Vasorin promotes endothelial differentiation of glioma stem cells via stimulating the transcription of VEGFR2.

Gliomas are highly vascularized malignancies, but current anti-angiogenic treatments have not demonstrated practical improvements in patient survival. Studies have suggested that glioma-derived endothelial cell (GdEC) formed by glioma stem cell (GSC) differentiation may contribute to the failure of this treatment. However, the molecular mechanisms involved in GSC endothelial differentiation remain poorly understood. We previously reported that vasorin (VASN) is highly expressed in glioma and promotes angiogenesis. Here, we show that VASN expression positively correlates with GdEC signatures in glioma patients. VASN promotes the endothelial differentiation capacity of GSC in vitro and participates in the formation of GSC-derived vessels in vivo. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) is a critical factor that mediates the regulation of VASN on GSC endothelial differentiation. Separation of cell chromatin fractionation and chromatin immunoprecipitation-sequencing analysis show that VASN interacts with Notch1 and co-translocates into the cell nuclei, where VASN binds to the VEGFR2 gene promoter to stimulate its transcription during the progression of GSC differentiation into GdEC. Together, these findings elucidate the role and mechanisms of VASN in promoting the endothelial differentiation of GSC and suggest VASN as a potential target for anti-angiogenic therapy based on intervention in GdEC formation in gliomas.

Insights into the Acceleration Mechanism of Intracellular N and Fe Co-doped Carbon Dots on Anaerobic Denitrification Using Proteomics and Metabolomics Techniques.

Bulk carbon-based materials can enhance anaerobic biodenitrification when they are present in extracellular matrices. However, little information is available on the effect of nitrogen and iron co-doped carbon dots (N, Fe-CDs) with sizes below 10 nm on this process. This work demonstrated that Fe-NX formed in N, Fe-CDs and their low surface potentials facilitated electron transfer. N, Fe-CDs exhibited good biocompatibility and were effectively absorbed by Pseudomonas stutzeri ATCC 17588. Intracellular N, Fe-CDs played a dominant role in enhancing anaerobic denitrification. During this process, the nitrate removal rate was significantly increased by 40.60% at 11 h with little nitrite and N2O accumulation, which was attributed to the enhanced activities of the electron transport system and various denitrifying reductases. Based on proteomics and metabolomic analysis, N, Fe-CDs effectively regulated carbon/nitrogen/sulfur metabolism to induce more electron generation, less nitrite/N2O accumulation, and higher levels of nitrogen removal. This work reveals the mechanism by which N, Fe-CDs enhance anaerobic denitrification and broaden their potential application in nitrogen removal.

Effect of sludge humic acid-derived nano-biochars on anaerobic degradation of sulfamethoxazole by Shewanella oneidensis MR-1.

Some nano-biochars (nano-BCs) as electron mediators could enter into cells to directly promote intracellular electron transfer and cell activities. However, little information was available on the effect of nano-BCs on SMX degradation. In this study, nano-BCs were prepared using sludge-derived humic acid (SHA) and their effects on SMX degradation by Shewanella oneidensis MR-1 were investigated. Results showed that nano-BCs (Carbon dots, CDs, <10 nm) synthesized using SHA performed a better accelerating effect than that of the nano-BCs with a larger size (10-100 nm), which could be attributed to the better electron transfer abilities of CDs. The degradation rate of 10 mg/L SMX in the presence of 100 mg/L CDs was significantly increased by 84.6% compared to that without CDs. Further analysis showed that CDs could not only be combined with extracellular Fe(III) to accelerate its reduction, but also participate in the reduction of 4-aminobenzenesulphonic acid as an intermediate metabolite of SMX via coupling with extracellular Fe(III) reduction. Meanwhile, CDs could enter cells to directly participate in intracellular electron transfer, resulting in 32.2% and 25.2% increases of electron transfer system activity and ATP level, respectively. Moreover, the activities of SMX-degrading enzymes located in periplasm and cytoplasm were increased by around 2.2-fold in the presence of CDs. These results provide an insight into the accelerating effect of nano-BCs with the size of <10 nm on SMX degradation and an approach for SHA utilization.

Genetic predisposition to impaired beta-cell function modifies the association between serum pyrethroid levels and the risk of type 2 diabetes: A gene-environment interaction study.

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98-1.56) and 0.91 (0.77-1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02-1.47) and 0.95 (0.78-1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03-7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78-5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

Association between polychlorinated biphenyls exposure and incident type 2 diabetes mellitus: A nested case-control study.

