The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human models in biomedical research. In response to this demand, organoids and organ chips were integrated for greater physiological relevance and dynamic, controlled experimental conditions. This innovative platform-the organoids-on-a-chip technology-shows great promise in disease modeling, drug discovery, and personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, and industry stakeholders. This review traces the evolution from organoids to organoids-on-a-chip, driven by the necessity for advanced biological models. We summarize the applications of organoids-on-a-chip in simulating physiological and pathological phenotypes and therapeutic evaluation of this technology. This section highlights how integrating technologies from organ chips, such as microfluidic systems, mechanical stimulation, and sensor integration, optimizes organoid cell types, spatial structure, and physiological functions, thereby expanding their biomedical applications. We conclude by addressing the current challenges in the development of organoids-on-a-chip and offering insights into the prospects. The advancement of organoids-on-a-chip is poised to enhance fidelity, standardization, and scalability. Furthermore, the integration of cutting-edge technologies and interdisciplinary collaborations will be crucial for the progression of organoids-on-a-chip technology.
Organoids/physiology* ; Humans ; Biomedical Research/methods* ; Lab-On-A-Chip Devices ; Animals ; Microphysiological Systems

Objective:To evaluate the medium and long-term clinical efficacy of the treatment of lumbar degenerative diseases in Dynesys dynamic internal fixation combined with decompression.Methods:From March 2008 to March 2015, 145 patients (84 males and 61 females, mean age 55.9±7.1 years old) with symptoms of lumbar degenerative diseases (69 lumbar disc herniation, 53 lumbar spinal stenosis and 23 I grade lumbar degenerative spondylolisthesis) were treated by the lumbar discectomy using Dynesys dynamic internal fixation combined with decompression. The clinical symptoms before and after surgery were assessed by visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI). Lumbar lateral radiographs were used to measure the height of intervertebral space between the surgical segment and the adjacent segment. The range of motion (ROM) between the surgical segment and the adjacent segment was measured by lumbar dynamic position X-ray. Surgical and adjacent segments degenerative were classified according to the Pfirrmann grade classification.Results:The VAS score, ODI and JOA score of lower back and lower limbs in patients with lumbar disc herniation were improved from 6.6±1.7, 7.1±1.4, 63.1%±10.2%, 12.5±2.4 preoperatively to 2.6±1.0, 2.8±0.9, 30.9%±9.8%, 22.4±2.1 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with lumbar spinal stenosis were improved from 6.3±2.2, 6.9±1.3, 63.4%±8.5%, 12.8±2.7 preoperatively to 2.4±1.2, 2.8±1.0, 35.1%±12.0%, 22.2±2.2 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with I degree lumbar degenerative spondylolisthesis were improved from 5.7±2.3, 6.7±0.9, 65.7%±10.0%, 12.5±2.7 preoperatively to 2.2±1.2, 2.7±1.1, 37.0%±11.8%, 22.4±2.6 at the latest follow-up. The differences were statistically significant. Comparing to preoperational value, the height of the operative segment and caudal intervertebral space were decreased at the 1 year postoperatively and last follow-up. But the difference was not significant. As for cranial adjacent segment, the height of intervertebral space preoperatively was decreased from 12.1±1.9 mm preoperatively to 11.7±1.6 mm at 1 year postoperatively, and to 11.3±1.8 mm at the latest follow-up. The difference between them was statistically significant ( F=6.46, P=0.001). The ROM of surgical segments was decreased from 7.6°±2.2° preoperatively to 5.5°±1.6° at 1 year postoperatively, and to 2.9°±1.4° at the latest follow-up. The difference between them was statistically significant ( F=267.9, P<0.001). Conversely, the ROM of cranial and caudal segments was increased from 8.2°±2.4°, 6.5°±1.6° preoperatively to 9.1°±2.1°, 7.1°±1.9° at 1 year postoperatively, and to 10.6°±2.5°, 7.2°±1.8° at the latest follow-up. The difference between them was statistically significant ( F=38.66, 3.81, P<0.001, 0.023). At the latest follow-up, 120 (51.9%) adjacent segments were to be defined adjacent segment degeneration which includes 103 radiological adjacent segment degeneration and 17 symptomatic adjacent segment degenerations. Conclusion:Dynesys dynamic internal fixation combined with decompression could achieve satisfying mid- and long-term therapeutic effect in the treatment of lumbar degenerative diseases. The ROM of surgical segments decreased with time, although part of the ROM was still retained at the latest follow-up. However, it does not seem to avoid the degeneration of adjacent segment.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective: To investigate thestatus and control of blood lipid level among patients with type 2 diabetes mellitus（T2DM）in rural communities of Zhejiang Province，and to provide evidence for blood lipid control for T2DM. Methods: A sample of 10 343 patients with T2DM managed by communities from Jiashan，Suichang and Yongkang in 2016 were recruited. Through the diabetes registry system，physical examination and laboratory tests，data of demographic features，blood pressure，body mass index（BMI），waist circumstance（WC），glycated hemoglobin（HbA1c），total cholesterol（TC），triglyceride（TG），low-density lipoprotein cholesterol（LDL-C）and high-density lipoprotein cholesterol（HDL-C）were collected to learn the status of blood lipid control. Logistic regression analysis was conducted to explore the influencing factors for blood lipid control. Results: The control rate of TC，TG，LDL-C and HDL-C in patients with T2DM was 29.84%，58.72%，48.25% and 61.27%，respectively. About 11.76% of patients had all the four indicators in control，while 9.22% of patients failed in all. The higher control rates of all of the four indicators were seen in males than females，in older age，in lower BMI and in normal people than in central obese people（all P<0.05）. The results of multivariate logistic regression analysis showed that sex（OR=3.556，95%CI：3.070-4.119），age（OR=1.130，95%CI：1.060-1.204），WC（OR=0.989，95%CI：0.980-0.998）， BMI（OR=0.768，95%CI：0.688-0.857），systolic blood pressure（OR=0.991，95%CI：0.984-0.999），HbA1c level（OR=0.914，95%CI：0.876- 0.953），smoking（OR=0.768，95%CI：0.639-0.924）and drinking（OR=0.688，95%CI：0.536-0.884）were associated with the control of TC，TG，LDL-C and HDL-C in patients with T2DM. Conclusion The control rate of blood lipid is low in patients with T2DM in rural communities of Zhejiang Province，surveillance and interventions should be focused on sex，overweight/obesity，smoking，alcohol intake，blood glucose and blood pressure.

