AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Objective: To investigate the molecular mechanism of Syk in phagocytosis induced by CD36 antibodies. Methods: In vitro, two CD36 monoclonal antibodies, GZ1 (IgG2a) and GZ4 (IgG1), at different concentrations were co-incubated with platelets from CD36-positive blood donors, and the affinity of the antibodies for platelets was assessed using flow cytometry. CD36 positive platelets from donors were labeled with Red-SE. The GZ1 and GZ4 antibodies were added together with dye-labeled platelets to peripheral blood from blood donors for phagocytosis experiments. The expression of the Spleen Tyrosine Kinase (Syk), P-Syk, P38 MAPK and P-P38 were detected using Western blot(WB). In the in vitro phagocytosis inhibition assay, Fcγ receptor (FcγR) antibodies or Syk inhibitor (R406) were pre-incubated with monocytes prior to performing the phagocytosis experiment. In vivo experiments were performed using female C57BL/6J mice. R406 was administered via intraperitoneal injection, followed by tail vein infusion of GZ1 or GZ4 antibodies. Additionally, a treatment group was set up in which the antibodies were infused first, followed by administration of R406. Changes in platelet counts were analyzed using a blood routine analyzer, and antibody binding to platelets was detected by flow cytometry. Results: GZ1 had higher affinity for CD36positive platelets than GZ4. The phagocytosis rate induced by GZ1 was significantly higher than that of GZ4 [(42.12±2.25)% vs (16.25±6.45)%, P<0.001]. Moreover, GZ1-mediated platelet phagocytosis mainly depends on FcγRⅠ of monocytes, while GZ4-mediated platelet phagocytosis mainly relies on FcγRⅡ of monocytes. WB results showed that the GZ1 group significantly upregulated the expression of Syk and phosphorylated Syk (P-Syk), and induced phosphorylation of the downstream P38 MAPK signaling pathway. Pretreatment of monocytes with R406 inhibited the phagocytosis of antibodyopsonized platelets by monocytes. After injecting GZ1 or GZ4 antibodies into C57BL/6 female mice through the tail vein, GZ1 mAbs had a stronger binding rate to the platelets compared with GZ4 mAbs, leading to a significant decrease in platelet count. After pre-injecting R406 into mice, the platelet count reduction in both the GZ1 and GZ4 groups was alleviated, and the binding rate of antibodies to platelets was also significantly reduced. However, administration of R406 after antibody injection failed to prevent the decrease in platelet counts in mice. Conclusion: This study indicates that Syk plays an important role in the phagocytosis of anti-CD36 opsonized platelets by monocytes/macrophages and is closely associated with the activation of the P38 MAPK signaling pathway.

Objective To develop a tumor vaccine containing broad-spectrum neoantigen tumor cell lysate(TCL)and CpG adjuvant,and to effectively deliver it to lymph node dendritic cells.Methods A novel polymer,9-fluorenylmethoxycarbonyl-polyethylene glycol-glycocholic acid(Fmoc-PEG-GCA),was employed to encapsulate the TCL and CpG through π-π stacking,resulting in high-density polyethylene glycol-modified glycocholic acid-decorated micelles TCL/CpG@GNP.The vaccine′s drug loading,encapsulation efficiency,particle size,polydispersity index(PDI),zeta potential,morphology,stability,cellular safety,uptake capability,immune stimulation effects on bone marrow-derived dendritic cells(BMDCs)and in vivo anti-tumor efficacy were evaluated.Results The vaccine TCL and CpG demonstrated a drug loading capacity of 6.26%and the encapsulation rate was 37.59%.The drug loading capacity of CpG was 7.05%,and the encapsulation efficiency was 56.86%.The particle size measured(139.26±27.23)nm,with a PDI of 0.249±0.015,indicating favorable dispersion properties.The zeta potential was recorded at(-21.23±0.36)mV.The TCL/CpG@GNP vaccine demonstrated good stability,cell safety and uptake ability,and can promote the activation and maturation of BMDCs.In tumor-bearing mouse models,TCL/CpG@GNP inhibited tumor growth,increased the proportion of T lymphocytes in peripheral blood,and elevated IFN-γ levels in spleen.Conclusion The TCL/CpG@GNP tumor vaccine can effectively activate BMDCs and induce strong anti-tumor immune memory in a mouse lung cancer model.