BACKGROUND: Previous epidemiological studies indicated that the association between polychlorinated biphenyls (PCB) and type 2 diabetes mellitus (T2DM) was inconclusive. OBJECTIVE: We investigated the association between PCBs exposure and incident T2DM in a nested case-control study, and further explored the relationship between PCBs and 5-year fasting blood glucose (FBG) changes. METHODS: Baseline concentrations of seven indicator-PCB (PCB-28, 52, 101, 118, 138, 153, 180) were measured in 1006 pairs of incident T2DM cases and matched controls nested within the Dongfeng-Tongji cohort. Conditional logistic regression models and pre-adjusted residuals method were used to assess the associations between PCBs and incident T2DM. We further computed beta coefficients (ßs) of 5-year FBG changes using multivariable generalized linear regression. RESULTS: Non-dioxin-like PCBs (NDL-PCBs) were significantly associated with higher T2DM incidence after adjustment for all covariates. Significant differences were observed for extreme quartiles comparisons (Q4 vs. Q1) of PCBs except PCB-138, and the incidence of T2DM were 1- to 3-fold higher among those in the highest versus lowest PCBs quartiles. Serum NDL-PCBs were positively associated with changes in FBG (P for overall association ≤0.01). Additionally, triglycerides mediated the associations between PCBs and T2DM incidence. CONCLUSION: Our findings showed positive associations of NDL-PCBs with incident T2DM and 5-year FBG changes. PCBs increased incident T2DM via lipid metabolic pathways.

Effectiveness and safety of novel motorized spiral enteroscopy: a systematic review and meta-analysis.

BACKGROUND: Motorized spiral enteroscopy (MSE) is a novel advance in small bowel examination that is characterized as fast with a deep insertion. The aim of this study was to elucidate the effectiveness and safety of MSE. METHODS: Relevant articles that were published before November 1, 2022 were identified by searching PubMed, EMBASE, Cochrane, and the Web of Science. The technical success rate (TSR), total (pan)-enteroscopy rate (TER), depth of maximum insertion (DMI), diagnostic yield, and adverse events were extracted and analyzed. Forest plots were graphed based on random effects models. RESULTS: A total of 876 patients from 8 studies were eligible for analysis. The pooled results of the TSR were 95.0% [95% confidence interval (CI) 91.0-98.0%, I2 = 78%, p < 0.01] and the pooled outcome of the TER was 43.1% (95% CI 24.7-62.5%, I2 = 95%, p < 0.01). The pooled results of the diagnostic and therapeutic yields were 77.2% (95% CI 69.0-84.5%, I2 = 84%, p < 0.01) and 49.0% (95% CI 38.0-60.1%, I2 = 89%, p < 0.01), respectively. The pooled estimates of adverse and severe adverse events were 17.2% (95% CI 11.9-23.2%, I2 = 75%, p < 0.01) and 0.7% (95% CI 0.0-2.1%, I2 = 37%, p = 0.13), respectively. CONCLUSION: MSE is a novel alternative approach for small bowel examination that can achieve high TER and diagnostic and therapeutic yields, and relatively low rates of severe adverse events. Head-to-head studies comparing MSE and other device-assisted enteroscopies are warranted.

Association of serum phthalates exposure with incident type 2 diabetes risk in Chinese population: A nested case-control study.

Prospective epidemiological evidence was lacking on the association of phthalates (PAEs) exposure with incident type 2 diabetes mellitus (T2DM) risk. In present nested case-control study, we identified 1006 T2DM cases and matched 1006 controls based on Dongfeng-Tongji cohort study, and 6 PAEs were detected in baseline serum. The conditional logistic regression model, Bayesian kernel machine regression (BKMR) model and Quantile-based g-computation were applied to evaluate the associations of determined PAEs, either as individuals or as a mixture, with incident T2DM risk. Subgroup analysis was conducted to identify the potential sensitive population of PAEs effects on T2DM. After multiple adjustment, no statistically significant association was observed between single or mixture of PAEs and incident T2DM risk in the whole population. However, serum levels of Di-n-butyl phthalate (DnBP) [OR= 2.06; 95% CI: (1.11-3.96)], Σdibutyl phthalate (ΣDBP) [OR= 1.96; 95% CI: (1.06-3.76)], and Σlow-molecular- weight phthalate (ΣLMW) [OR= 2.27; 95% CI: (1.17-4.57)] were significantly associated with T2DM in current drinker group. Moreover, significant potential interactions were observed among Di-iso-butyl phthalate (DiBP), DnBP, Butyl-benzyl phthalate (BBP), ΣDBP, and ΣLMW with drinking status on T2DM risk (P for interaction = 0.036, 0.005, 0.049. 0.010, and 0.005). We did not find significant associations between serum PAEs levels and T2DM in the whole population. However, current alcohol drinkers expose to higher levels of DnBP, ΣDBP, and ΣLMW had higher risk of T2DM.

