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 explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

Objective:To discuss the ameliorative effect of total flavonoids from corn silk(TFCS)on kidney injury in the rats with urate nephropathy,and to clarify the possible mechanism.Methods:Sixty male Wistar rats were randomly divided into control group,model group,positive control group[benzbromarone(BZM)group,5 mg·kg-1·d-1],low dose of TFCS group(20 mg·kg-1·d-1),medium dose of TFCS group(40 mg·kg-1·d-1),and high dose of TFCS group(80 mg·kg-1·d-1),and there were 10 rats in each group.Except for control group,the rats in the other groups were administered potassium oxonate(350 mg·kg-1)and adenine(70 mg·kg-1)by gavage for 4 weeks to establish the hyperuricemic nephropthy models.The rats in different doses of TFCS groups were treated with TFCS for 2 weeks.Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated;HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of uric acid(UA),creatinine(Cr),blood urea nitrogen(BUN),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the serum and levels of β2-microglobulin(β2-MG)and microalbumin(ALB)in the urine of the rats in various groups;Western blotting method was used to detect the expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),and ATP-binding cassette transporter G2(ABCG2)proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the renal blood perfusion volume of the rats in model group was significantly decreased(P<0.01).Compared with model group,the renal blood perfusion volumes of the rats in BZM group and low,medium,and high doses of TFCS groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the kidney weight of the rats in model group was increased,with visible white granular spots on the surface,absence of blood color,and kidney volume was increased.Compared with model group,the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased,with color tending toward that in control group,and the white granular spots on the surface were significantly reduced.Compared with model group,the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).The HE staining results showed there were no abnormalities in kidney tissue structure in control group,while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group;compared with model group,the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups.The Masson staining results revealed no obvious collagen fiber deposition in control group,whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group,and the collagen volume fraction(CVF)was increased compared with control group(P<0.01);compared with model group,the CVFs of the rats in BZM group and different doses of TFCS groups were decreased(P<0.01).The ELISA results showed that compared with control group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in model group were increased(P<0.01);compared with model group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).Compared with control group,the levels of β2-MG and ALB in urinary in model group were increased(P<0.01);compared with model group,the levels of β2-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased(P<0.01),while the expression level of ABCG2 protein was decreased(P<0.01).Compared with model group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01),and the expression level of ABCG2 protein was increased(P<0.01).Conclusion:TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model,and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.

BACKGROUND:Due to natural degradation,excellent biocompatibility and good mechanical properties,magnesium alloy has become a very valuable implant material in the biomedical field.However,the rapid degradation rate of magnesium alloy limits its further development and application. OBJECTIVE:To review the principle of the degradation of magnesium and its alloys in a physiological environment.The current research status of alloying elements selection is mainly introduced from the aspects of the safety of elements and their influence on the properties of magnesium and its alloys. METHODS:The articles were searched by using the databases of CNKI,PubMed,Web of Science and Elsevier.The key words were"magnesium(alloy),metal name(such as:bismuth(Bi),aluminum(Al)),corrosion,biocompatibility,metal toxicity,scaffold(stent)/screw"in Chinese and English.The search period was from 2013 to 2023.As a result,70 articles were applied for analysis after reading the contents of the articles. RESULTS AND CONCLUSION:Magnesium alloy has been widely studied in the medical field.Although some products have been applied in clinical practice,the high degradation rate of magnesium alloy in the human environment is still the main limitation of large-scale clinical application.The focus of future development is to control its corrosion rate.Alloying is a kind of method to improve the corrosion resistance of magnesium alloys,and various properties can also be improved by adding different alloy components.However,simple alloying cannot satisfy the pursuit of diversified properties of magnesium alloys.To develop multifunctional magnesium alloy products with excellent performance,it is necessary to combine various optimization methods,such as alloying and surface modification,to make up for the shortcomings of their respective methods in the future.In addition,the alloy structure updating with preparation process improvement is combined to enhance the properties of magnesium alloy.

Objective To construct a model for predicting the benign and malignant risk of the patients with gastric diseases using con-ventional laboratory indicators such as tumor markers,blood routine,and coagulation indicators,and validate its predictive value.Methods The medical records of patients with gastric diseases who visited the First Affiliated Hospital of Guangzhou Medical Univer-sity from January 2018 to January 2023 were analyzed retrospectively.According to the pathological results,the patients were divided into the gastric cancer(GC)group(n=134)and chronic non-atrophic gastritis(CNAG)group(n=298).Their routine test data such as serum and whole blood tests were collected.The statistical analysis was conducted using the R 4.2.3 software,and a model for pre-dicting the risk of GC was constructed and validated.Results A model for predicting the risk of GC was constructed successfully using the Logistic regression analysis,which included D-dimer,carcinoembryonic antigen(CEA),carbohydrate antigen 72-4(CA72-4)and hemoglobin(Hb).A visual nomogram was plotted as the final prediction model.The areas under the receiver operating characteristic(ROC)curve(AUCROC)of the model in the training and testing sets were 0.809(95%CI:0.754-0.864)and 0.808(95%CI:0.724-0.892),respectively.The sensitivity and specificity of the model were 58.5%and 93.3%,respectively,indicating that it had good pre-dictive ability.Conclusion The model for predicting the malignant risk of patients with gastric diseases constructed using routine tes-ting indicators has good accuracy and can effectively predict the risk of gastric disease transforming into gastric cancer.It helps to find early gastric cancer patients in clinical practice and take targeted prevention and intervention measures.

