1.Construction of Organoid-on-a-chip and Its Applications in Biomedical Fields
Rui-Xia LIU ; Jing ZHANG ; Xiao LI ; Yi LIU ; Long HUANG ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2026;53(2):293-308
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.
2.Construction of Organoid-on-a-chip and Its Applications in Biomedical Fields
Rui-Xia LIU ; Jing ZHANG ; Xiao LI ; Yi LIU ; Long HUANG ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2026;53(2):293-308
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.
3.Association between circadian syndrome, metabolic syndrome and mild cognitive impairment in older adults
Jie LU ; Rui LIU ; Shi TANG ; Tingting HOU ; Lin CONG ; Yongxiang WANG ; Yifeng DU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(3):208-214
Objective:To explore the association between circadian syndrome (CircS), metabolic syndrome (MetS) and mild cognitive impairment (MCI) in elderly rural adults in China.Methods:From March to September 2018, totally 5 765 participants aged 60 years or older from 52 villages in Yanlou Town, Yanggu County, Shandong Province were selected. The data included demographic, underlying disease and neuropsychological data were collected by questionaire survey. Having ≥3 of the following components was defined as MetS: elevated waist circumference, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting glucose. Having ≥4 of the following components was defined as CircS: short sleep (<6 h/d), depression and five other components which were used to define MetS, with elevated waist circumference as a mandatory item. MCI was diagnosed according to Petersen's criteria and further classified into amnestic MCI (aMCI) and non-amnestic MCI (naMCI) based on whether the memory domains impaired.Data were analyzed using multivariable Logistic regression and general linear regression models by R statistical software.Results:In the total sample ( n=4 898), 1 280 participants were diagnosed with MCI, of which 1 075 were aMCI and 205 were naMCI.Compared to the normal group, CircS alone was significantly associated with increased risks of MCI ( B=0.695, P=0.039) and aMCI ( B=0.782, P=0.024), as well as lower verbal fluency scores ( B=-0.244, P=0.045). No significant associations were found between MetS alone or both MetS and CircS and cognitive impairment( P>0.05). At the component level, short sleep and depression were associated with increased risks of MCI ( B=0.167, P=0.025; B=0.605, P<0.001) and aMCI ( B=0.185, P=0.020; B=0.600, P<0.001). Conclusion:Individuals with CircS are at a higher risk of cognitive impairment, CircS is more strongly associated with cognitive impairment than MetS, with short sleep duration and depressive symptoms potentially playing key roles.
4.Treatment of hypertensive nephropathy based on"five viscera in one"view
Hong WANG ; Lu-fan SHEN ; Rui-ling MA ; Ming-shuang HOU ; Hong-ying LÜ ; Guan-jun JIA ; Lin YI
The Chinese Journal of Clinical Pharmacology 2025;41(1):121-126
Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.
5.Teaching evaluation of immersive stomatological humanistic courses empowered by on-site teaching mode in museums
Geng DOU ; Jiani LIU ; Jing YU ; Rui HOU ; Ning YANG ; Feng DING ; Li'an WU ; Yimin ZHAO
STOMATOLOGY 2025;45(10):765-770
This study innovatively incorporates on-site teaching with the International Museum of Stomatology into the curriculum to establish an immersive and intuitive teaching mode,promoting education from both theoretical and practical dimensions.The teaching effect is comprehensively evaluated to explore the pathway to optimization.Multi-dimensional questionnaires are designed to collect feedback data from students on teaching satisfaction,knowledge mastery,professional identity,and humanistic literacy perception,fol-lowed by in-depth quantitative and qualitative analyses.The results demonstrate that this teaching mode significantly enhances literacy,playing a critical role in helping stomatological students fully understand professional knowledge and humanistic connotations while sub-stantially improving their professional identity.This teaching mode gives a direction for innovative stomatological education,holds sig-nificant importance for cultivating stomatological professionals with both clinical skills and humanistic literacy,possessing substantial potential for promotion,application,and further refinement.
