Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Objective: To analyze the situation of blood return in medical institutions in Qingdao, and provide a reference basis for improving blood utilization efficiency. Methods: Data on whole blood donations, and the distribution and return of various blood components from 2022 to 2024 at the Qingdao Central Blood Station were collected. The overall trend of blood return, return situation of various blood components, main reasons for blood return, and related influencing factors were analyzed. Results: The average blood return rate from 2022 to 2024 was 1.43‰ (1 249/875 007), showing an overall downward trend (P<0.05). The return rate of red blood cell (RBC) components increased year by year over the three years, while those of plasma components and cryoprecipitated antihemophilic factors decreased. Regarding the reasons for blood return, the return rates due to direct antiglobulin test (DAT) positivity and unexpected antibody positivity increased year by year, whereas those due to leakage and other reasons decreased. Univariate analysis of the causes of RBC components return showed that DAT positivity rates differed significantly by sex, age, and blood type, but not by donation season; unexpected antibody positivity rate differed significantly by sex, but not by age, blood type, or donation season. Multivariate analysis indicated that female gender, age>30 years, and blood type A or AB were independent risk factors for DAT positivity, while female gender was an independent risk factor for unexpected antibody positivity. The return rate due to DAT positivity differed significantly among medical institutions of different levels, while that due to unexpected antibody positivity did not show a significant difference. Some donors who tested positive for DAT (76.92%, 60/78) or unexpected antibody (71.15%, 37/52) became antibody-negative upon subsequent donations. Comparing RBC donors with DAT positivity who became negative upon subsequent donations with those who remained positive, the difference in donation interval was statistically significant. Conclusion: Over the past three years, the overall blood return rate in Qingdao has declined, but the return rate of RBC components has increased. Further investigation and targeted interventions are needed to enhance the utilization of blood resources and ensure safe clinical blood transfusion.

Optical coherence tomography angiography(OCTA)is an innovative non-invasive imaging technology that enables non-invasive, layered, and three-dimensional quantitative visualization of the retinal and choroidal capillary networks by detecting blood flow signals in a contrast-free manner. With its non-invasiveness, high resolution, and quantifiability, OCTA demonstrates significant potential in disease screening, precise staging, treatment decision-making, and prognosis prediction. Its core advantage lies in the accurate quantification of key microcirculation parameters, such as vessel density(VD), non-perfusion area(NPA), foveal avascular zone(FAZ)morphology, and neovascular activity. In diabetic retinopathy(DR), retinal vascular occlusive diseases(RVO/RAO), age-related macular degeneration(ARMD), and glaucoma, OCTA can sensitively detect reduced vessel density in the deep capillary plexus before clinically visible lesions appear, providing a basis for early screening and risk stratification. Additionally, OCTA has shown important value in managing uveitis, pathological myopia, and other ocular conditions. This review systematically elaborates on the technical principles, key quantitative parameters, and core application value of OCTA in the management of various ophthalmic diseases and presents scientific prospects for the application of OCTA in standardized ophthalmic treatment. With further advancements in hardware scanning speed, wide-field imaging capabilities, artificial intelligence algorithms, and multi-modal integration, OCTA is expected to become an essential component of standard ophthalmic diagnosis and treatment. It may also provide a non-invasive window for microcirculation research in neurological and systemic diseases.

Purpose To investigate the relationship between SERPINA4 expression and clinicopathological fea-tures and prognosis in metastatic colorectal cancer(CRC).Methods EnVision two-step immunohistochemical method was used to detect the expression of SERPINA4 protein in 104 cases of primary and metastatic tumor paraffin tissues of metastatic colorectal cancer and adjacent intestinal normal mucosa,and its relationship with clinicopathological features of patients was analyzed.qRT-PCR was used to detect the expression of SERPINA4 mRNA in 11 pairs of metastatic CRC metastases and paired primary tumor paraffin-embedded tissue samples.The survival of patients was followed up,and the relationship between SERPINA4 expression and patient prognosis was analyzed by Kaplan-Meier method.Re-sults Immunohistochemical results showed that the strong positive expression rate of SERPINA4 was 97.10％in nor-mal mucosa,71.20％in primary lesions,and 39.40％in metastatic lesions.The difference between the three groups was statistically significant(P＜0.001).qRT-PCR results showed that SERPINA4 mRNA was lowly expressed in me-tastatic lesions of metastatic CRC(P＜0.05).The expression of SERPINA4 in metastatic lesions was significantly cor-related with histological grade,N stage and M stage of the tumor(P＜0.05),but not significantly correlated with age,gender,tumor location and T stage of patients(P＞0.05).The survival time of patients with metastatic colorectal cancer with high expression of SERPINA4 was longer than that of patients with low expression.Conclusion The ex-pression of SERPINA4 is of great significance in the survival and prognosis of patients with metastatic CRC.

