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 explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

OBJECTIVE To investigate the in vitro inhibitory mechanism of allicin against carbapenem-resistant Klebsiella pneumoniae(CRKP).METHODS The standard microbroth dilution method was employed to determine the minimum inhibitory concentration(MIC)of allicin against the experimental CRKP.Growth curve experiments were conducted to verify the relationship between allicin concentration and antibacterial action.RNA sequencing(RNA-seq)was performed on allicin-treated CRKP and a normal control group to explore the molecular mecha-nism of allicin inhibiting CRKP growth.RESULTS The MIC of allicin against CRKP was 140 mg/ml.A total of 1 775 differentially expressed genes were screened from the normal control group and the allicin-treated group,with 845 genes upregulated and 930 genes downregulated.The expression of bacterial phosphotransferase system(PTS)genes showed significant differences between the control group and the treated group(P＜0.05),and the expression levels of EIIA-EIID genes decreased(P＜0.05).CONCLUSION Based on the analysis of RNA-seq re-sults,it is found that allicin may inhibits the growth of CRKP by disrupting its sugar transport system,thereby affecting its biofilm formation.

BACKGROUND:Formononetin demonstrates potent anti-inflammatory and antioxidant abilities.However,its protective effect on nucleus pulposus mesenchymal stem cells is not yet clear.OBJECTIVE:To investigate the effect and mechanism of formononetin on nucleus pulposus mesenchymal stem cells under an inflammatory microenvironment.METHODS:(1)Primary nucleus pulposus mesenchymal stem cells were isolated from the intervertebral discs of SD rats,and flow cytometry was performed to identify the surface markers of mesenchymal stem cells.(2)The CCK-8 assay was employed to evaluate the impact of lipopolysaccharide and formononetin on the proliferation viability of nucleus pulposus mesenchymal stem cells,aiming to determine the appropriate concentration of formononetin for subsequent cell treatments.(3)An inflammatory microenvironment was simulated by adding 5 μg/mL lipopolysaccharide to the DMEM/F-12 culture medium,and nucleus pulposus mesenchymal stem cells were treated with different concentrations of formononetin for 24 hours.Levels of inflammation markers were detected using western blot assay,real-time quantitative PCR,and immunofluorescence.Western blot assay was conducted to measure the protein levels of the nuclear factor kappa B signaling pathway.RESULTS AND CONCLUSION:(1)The nucleus pulposus mesenchymal stem cells cultured in adherent wall were shuttle-shaped with good growth status.The results of flow cytometry showed that the surface markers of mesenchymal stem cells were positive for CD29,CD44,and CD90,and the surface markers of hematopoietic stem cells were negative for CD34 and CD45.(2)The treatment with formononetin at 12.5,25,50,100,and 200 μmol/L concentrations for 24 hours had no significant proliferation inhibitory effect on nucleus pulposus mesenchymal stem cells.Compared with the lipopolysaccharide group,the cell viability of nucleus pulposus mesenchymal stem cells treated with 12.5,25,and 50 μmol/L formononetin for 24 hours was significantly increased,so formononetin at 12.5,25,and 50 μmol/L concentrations was subsequently selected as the low,medium,and high concentrations for treating nucleus pulposus mesenchymal stem cells.(3)Compared with the lipopolysaccharide group,the protein and mRNA expressions of matrix metalloproteinase-3,matrix metalloproteinase-13,and tumor necrosis factor-α in nucleus pulposus mesenchymal stem cells in the low,medium,and high concentrations of formononetin groups were significantly decreased(P＜0.05)in a dose-dependent manner.(4)Compared with the lipopolysaccharide group,the expressions of phosphorylated nuclear factor kappa B and phosphorylated nuclear factor kappa B inhibitor protein in nucleus pulposus mesenchymal stem cells in the low,medium,and high concentrations of formononetin groups were significantly decreased(P＜0.05)in a dose-dependent manner.The above results suggest that formononetin may attenuate lipopolysaccharide-induced inflammation in rat nucleus pulposus mesenchymal stem cells by inhibiting the activation of the nuclear factor kappa B signaling pathway.

