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.

Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

Objective To investigate the neuroprotective effects and mechanisms of abscisic acid(ABA)in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mouse models.Methods Eight-week-old C57BL/6J mice were randomly divided into three groups,control group(Ctrl),MPTP group,and MPTP+ABA group,12 mice in each group.Except for the control group,mice in the other groups were intraperitoneally injected with MPTP 25 mg/kg daily for 8 consecutive days to establish a subacute PD model.The MPTP+ABA group received intraperitoneal injections of ABA 25 mg/kg daily for 11 consecutive days,starting 3 days prior to MPTP administration.Behavioral tests were performed 24 hours after the last administration.On day 3,the expression of tyrosine hydroxylase(TH)and glial fibrillary acidic protein(GFAP)in the substantia nigra pars compacta(SNc)and striatum(STR)was analyzed by Western blotting,and mRNA levels of inflammatory factors were measured by Real-time PCR.Immunofluorescent staining was used to detect the expression of TH,GFAP,and ionized calcium-binding adapter molecule 1(Iba1).Results Compared with the control group,MPTP-treated mice exhibited impaired motor function,a reduced number of TH-positive dopaminergic neurons in the SNc,down-regulated TH protein expression in both the SNc and striatum,up-regulated GFAP protein expression,increased numbers of GFAP-and Iba1-positive cells,and elevated levels of pro-inflammatory factors.In contrast,the MPTP+ABA group showed improved motor function,increased TH-positive neurons in the SNc,up-regulated TH protein expression,down-regulated GFAP protein expression,reduced numbers of GFAP-and Iba1-positive cells,and decreased pro-inflammatory factor levels compared to the MPTP group.Conclusion ABA ameliorates motor dysfunction in MPTP-induced PD model mice,reduces degeneration and death of dopaminergic neurons in the SNc,suppresses the proliferation and activation of astrocytes and microglia in the SNc and striatum,and alleviates neuroinflammation.These results suggest that ABA exerts neuroprotective effects in MPTP-induced PD model mice.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Immunotherapy has become a pivotal treatment regimen for hepatocellular carcinoma (HCC); however, its efficacy is influenced by various factors. Hepatitis B virus (HBV) infection is one of the primary etiological factors leading to HCC. HBV DNA replication can alter the immune microenvironment through multiple mechanisms, notably by upregulating the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), thereby facilitating tumor immune escape. Paradoxically, this upregulation of PD-1/PD-L1 may enhance the response rate to PD-1/PD-L1 inhibitors and potentiate the antitumor effect. This review aims to summarize current research progress on the relationship between HBV DNA load and the efficacy of PD-1/PD-L1 inhibitors, explore the underlying mechanisms, and provide a scientific basis for promoting personalized treatment strategies for patients with HBV-related HCC.

Objective To explore the effect of a shared care applied to pregnancy care among pregnant women with hypertensive disorder of pregnancy(HDP).Methods A total of 88 pregnant women with HDP who received ob-stetric check-ups in a tertiary A-level matemity hospital in Nanjing City from January to October 2023 were conve-niently selected as the research subjects.According to the order of obstetric examinations,44 pregnant women with HDP from June to October 2023 were selected as an experimental group,and 44 pregnant women with HDP from January to May 2023 were selected as a control group.The experimental group received the shared care clinic management model,and the control group received the routine management.The scores of the rate of blood pres-sure attainment,the incidence of disease progression,the questionnaire on knowledge of HDP,the Hypertension Self-Management Scale,the Pregnancy-Related Anxiety Scale,and the Patient Satisfaction Questionnaire were compared between the 2 groups.Results 41 patients in the experimental group and 39 patients in the control group com-pleted the study.After the intervention,the blood pressure compliance rate of pregnant women with HDP in the experimental group was 95.12％,higher than 79.49％in the control group.The incidence of disease progression was 7.32％,lower than 25.64％in the control group.HDP Knowledge Questionnaire score(25.24±4.07),Hypertension Self-Management Scale score(114.39±14.89),and Patient Satisfaction Questionnaire score(19.56±1.14)were higher than that of the control group.The score of Pregnancy-Related Anxiety Scale was(18.02±2.15),lower than(23.18±9.58)in the control group.The score of Patient Satisfaction Questionnaire was(19.56±1.14),higher than that(17.26±2.25)in the control group.The differences were statistically significant(P＜0.001).Conclusion The shared care clinic model can improve HDP pregnant women's blood pressure control compliance,HDP knowledge,and self-management,reduce the incidence of disease progression,pregnancy-related anxiety,and improve satisfaction,which provides a reference for optimising the HDP management model.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Organophosphorus nerve agents are the most threatening chemical warfare agents and terrorist agents.The number of nerve agents and their related chemicals involved in the verification of Chemical Weapon Convention(CWC)exceeds ten million,with the majority being isomers.Accurate structural identification of these chemicals has always been one of the challenges in CWC related verification analysis.In this work,a total of 17 kinds of alkyl phosphonate isomers and structural analogs from 5 groups were designed and synthesized,and then analyzed by gas chromatography-mass spectrometry(GC-MS)and gas chromatography-infrared spectroscopy(GC-FTIR).The spectra of isomers or structural analogs obtained from two techniques as well as the structural information provided therein were compared and analyzed.The results showed that for isomers or structural analogs with similar MS spectra,FTIR spectra could provided more structural fingerprint information of compounds and had advantages in confirming structures.Combined with the excellent separation ability of GC,GC-FTIR can be used to assist GC-MS in the structural confirmation of alkyl phosphates,achieving rapid and accurate identification of isomers or structural analogues.