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.

Objective To evaluate the efficacy and safety of 450nm semiconductor blue laser vaporization prostatectomy in high-risk benign prostatic hyperplasia (BPH) patients without discontinuing anticoagulant drugs, so as to provide a safe and effectiveminimally invasive treatment option for such patients. Methods A total of 40 high-risk BPH patients who underwent 450nm semiconductor blue laser vaporization prostatectomy in our hospital during Sep. 2023 and Dec. 2024 were selected as the research subjects. The patients were divided into two groups: the oral medication group took oral anticoagulants during the perioperative period, while the discontinuation group discontinued anticoagulants, with 20 cases in either group. The perioperative indicators and changes including international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax) and post-void residual (PVR) were compared between the two groups.Results There were no statistically significant differences between the oral medication group and discontinuation group in operation time [(28.83±15.52)min vs. (26.43±14.02)min], postoperative catheter indwelling time [(3.04±0.89) d vs. (3.23±1.01) d], bladder irrigation time [(27.36±7.54) h vs. (25.46±7.10) h], and decrease in hemoglobin [(8.08±1.82)g/L vs. (7.56±1.68)g/L] (all P＞0.05). Three month after surgery, Qmax in both groups was higher, while IPSS, QoL and PVR were significantly lower (P＜0.05), but there were no statistically significant differences between the two groups (P＞0.05). No serious complications such as urinary incontinence or massive hemorrhage occurred.Conclusion 450nm semiconductor blue laser vaporization prostatectomy for high-risk BPH patients is characterized by high vaporization efficiency and good hemostatic effects. It can significantly improve the clinical symptoms with high safety, especially for high-risk patients who cannot discontinue anticoagulants.

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.

Background and purpose:Internal mammary sentinel lymph node biopsy(IMSLNB)is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer,which can provide accurate lymph staging and guide adjuvant treatment decision,but its clinical application has been controversial.The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer.Methods:In this study,a retrospective cohort of 7 949 patients with breast cancer from January 1,2016 to December 31,2021 was analyzed.After applying propensity score matching,the patients were divided into IMSLNB group and no-IMSLNB group,and the regional recurrence-free survival(RRFS),local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups were compared.This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University(approval number:SDTHEC20130324).Results:A total of 990 patients were included in the final analysis(330 in the IMSLNB group and 660 in the no-IMSLNB group).IMSLN metastasis was found in 54 patients in the IMSLNB group,including 47 patients with axillary lymph node(ALN)metastasis and 7 patients with IMSLN metastasis only.The IMSLN transfer rate was 16.4%.The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS[98.4%vs 94.2%,hazard ratio(HR)=0.509;95%CI:0.312-0.828,P=0.007]and 5-year DFS(92.5%vs 87.3%,HR=0.214,95%CI:0.206-0.222,P=0.011)compared with no-IMSLNB group.However,no significant differences were observed in 3-year OS(99.1%vs 99.4%,HR=0.618,95%CI:0.231-1.655,P=0.338)or 5-year OS(98.5%vs 99.1%,HR=0.52,95%CI:0.51-0.53,P=0.392)between the two groups.The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group(99.09%vs 97.73%,HR=0.066;95%CI:0.061-0.071,P=0.048),while no significant differences were observed in 3-year LRFS(99.70%vs 98.19%,HR=0.209;95%CI:0.201-0.217,P=0.130)or DMFS(95.76%vs 96.06%,HR=0.865,95%CI:0.858-0.872,P=0.820)between the two groups.The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB(P＜0.05):diagnosis age(≤50 years),premenopausal status,BMI(≤24),lymphovascular invasion(LVI,present),tumor location(lateral),molecular subtype[hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-)],histological type(invasive ductal carcinoma),and axillary lymph node status(positive).Conclusion:IMSLNB can provide more accurate regional lymph node staging for early breast cancer,help optimize adjuvant radiotherapy strategies,and improve patients'DFS and RRFS.It can be promoted as a minimally invasive staging technique for regional lymph nodes.

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.

