OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Objective To investigate the entrance surface dose (ESD) of dental radiological diagnosis and treatment devices in Nanping City of Fujian Province, China, assess the radiation risk differences between cone beam computed tomography (CBCT) and conventional oral panoramic tomography (COPT), and compare the output dose levels between domestic and imported devices and between public and private medical institutions, and to provide evidence for optimizing radiation protection strategies. Methods A cross-sectional survey was conducted on 38 extraoral dental X-ray devices from 38 dental institutions in Nanping City. Measurements of ESD for different exposure types (adult/child COPT and CBCT) were performed using an adult head-and-neck phantom and thermoluminescent dosimeters. A statistical analysis (Mann-Whitney U test) was applied to compare dose differences by device type and institution type. Results The median tooth-region doses for adult/child CBCT (8.97/6.80 mGy) were significantly higher than those of adult/child COPT (0.33/0.24 mGy), with the 75th percentile values (12.44/8.18 mGy) exceeding the national guideline level of 7 mGy. Domestically manufactured devices demonstrated higher median doses and greater dose variability compared to imported devices (P < 0.05). Private institutions exhibited inferior dose control stability relative to public institutions (P < 0.001). CBCT delivered substantially higher radiation exposure to the thyroid and ocular lenses, with child lens dose reaching 5.9 times that of COPT. Conclusion Dental CBCT radiation doses in Nanping City exceed the guideline level. Enhanced protection for sensitive organs, restriction of unnecessary pediatric examinations, technological upgrades for domestic devices, and strengthened regulation and operational standardization of private institutions are critical to achieve precise radiation protection and improved medical quality.

The defocus curve, which quantifies visual performance under various defocus states to accurately evaluate the eye's ability to achieve clear vision across a continuous range of distances, is a vital tool for assessing visual quality. With the aging population and improved quality of life driving a significant increase in the demand for presbyopia correction, the application of the defocus curve has continually expanded in ophthalmic clinical practice, particularly in the perioperative period of presbyopia-correcting corneal refractive surgery and refractive cataract surgery, where it aids in personalized surgical planning and proves valuable for patient education and postoperative visual quality assessment. This article systematically reviews the examination methodology, influencing factors, analytical approaches, and recent clinical advancements of defocus curves, focusing on the potential impact of variables such as pupil diameter, contrast sensitivity, and chart selection on results; it further discusses current limitations including lack of standardization and insufficient assessment of dynamic visual performance, and proposes future research directions based on the latest literature. The aim is to provide valuable insights for researchers and clinicians, promote the standardized and normative application of defocus curves, and ultimately enhance the overall efficacy of presbyopia correction and patients' quality of visual life.

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

OBJECTIVE To study the effect of different doses of aspirin on clinical efficacy in acute stage of Kawasaki’s disease, and to explore the optimal dose of aspirin. METHODS A total of 150 patients suffered from Kawasaki’s disease were randomly selected by hospital information system from March to May 2022 for retrospective analysis. According to different doses of aspirin, they were divided into three groups: high dose group(>50 mg·kg−1·d−1), medium dose group(30−50 mg·kg−1·d−1) and low dose group(<30 mg·kg−1·d−1). The antipyretic time, the incidence of non-response to intravenous human immunoglobulin, the improvement of laboratory indexes and prevalence of adverse drug reaction were compared among the three groups. RESULTS There was no significant difference in body temperature recovery among the three groups under different doses of aspirin. There was no significant difference in patients with non-response to intravenous human immunoglobulin among the three groups. Before treatment, there were no significant differences in white blood cell(WBC) count, blood platelet(PLT) count and C-reactive protein(CRP) concentration among the three groups. After treatment, the count of WBC, PLT and CRP in the three groups was significantly improved compared with that before treatment, and the difference was statistically significant(P<0.05). However, there was no significant difference in the above indexes among the three groups after treatment. There was a higher incidence of adverse reactions in children treated with medium or high dose aspirin. CONCLUSION Different doses of aspirin combined with intravenous human immunoglobulin have good therapeutic effect on Kawasaki’s disease, but considering the safety and economy of aspirin, low dose administration is recommended.

