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.

ObjectiveTo explore the typical syndromes and their characteristic of symptoms and signs with high diagnostic value in patients with metabolic syndrome （MS）. MethodsTraditional Chinese medicine （TCM） diagnostic information was collected from 135 MS patients. Syndrome element differentiation and latent class analysis （LCA） were applied to identify the major TCM syndromes in MS patients. Symptoms were analyzed based on the differentiated syndromes， and a binary logistic regression model was constructed to determine symptoms and signs with high diagnostic value. ResultsA total of 135 MS patients were included， involving 163 symptoms and signs with a total frequency of 1749； twenty-three syndrome elements were extracted， 367 times frequency in total， among which 8 syndrome elements occurred ≥10 times with 323 frequencies （88.01% of the total）. These included location-related elements such as kidney （48 times）， spleen （14 times）， and stomach （14 times）， and nature-related elements such as phlegm （71 times）， yin deficiency （64 times）， dampness （57 times）， heat （42 times）， and qi deficiency （13 times）. Based on LCA， the 135 patients were categorized into two groups distinguished by the syndrome elements of dampness and phlegm， forming the "phlegm-dampness syndrome" as the major syndrome type. Nine high-frequency symptoms and signs associated with the phlegm-dampness syndrome were identified，i.e. obesity （39 times）， greasy coating （38 times）， slippery pulse （33 times）， white coating （31 times）， preference for fatty and heavy foods （30 times）， excessive urination （30 times）， fatigue and lack of strength （29 times）， wiry pulse （25 times）， and dark red tongue （25 times）. A binary logistic regression model was constructed combining these nine symptoms and signs with the LCA classification results， ultimately identifying obesity， greasy coating， fatigue and lack of strength， and white coating as independent factors associated with the phlegm-dampness syndrome in MS patients （P＜0.05）. ConclusionThe major TCM syndrome in MS patients is phlegm-dampness syndrome， and obesity， greasy coating， fatigue and lack of strength， and white coating are the typical symptoms and signs for diagnosing phlegm-dampness syndrome in MS patients.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10％YSJTD drug-containing serum(30 mmol/L high glucose+10％drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P＜0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P＜0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P＜0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P＜0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P＜0.05).Compared to the model group,the 10％YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P＜0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.

Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10％YSJTD drug-containing serum(30 mmol/L high glucose+10％drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P＜0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P＜0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P＜0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P＜0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P＜0.05).Compared to the model group,the 10％YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P＜0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.

This article reviews the overview of dyadic coping, assessment tools, and the current application status of dyadic coping interventions in patients with gestational diabetes mellitus (GDM) and their spouses, aiming to provide a reference for related research.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.