Novel gold-platinum nanoparticles serve as broad-spectrum antioxidants for attenuating ischemia reperfusion injury of the kidney.

Kidney ischemia reperfusion injury (IRI) is a common and inevitable pathological condition in routine urological practices, especially during transplantation. Severe kidney IRI may even induce systemic damage to peripheral organs, and lead to multisystem organ failure. However, no standard clinical treatment option is currently available. It has been reported that kidney IRI is predominantly associated with abnormally increased endogenous reactive oxygen species (ROS). Scavenging excessive ROS may reduce the damage caused by oxidative stress and subsequently alleviate kidney IRI. Here, we reported a simple and efficient one-step synthesis of gold-platinum nanoparticles (AuPt NPs) with a gold core having a loose and branched outer platinum shell with superior ROS scavenging capacity to possibly treat kidney IRI. These AuPt NPs exhibited multiple enzyme-like anti-oxidative properties simultaneously possessing catalase- and peroxidase-like activity. These particles showed excellent cell protective capability, and alleviated kidney IRI both in vitro and in vivo without obvious toxicity, by suppressing cell apoptosis, inflammatory cytokine release, and inflammasome formation. Meanwhile, AuPt NPs also had an effect on inhibiting the transition to chronic kidney disease by reducing kidney fibrosis in the long term. Thus, AuPt NPs might be a good therapeutic agent for kidney IRI management and may be helpful for the development of clinical treatments for kidney IRI.

Selective Single-Cell Expansion on a Microfluidic Chip for Studying Heterogeneity of Glioma Stem Cells.

Accumulating evidence suggests that a subpopulation of stem-cell-like tumor cells in glioma (GSCs) is the major factor accounting for intratumoral heterogeneity and acquired chemotherapeutic resistance. Therefore, understanding intratumoral heterogeneity of GSCs may help develop more effective treatments against this malignancy. However, the study of GSCs' heterogeneity is highly challenging because tumor stem cells are rare. To overcome the limitation, we employed a microfluidic single-cell culture approach to expand GSCs by taking advantage of the self-renewal property of stem cells. Stemness of the recovered cells was confirmed by immunofluorescence, RT-PCR, RNA-sequencing, and cell function assays. The recovered cells were classified into three groups based on their morphological characteristics, namely, the tight-format (TF), the loose-format (LF), and the limited-size group (LS). The serial passage assay showed that the LS group has a lower sphere-forming rate than the LF and TF group, and the invasion assay showed that the LF and TF cells migrated longer distances in Matrigel. The transcriptomic analysis also revealed differences in gene expression profiling among these GSC subtypes. The abovementioned results suggest that GSCs have transcriptional and functional heterogeneities that correlate with morphological differences. The presented microfluidic single-cell approach links morphology with function and thus can provide an enabling tool for studying tumor heterogeneity.

Association between serum pyrethroid insecticide levels and incident type 2 diabetes risk: a nested case-control study in Dongfeng-Tongji cohort.

Pyrethroid insecticides have been extensively used worldwide, but few studies explored the prospective association between pyrethroid exposure and incident type 2 diabetes (T2D). We conducted a nested case-control study of 2012 paired cases and controls, and measured eight pyrethroid insecticides in the baseline sera. We used conditional logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals, and constructed multiple-pollutant models to investigate the association of pyrethroid mixture with incident T2D risk. The median concentrations (detection rates) were 3.53 µg/L (92.45%), 0.52 µg/L (99.80%), 1.16 µg/L (90.61%) and 1.43 µg/L (99.95%) for permethrin, cypermethrin, fenvalerate, and deltamethrin, respectively. Compared to participants with serum fenvalerate levels in the first quartile, the multivariable-adjusted ORs of incident T2D were 1.20 (95% CI 0.86-1.67), 1.41 (0.97-2.05), and 2.29 (1.27-4.11) for the second, third and fourth quartile (P trend = 0.01). Spline analysis further confirmed the positive association between serum fenvalerate levels and incident T2D risk (P for overall association = 0.006). Furthermore, mixture models revealed a positive association of pyrethroid mixture with incident T2D risk, with serum fenvalerate ranked as the top contributor (proportion of relative contribution: > 70%). We found that high concentrations of serum pyrethroid insecticides were significantly associated with an increased risk of incident T2D. The elevated risk was largely explained by fenvalerate. Further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms, given the widespread use of pyrethroids and the global pandemic of diabetes.