OBJECTIVE To establish a method for determination cinoxate and other 30 kinds of sunscreen agents in sunscreen cosmetics by HPLC. METHODS Twenty-one fat-soluble sunscreen agents(1#−21#) were ultrasonically extracted by the mixed solution of methanol-tetrahydrofuran(1∶1), 10 kinds of water-soluble sunscreen agents(22#−31#) were ultrasonically extracted by the mixed solution of methanol-tetrahydrofuran-water(2∶3∶5) from the samples. Agilent Zorbax SB C18(4.6 mm× 250 mm, 5 μm) column was used to separate cinoxate and other fat-soluble sunscreen agents(1#−20#), Agilent Zorbax SB C18(2.1 mm× 100 mm, 3.5 μm) column was used to separate polysiloxane-15(21 #) , Waters Symmetry C18(4.6 mm× 250 mm, 5 μm) column was used to separate 10 water-soluble sunscreen agents. Methanol-isopropanol-water, isopropanol-tetrahydrofuran-water, and methanol-acetonitrile-0.02 mol·L−1 ammonium acetate solution(add phosphoric acid to adjust pH to 5.0) were used as mobile phase in gradient elution respectively. The flow rates were 1.2, 0.5, 1.0 mL·min−1. The detection wavelengths were 358nm(7 #, 11 #) , 295 nm(23#−25#, 27#−31#), 311 nm(other components). The injection volumes were 5 µL(polysiloxane-15) and 10 µL(other component), the column temperature was set at 30℃. RESULTS The linear relationships(r>0.9999) of 31 sunscreen agents were good in corresponding concentration range. The limit of detection were in the range of 0.002%−0.02%. The recoveries of two substrates at three different supplemental levels ranged from 92.4% to 110.3%, with the RSDs of 0.02%−4.5%. Forty batches of domestic and imported sunscreen cosmetics were determined by this method, 17 kinds of approved sunscreen agents were detected, of which polysiloxane-15 were detected in 10 batches of samples. By comparing with the current method in Safety and Technical Standards for Cosmetics(2015 edition) , it was found that the extraction efficiency of fat-soluble sunscreen agents was superior to the current method, the stability of drometrizole trisiloxan was improved, cinoxate, polysiloxane-15 and other 7 kinds of sunscreens were added. CONCLUSION This method is accurate, sensitive and reliable, which can be used for the detection and analysis of sunscreen in sunscreen cosmetics.

Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Objective To analyze the influencing factors and benchmark value of anesthesia cost in GB25 group in CHS-DRG Group Division Strategy(1.0),and explore the cost control strategy for surgical patients.Methods The data of 152 GB25 cases in sample hospitals were analyzed statistically.Through single factor analysis and multiple stepwise regression analysis,the influencing factors of anesthesia expenses were analyzed,and the evaluation system of hospital anesthesia expenses was built according to the payment standard of GB25 group and the average level of the city.Results Univariate analysis showed that there was significant difference in the influence of laparoscopic surgery or not,operation duration and anesthesiologist on anesthesia cost(P＜0.05);Stepwise regression further analysis showed that the length of operation and the anesthesiologist were the main influencing factors of anesthesia costs.Early warning shall be given when the anesthetic cost is greater than the median in the hospital,and rewards shall be given when the anesthetic cost is less than the average level in the city.Conclusion Hospitals should pay attention to standardize the diagnosis and treatment process,shorten the operation time,and reduce the anesthesia cost.At the same time,they should actively promote the clinical pathway management,and establish and improve the internal assessment mechanism of DRG.

Objective:To compare the teaching effect of basic medical integrated courses and clinical medical integrated courses based on organ system with the traditional teaching model based on discipline,so as to provide theoretical reference for training medical talents.Methods:The program of integration of basic medical courses and clinical medical courses was formulated.The current clinical medical students who participated in the medical licensing examination were selected as the research objects under the three teaching models of basic and clinical medical integrated courses,clinical medical integrated courses,and discipline-based courses.The students'scores of comprehensive basic medicine,comprehensive clinical medicine,and medical licensing examination were analyzed to preliminarily evaluate the implementation effect of the integrated teaching model of basic medicine and clinical medicine.Result:There was no significant difference in the examination scores of students under the three teaching modes.Conclusion:The organ system-based integrated teaching model has no significant effect on students'academic performance in the short term.