Objective To investigate the clinical characteristics of preoperative intestinal symptoms in patients with bowel endometriosis and to compare the effects of shaving versus segmental bowel resection on postoperative intestinal function.Methods A total of 105 patients diagnosed with bowel endometriosis and treated by the same surgical team at the Obstetrics and Gynecology Hospital,Fudan University between Aug 1,2013 and Dec 30,2017 were prospectively enrolled in this study.Clinical data were collected via outpatient visits and telephone follow-ups at four time points:preoperative(T0)and postoperative(T1:Nov 2018;T2:Nov 2020;T3:Apr 2024).The primary outcome was bowel symptoms and gastrointestinal function scores;secondary outcome was pain scores.A generalized estimating equation(GEE)model was used to analyze the interaction effect of surgical approach and follow-up time on outcomes.Results Ultimately,a total of 89 patients were included(15.24%loss to follow-up),among whom 79 patients(88.76%)underwent shaving excision.Preoperatively,46 patients(51.68%)presented with bowel symptoms,primarily anus bulge(21 cases,46.65%)and diarrhea(15 cases,32.61%)during menstruation.Postoperatively,there was a significant increase in constipation rates(T1:71.43%;T2:50.00%;T3:72.00%).Both surgical groups exhibited significant improvements in dysmenorrhea,gastrointestinal discomfort scores as well as gastrointestinal quality of life index(P<0.000 5).However,the segmental resection group had significantly higher scores for low anterior resection syndrome,constipation compared with the shaving excision group(P=0.02 and P=0.05).Conclusion Approximately half of the patients with bowel endometriosis exhibit typical bowel symptoms preoperatively,such as anus bulge and diarrhea.Both shaving excision and segmental resection effectively alleviate pain;however,shaving excision demonstrates an advantage regarding preservation of bowel function,whereas segmental resection may elevate risks associated with postoperative constipation or altered defecation patterns due to structural changes.The selection of surgical approach should carefully balance lesion removal and functional preservation,moreover,be sure that potential risks are thoroughly informed to patients prior to surgery.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.

Objective This study aims to explore the impact of esketamine combined with hip pericapsular nerve block on perioperative stress reactions,immune function,cognitive function,and postoperative analgesic efficacy in elderly patients undergoing total hip replacement.Methods From February 2022 to February 2025,110 elderly patients who received total hip arthroplasty in the hospital were enrolled as the research participants.They were allocated into a control group and an observation group by means of a random number table,with 55 cases in each group.All patients received total hip arthroplasty.Patients in the control group were given 20 mL of ropivacaine combined with pericapsular nerve block anesthesia of the hip joint,while those in the observation group were given esketamine combined with pericapsular nerve block anesthesia of the hip joint.The blood pres-sure,heart rate(HR),oxygen saturation(SpO?),and respiratory rate(RR)of the two groups were compared at admission(T1),immediately after anesthesia(T2),skin incision(T3),30 minutes after surgery initiation(T4),incision suture(T5),and immediately after surgery completion(T6).Both groups underwent detection,assess-ment,and comparison of immune function indices,serum stress markers,and cognitive function scores before the operation and 3 days post-surgery.The Visual Analogue Scale(VAS)pain scores at 3,6,and 9 hours after surgery were contrasted between the two groups.Additionally,statistical analysis was performed on the incidence of adverse reactions in both groups.Results The HR,mean arterial pressure(MAP),SpO?,RR,and bispectral index(BIS)of the two groups from T1 to T6 were compared using repeated measures analysis of variance.The results showed that:(1)There were statistically significant differences in HR,MAP,SpO?,and BIS at different time points(F=118.378,70.002,44.910,242.439,all P<0.001).