Objective:To investigate the effect of altitude on the risk of pre-eclampsia (PE).Methods:This cross-sectional study included 19 246 pregnant women who delivered in Gansu Provincial Hospital from January 2016 to December 2020. General clinical data, pregnancy outcomes and neonatal outcomes were collected. The diagnosis of PE was based on the disease diagnosis coding of medical record information system and the Chinese guidelines for the diagnosis and treatment of hypertensive disorders in pregnancy (2020). According to the altitude of residence, the subjects were divided into low altitude group (9 931 cases), middle altitude group (9 068 cases) and high altitude group (247 cases). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between altitude and the risk of PE, after adjusting for confounding factors such as age, ethnicity, mode of conception, gestational diabetes mellitus, and hemoglobin level.Results:(1) Among the 19 246 pregnant women, 752 (3.91%, 752/19 246) were diagnosed with PE. The incidence of PE in the low altitude group, middle altitude group and high altitude group was 2.95% (293/9 931), 4.91% (445/9 068) and 5.67% (14/247), respectively. With the increase of living altitude, the incidence of PE increased significantly ( P<0.001). (2) The results of univariate logistic analysis showed that compared with the low altitude area, the risk of PE in pregnant women living in the middle altitude area and high altitude area increased by 70% ( OR=1.70, 95% CI: 1.46-1.97; P<0.001) and 98% ( OR=1.98, 95% CI: 1.14-3.43; P=0.016). (3) The results of multivariate logistic regression analysis showed that after fully adjusting for confounding factors, the risk of PE increased by 40% for every 500 meters of elevation ( OR=1.40, 95% CI: 1.25-1.57; P<0.001). Compared with those living in low altitude areas, the risk of PE in pregnant women living in middle altitude and high altitude areas increased by 72% ( OR=1.72, 95% CI: 1.47-2.00; P<0.001) and 100% ( OR=2.00, 95% CI: 1.07-3.74; P=0.030). Conclusion:In the high-altitude environment of Gansu Province, the risk of PE gradually increases with the increase of altitude.

Objective:To compare the uncertainty of dose calibration systems between EBT4 and EBT3 films, and to evaluate the effectiveness and accuracy of EBT4 films in radiotherapy dose measurements.Methods:EBT4 and EBT3 films were irradiated with clinical 6 MV photon beams at doses ranging from 0 to 1,600 MU. Films were scanned after resting for 0 and 24 h to establish dose calibration functions based on net optical density. The dose uncertainties introduced by function fitting, dose resolution, film non-uniformity, scan repeatability, and scanner non-uniformity during calibration of the two films were obtained through experimental tests and mathematical calculations. Independent-sample t-tests were used to compare differences in fitting uncertainty and dose resolution between the two films, while homogeneity of variance tests were used to compare differences in film non-uniformity and scan repeatability. The combined total uncertainty was then calculated and compared. Finally, the total combined uncertainty was calculated by integrating all individual sources of uncertainty and compared between the two films. Results:Within the absorbed dose range of 1-12 Gy, EBT4 films exhibited significantly lower dose uncertainties from function fitting and dose resolution than EBT3 films at the same standing time ( P<0.01). No significant differences were observed between the two films in terms of non-uniformity and scan repeatability ( P>0.05). The total dose uncertainties of EBT4 and EBT3 films at 0 h standing were 5.65% and 7.87%, respectively, while the total uncertainties at 24 h standing were 4.73% and 6.33%, respectively. Overall, the dose calibration system of EBT4 films demonstrated consistently lower total uncertainty. Conclusion:Under identical conditions, EBT4 films demonstrate superior and more stable dose uncertainty compared with EBT3 films, thereby meeting the clinical requirements for radiation dose measurements with higher precision.