6.A randomized,double-blind,placebo-controlled,multicenter clinical study of Shengxuebao Mixture in treating cancer-related anemia
Zhu LIU ; Xiangrong LI ; Xiaojun DAI ; Yanjun WANG ; Xiao LI ; Keqiong WANG ; Tao WU ; Miaowen ZHONG ; Hongjiang YU ; Ji FENG ; Zuowei HU ; Kainan LI ; Shaowei CHEN ; Chunhua LI ; Zhengchuan FU ; Rui ZHANG ; Yongfa CHEN ; Hongyu XU ; Tao REN ; Yibo YAO ; Jianxu JIN ; Pengyin WANG ; Zhijiang HE ; Jian SHEN ; Lei WANG ; Min LI ; Wenming CHANG ; Xinyi CHEN ; Li HOU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1447-1459
Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.
7.Comparison of two methods for establishing mouse models of acute exacer-bation of chronic obstructive pulmonary disease
Hongping ZHANG ; Runhua HOU ; Yuanyuan YE ; Zeping YANG ; Guanqin ZHENG ; Mengzhu LI ; Jiarui FAN ; Chunyun ZHANG ; Rui CHEN ; Defu LI
Chinese Journal of Pathophysiology 2025;41(10):2073-2080
AIM:To compare the degree of disease simulation between the two mouse models of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD)using intranasal instillation of lipopolysaccharide(LPS)and fine particulate matter(PM2.5)for 3 d based on exposure to cigarette smoke(CS)for 90 d.METHODS:Thirty-two male C57BL/6 mice were randomly divided into 4 groups:control group(n=8),CS group(n=8),CS+PM2.5 group(n=8)and CS+LPS group(n=8).The AECOPD models in CS+PM2.5 and CS+LPS groups were established by CS exposure combined with intranasal PM2.5 and LPS instillation.Lung function,lung pathology and airway goblet cell hyperplasia using histologi-cal staining were measured.To evaluate the degree of lung inflammation and mucus secretion in mice,the prorein levels of mucin 5AC(MUC5AC),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the bronchoalveolar lavage fluid(BALF)were detected by ELISA and total white blood cell(WBC)counts and the BALF differential cell counts(neutro-phils,macrophages,lymphocytes)were detected by Giemsa staining.RESULTS:In CS group,lung function decreased(P<0.05),and bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen de-position were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05),compared with control group.Compared with CS group,lung function decreased(P<0.05),the bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+PM2.5 and CS+LPS groups.Compared with CS+PM2.5 group,lung function decreased(P<0.05),the bronchial inflamma-tion index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+LPS group.CONCLUSION:Exposure to CS combined with both intrana-sal PM2.5 and LPS instillation allowed for establishing AECOPD models in mice,and CS exposure combined with intrana-sal LPS instillation better simulated AECOPD characteristics.
8.Study on the diagnostic value of diffusion kurtosis imaging parameters in Parkinson's disease with mild cognitive impairment
Dan LU ; Shulan CUI ; Yuhong LIU ; Pengcheng MA ; Rui HOU ; Jin WANG
Journal of Practical Radiology 2025;41(6):920-923
Objective To explore the value of diffusion kurtosis imaging(DKI)in the diagnosis of Parkinson's disease with mild cognitive impairment(PD-MCI)patients.Methods A total of 18 patients with Parkinson's disease cognitive normal(PDN),22 patients with PD-MCI,and 24 healthy controls(HC)were prospectively included.All participants underwent DKI,and regions of interest(ROI)were selected in the substantia nigra,red nucleus,striatum,and posterior cingulate gyrus for post-processing.The diagnostic efficacy of DKI parameters on PD patients' cognitive status was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the PDN group,the PD-MCI group had a longer disease duration and a higher H-Y stage.Compared with the HC group,the PD-MCI group showed significantly lower mean kurtosis(MK),radial kurtosis(RK),axial kurtosis(AK),and fractional anisotropy(FA)values in the substantia nigra and posterior cingulate gyrus.In the PDN group,FA and MK values in the substantia nigra were significantly decreased,while FA values in the striatum and posterior cingulate gyrus were significantly increased(P<0.05).Compared with the PDN group,the PD-MCI group showed significantly decreased DKI parameter values in the substantia nigra and posterior cingulate gyrus,and significantly decreased RK,AK,and FA values in the striatum(P<0.05).The FA values of striatum,posterior cingulate gyrus and joint predictors were the most effective in the diagnosis of PD-MCI and the area under the curve(AUC)were 0.826,0.853 and 0.960,respectively.Conclusion DKI can detect microstructural changes in PD patients.Microstructural alterations in the striatum and posterior cingulate gyrus have an impact on early cognitive function changes in PD patients.FA demonstrate high sensitivity and specificity in the diagnosis of PD-MCI,and the combined diagnostic efficacy across multiple regions is even higher.
