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 analyze the impact of serum anti-Müllerian hormone (AMH) on the rate and number of euploid blastocysts among women undergoing intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidies (PGT-A).Methods:A retrospective cohort study was performed by analyzing clinical data from 504 patients approaching ICSI cycle with PGT-A in Reproductive Medicine Center of Peking University Third Hospital from January 1st 2018 to December 31st 2020. According to serum AMH level measured before ovarian stimulation, subjects were divided into two groups: the low AMH group (AMH<1.00 μg/L, 85 patients) and the normal AMH group (AMH≥1.00 μg/L, 419 patients). Rates and number of euploid blastocysts were compared between the two groups (82 patients per group) after using propensity score matching (PSM) to adjust confounding variables, including age, body mass index (BMI), history of recurrent miscarriage and ovarian stimulation protocols.Results:1) The rate and number of euploid blastocysts were significantly lower in the low AMH group [50.0% (0, 100.0%), 1 (0, 1)] than in the normal AMH group [60.0% (33.3%, 100.0%), P=0.025; 1 (1, 2), P<0.001]. 2) After PSM, the rate of euploid blastocysts was 50.0% (0, 100.0%) in the low AMH group and 50.0% (19.2%, 100.0%) in the normal AMH group, with no significant difference ( P=0.265). Patients in the low AMH group had significantly fewer euploid blastocysts [1 (0, 1) vs. 1 (1, 2), P=0.004] and were less likely to have at least one euploid blastocyst [57.3% (47/82) vs. 76.8% (63/82), P=0.008]. 3) A total of 378 (75.0%) cycles had at least one euploid embryo. The area under the curve (AUC) value of AMH combined with age in predicting the presence of at least one euploid embryo was better than that of age alone (0.78 vs. 0.75, P=0.024). Conclusion:Serum AMH level is not independently associated with the rate of blastocyst euploidy after adjusting for age, BMI, history of recurrent abortion and ovulation induction protocol. AMH combined with age can be used to predict the possibility of having at least one euploid embryo per cycle.

Objective:To analyze the impact of serum anti-Müllerian hormone (AMH) on the rate and number of euploid blastocysts among women undergoing intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidies (PGT-A).Methods:A retrospective cohort study was performed by analyzing clinical data from 504 patients approaching ICSI cycle with PGT-A in Reproductive Medicine Center of Peking University Third Hospital from January 1st 2018 to December 31st 2020. According to serum AMH level measured before ovarian stimulation, subjects were divided into two groups: the low AMH group (AMH<1.00 μg/L, 85 patients) and the normal AMH group (AMH≥1.00 μg/L, 419 patients). Rates and number of euploid blastocysts were compared between the two groups (82 patients per group) after using propensity score matching (PSM) to adjust confounding variables, including age, body mass index (BMI), history of recurrent miscarriage and ovarian stimulation protocols.Results:1) The rate and number of euploid blastocysts were significantly lower in the low AMH group [50.0% (0, 100.0%), 1 (0, 1)] than in the normal AMH group [60.0% (33.3%, 100.0%), P=0.025; 1 (1, 2), P<0.001]. 2) After PSM, the rate of euploid blastocysts was 50.0% (0, 100.0%) in the low AMH group and 50.0% (19.2%, 100.0%) in the normal AMH group, with no significant difference ( P=0.265). Patients in the low AMH group had significantly fewer euploid blastocysts [1 (0, 1) vs. 1 (1, 2), P=0.004] and were less likely to have at least one euploid blastocyst [57.3% (47/82) vs. 76.8% (63/82), P=0.008]. 3) A total of 378 (75.0%) cycles had at least one euploid embryo. The area under the curve (AUC) value of AMH combined with age in predicting the presence of at least one euploid embryo was better than that of age alone (0.78 vs. 0.75, P=0.024). Conclusion:Serum AMH level is not independently associated with the rate of blastocyst euploidy after adjusting for age, BMI, history of recurrent abortion and ovulation induction protocol. AMH combined with age can be used to predict the possibility of having at least one euploid embryo per cycle.

