermal decomposition method, hydrothermal/solvothermal synthesis method, and chemical precipitation/mixing method as well as an in-depth analysis of their applications in tumor immunotherapy including immune regulation, regulation of tumor microenvironment and enhanced magnetic resonance imaging were reviewed.

Autoimmune oophoritis is a rare cause of primary ovarian insufficiency(POI), and some patients may also have concurrent adrenal insufficiency. This condition significantly impairs reproductive function and is often difficult to distinguish from common causes of POI, leading to missed or incorrect diagnoses. This paper reports a case of autoimmune oophoritis treated in our department and provides an updated summary of recent advances in the understanding of this condition, with the aim of raising clinical awareness and improving diagnostic accuracy among healthcare professionals.

Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The pla-centa tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Mean-while,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense in-terference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation in-duced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P＜0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P＜0.05).On the con-trary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P＜0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

Objective:To investigate the impacts of 1,25-dihydroxyvitamin D 3 (VD) and Lactobacillus plantarum (LP) on intestinal flora in animals with metabolic dysfunction-associated fatty liver disease (MAFLD) and their possible mechanisms. Methods:A methionine- choline-deficient (MCD) diet-induced rat model of MAFLD was created. Forty 10-week-old male Sprague-Dawley rats were randomized into methionine-choline-sufficient (MCS) group, MCD group, VD group, LP group, and VD-LP group, with 8 rats in each group. The intervention groups (VD group, LP group, and VD-LP group) were gastrically fed with VD peanut oil solution (6 ng/100 g daily), Lactobacillus plantarum solution (2×10 9CFU/100 g daily), and a combination of these two solutions, respectively. MCS group, MCD group, and LP group were given the same volume of peanut oil on a daily basis. Fecal samples from rats were collected at week 4 and analyzed using 16S rRNA gene sequencing for fecal flora structure. Portal vein blood samples were collected to detect liver biochemistry and lipopolysaccharide (LPS) levels. Pathological changes in liver and terminal ileum tissues were observed using hematoxylin and eosin (H&E) staining. Results:Compared with the MCS group, the MCD group exhibited massive steatosis and lipid infiltration in liver tissues, markedly thinned ileum mucosa, severely damaged villi structure, excessive necrotic and shedding of epithelial cells, and infiltration of inflammatory cells. Compared with the histopathological changes in the MCD group, the steatosis and lipid infiltration of liver tissue, the damage to the ileal mucosa structure and epithelial cells, and the infiltration of inflammatory cells were alleviated in the VD group, LP group, and VD-LP group. Compared with MCS group, the MCD group had significantly higher serum alanine aminotransferase (ALT) (158.50±14.03 U/L vs. 20.38±7.39 U/L), aspartate aminotransferase (AST) (43.88±11.36 U/L vs. 25.75±5.90 U/L), total bile acid (TBA) (140.60±11.77 μmol/L vs. 19.96±4.31 μmol/L), and LPS (16.57±1.19 pg/ml vs. 7.43±0.95 pg/ml) (All P<0.001),which confirmed the successful establishment of rat models of MAFLD. Serum ALT, AST, TBA, and LPS levels in all the three intervention groups were significantly lower than those in MCD group, and the most significant reductions in ALT (51.38±9.05 U/L vs. 158.50±14.03 U/L), AST (55.88±12.19 U/L vs. 143.88±11.36 U/L), TBA (21.00±8.17 μmol/L vs. 140.60±11.77 μmol/L), and LPS (9.72±0.71 pg/ml vs. 16.57±1.19 pg/ml) were seen in the VD-LP group. The microbiota in the MCD group predominantly featured Muribaculaceae, while the MCS group and other intervention groups primarily harbored Lactobacillus. Firmicutes and Lactobacillus were significantly decreased in the MCD group ,while Bacteroidete, Proteobacteria, Verrucomicrobiota, Prevotellaceae UCG-003, Escherichia coli, Bacteroides, and Enterococcus increased significantly. The opposite was true for each intervention group. There were significant differences in Lactobacillus between MCD group and the other four groups. Conclusion:VD and LP can remarkably improve lipid deposition in MAFLD by regulating intestinal flora.

Objective:To analyze the application effect of the case-based learning (CBL), lecture-based learning (LBL) and seminar three-track stereoscopic model in the teaching of health management for chronic diseases.Methods:In this non-randomized controlled trial, a total of 70 five-year clinical medicine major undergraduate students were continuously selected as the research subjects in the Air Force Medical University during 2023-2024 year. The students enrolled the chronic disease health management course. Thirty-five cases in 2023 were assigned to the control group, while 35 cases in 2024 were assigned to the experimental group. The control group were taught by the traditional teaching method, while experimental group were taught with a combined model of CBL, LBL, and Seminar. The number of class hours for both groups were 30, with a class frequency of 2 class hours per week. The intervention period began with the first class and ended after the last class, totaling 15 weeks. The general information, medical professional courses and basic knowledge of chronic disease health management scores in the two groups were collected before intervention. The learning effect and satisfaction rate were evaluated through teaching satisfaction score, assessment assignments, practical ability score and excellent rate, autonomous learning ability score at 15 weeks after the intervention.Results:Among the 70 participants, 37 were male and 33 were female, with a mean age of (21.00±0.27) years. Before the intervention, there was no statistically significant differences in the general information, medical professional courses and basic knowledge of chronic disease health management scores between the two groups (all P>0.05). Fifteen weeks after the intervention, the experimental group had significantly higher scores in teaching content score, teaching method score, assessment assignment, final grade, practical ability scores, excellent rate of practical ability, self-management ability score, information literacy score, and learning cooperation ability score when compared to those in the control group [(93.3±6.9) vs (80.1±7.8) points, (97.1±6.3) vs (81.0±9.6) points, (91.1±7.8) vs (80.1±8.9) points, (92.9±9.4) vs (81.8±9.8) points, (91.3±7.6) vs (80.3±8.7) points, 54.3% vs 22.9%, (27.3±4.8) vs (22.8±6.8) points, (26.9±3.9) vs (20.8±4.1) points, (35.9±8.1) vs (28.9±7.1) points] (all P<0.05). Conclusion:Implementing of CBL, LBL, and Seminar teaching model in the chronic disease health management curriculum significantly enhances teaching effectiveness and improves students' overall competencies.