9.Study on the distribution of FMR1 CGG repeat numbers among 16 610 women of childbearing age in China
Yahui SHEN ; Wei HOU ; Xiaolin FU ; Manli ZHANG ; Xiaoxiao XIE ; Chunyan ZHANG ; Jiaxin BIAN ; Xiao MAO ; Juan WEN ; Chunyu LUO ; Hua JIN ; Qian ZHU ; Qingwei QI ; Yeqing QIAN ; Jing YUAN ; Yanyan ZHAO ; Ailan YIN ; Shutie LI ; Yulin JIANG ; Rui XIAO ; Yanping LU
Chinese Journal of Reproduction and Contraception 2025;45(4):398-402
Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.
10.Camera inversion technique in laparoscopic sphincter-preserving surgery for mid to low rectal cancer
Rui HOU ; Ganbin LI ; Xiaoyuan QIU ; Xiao ZHANG ; Guole LIN
Chinese Journal of Gastrointestinal Surgery 2025;28(6):679-683
Objective:To explore the application of the camera inversion technique in laparoscopic sphincter-preserving surgery for mid to low rectal cancer.Methods:A retrospective study with historical controls was conducted on patients with non-metastatic mid to low rectal cancer which received laparoscopic total mesorectal excision at Peking Union Medical College Hospital from January 2019 to June 2024. The experimental group (2021.7-2024.6) utilized the camera inversion technique (rotating the lens 180° to position the bevel upward and switching the system to reverse display mode for improved visualization and operative angles) during key surgical steps (such as intraoperative mobilization of the mid-to-lower rectum and anastomosis), while the control group (2019.1-2021.6) did not. Clinical data and surgical videos were collected to analyze indicators like operative time, blood loss, mesorectal integrity, surgical complications, and postoperative hospital stay.Results:A total of 624 patients with non-metastatic mid to low rectal cancer were included, including 412 males and 212 females, with an average age of 59.8 years and an average tumor distance of 5.6 cm from the anal verge. The experimental group comprised 301 patients, while the control group had 323 patients.The proportion of abdominal ISR (intersphincteric resection) was significantly higher in the experimental group [19.3% (58/301) vs. 10.2%(33/323), χ 2=10.140, P=0.001], with a reduction in operative time [(161.8±67.8) minutes vs. (150.2±68.5) minutes, t=2.134, P=0.033] and a decrease in postoperative hospital stay [(7.8±2.1) days vs. (8.3±3.4) days, t=2.003, P=0.046]. The experimental group also demonstrated advantages in intraoperative blood loss, mesorectal integrity rate, and postoperative complications such as urinary retention, though these differences were not statistically significant (all P>0.05). Conclusion:In laparoscopic surgery for mid to low rectal cancer, using camera inversion technique during distal rectum dissection and transanal anastomosis can provide better surgical field exposure, facilitate precise operations within the correct anatomical plane, and minimize collateral damage. The camera inversion technique is safe and effective.

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