Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Extracellular vesicles(EVs)are small vesicles secreted by cells,widely present in various body fluids,and they play important biological roles.In recent years,EVs have garnered significant attention as novel diagnostic and thera-peutic tools in multiple ocular diseases.Glaucoma,as a common cause of irreversible blindness,is primarily caused by optic nerve damage associated with pathologically elevated intraocular pressure.Emerging evidence indicates that EVs hold considerable therapeutic potential in glaucoma management,particularly in modulating aqueous humor circulation and pro-viding retinal neuroprotection.This review summarizes the latest research progress on EVs in the treatment of glaucoma.

Objective:This study evaluated the accuracy of internal mammary sentinel lymph node biopsy(IM-SLNB)in patients with early-st-age breast cancer after receiving neoadjuvant therapy(NAT).It explored the benefits of IM-SLNB in guiding cancer staging,evaluating progn-osis,and optimizing adjuvant treatment strategies.Methods:A retrospective study was conducted to collect clinical data of patients who re-ceived IM-SLNB following NAT in Shandong Cancer Hospital and Institute from October 2013 to November 2023.We analyzed the influence of clinicopathological characteristics on internal mammary lymph node(IMLN)metastasis and assessed the prognostic significance of IMLN me-tastasis following NAT.Results:The study included 132 breast cancer patients who underwent IM-SLNB following NAT.The metastasis rates of axillary lymph nodes(ALN)and internal mammary lymph nodes(IMLN)were 90.9%(120/132)and 9.1%(12/132),respectively.The perce-ntages of patients in the following groups were as follows:ALN-positive/IMLN-positive(8.3%,11/132),ALN-positive/IMLN-negative(43.1%,57/132),ALN-negative/IMLN-positive(0.7%,1/132),and ALN-negative/IMLN-negative(47.7%,63/132).The detection rate of internal mam-mary sentinel lymph nodes(IM-SLN)after NAT was 98.5%(132/134);two patients could not undergo IM-SLNB owing to surgical difficulties.Among the 12 cases of IMLN metastasis,6 patients experienced a change in postoperative pathological staging:2 shifted from stage ⅢA toⅢC,2 from stage ⅡB to ⅢC,1 from stage ⅡA to ⅢA,and 1 from stage ⅡA to ⅢC.IMLN metastasis was determined to be an independ-ent risk factor for disease-free survival(DFS)and overall survival(OS)(P<0.05).Patients with IMLN metastasis demonstrated significantly lower DFS and OS than those without IMLN metastasis(P<0.05).Conclusions:The pathological status of both ALN and IMLN should be con-sidered in the axillary pathological response after NAT.Patients with detectable IMLN during surgery after NAT should undergo IM-SLNB to ensure comprehensive lymph node staging.The status of IMLN metastasis following NAT serves as an independent prognostic factor.

Sentinel lymph node biopsy(SLNB)has become the standard technique for axillary staging in breast cancer,promoting a more in-dividualized approach to axillary surgery.This review discusses several current emerging issues in SLNB for patients with breast cancer:inpa-tients with 1-2 positive sentinel lymph nodes(SLNs),studies such as SENOMAC have reinforced the safety of omitting axillary lymph node dissection(ALND),although careful consideration remains necessary for patients with abnormal axillary imaging findings and in the context of post-operative regional nodal radiotherapy strategies.Omission of SLNB may be appropriate in early-stage patients with clinically and ra-diologically negative axilla under strictly defined conditions to further minimize surgical trauma.In parallel,techniques for SLNB after neoad-juvant therapy continue to advance,with tumor safety outcomes becoming increasingly reliable,and the dual de-escalation of both surgery and radiotherapy may be anticipated.In addition,regional lymph nodes serve not only as the initial site of tumor metastasis but also as crit-ical hubs of the adaptive immune response,positioning SLNs a potential window into tumor immune surveillance.