BACKGROUND:As an emerging treatment method,stem cell therapy is expected to improve the ovarian environment,delays the aging of ovarian granulosa cells,and brings new hope to older pregnant women.OBJECTIVE:To review the mechanism and research progress of stem cells against ovarian granulosa cell senescence.METHODS:CNKI and PubMed databases were retrieved for articles on stem cell therapy for ovarian granulosa cell senescence.Chinese and English search terms were"stem cells,ovary granulosa cells,aging."Finally,67 articles were included for analysis.RESULTS AND CONCLUSION:(1)This review summarizes five mechanisms of ovarian granulosa cell senescence:DNA damage and decreased repair capacity,oxidative stress,impaired mitochondrial function,inflammatory response,and changes in hormone levels.(2)This article summarizes five main mechanisms of stem cells in the treatment of ovarian granulosa cell senescence:promoting proliferation and inhibiting apoptosis,differentiation potential and regeneration ability,secreting factors,anti-oxidation,anti-inflammatory response,and immune regulation.(3)At present,there are various types of stem cells that can cooperate to treat ovarian granulosa cell senescence through a variety of ways,and stem cell therapy has broad prospects in restoring female fertility.

BACKGROUND:With the increase of age,the function of bone marrow-derived mesenchymal stem cells is gradually reduced,and delaying the aging of bone marrow-derived mesenchymal stem cells itself has become an important topic.OBJECTIVE:To explore ways to delay the aging of bone marrow-derived mesenchymal stem cells by changing the expression of telomerase Cajal body protein 1(TCAB1)gene.METHODS:Mouse bone marrow-derived mesenchymal stem cells were cultured by cell adhesion method.TCAB1 gene in bone marrow-derived mesenchymal stem cells was overexpressed and interfered by recombinant lentivirus technique.The expression of aging related genes P16,P21,P53,and P27 was detected by qPCR.The relative length of telomeres was detected by qPCR.The expression of aging proteins P16,P21,P53,and P27 was detected by western blot assay.Cell proliferation was detected by CCK-8 assay.Annexin V-PE/7-AAD apoptosis kit was used to detect the degree of cell apoptosis.RESULTS AND CONCLUSION:Bone marrow-derived mesenchymal stem cell lines overexpressing TCAB1 gene had decreased expression of senescence related genes and proteins,increased Telomere relative length,stronger cell proliferation,less apoptosis,and a youthful state.The expression of age-related genes and proteins in bone marrow mesenchymal stem cells interfering with TCAB1 gene increased,and the relative telomere length decreased;cell proliferation ability was weak;cell apoptosis was more,and cells showed senescence.These results indicate that increasing the expression of TCAB1 in an appropriate range can delay the rate of cell senescence.

Objective:To explore the application of dental scenario-based clinical thinking teaching and examination system in oral education.Methods:A total of 70 resident physicians from the 2022 class at the dental base of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were selected and randomly divided into a control group (30 participants) and an experimental group (40 participants). The control group was taught using traditional teaching methods, and the experimental group was taught and trained using the dental scenario-based clinical thinking teaching and examination system. After one year of teaching, both groups participated in a unified annual assessment. Finally, the teaching effectiveness was evaluated through a questionnaire survey on the experimental group. The questionnaire data were analyzed using the Chi-square test in IBM SPSS 24.0 statistical software, and the t-test was conducted using GraphPad Prism 8.0.2 software. Results:The average score before teaching was (78.83±2.61) in the control group and (78.28±3.29) in the experimental group, with no statistical significant difference between the two groups ( t=0.77, P=0.447). The average score in the annual assessment after teaching was (78.57±3.50) in the control group and (81.75±4.63) in the experimental group, with statistical significant difference between the two groups ( t=3.15, P=0.002). The questionnaire survey indicated that students highly recognized the dental scenario-based clinical thinking teaching and examination system, noting its advantages of innovative and interesting lectures, the ability to improve clinical thinking skills, and not being limited by location or time. Conclusions:The dental scenario-based clinical thinking teaching and examination system can stimulate students' interest and enthusiasm for independent learning. The system has received high levels of acceptance among students. The application and development of the dental scenario-based clinical thinking teaching and examination system hold significant value.