Objective:To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).Methods:Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).Results:The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c. 963G>A (p.Q321=) and c. 994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c. 963G>A was classified as a pathogenic variant (PVS1+ PM2_Supporting+ PM3), whilst the c. 994A>T was classified as a variant of uncertain significance (PM2_Supporting+ PP3). Conclusion:Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Objective To explore the mechanism of immediate effect regulated by acupuncture on acupoints in patients with migraine without aura(MwoA)during the interictal period.Methods A total of 28 MwoA patients were enrolled and resting-state functional magnetic resonance imaging(rs-fMRI)were performed at baseline and after acupuncture for 30 minutes.Paired t test was used to compare the differences of regional homogeneity(ReHo)and voxel-mirrored homotopic connectivity(VMHC)between two groups.Additionally,the correlation between the changes of rs-fMRI indexes and clinical scores was analyzed.Results In MwoA patients after acupuncture for 30 minutes,the mean regional homogeneity(mReHo)was decreased in the right lingual gyrus and right cere-bellum and was increased in the right middle frontal gyrus,while the z transformation voxel-mirrored homotopic connectivity(zVMHC)was significantly decreased in the bilateral cuneus compared with baseline.There was no significant correlation between imaging data and clinical scales.Conclusion Patients with MwoA after acupuncture for 30 minutes show abnormal ReHo and VMHC in multiple brain regions,which suggest that the mechanism of immediate effect may act through regulating pain-related brain regions.

[Purpose]To analyze the trend of incidence and mean age at diagnosis of lymphoma in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Continuous and com-pleted data of cancer incidence from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province,and all indicators meeting the requirements.Joinpoint 4.7.0.0 software was used to analyze the trend of lymphoma incidence,the average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated.A birth cohort was built from 1929 to 2019,to ana-lyze the change trend of lymphoma incidence rate among people born in different periods.[Re-sults]From 2009 to 2019,the AAPC of lymphoma incidence rate in cancer registration areas of Jiangsu Province was 5.74％,5.55％for men and 5.02％for women.The AAPC in urban areas was higher than that in rural areas(6.26％vs 4.90％).The age-standardized incidence rate(ASIR)of lymphoma increased by 3.40％annually on average.The rising amplitude of ASIR of women(3.16％)was higher than that of men(3.05％),and the rising amplitude of ASIR of lymphoma in urban areas(3.39％)was higher than that in rural areas(2.43％).The birth cohort analysis showed that the incidence rate of lymphoma fluctuated greatly before the age of 40,and there was no sig-nificant trend of change,while the incidence rate in age groups of 40 years old and above showed an overall upward trend.The average age at onset of lymphoma showed an upward trend from 2009 to 2019,with an average annual increase of 0.35 years old(P＜0.001).The standardized average age at onset for lymphoma still showed a significant upward trend,with an average annual increase of 0.15 years old(P=0.016).Compared with 2009,the standardized age specific incidence of lym-phoma in 2019 showed an overall backward trend,while the standardized incidence in all age groups after 60 years old(except for the age group of 70～74 years old)increased.The proportion of lymphoma in people above 60 years old was 56.16％in 2019,which was higher than that in 2009(52.57％).[Conclusion]The incidence rate of lymphoma in Jiangsu Province was increasing year by year from 2009 to 2019.The age at onset tended to shift back,and the trend was more pronounced in male than female.

Pancreatic fibrosis (PF) is primarily distinguished by the stimulation of pancreatic stellate cells (PSCs) and excessive extracellular matrix deposition, which is the main barrier impeding drug delivery and distribution. Recently, nanomedicine, with efficient, targeted, and controllable drug release characteristics, has demonstrated enormous advantages in the regression of pancreas fibrotic diseases. Notably, paracrine signals from parenchymal and immune cells such as pancreatic acinar cells, islet cells, pancreatic cancer cells, and immune cells can directly or indirectly modulate PSC differentiation and activation. The intercellular crosstalk between PSCs and these cells has been a critical event involved in fibrogenesis. However, the connections between PSCs and other pancreatic cells during the progression of diseases have yet to be discussed. Herein, we summarize intercellular crosstalk in the activation of PSCs and its contribution to the development of common pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes. Then, we also examine the latest treatment strategies of nanomedicine and potential targets for PSCs crosstalk in fibrosis, thereby offering innovative insights for the design of antifibrotic nanomedicine. Ultimately, the enhanced understanding of PF will facilitate the development of more precise intervention strategies and foster individually tailored therapeutic approaches for pancreatic diseases.