Objective:To evaluate the efficacy and safety of first-line immune checkpoint inhibitors (ICIs) combined with chemotherapy in the treatment of extensive-stage small cell lung cancer (ESCLC).Methods:Clinical data of 109 ESCLC patients admitted to the First People′s Hospital of Lianyungang from January 2019 to December 2023 were retrospectively collected. According to different treatment methods, patients were divided into the immunochemotherapy group (first-line treatment with ICIs combined with chemotherapy) and the chemotherapy group (chemotherapy alone). Kaplan-Meier method was used for survival analysis of patients with different treatment methods, and a Cox regression model was established to analyze the factors affecting the prognosis of ESCLC patients.Results:A total of 109 patients were included, with 43 cases (39.4%) in the immunochemotherapy group and 66 cases (60.6%) in the chemotherapy group. At the first efficacy evaluation, there were no significant differences in objective response rate (ORR) and disease control rate (DCR) between the two groups (all P>0.05). There were no significant differences in the proportions of grade 3-4 myelosuppression and radiation pneumonia between the two groups (all P> 0.05), and only 2 cases (4.7%) in the immunochemotherapy group had severe immune-related adverse events (irAE). The overall survival (OS) of the immunochemotherapy group was longer than that of the chemotherapy group (13.6 months vs 11.5 months, P=0.024), but the median progression-free survival (PFS) showed no significant difference compared to the chemotherapy group (8.4 months vs 6.0 months, P=0.068). Among patients without liver or brain metastasis, the OS of the immunochemotherapy group was longer than that of the chemotherapy group (19.3 months vs 12.1 months, P=0.017), while among patients with liver or brain metastasis, there was no significant difference in OS between the two groups ( P>0.05). Multivariate Cox regression analysis showed that male gender ( HR=0.284, 95% CI: 0.133-0.605, P=0.001), first-line ICIs treatment ( HR=0.607, 95% CI: 0.372-0.988, P=0.045), and chest radiotherapy ( HR=0.538, 95% CI: 0.307-0.942, P=0.030) were independent protective factors for the prognosis of ESCLC patients, and liver metastasis ( HR=1.907, 95% CI: 1.191-3.053, P=0.007) was an independent risk factor. Conclusions:First-line ICIs combined with chemotherapy can significantly prolong the OS of ESCLC patients with good safety. Patients without liver or brain metastasis benefit more significantly from immunotherapy.

Objective:To evaluate the relationship between transverse sinus stenosis (TSS) and cerebral blood flow in normal adults based on four-dimensional flow (4D Flow) MRI.Methods:The study was a cross-sectional study. Totally 81 normal volunteers who underwent magnetic resonance venography (MRV) and 4D Flow MRI were prospectively enrolled at Beijing Friendship Hospital, Capital Medical University from January 2020 to December 2022. Based on MRV evaluation of transverse sinus dysplasia, the volunteers were divided into a dysplasia group (26 cases) and a non-dysplasia group (55 cases); The area of the stenosis and the normal transverse sinus at the distal end were measured. The degree of TSS and the bilateral average transverse sinus stenosis (BA-TSS) were calculated. TSS was determined using TSS levels of 1/3, 1/2, and 2/3 as thresholds, and was divided into three groups: no TSS group, unilateral TSS group, and bilateral TSS group, with 28, 39, and 14 cases, 37, 37, and 7 cases, and 43, 36, and 2 cases, respectively. Based on 4D Flow MRI, the blood flow of the internal carotid artery, vertebral artery, superior sagittal sinus, straight sinus, and transverse sinus distal and proximal ends were measured. The cerebral blood flow (bilateral internal carotid artery blood flow+bilateral vertebral artery blood flow), venous sinus return blood flow 1 (superior sagittal sinus blood flow+straight sinus blood flow), return blood flow 2 (sum of bilateral transverse sinus distal end blood flow), return blood flow 3 (sum of bilateral transverse sinus proximal end blood flow), and the ratio of return blood flow to cerebral blood flow were calculated. Independent sample t-test was used to compare the differences between the group with and without transverse sinus dysplasia; Single factor analysis of variance was used to compare the differences between the TSS free group, unilateral TSS group, and bilateral TSS group. Based on single factor linear regression, the relationships between BA-TSS and blood flow parameters were analyzed.Results:There was no statistically significant difference in various blood flow parameters between the group with and without transverse sinus dysplasia (all P>0.05). When using 1/3, 1/2, and 2/3 as thresholds, there was no statistically significant difference in various blood flow parameters between the non TSS group, unilateral TSS group, and bilateral TSS group (all P>0.05). BA-TSS was linearly positively correlated with cerebral blood flow (β=0.986, 95% CI 0.108-1.865, P=0.028), but not linearly correlated with return blood flow 1, 2, and 3 (all P>0.05). The degree of BA-TSS was linearly negatively correlated with return blood flow 1/cerebral blood flow (β=-0.001, 95% CI -0.002-0, P=0.009) and return blood flow 2/cerebral blood flow (β=-0.001, 95% CI -0.002-0, P=0.018), but not with return blood flow 3/cerebral blood flow ( P=0.076). Conclusion:The BA-TSS degree in normal adults is positively correlated with cerebral blood inflow and negatively correlated with the proportion of venous sinus outflow.

The glymphatic system is an important pathway for fluid drainage and metabolic waste clearance in the central nervous system. Its core mechanism involves the active cerebrospinal fluid-interstitial fluid circulation process mediated by perivascular spaces and aquaporin-4 channels located on astrocytic endfeet. This process is crucial for eliminating neurotoxic substances such as β-amyloid and tau proteins, as well as maintaining homeostasis in the central nervous system. Recent studies have shown that dynamic changes in the glymphatic system are associated with recovery after ischemic stroke. This article elaborates on the role of the glymphatic system in ischemic stroke and evaluates its potential value as a novel therapeutic target, providing new insights for post-stroke treatment strategies.

