Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

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 pathophysiological molecular mechanism of the up-regulation of CircPDS5B level involved in premature birth.Methods The placental tissues of full-term infants(Group 1,gestational age≥37 weeks),late premature infants(Group 2,34 weeks≤gestational age<37 weeks),premature infants(Group 3,32 weeks

AIM:This study aimed to identify the key active components and signaling pathways in the tradi-tional Chinese medicine Fructus Aurantii that contribute to the prevention and treatment of cardiac hypertrophy,along with experimental validation.METHODS:H9C2 cardiomyocytes were pretreated with nobiletin(NOB)for 1 h and then ex-posed to 100 nmol/L angiotensin Ⅱ(Ang Ⅱ)for 24 h.RT-qPCR was used to quantify the mRNA expression of hypertrophy-related genes,including atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and myosin heavy chain 7(MYH7).Immunofluorescence staining was employed to assess the surface area of cardiomyocytes.Additionally,a kit was utilized to measure levels of pyroptosis-related factors such as lactate dehydrogenase(LDH),interleukin-1β(IL-1β),IL-18 and caspase-1,while Western blot was performed to evaluate the expression of gasdermin D and caspase-1.RESULTS:Network pharmacology analyses indicated that NOB is the key active component in Fructus Aurantii that regu-lates cardiac hypertrophy,potentially through the pyroptosis pathway.Further molecular biology experiments confirmed that NOB inhibits Ang Ⅱ-induced cardiac hypertrophy and pyroptosis.Furthermore,the involvement of the pyroptosis pathway was highlighted in the protective effects of NOB against cardiac hypertrophy.CONCLUSION:The active compo-nent NOB in the traditional Chinese medicine Fructus Aurantii alleviates cardiac hypertrophy by inhibiting pyroptosis.

Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective:To investigate the factors influencing left atrial fibrosis in patients with atrial fibrillation(AF)and the association of Periostin protein,serum transforming growth factor-β2(TGF-β2)with left atrial fibrosis.Methods:We enrolled 100 AF patients admitted to Gansu Provincial People's Hospital between March 2021 and March 2023.They were divided into control group(＜10％,n=53)and fibrosis group(≥10％,n=47)according to their left atrial low voltage region.Univariate and multivariate Logistic regression were used to analyze the influ-encing factors of left atrial fibrosis in AF patients and construct a nomogram model.The diagnostic value of related factors and their combined detection for left atrial fibrosis in AF patients were analyzed by receiver operating char-acteristic curve(ROC).Spearman correlation analysis was used to analyze the association of Periostin protein,TGF-β2 with left atrial fibrosis in AF patients.Results:Compared to patients in the control group,those in the fibrosis group had significant higher left atrial diameter(LAD)[(37.08±3.19)mm vs.(33.45±2.45)mm],levels of ser-um uric acid(SUA)[(313.75±49.06)μmol/L vs.(279.88±38.15)μmol/L],Periostin protein[(83.27±3.98)ng/L vs.(75.21±3.04)ng/L],TGF-β2[(4346.84±321.34)ng/L vs.(4186.02±306.91)ng/L],and signifi-cant lower left atrial ejection fraction(LVEF)[(62.28±5.00)％vs.(67.24±3.07)％](P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that LAD(OR=1.663,95％CI 1.238～3.887,P=0.001),SUA(OR=1.586,95％CI 1.164～2.892,P＜0.001),Periostin protein(OR=1.997,95％CI 1.513～4.585,P=0.001),TGF-β2(OR=2.013,95％CI 1.543～5.864,P＜0.001)were independent risk factors for left atrial fi-brosis in AF patients,while LVEF was an independent protective factor(OR=0.524,95％CI 0.141～0.920,P=0.002).The nomogram model for left atrial fibrosis in AF patients:logit(P)=4.631+0.445 × LVEF+0.546 × LAD+0.575 × SUA+0.530 × Periostin protein+0.347 × TGF-β2.ROC curve showed that the area under the curve(AUC)of combined detection(0.893,95％CI 0.842～0.932)was significantly higher than SUA(AUC=0.637,95％CI 0.566～0.704),LVEF(AUC=0.701,95％CI 0.632～0.763),LAD(AUC=0.649,95％CI 0.579～0.715),Periostin protein(AUC=0.676,95％CI 0.606～0.740),TGF-β2(AUC=0.641,95％CI 0.570～0.707)alone(Z=5.265,6.399,6.379,6.040,6.483,P＜0.001 all).Spearman correlation analysis showed that Perios-tin protein and TGF-β2 were significantly positive correlated with left atrial fibrosis in AF patients(r=0.536,0.578,P＜0.001 all).Conclusion:Periostin protein and TGF-β2 were independent risk factors for left atrial fi-brosis in AF patients and were significantly positive correlated with it,a combination of above-mentioned indexes,cardiac function indexes and uric acid had good diagnostic value for left atrial fibrosis.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.