Objective:To validate the effectiveness of the leaf position data of multi-leaf collimator (MLC) recorded in the Infinity medical linear accelerator log file (LF).Methods:In this study, the establishment of the film dose calibration curve involved two steps. Initially, the pixel values obtained from scanning the film were converted into net optical density values. Subsequently, a sixth-order polynomial fit was performed on the net optical density and dose data. The picket fence (PF) tests were performed on the electronic portal imaging device (EPID) and film, and the corresponding acquired PF test images were analyzed using the relative leaf travel distance, relative leaf position, relative leaf pair full-width half -maximum (FWHM), and relative leaf pair neighbor region width analysis index, and compared with the relevant results in LF. In addition, to investigate the effect of gravity on the recorded leaf position data by the Infinity medical linear accelerator LF, the above PF tests were executed at 0°, 90°, 180°, and 270° gantry angles, respectively. Intergroup differences were assessed with the Wilcoxon rank-sum test.Results:The film dose calibration curve demonstrated high goodness-of-fit, with a correlation coefficient ( R2) of 0.9994. Across all gantry angles, the dispersion of overall leaf position data for EBT3 film, EPID, and LF followed a consistent pattern based on four analysis metrics: EBT3 film > EPID > LF. Moreover, for each analysis metric, inter-tool differences in standard deviations of results were consistently below 0.1 mm, and this pattern was invariant to gantry angle. Conclusions:The leaf position data recorded in the Infinity medical linear accelerator LF have a high degree of accuracy, and can be used as reference for the actual position of the MLC leaf. Furthermore, gravitational forces exhibit negligible impact on leaf position data acquired via LF.

Objective:To describe the epidemiological characteristics of 22 common respiratory patho-gens in patients with pneumonia in Yinzhou,Ningbo,from January 1,2015 to December 21,2024.Methods:The test data of 22 common respiratory pathogens in patients diagnosed with pneumonia or lung infection in the Yinzhou Regional Health Information Platform from January 1,2015 to December 21,2024 were collected.The positive cases,positive rates,and positive proportions were calculated.The epidemiological characteristics were described by the year,sex,age group,season,and coronavirus disease 2019(COVID-19)pandemic period.Results:A total of 77 531 pneumonia patients were included,with 492 696 respiratory pathogen tests performed.The number of respiratory pathogen tests and positive cases of pneumonia patients in Yinzhou showed an upward trend.In the study,34.63％of the pneumo-nia patients tested positive for at least one pathogen,and the pathogen non-detection rate decreased from 79.44％in 2015 to 58.38％in 2024.The overall pathogen positive rate was 9.12％,which decreased during the COVID-19 pandemic and had not returned to the historical level after the COVID-19 pande-mic.The positive rate was highest in children aged 6-17 years(13.99％),and lowest in the elderly over 60 years(4.16％).The top 3 highest number of positive cases was Mycoplasma pneumoniae,influenza A virus,and influenza B virus;the top 3 highest positive rates of pathogen tests were Mycoplasma pneu-moniae(25.26％),rhinovirus(12.02％),and Bordetella pertussis(11.66％).The pathogen spectrum proportion in men was similar to that in women,only showing a higher ratio of Mycobacterium tuberculosis and a slightly lower ratio of Mycoplasma pneumoniae(P＜0.001).Mycoplasma pneumoniae,respiratory syncytial virus,and rhinovirus infections were more common in children,while influenza virus,Mycobac-terium tuberculosis,and Streptococcus pyogenes infections were more common in adults and the elderly(P＜0.001).Influenza virus and human metapneumovirus infections were more common in winter,rhi-novirus and Bordetella pertussis infections were more common in spring,and Mycoplasma pneumoniae in-fections were relatively more common in fall(P＜0.001).After the COVID-19 pandemic,the propor-tions of rhinovirus,respiratory syncytial virus,and human metapneumovirus infections in the pneumonia patients increased signi-ficantly,reaching 7.53％,4.26％,and 2.25％,respectively,while the propor-tions of influenza B virus and Mycobacterium tuberculosis infections decreased to 4.14％and 2.80％,re-spectively(P＜0.001).Conclusion:In the past decade,the scale of respiratory pathogen infection in the pneumonia population in Yinzhou had expanded significantly,and there were differences in distribu-tion by the year,gender,age group,and season.The respiratory pathogen spectrum in pneumonia pa-tients after the COVID-19 pandemic had a trend of diversification.