Purpose To investigate the diagnostic significance of modified lung ultrasound score(MPUS)for pediatric bacterial and viral pneumonia.Materials and Methods A total of 93 eligible children with suspected community-acquired pneumonia in Quanzhou Maternal and Child Care Hospital(Quanzhou Children’s Hospital)from December 2022 to June 2023 were elected as the study subjects.All these children received lung ultrasound and the MLUS was recorded according to the ultrasound manifestations of A line,B line and lung consolidation.According to the etiological results,the children were divided into a bacterial pneumonia group and a viral pneumonia group.According to disease severity,the children were divided into the mild group and the severe group.The MLUS was used to analyze the diagnostic significance of pediatric bacterial and viral pneumonia.Results The MLUS in the mild pneumonia group was 7(4,13)points and the MLUS in the severe pneumonia group was 20(14,30)points,and MLUS scores of pneumonia in the two groups were different(Z=-5.205,P<0.05).By drawing receiver operating characteristic curve,MLUS score of 14.5 was used as the cut-off point,the sensitivity for diagnosing severe pneumonia was 75.9%,the specificity was 82.8%.Area under the curve was 0.838.There was no significant differences in MLUS of 8.00(4.00,16.00)between the bacterial pneumonia group and 13.00(7.00,21.75)between the viral pneumonia group(Z=-1.981,P>0.05).The MLUS of 10.00(5.25,17.75)in the mild bacterial pneumonia group and 5.00(4.00,9.50)in the mild viral pneumonia group were significantly different(Z=-3.403,P<0.05).There was no significant differences in MLUS between the severe bacterial pneumonia group and the severe viral pneumonia group(t=0.017,P>0.05).In mild pneumonia,the cut-off value for the modified lung ultrasound score of 10.5 predicted moderate diagnostic efficacy of mild bacterial pneumonia,the area under the curve was 0.747,sensitivity was 50%and specificity was 87.5%.Large-area lung consolidation was more common in the bacterial pneumonia group than in the viral pneumonia group(χ2=8.360,P<0.05).Conclusion The modified lung ultrasound score can effectively evaluate the severity of pediatric bacterial pneumonia and viral pneumonia.For the identification of the two,MLUS may be a certain guiding significance.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

Objective To explore the clinical characteristics of the patients with follicular cysts and menstrual disorders.Methods A total of 178 women with follicular cysts complicated by menstrual disorders were recruited,who were aged 23-53(38.62±6.35)years and came to the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital between August 2022 and July 2024.The participants were divided into three groups according to the age,with 27 women in the age group of 21-30 years(Group 1),77 in the age group of 31-40 years(Group 2),and 74 in the age group of>40 years(Group 3).The age and menstruation of these patients were collected,the body height,weight,follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),progesterone(Po),total testosterone(TT),prolactin(PRL),anti-müllerian hormone(AMH)and thyroid function[blood routine and blood clotting for patients with abnormal uterine bleeding(AUB)]were measured,and the diameter of ovarian cyst and the thickness of endometrium were examined.The clinical characteristics of the patients with follicular cysts complicated by menstrual disorders were described and compared with each other among the three age groups.Results ① Among 178 patients,61(34.3%)patients presented with complaints of cessation of regular menstruation or amenorrhea and 117(65.7%)with complaints of AUB.Out of 178 patients,13(7.3%)patients developed anemia due to AUB,and all the patients were treated with medication.② Follicular cysts disappeared in 1 month for 124(69.7%)patients,disappeared in 2 months for 176(98.9%)patients,and disappeared in 3 months for 178(100%)patients.A total of 177(99.4%)patients had follicular cysts with a diameter less than 5 cm,and only 1(0.6%)patient had follicular cysts with a diameter≥5 cm.③ The overall prevalence of diminished ovarian reserve(DOR)in patients with follicular cysts complicated by menstrual disorders was 82.0%,and the prevalence of DOR was 70.2%for the patients under 40 years old.The prevalence of DOR in three age groups was 37.0%(10/27),81.8%(63/77),and 98.6%(73/74),respectively.The prevalence of DOR gradually increased with age.④ The median AMH values for Group 1,Group 2,and Group 3 were 1.55,0.51,and 0.15 ng/mL,respectively.The FSH level in Group 3 was significantly higher than that in Groups 1 and 2(adjusted P<0.05),while the AMH level was significantly lower than that in Groups 1 and 2(adjusted P<0.05).The AMH level in Group 2 was lower than that in Group 1(adjusted P<0.05).Conclusion Patients with follicular cysts complicated by menstrual disorders are recommended to receive medication treatment,rather than just expecting treatment.The prevalence of DOR in patients with follicular cysts complicated by menstrual disorders is significantly higher than that in normal women,even in women younger than 40 years old.Therefore,it is essential to evaluate the ovarian reserve of these patients while treating menstrual disorders,particularly for young women with fertility needs.