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.

Molar-incisor hypomineralization (MIH) is a developmental defect of enamel that is characterized primarily by abnormal enamel mineralization affecting the first permanent molars and permanent incisors. Due to insufficient mineralization, teeth affected by MIH are prone to post-eruptive breakdown and caries, potentially leading to sequelae such as tooth sensitivity and occlusal problems. The diagnosis of MIH is primarily based on relevant perinatal and infantile medical history, the characteristic distribution of affected teeth, and the morphological features of the enamel defects. Based on the extent and severity of the enamel defect, MIH is classified as mild or severe. Diagnosis and treatment strategies emphasize early screening, diagnosis, and intervention, prioritizing prevention, providing symptomatic care, and implementing regular recall assessments. Mild MIH predominantly manifests as demineralized enamel opacities or discoloration, typically without significant enamel breakdown. Treatment focuses on caries prevention and aesthetic restoration, employing techniques such as remineralization, micro-abrasion, resin infiltration, bleaching, fluoride application, and fissure sealants. Severe MIH typically presents with extensive enamel opacities accompanied by substantial enamel breakdown and may be complicated by caries and tooth sensitivity. Management primarily involves restoring the structural defects or, for teeth that cannot be preserved, extraction followed by orthodontic treatment. Comprehensive management often requires a multimodal approach integrating various therapeutic modalities to restore both the function and aesthetics of the affected teeth and overall dentition. This article provides a review of advancements in diagnosis and the treatment strategies for MIH, offering a reference for clinical practice.

This paper systematically elaborates on the key points of diagnosis and differential diagnosis of salivary gland tumors characterized by a substantial amount of extracellular mucus as a main or prominent feature, and clarifies the core differential features. The term "mucus-rich" specifically denotes that mucus is a major component of the tumor, rather than a focal or minor one. This phenomenon is associated with distinct histogenetic mechanisms: it may result from specific genetic mutations (e.g., AKT1 E17K in mucinous adenocarcinoma) that drive ductal epithelial differentiation into mucus-secreting cells, or from myoepithelial cells secreting glycosaminoglycans that form a myxoid stroma. Salivary gland tumors with abundant extracellular mucus include mucinous cystadenoma, sialadenoma papilliferum-like intraductal papillary tumors, mucinous myoepithelioma, pleomorphic adenoma with mucin-rich stroma, mucinous adenocarcinoma, low-grade mucoepidermoid carcinoma, mucin-rich salivary duct carcinoma and intestinal-type adenocarcinoma. The diagnosis of these tumors is complicated by the dual nature of extracellular mucus: while it is a defining feature of some entities, it can also obscure key diagnostic architectural features in others, leading to histological overlap and inconspicuous diagnostic areas. Given the frequent histological morphological overlap among these tumors, immunohistochemical findings and molecular characteristics have emerged as crucial differential diagnostic criteria. Core differential diagnostic points include the following: histologically, there must be meticulous identification of typical structures obscured by mucin (such as squamoid cells in mucoepidermoid carcinoma and apocrine features in salivary duct carcinoma); in immunohistochemical staining, CK20 is useful for distinguishing intestinal-type adenocarcinoma (positive) from mucinous adenocarcinoma (negative), while androgen receptor aids in differentiating salivary duct carcinoma (positive) from mucoepidermoid carcinoma (negative); and molecular testing plays a critical role in definitive diagnosis (e.g., the AKT1 E17K mutation for mucinous adenocarcinoma, MAML2 rearrangement for mucoepidermoid carcinoma, and MEF2C::SS18 fusion for microsecretory adenocarcinoma). This paper systematically summarizes the core pathological features and differential diagnostic points of mucin-rich salivary gland tumors, aiming to provide a practical reference for clinical pathological diagnosis.

Objective: To examine the association between parent-child communication frequency about school related matters and depressive symptom risk among children and adolescents and to characterize its dose response pattern, so as to provide a reference for family intervention and school mental health promotion. Methods: Data were obtained from the 2022 China Family Panel Studies(CFPS), conducted from May to December 2022. A total of 1 896 children and adolescents aged 10-15 years were included. The 8 item Center for Epidemiologic Studies Depression Scale (CES-D8) was adopted to assess depressive symptoms among children and adolescents. Data on the parent-child communication frequency about school related matters was obtained from CFPS Child Proxy Questionnaire. Multivariable Logistic regression, sensitivity analyses, and exploratory segmented regression were performed. Results: A total of 375 participants were screened positive for depressive symptoms, with a prevalence of 19.8%. The prevalence decreased from 23.3% in the "never" group to 10.6% in the "very often" group ( χ 2=19.30, P <0.05). In the fully adjusted model, the point estimate for the "very often" group suggested lower odds of a positive screen ( OR =0.52), and the test for trend was statistically significant ( P =0.03). The association was more pronounced among children aged 10-12 years ( OR=0.31, 95%CI=0.11-0.86, P <0.05). Sensitivity analyses yielded directionally consistent results, but the statistical evidence was weakened ( OR=0.83, P trend =0.08). Dose response analysis showed a statistically significant overall association between parent-child communication frequency about school related matters and depressive symptom risk ( P =0.04), with no significant departure from linearity ( P = 0.14 ). Among the prespecified cut points, exploratory segmented regression showed relatively better model fit at an ordinal frequency score of 4.5, between "often" and "very often" (likelihood ratio test P =0.03). However, the overall test for nonlinearity was not statistically significant ( P =0.14), and the finding should therefore be interpreted as exploratory. Conclusion More frequent parent-child communication about school related matters is associated with lower depressive symptom risk, suggesting that routine communication about such matters may help reduce the risk of depressive symptoms in children and adolescents.