Background and purpose:Internal mammary sentinel lymph node biopsy(IMSLNB)is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer,which can provide accurate lymph staging and guide adjuvant treatment decision,but its clinical application has been controversial.The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer.Methods:In this study,a retrospective cohort of 7 949 patients with breast cancer from January 1,2016 to December 31,2021 was analyzed.After applying propensity score matching,the patients were divided into IMSLNB group and no-IMSLNB group,and the regional recurrence-free survival(RRFS),local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups were compared.This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University(approval number:SDTHEC20130324).Results:A total of 990 patients were included in the final analysis(330 in the IMSLNB group and 660 in the no-IMSLNB group).IMSLN metastasis was found in 54 patients in the IMSLNB group,including 47 patients with axillary lymph node(ALN)metastasis and 7 patients with IMSLN metastasis only.The IMSLN transfer rate was 16.4%.The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS[98.4%vs 94.2%,hazard ratio(HR)=0.509;95%CI:0.312-0.828,P=0.007]and 5-year DFS(92.5%vs 87.3%,HR=0.214,95%CI:0.206-0.222,P=0.011)compared with no-IMSLNB group.However,no significant differences were observed in 3-year OS(99.1%vs 99.4%,HR=0.618,95%CI:0.231-1.655,P=0.338)or 5-year OS(98.5%vs 99.1%,HR=0.52,95%CI:0.51-0.53,P=0.392)between the two groups.The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group(99.09%vs 97.73%,HR=0.066;95%CI:0.061-0.071,P=0.048),while no significant differences were observed in 3-year LRFS(99.70%vs 98.19%,HR=0.209;95%CI:0.201-0.217,P=0.130)or DMFS(95.76%vs 96.06%,HR=0.865,95%CI:0.858-0.872,P=0.820)between the two groups.The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB(P＜0.05):diagnosis age(≤50 years),premenopausal status,BMI(≤24),lymphovascular invasion(LVI,present),tumor location(lateral),molecular subtype[hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-)],histological type(invasive ductal carcinoma),and axillary lymph node status(positive).Conclusion:IMSLNB can provide more accurate regional lymph node staging for early breast cancer,help optimize adjuvant radiotherapy strategies,and improve patients'DFS and RRFS.It can be promoted as a minimally invasive staging technique for regional lymph nodes.

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.

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.

Type Ⅳ cardiorenal syndrome(CRS)is a subtype of CRS characterized by cardiac structural damage and/or functional decline secondary to chronic kidney disease.Clinically,it often manifests as fatigue,shortness of breath,edema,oliguria,and difficulty lying flat at night,which align with the TCM pattern of"deficiency of primordial qi and excess of yin-pathogenic fire".Li Dongyuan proposed the theory that"yin-pathogenic fire and primordial qi are opposites",emphasizing the dynamic relationship of"mutual growth and decline"between primordial qi and yin fire.From this perspective,the development and progression of Type Ⅳ CRS are believed to correspond to the fluctuations in the balance of primordial qi and yin-pathogenic fire.Based on this theory,the core pathogenesis of Type Ⅳ CRS is summarized as"imbalance between qi and fire",where"deficiency of primordial qi"is the root cause,often attributed to damage to the heart,spleen,and kidney,while"exuberance of yin-pathogenic fire"represents the pathological manifestation.In clinical practice,the treatment should focus on reinforcing primordial qi and subduing yin-pathogenic fire,with tailored approaches according to the stages of disease progression.In the early stage,when primordial qi lacks a foundation for generation and yin-pathogenic fire begins to emerge,the treatment should aim to consolidate the root of primordial qi and suppress the budding of yin-pathogenic fire.In the middle stage,when primordial qi is insufficiently produced and yin-pathogenic fire becomes predominant,the treatment should focus on nourishing the source of primordial qi and curbing the exuberance of yin-pathogenic fire.In the late stage,when primordial qi becomes dispersed and yin-pathogenic fire is unconstrained,the treatment should prioritize consolidating the foundation of primordial qi and restraining the chaotic movement of yin-pathogenic fire.