Association of serum BPA levels with changes in lipid levels and dyslipidemia risk in middle-aged and elderly Chinese.

Previous evidences exploring the associations of BPA with lipid changes and dyslipidemia did not obtain consistent results. To evaluate whether serum BPA concentration was associated with changes in blood lipid levels and incident dyslipidemia risk in middle-elderly Chinese adults, we conducted a prospective study with 1093 participants (average 62.65 years old) derived from the Dongfeng-Tongji cohort which was founded in 2008 and followed up each 5 years. Serum BPA levels were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Changes in lipid levels were named as Δ lipids which equal to Lipid2013 - Lipid2008. The diagnosis of dyslipidemia was according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in 2016. We used multivariable linear regression and Logistic regression to explore the relations between serum BPA levels and changes in lipid levels and incident dyslipidemia risk, respectively. Besides, restricted cubic splines were used to explore the dose-response relations. After 5 years' follow-up, 51 individuals developed with hypercholesterolemia, 87 with hypertriglyceridemia, 34 with high-LDL-cholesterolemia, 74 with low-HDL-cholesterolemia, and 199 with dyslipidemia. At baseline serum BPA levels were positively related to TC, LDL-c, and Non-HDL-c levels. In the prospective study, each Ln-BPA increase was associated with 0.05 (95% CI: 0.02, 0.09) mmol/L increase in Δ TC, 0.07 (95% CI:0.03, 0.11) mmol/L increase in Δ Non-HDL-c, 0.05 (95% CI: 0.01, 0.08) increase in Δ TC/HDL-c, and 0.05 (95% CI: 0.01, 0.08) increase in Δ Non-HDL-c/HDL-c. We only observed significant associations in females but not in males. Besides, serum BPA levels were positively associated with hypercholesterolemia (OR=1.12, 95% CI: 1.01, 1.25). The restricted cubic splines obtained similar results. In conclusion, serum BPA was associated TC and Non-HDL-c changes, and BPA was also associated with increased risk of hypertriglyceridemia. Further prospective studies with large sample size are warranted to validate our findings.

Associations between serum PFOA and PFOS levels and incident chronic kidney disease risk in patients with type 2 diabetes.

Chronic kidney disease (CKD) is a common comorbidity among patients with type 2 diabetes. Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been linked to poorer kidney function in general population, but the related studies in individuals with diabetes were very limited. We aimed to examine the longitudinal associations of PFOA and PFOS exposure and CKD incidence among diabetes patients. Baseline levels of PFOA and PFOS were measured in serum in 967 diabetes patients from the Dongfeng-Tongji cohort. Multivariable logistic regression models were used to characterize the relationship between serum PFOA and PFOS levels and incident CKD risk (defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2). During 10-years follow-up, 267 incident CKD cases were identified. Only PFOS level was significantly associated with lower risk of CKD incidence (adjusted OR: 0.67; 95%CI: 0.51, 0.88). Such inverse association was only observed among participants with lower eGFR levels (< 70 mL/min/1.73 m2), although the interaction did not achieve statistical significance. Notably, an inverted U-shaped relationship between eGFR and serum PFOS level (Pfor nonlinearity < 0.001) was observed based on the 1825 subjects with available data at baseline. PFOS exposure was negatively associated with CKD incidence in patients with diabetes, especially in those with baseline eGFR levels < 70 mL/min/1.73 m2. This may be explained by the implication of baseline kidney function on the serum PFAS concentrations which in turn affect the relationship between PFOS exposure and the incident CKD risk among diabetes.

Public availability of information from officially accredited medical schools in China.