Objective:To investigate the effect of gonadotropin-releasing hormone agonist (GnRH-a) down-regulation combined with artificial cycle (AC) protocol on pregnancy outcomes in patients with unexplained repeated implantation failure (RIF).Methods:The clinical data of 1 285 frozen-thawed cycles of unexplained RIF patients who underwent frozen-thawed embryo transfer from January 2018 to December 2019 in the Reproductive Medical Center of Peking University Third Hospital were retrospectively analyzed. They were divided into two groups according to different endometrial preparation protocols: GnRH-a down-regulation combined with AC protocol group (named GnRH-a+AC group, 411 cycles) and AC group (874 cycles). The general clinical data, cycle characteristics and clinical outcomes between the two groups were compared. Multiple logistic regression analysis was used to analyze the influencing factors of clinical pregnancy and live birth.Results:There was no significant difference in the general data between the two groups ( P>0.05). The endometrial thickness of GnRH-a+AC group [(10.26±1.73) mm] was thicker than that of AC group [(9.66±1.54) mm], and the difference was statistically significant ( P=0.002). The clinical pregnancy rate [42.58% (175/411)] and the embryo implantation rate [32.52% (200/615)] of GnRH-a+AC group were higher than those of AC group [35.59% (311/874), P=0.016; 27.20% (346/1 271), P=0.017], and the differences were statistically significant. The live birth rate of GnRH-a+AC group [33.57% (138/411)] showed an increasing tendency, but there was no significant difference compared with AC group [28.73% (251/874), P>0.05]. The multivariate logistic regression analysis showed that the clinical pregnancy rate was negatively correlated with age and body mass index (BMI; OR=0.953, 95% CI: 0.924-0.982; OR=0.959, 95% CI: 0.926-0.994), and positively correlated with GnRH-a protocol ( OR=1.329, 95% CI: 1.039-1.699); the live birth rate was only negatively correlated with age and BMI ( OR=0.947, 95% CI: 0.917-0.977; OR=0.963, 95% CI: 0.927-0.998) and GnRH-a protocol was not an influencing factor ( P>0.05). Endometrial thickness ≥7 mm was not the influencing factor of clinical pregnancy rate and live birth rate (all P>0.05). Conclusion:For RIF patients, GnRH-a down-regulation combined with AC protocol can significantly increase endometrial thickness, improve endometrial receptivity and clinical pregnancy rate, but there is no statistical significance in the live birth rate, which still needs to be further studied in large scale.

Objective:To investigate the effect of gonadotropin-releasing hormone agonist (GnRH-a) down-regulation combined with artificial cycle (AC) protocol on pregnancy outcomes in patients with unexplained repeated implantation failure (RIF).Methods:The clinical data of 1 285 frozen-thawed cycles of unexplained RIF patients who underwent frozen-thawed embryo transfer from January 2018 to December 2019 in the Reproductive Medical Center of Peking University Third Hospital were retrospectively analyzed. They were divided into two groups according to different endometrial preparation protocols: GnRH-a down-regulation combined with AC protocol group (named GnRH-a+AC group, 411 cycles) and AC group (874 cycles). The general clinical data, cycle characteristics and clinical outcomes between the two groups were compared. Multiple logistic regression analysis was used to analyze the influencing factors of clinical pregnancy and live birth.Results:There was no significant difference in the general data between the two groups ( P>0.05). The endometrial thickness of GnRH-a+AC group [(10.26±1.73) mm] was thicker than that of AC group [(9.66±1.54) mm], and the difference was statistically significant ( P=0.002). The clinical pregnancy rate [42.58% (175/411)] and the embryo implantation rate [32.52% (200/615)] of GnRH-a+AC group were higher than those of AC group [35.59% (311/874), P=0.016; 27.20% (346/1 271), P=0.017], and the differences were statistically significant. The live birth rate of GnRH-a+AC group [33.57% (138/411)] showed an increasing tendency, but there was no significant difference compared with AC group [28.73% (251/874), P>0.05]. The multivariate logistic regression analysis showed that the clinical pregnancy rate was negatively correlated with age and body mass index (BMI; OR=0.953, 95% CI: 0.924-0.982; OR=0.959, 95% CI: 0.926-0.994), and positively correlated with GnRH-a protocol ( OR=1.329, 95% CI: 1.039-1.699); the live birth rate was only negatively correlated with age and BMI ( OR=0.947, 95% CI: 0.917-0.977; OR=0.963, 95% CI: 0.927-0.998) and GnRH-a protocol was not an influencing factor ( P>0.05). Endometrial thickness ≥7 mm was not the influencing factor of clinical pregnancy rate and live birth rate (all P>0.05). Conclusion:For RIF patients, GnRH-a down-regulation combined with AC protocol can significantly increase endometrial thickness, improve endometrial receptivity and clinical pregnancy rate, but there is no statistical significance in the live birth rate, which still needs to be further studied in large scale.