Objective To study early treatment strategy for brain hernia combined with hemorrhagic shock and the effect on prognosis of patients with severe head injury.Methods 252 cases of patients with severe head inju-ry and brain hernia combined with hemorrhagic shock in the mergency intensive care unit were divided into the obser-vation group and control group according to the stochastic indicator method,each group in 126 cases.The two group were treated with early treatment strategy and traditional treatment mode,respectively.The advantages and effect of two modes were analyzed.Results The majority of patients had united injury,such as soft tissue injuries,pelvis and spine fractures.There were 136 cases of patients with mild brain hernia and the rate of patients with hemorrhagic shock was 62.30%(157/252).The mortality was 34.13% in the observation group and 48.41% in the control group.There was significant difference(χ2 =5.306,P=0.021).The ratio of patinents with mild disability was 56.35%(71/126) in the observation group and the control group was 35.71%(45/126).The severe disability,vegetative state and death was 43.65%(55/126) in the observation group after the follow-up of 6 months.It was significantly lower than that of the control group(χ2 =5.306,P=0.001).Conclusion The early strategy treatment has a positive effect on reducing the mortality of brain hernia combined with hemorrhagic shock of patients with severe head injury the GOS for the prognosis disability increases significantly.

To investigate whether peroxisome proliferators-activated receptor-y (PPARγ) ligand Troglitazone can reduce endothelial injury and activation during storage of harvested saphenous vein grafts. Segments of human saphenous vein graft were collected from 9 patients undergoing coronary bypass surgery and then divided into two equal parts of control and test specimens, were stored in ei-ther heparinized blood (control group) or heparinized blood containing 20 μmol/L troglitazone (test group) for 1 h at room temperature. Tissue distribution and protein expression of VCAM-1, ICAM-1, and endothelial nitric oxide synthase (eNOS) were compared using immunohistochemistry and West-ern blot analysis. Myeloperoxidase (MPO) activity, a marker of neutrophil sequestration in human saphenous vein grafts, was also measured in each group. The expression of ICAM-1 (753±132 versus 7201±934; P<0.01) , VCAM-1 (3731±294 versus 8292±793; P<0.01), and MPO activity (1.52±0.42 U/g, 5.04±1.26 U/g P<0.01) were significantly lower in test group. In contract, eNOS expression (7983±834 versus 3989±1008; P<0.01) was significantly higher in test group. PPARγ ligand troglita- zone might reduce endothelial injury during the storage period of human saphenous vein grafts.

In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups: the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 min, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group. MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced (P<0.05). And the cell ultrastructure was obviously improved. But the activity of SOD had no change (P>0.05). It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis.

In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2groups: the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 min, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group, MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced (P＜0.05). And the cell ultrastructure was obviously improved. But the activity of SOD had no change (P＞0.05). It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis.

Summary: The effects of diazoxide treatments on electrophysiologyic properties in guinea pig papillary muscles undergoing ischemia/reperfusion was studied using intracellular microelectrode technique. Twenty-four guinea pigs were randomly divided into three groups (n=8 in each group). In control group, St.Thomas solution was given. In experimental group, St.Thomas solution with diazoxide (100 mol/L) was given. In pretreatment group, the muscle was treated with diazoxide 20 min before arrested with St.Thomas cardioplegia. The results showed that the APD50 and APD90 in experimental and pretreatment groups were significantly shorter after 5 and 10 min reperfusion (P<0.01, P<0.05), but longer after 30 min reperfusion (P<0.01, P<0.05) than in control group. In experimental and pretreatment groups, APA, OS, Vmax recovered more quickly than those in control group. The time to re-systole after reperfusion in control group was longer than that in experimental and pretreatment groups. There was no significant difference in RP among three groups. The time of arrest in pretreatment group was longer than that in experimental and pretreatment group (P<0.05). This study indicates that protective effects of St.Thomas solution with diazoxide is better than that of pretreatment with diazoxide or St.Thomas solution alone.

This study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly divided into two groups, a treatment group and a control group. The rats of the treatment group were treated intraperitoneally with 3-nitropropionic acid (3-NPA, 4 mg/kg)and the rats of the control group were treated with saline. 24 h after the treatment, the isolated hearts were mounted on a Langendorff apparatus. After 30 min, the hearts were subjected to 30-min ischemia and 60-min reperfusion. The HR, LVDP and ±dp/dtmax were measured at pre-ischemia and 30 min, 60 min after the reperfusion. Coronary effluent was collected 15 min after the reperfusion for the determination of CK and LDH. At the end of the 60-min reperfusion the heart was removed for the determination of myocardial SOD and MDA. Our results showed that in the 3-NPA group LVDP and ±dp/dtmax recovered significantly better, myocardial MDA, CK and LDH were significantly lower and the myocardial SOD was significantly higher than in the control group.It is concluded that chemical preconditioning by 3-nitropropionate has cardioprotective effects against ischemia-reperfusion injury.