Objective To identify the pathogenic gene and variant for a family with branchio-otic syndrome.Methods The clinical data of this family were collected,and the peripheral blood was extracted for deafness gene NGS panel analysis.Pathogenic variation detected was verified by Sanger sequencing.Results The family contained 17 members in three-generations,3 of whom exhibited autosomal dominant,hearing loss,preauricular fistula and branchial cleft fistula,which were in accordance with the clinical diagnosis criteria of branchio-otic syndrome.A no-vel heterozygous variant c.963dupT(p.E322X)in EYA1 gene was identified,which co-segregated with the branchi-o-otic syndrome phenotype in the family.The variant was a nonsense variant resulting in the premature appearance of the stop codon.According to the American College of Medical Genetics and Genomics(ACMG)guidelines and the criteria,the variant was classified as pathogenic.Conclusion We identified a novel pathogenic variant EYA1:c.963dupT(p.E322X)in a family with branchio-otic syndrome.

Glaucoma,characterized by optic nerve damage and progressive damage to retinal ganglion cells(RGCs),is the leading cause of irreversible blindness.However,the specific mechanism of RGC damage has not been fully elucida-ted.In recent years,there is increasing evidence that microglia,especially disease-associated microglia(DAM),may play an important role in glaucomatous ganglion cell injury.In this paper,we reviewed the role and mechanism of DAM in RGC damage in glaucoma,aiming to provide new insights for further research on the mechanism of RGC damage and subsequent protection of RGCs.

Background and purpose:With the progressive development of breast cancer surgery toward more individualized and minimally invasive approaches,sentinel lymph node biopsy(SLNB)has replaced axillary lymph node dissection(ALND)as the standard method for axillary management in certain early-stage breast cancer patients.However,there is ongoing debate in clinical practice regarding whether regional lymph node irradiation(RNI)is necessary for patients with sentinel lymph node(SLN)positive status who have not undergone ALND.This study aimed to analyze the clinicopathological features and survival prognosis of patients with SLN-positive status who did not undergo ALND,evaluate the clinical application value of RNI,and provide evidence to support clinical treatment decisions for this group of patients.Methods:This single-center retrospective study screened breast cancer patients who underwent SLNB at Shandong Cancer Hospital from September 1,2014,to August 31,2023.All patients signed informed consent for treatment.Based on whether postoperative radiotherapy included regional lymph node irradiation(internal mammary and/or axillary and/or supra-/infra-clavicular fields),patients were divided into the RNI group and the no-RNI group for follow-up.Additionally,patients were further divided into multiple subgroups based on factors such as the type of breast surgery,tumor molecular subtype,and histological grade,to compare the clinical value of RNI among subgroups.The primary endpoint was locoregional recurrence-free survival(LRRFS),and the secondary endpoints included invasive disease-free survival(iDFS)and overall survival(OS).The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:Clinical data of 8 328 breast cancer patients'were screened for this study,and after applying inclusion and exclusion criteria,356 patients were included in the analysis,with 186 in the RNI group and 170 in the no-RNI group.There were no significant differences between the two groups in terms of age,body mass index(BMI),menopausal status,tumor location,pathological type,histological grade,vascular invasion,estrogen receptor(ER)and progesterone receptor(PR)status,and human epidermal growth factor receptor 2(HER-2)expression(P＞0.05).However,the number of positive SLNs,T stage,and the proportion of patients undergoing total mastectomy(TM)were significantly higher in the RNI group than in the no-RNI group(P=0.006,P=0.043,P＜0.001).After a median follow-up of 38 months,no recurrence or metastasis was observed in the RNI group,while the recurrence and metastasis rate in the no-RNI group was 3.5%(6/170).Of these,4 cases had local regional recurrence,and 2 had distant metastasis.The RNI group showed superior iDFS compared to the no-RNI group(P=0.017),however there was no statistically significant difference in LRRFS and OS(P=0.051 and P=0.356).Exploratory subgroup analysis indicated that patients with tumor diameter＞2 cm(P=0.033)and triple-negative molecular(TNBC)(P=0.020)might benefit from RNI treatment in terms of LRRFS.Conclusion:For certain high-risk patients,such as those with larger tumor diameter,TNBC,or high non-SLN metastatic risk,RNI still plays an important role in reducing the risk of recurrence and metastasis in breast cancer.In clinical practice,an individualized RNI strategy should be developed based on the patient's residual lymph node tumor load,biological behavior of the tumor,and surgical method.