Microgravity-induced cardiac remodeling presents a substantial challenge that constrains the advancements in the international space industry,which mainly manifests as alterations in the morphology,structure,and function of the heart.This paper analyzed the core pathogenesis and treatment of microgravity-induced cardiac remodeling based on the theory of"yang transforming qi and yin forming shape"in Huangdi Neijing."Yang transforming qi"reflects the changes in cardiac function,whereas"yin forming shape"reflects the changes in cardiac morphology and structure.Based on the basic and clinical research of space cardiac dysfunctions,the core pathogenesis of microgravity-induced cardiac remodeling is the insufficiency of"yang transforming qi",accompanied by yin excess and yang deficiency due to excessive"yin forming shape"in the early stage,which evolves into deficiency of both yin and yang in the late stage.Thus,this paper specifically refined the treatment methods and corresponding formulas,including warming viscera yang to transform qi,draining yin blood to restore yang qi,and consolidating yin and yang to nourish primal energy.These insights provide systematic theoretical support and conceptual inspiration for the traditional Chinese medicine treatment of microgravity-induced cardiac remodeling.

Background and purpose:As one of the first-line treatment methods for differentiated thyroid cancer(DTC),131I treatment is an important therapeutic approach for most patients with medium-high recurrence risk DTC after total or near-total thyroidectomy.Risk stratification and real-time dynamic assessment before 131I treatment after surgery are important steps in deciding on 131I treatment,enabling individualized treatment.This retrospective study aimed to explore the role of diagnostic whole body scan(DxWBS)in the decision-making of treatment for DTC after surgery and before 131I therapy.Methods:DTC patients who underwent pre-ablation evaluation were included.Patients were divided into low,medium and high sTg groups based on their pre-131I treatment stimulated thyroglobulin(sTg)levels(＜1 ng/mL,1 ng/mL≤sTg＜10 ng/mL,sTg≥10 ng/mL).The concordance rates of DxWBS and post treatment whole body scan(RxWBS)in each patient of the whole cohort were compared.The lesion detection rate between DxWBS and RxWBS in different sTg level groups was also explored.The"thyroid stunning effect"by DxWBS was evaluated by RxWBS.Through these analyses,the role of DxWBS in 131I treatment decision-making and its predicting treatment objectives were assessed.This study was approved by the Ethics Committee of Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences(ethics number:JS-2151).Results:A total of 91 patients were included.The low,medium and high sTg groups accounted for 15.4%(14/91),34.1%(31/91)and 50.5%(46/91)of the patients,respectively.Comparison of DxWBS and RxWBS results in the same patients in each sTg group showed no evidence of a stunning effect on 131I treatment.The overall concordance rate between DxWBS and RxWBS was 89.0%(81/91);In different sTg level groups was 100.0%(14/14),90.3%(28/31),84.8%(39/46)respectively.Taking sTg levels into consideration,DxWBS accurately predicted the need for total thyroidectomy,with a 100%(20/20)agreement with RxWBS.Among the 71 patients who received adjuvant therapy and/or remnant ablation due to suspected elevated Tg or high recurrence risk stratification or the iodine-avid metastatic lesions identified by DxWBS,87.5%(63/71)showed only residual thyroid tissue by DxWBS;Through the purpose verification by RxWBS and single photon emission computed tomography(SPECT)/CT,only 12.7%(9/71)of cases were verified as adjuvant or tumoricidal treatment due to iodine-avid cervical lymph node and/or lung metastasis identified by RxWBS,87.3%(62/71)were residual thyroid ablation.In the medium and high sTg group,the overall detection rate of functional cervical lymph node metastasis by DxWBS and RxWBS was 5.5%(5/91).For the detection of functional lung metastases,the overall detection rate of DxWBS was slightly lower than that of RxWBS(3.3%vs 5.5%).This indicates that DxWBS can be used to accurately pre-judge the purposes of 131I treatment,particularly for thyroid ablation and adjuvant therapy.Conclusion:DxWBS did not induce"thyroid stunning"effect.Integrating DxWBS as a theranostic tool into the real-time decision-making and evaluation system of 131I treatment,as well as with sTg and other biochemical indicators,may help to bridge the limitations of static evaluations based on pathology and clinical data,and provides a clear understanding and more precise objectives of 131I treatment.