Objective:To explore the effect of pregnancy outcome of the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer cycle on the next frozen-thawed embryo transfer cycle. Methods:A retrospective cohort study was designed by collecting data from 6658 infertile patients in Department of Reproductive Endocrinology, Women's Hospital of Zhejiang University from January 2010 to December 2019. Two groups were included, the fresh embryo-frozen embryo group ( n=4310) and the frozen embryo-frozen embryo group ( n=2348), and each group was divided into four subgroups according to the pregnancy outcome of the first transfer cycle: non-pregnancy subgroup, biochemical pregnancy subgroup, pregnancy loss subgroup, and live birth subgroup. In each group, the live birth rate (LBR) of the second transfer cycle was compared among the four subgroups. Results:In the second transfer cycle of the fresh embryo-frozen embryo group, LBR in each subgroup was 31.3% (972/3109), 33.7% (92/273), 33.3% (169/507), and 39.2% (165/421), respectively. Compared with non-pregnancy subgroup, the difference of LBR in the live birth subgroup was statistically significant [after adjustment, a P<0.001, a OR(95% CI)=1.555(1.245-1.942)]. In the second transfer cycle of the frozen embryo-frozen embryo group, LBR in each subgroup was 37.3% (655/1754), 47.0% (79/168), 45.4% (122/269), and 44.6% (70/157), respectively. Compared with non-pregnancy subgroup, the differences of LBR in biochemical pregnancy subgroup, pregnancy loss subgroup and live birth subgroup were statistically significant [after adjustment, a P=0.018, a OR(95% CI)=1.471(1.069-2.026); a P=0.014, a OR(95% CI)=1.388 (1.069-1.802); a P=0.035, a OR(95% CI)=1.452(1.026-2.054)]. Conclusion:In the fresh embryo-frozen embryo group, live birth in the first transfer cycle is associated with increased LBR in the subsequent cycles, while in the frozen embryo-frozen embryo group, biochemical pregnancy, pregnancy loss, or live birth in the first transfer cycle are associated with increased LBR in the following cycles.

Objective:To explore the effect of pregnancy outcome of the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer cycle on the next frozen-thawed embryo transfer cycle. Methods:A retrospective cohort study was designed by collecting data from 6658 infertile patients in Department of Reproductive Endocrinology, Women's Hospital of Zhejiang University from January 2010 to December 2019. Two groups were included, the fresh embryo-frozen embryo group ( n=4310) and the frozen embryo-frozen embryo group ( n=2348), and each group was divided into four subgroups according to the pregnancy outcome of the first transfer cycle: non-pregnancy subgroup, biochemical pregnancy subgroup, pregnancy loss subgroup, and live birth subgroup. In each group, the live birth rate (LBR) of the second transfer cycle was compared among the four subgroups. Results:In the second transfer cycle of the fresh embryo-frozen embryo group, LBR in each subgroup was 31.3% (972/3109), 33.7% (92/273), 33.3% (169/507), and 39.2% (165/421), respectively. Compared with non-pregnancy subgroup, the difference of LBR in the live birth subgroup was statistically significant [after adjustment, a P<0.001, a OR(95% CI)=1.555(1.245-1.942)]. In the second transfer cycle of the frozen embryo-frozen embryo group, LBR in each subgroup was 37.3% (655/1754), 47.0% (79/168), 45.4% (122/269), and 44.6% (70/157), respectively. Compared with non-pregnancy subgroup, the differences of LBR in biochemical pregnancy subgroup, pregnancy loss subgroup and live birth subgroup were statistically significant [after adjustment, a P=0.018, a OR(95% CI)=1.471(1.069-2.026); a P=0.014, a OR(95% CI)=1.388 (1.069-1.802); a P=0.035, a OR(95% CI)=1.452(1.026-2.054)]. Conclusion:In the fresh embryo-frozen embryo group, live birth in the first transfer cycle is associated with increased LBR in the subsequent cycles, while in the frozen embryo-frozen embryo group, biochemical pregnancy, pregnancy loss, or live birth in the first transfer cycle are associated with increased LBR in the following cycles.

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.