(2)There were statistically significant differences in HR,MAP,SpO?,and BIS between the observation group and the control group(F=206.643,195.586,93.077,3.953,P<0.001,P<0.001,P<0.001,P=0.049).(3)There were statistically significant differences in the changing trends of HR,MAP,SpO?,RR,and BIS between the two groups(F=18.583,14.158,23.350,4.883,6.698,all P<0.001).At 3 days after surgery,the levels of CD4? and CD4?/CD8? in the observation group were lower than those in the control group(P<0.05).The levels of malondialdehyde(MDA),superoxide dismutase(SOD),and cortisol in the observation group were lower than those in the control group during surgery and immediately after surgery(P<0.05).The Montreal Cognitive Assessment(MoCA)scores and Mini-Mental State Examination(MMSE)scores of both groups decreased 3 days after surgery,and those in the observation group were higher than those in the control group(P<0.05).The VAS pain scores of the observation group at 3,6,9 and 12 hours after surgery were lower than those of the control group.The incidence of adverse reactions in the observation group was lower than that in the control group(12.73%vs.29.09%,P<0.05).Conclusion Esketamine combined with pericapsular nerve block of the hip joint can significantly inhibit the perioperative stress response in elderly patients undergoing total hip arthroplasty,optimize the postoperative anal-gesic effect,and reduce the incidence of adverse reactions.

Purpose To explore the value of tumor intratumoral and peritumoral radiomics models based on dynamic contrast-enhanced MRI in predicting benign and malignant breast tumors.Materials and Methods This retrospective study analyzed clinical data and MRI imaging features from 309 patients with pathologically confirmed solitary breast tumors at the Second Affiliated Hospital of Xiamen Medical College from August 2018 to December 2022.The cohort was randomly divided into training(n=248)and testing(n=61)cohorts in an 8∶2 ratio.Using second-phase dynamic contrast-enhanced MRI images,five distinct peritumoral regions were segmented through 3D-Slicer software:intratumoral region,peritumoral 2 mm region,peritumoral 4 mm region,intratumoral combined with peritumoral 2 mm region and intratumoral combined with peritumoral 4 mm region.Radiomic features were extracted from these regions of interest.Machine learning algorithms integrated with Logistic regression analysis were employed for feature selection,with cross-validation techniques determining the optimal radiomic signature combination.Results Of 309 patients,150 were benign tumors and 159 were malignant tumors.The age,maximum diameter and enhancement type of benign and malignant breast tumors were statistically significant(Z/χ2=-7.695,-5.775,30.248;all P<0.001).For the region of interest of intratumoral combined with peritumoral 4 mm region,the area under curve,sensitivity,specificity,accuracy and F1 scores of the training and validation were 0.893,89.1%,75.0%,82.3%,0.838 and 0.881,74.2%,86.7%,80.3%,0.793,respectively.In the training set,the area under curve of intratumoral combined with peritumoral 4 mm region was significantly higher than that of intratumoral,peritumoral 2 mm,peritumoral 4 mm and intratumoral combined with peritumoral 2 mm regional imaging models(Z=2.506,2.982,3.392,2.157;all P<0.05).The Hosmer-Lemeshow test showed that the calibration curve of the model combined with region of interest of intratumoral combined with peritumoral 4 mm region was highly consistent with the ideal curve(training P=0.381,validation P=0.159).The decision curve indicated that the net benefit of the radiomics model in the region of interest of intratumoral combined with peritumoral 4 mm region was the highest when the risk threshold was between 0 and 1.0.Conclusion The radiomics model has good predictive performance in predicting benign or malignant breast tumors,among them the combined region of interest of intratumoral combined with peritumoral 4 mm region provides the best performance and highest benefit.The technology clinical application will provide a non-invasive predictive method for the differential diagnosis of benign and malignant breast tumors.