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 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 differences in reproductive tract microbiota between patients with moder-ate and severe intrauterine adhesions(IUA)and infertile patients with normal uterine cavities and the clinical sig-nificance.Methods:Thirty patients were enrolled in the study from June 1,2022 to September 12,2022.Among them,15 cases were confirmed as moderate to severe IUA by hysteroscopy(group A),and 15 cases of primary infertility were excluded from intrauterine diseases through outpatient hysteroscopy(group B).Perform high-throughput sequencing of secretions from the vagina,cervix,and uterine cavity separately.Results:There is no difference in the α diversity of intrauterine microbiota between the two groups,but the α diversity of intrauterine mi-crobiota in group A is significantly higher than that of cervical microbiota(P=0.036).At the genus level,the top 10 relative abundances are the same for both groups.At the species level,the abundance of lactobacillus iners in group A is significantly lower than that in group B(P=0.001).There is no statistically significant difference in the abundance of microorganisms in the vagina,cervix and uterine cavity of group A.Conclusions:The types of en-dometrial microbiota in IUA patients and infertile women are roughly the same,but the composition is different.There are differences in the diversity of reproductive tract microbiota in patients with IUA,with a higher diversity of microbiota in the uterine cavity.Which suggests that the pathogenesis of IUA may be related to the changes of endometrial microbiota,increased microbial diversity,complex microbial species,especially the imbalance of the microecology of lactobacillus,which is not conducive to the repair of endometrial damage.

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.

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 differences in reproductive tract microbiota between patients with moder-ate and severe intrauterine adhesions(IUA)and infertile patients with normal uterine cavities and the clinical sig-nificance.Methods:Thirty patients were enrolled in the study from June 1,2022 to September 12,2022.Among them,15 cases were confirmed as moderate to severe IUA by hysteroscopy(group A),and 15 cases of primary infertility were excluded from intrauterine diseases through outpatient hysteroscopy(group B).Perform high-throughput sequencing of secretions from the vagina,cervix,and uterine cavity separately.Results:There is no difference in the α diversity of intrauterine microbiota between the two groups,but the α diversity of intrauterine mi-crobiota in group A is significantly higher than that of cervical microbiota(P=0.036).At the genus level,the top 10 relative abundances are the same for both groups.At the species level,the abundance of lactobacillus iners in group A is significantly lower than that in group B(P=0.001).There is no statistically significant difference in the abundance of microorganisms in the vagina,cervix and uterine cavity of group A.Conclusions:The types of en-dometrial microbiota in IUA patients and infertile women are roughly the same,but the composition is different.There are differences in the diversity of reproductive tract microbiota in patients with IUA,with a higher diversity of microbiota in the uterine cavity.Which suggests that the pathogenesis of IUA may be related to the changes of endometrial microbiota,increased microbial diversity,complex microbial species,especially the imbalance of the microecology of lactobacillus,which is not conducive to the repair of endometrial damage.

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.

Objective:To analyze the diagnostic value of preoperative electromyography and spasticity assessment for patients with hemifacial spasm, and to define a relationship between intraoperative electrophysiological examination and prognosis in order to provide help for clinical diagnosis and treatment.Methods:Thirty-one patients with hemifacial spasm were selected for the clinical spasticity scoring and divided into a general spasm group ( n=27) and a severe spasm group ( n=4). All received preoperative neurophysiological examination to record their twitch discharge, facial nerve conduction velocity (MCV), lateral spread (LSR) of the spasm, brainstem auditory evoked potential (BAEP), and blink reflex. Electrophysiological monitoring then recorded intraoperative LSR. According to whether the LSR disappeared or not, the patients were divided into the LSR disappearance group (of 15) and the LSR residual group (of 16), and facial muscle activity was recorded again one, three and six months after the operation. Results:Preoperative EMG examination of both groups showed positive LSR and that facial nerve MCV was within the normal range. There were, though, significant differences between the two groups in the twitching discharge by needle electromyography, blink reflex and preoperative BAEP. One week after the operation, one member of the residual group and 3 from the disappearance patients of the former and latter group had recovered in terms of LSR, with 3 and 7 cases significantly relieved, respectively. Two months later, the corresponding figures were 5 and 7, 3 and 6, respectively. Half of a year after the surgery, 5 from the residual group and 12 from the disappearance group had fully recovered in terms of LSR, while 9 and 2 cases were significantly relieved. Altogether, there were significant differences within the two groups in terms of recovery among all the time points, with significantly better recovery in the LSR disappearance group than the LSR residual group at 1 week after operation, while there were no significant differences between the two groups in recovery 3 and 6 months after their operation.Conclusions:Preoperative electromyography can provide objective assessments of the scope, severity, and facial nerve excitability of patients with hemifacial spasm. Real-time intraoperative electrophysiology monitoring can help surgeons to objectively assess the effect of decompression and to find and avoid nerve traction injury in surrounding areas quickly.

Objective:To study the effect of rapamycin on the disorder of CD4 + T cell subsets in Graves′ ophthalmopathy(GO) mice, as well as the ophthalmopathy and hyperthyroidism phenotype, providing new possibilities for the treatment of GO. Methods:6-8 weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times. Rapamycin was given by embedding in the feed(14 ppm). The animals were euthanized 4 weeks after the final injection to obtain blood, spleen cells, thyroid glands, and orbital tissue. TT 4, thyrotropin receptor antibody(TRAb), thyroid, and orbital pathologic changes were detected, and the CD4 + T cell subgroup was evaluated by flow cytometry and immunohistochemistry. Results:After final immunization, the mice showed characteristics of GO: increased retrobulbar fibrosis and retrobulbar adipogenesis that indicated ophthalmopathy, increased autoantibodies, and serum total thyroxin that indicated hyperthyroidism. After the intervention of rapamycin, retrobulbar fibrosis and retrobulbar adipogenesis were significantly improved, and the incidence of ophthalmopathy was reduced from 80%-90% to 20%. Moreover, the increase of total thyroxin was reduced from 80% to 20%, and the metabolic condition and thyroid pathology were also improved. Flow cytometry of the spleen, immunohistochemistry of the thyroid and orbital tissue revealed that GO mice exhibited Th1 dominance in Th1/Th2 balance and reduction of Treg cells. After the intervention of rapamycin, flow cytometry showed that the ratio of Th1 and Th17 cells decreased and the ratio of Th2 and Treg cells increased. Immunohistochemistry of thyroid and orbital tissues also confirmed improvement of Th1/Th2 cell imbalance and Treg cell reduction.Conclusion:GO mouse model showed a significant imbalance of CD4 + T cell subsets, and rapamycin could not only regulate the disorder of CD4 + T cell subsets in GO mice, but also effectively improve the phenotype of ophthalmopathy and hyperthyroidism. Therefore, the imbalance of CD4 + T cell subsets is one of the etiological intervention targets of GO, and rapamycin is a potential intervention mode of GO, which can be further explored by randomized clinical studies in the future.