Objective: To develop machine learning identification models for the relatively high risk of social-emotional problems among Chinese school-aged children, and compare internal validation performances across different algorithms, so as to provide reference for preliminary identification of relatively high risk in school-aged children s social-emotional problems. Methods: Based on the 2022 proxy-reported data for children from the China Family Panel Studies (CFPS), a total of 3 575 children aged 6-15 years from 2 709 families who completed the survey between May and December 2022 were included. Relatively high risk of social-emotional problems was defined using a composite score constructed from 12 social emotional related items in the CFPS 2022 general questionnaire. Data were split approximately 7∶3 (modeling group: 2 503, validation group: 1 072) by household identifier (ID) to ensure all children from the same family were assigned to the same dataset. Candidate variable selection, missing value imputation parameter fitting, least absolute shrinkage and selection operator (LASSO) feature screening, model training, and hyperparameter tuning were performed within the development set, while internal validation was conducted in the validation set. Weighted AUC, Brier score, sensitivity, specificity, calibration curves, and decision curves were compared across Logistic regression, random forest (RF), gradient boosting decision trees (GBDT), support vector machines (SVM), and extreme gradient boosting (XGBoost). The Shapley additive explanations (SHAP) method was used for exploratory interpretation of the RF model, which achieved the highest AUC value in the validation set. Results: A total of 941 (26.3%) were classified as having relatively high risk of social emotional problems. A total of 659 and 282 high risk cases were in the modeling group and validation group, respectively, with no cross set split of households. LASSO retained 10 features. In the validation set, the RF model achieved the highest AUC of 0.672 (95% CI =0.624-0.717) and a Brier score of 0.184. The Logistic regression model achieved a validation AUC of 0.670 (95% CI =0.624-0.716). The incremental AUC gain of RF over Logistic regression was 0.002 (family cluster paired bootstrap 95% CI =-0.016 to 0.020, P =0.856). Following household ID splitting, all models showed moderate internal validation performance. Although RF achieved the highest numerical value, its incremental gain over Logistic regression was limited. Conclusion The model can serve as a reference for preliminary identification research on the relatively high risk of social emotional problems in school aged children, though its stability and applicability require further validation in external samples.

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 explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification.Methods:A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).Results:The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband′s father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+ PM2_Supporting+ PP2+ PP3+ PP4). Conclusion:The heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c. 728C>T variant of the TUBB8 gene, oocyte donation may be considered.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective:To investigate the correlation between statins and contrast-induced acute kidney injury (CI-AKI) and provide a reference basis for clinical practice.Methods:It was a retrospective cohort study. The adult patients were admitted to Peking University First Hospital from January 1, 2018, to December 31, 2020, and received at least one intravascular iodinated contrast administration during hospitalization. The clinical data of the patients were collected. The enrolled patients were divided into statin group and non-statin group according to statin exposure. The exposure of statins was defined as use of any type of statins within 48 hours before iodinated contrast administration. The primary outcome was in-hospital AKI defined as AKI developed after contrast administration and before discharge, with 30 days as the endpoint observation time, and the secondary outcome was post-contrast AKI (PC-AKI) defined as AKI onset within 72 hours after contrast administration. Cox regression model was applied to investigate the correlation between statin prescription prior to contrast administration and clinical outcomes. Pre-specified interaction analysis was conducted to examine modification effect of age, gender, baseline estimated glomerular filtration rate (eGFR), diabetes and the injection method of contrast.Results:Among 10 321 enrolled patients, the age was 63 (54, 71) years old, and 6 274 (60.8%) patients were males. There were 2 372 (23.0%) patients taking statins before the use of iodinated contrast agents, and the person-time incidence rate of in-hospital AKI was 2.5 per 1 000 person-days. The person-time incidence rate of statin users and statin non-users was 3.2 and 2.4 per 1 000 person-days, respectively. Compared with the non-statin group, age, serum creatinine and the proportions of males, admitted to the intensive care unit, lipid metabolism disorder, hypertension, diabetes, cerebrovascular diseases, cardiovascular diseases, using renin-angiotensin- aldosterone inhibitors, using diuretics, using non-steroidal anti-inflammatory drugs, using proton pump inhibitors, iodinated contrast administration via artery, eGFR<60 ml·min -1·(1.73 m 2) -1 were higher, while the proportions of general anesthesia surgery, severe liver diseases and tumors, and eGFR were lower in the statin group (all P<0.05). Among 10 321 patients, 5 867 patients had serum creatinine measurement within 72 hours after iodinated contrast administration, among which 70 patients (4.0 per 1 000 person-days) developed PC-AKI. Multivariate Cox regression analysis showed that statin use was an independent protective factor for in-hospital AKI ( HR=0.65, 95% CI 0.45?0.93, P=0.017) and PC-AKI ( HR=0.44, 95% CI 0.22?0.88, P=0.020). Subgroup analysis showed the significant interaction between diabetes and statin use ( P for interaction=0.039), and the protective effect of statins against in-hospital AKI was only observed in non-diabetic group ( HR=0.45, 95% CI 0.26?0.77). There were no significant differences in subgroups stratified by age, sex, baseline eGFR and the injection method of contrast (all P for interaction>0.05). Conclusions:Statin use prior to iodinated contrast administration is correlated with reduced risks of in-hospital AKI and PC-AKI in hospitalized patients, and the correlation between statin use and in-hospital AKI is more significant in non-diabetic patients. It is suggested that statin use before the application of iodinated contrast agents in hospitalized patients may prevent the occurrence of AKI.

OBJECTIVE: To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification. METHODS: A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
Humans ; Female ; Adult ; Mutation, Missense ; Oocytes/metabolism* ; Heterozygote ; Tubulin/genetics* ; Infertility, Female/genetics* ; High-Throughput Nucleotide Sequencing ; Pedigree