BACKGROUND: Medical education accreditation in China has been conducted by the Working Committee for the Accreditation of Medical Education (WCAME) and 129 medical schools have completed accreditation by December 2021. Despite studies on the standards, process and effectiveness of accreditation, the actual information transparency of accredited medical schools in China has not been examined. The study investigated the status of publicly available information from WCAME-accredited medical schools in China, and whether public availability of information had significant differences among different types of universities. METHODS: The 129 medical schools' official websites were reviewed for the 21 criteria of the WFME Global Standards for Quality Improvement: Basic Medical Education. Dichotomous method was used to record information as presence or absence. SPSS was utilized for descriptive and ANOVA analyses. RESULTS: The mean of the publicly available information on the 21 criteria was 13.77 ± 3.57, and only 5 (3.9%) accredited medical schools had all relevant information available. Publicly available information on Governance (100%) and Administration (100%) was the most, whereas information on Assessment in support of learning (16.3%) was the least. Public availability of information differed significantly among schools accredited with higher (18.15 ± 2.16), medium (13.69 ± 3.41) and lower results (12.79 ± 3.19) (F = 14.71, p < 0.05). Medical universities and comprehensive universities did not show significant differences in their overall information availability (F = 0.25, p > 0.05). Central government funded universities had a remarkably larger amount of publicly available information than local government funded universities (17.86 ± 1.98 vs. 12.75 ± 2.93, p < 0.05). CONCLUSION: Public availability of information from the accredited medical schools in China needs to be improved to promote transparency and continuous quality improvement, especially with regard to information on curriculum, assessment and quality assurance. Explicit information availability requirements need to be considered to include in medical education standards, and further studies are warranted to explore which information elements should be made publicly available.

Feasibility and clinical effectiveness of transjugular intrahepatic portosystemic shunt creation in pediatric and adolescent patients: a meta-analysis.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) is a useful approach in managing complications caused by severe portal hypertension (PH) in adults. In children, TIPS is technically challenging, and previous studies of TIPS in children have yielded inconsistent results. This study aimed to elucidate the feasibility and clinical effectiveness of TIPS in pediatric and adolescent patients. METHODS: This meta-analysis study identified relevant publications through medical databases. The primary outcomes included technical success, hemodynamic success, and clinical success. The secondary outcomes were primary patency rate, shunt revision rate, and secondary patency rate. RESULTS: A total of 286 patients representing 13 studies were eligible for analysis. The pooled rates of technical success, hemodynamic success, and clinical success were 95% (95% CI 88-99), 89% (95% CI 81-95), and 93% (95% CI 86-98), respectively. The portosystemic gradient decreased from 21.5 mmHg before TIPS to 8.3 mmHg after TIPS. The pooled estimates of primary patency rate, shunt revision rate, and secondary patency rate were 84% (95% CI 72-94), 35% (95% CI 21-51), and 100% (95% CI 92-100), respectively. CONCLUSION: Study results suggest that TIPS may be feasible and effective in children with PH of various etiologies as for long-term management.

Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model.

Extracellular matrix (ECM) rigidity has important effects on cell behaviors and increases sharply in liver fibrosis and cirrhosis. Hepatic blood flow is essential in maintaining hepatocytes' (HCs) functions. However, it is still unclear how matrix stiffness and shear stresses orchestrate HC phenotype in concert. A fibrotic three-dimensional (3-D) liver sinusoidal model is constructed using a porous membrane sandwiched between two polydimethylsiloxane (PDMS) layers with respective flow channels. The HCs are cultured in collagen gels of various stiffnesses in the lower channel, whereas the upper channel is pre-seeded with liver sinusoidal endothelial cells (LSECs) and accessible to shear flow. The results reveal that HCs cultured within stiffer matrices exhibit reduced albumin production and cytochrome P450 (CYP450) reductase expression. Low shear stresses enhance synthetic and metabolic functions of HC, whereas high shear stresses lead to the loss of HC phenotype. Furthermore, both mechanical factors regulate HC functions by complementing each other. These observations are likely attributed to mechanically induced mass transport or key signaling molecule of hepatocyte nuclear factor 4α (HNF4α). The present study results provide an insight into understanding the mechanisms of HC dysfunction in liver fibrosis and cirrhosis, especially from the viewpoint of matrix stiffness and blood flow.NEW & NOTEWORTHY A fibrotic three-dimensional (3-D) liver sinusoidal model was constructed to mimic different stages of liver fibrosis in vivo and to explore the cooperative effects of matrix stiffness and shear stresses on hepatocyte (HC) functions. Mechanically induced alterations of mass transport mainly contributed to HC functions via typical mechanosensitive signaling.

Self-assembled microcage fabrication for manipulating and selectively capturing microparticles and cells.

Single-cell-scale selective manipulation and targeted capture play a vital role in cell behavior analysis. However, selective microcapture has primarily been performed in specific circumstances to maintain the trapping state, making the subsequent in situ characterization and analysis of specific particles or cells difficult and imprecise. Herein, we propose a novel method that combines femtosecond laser two-photon polymerization (TPP) micromachining technology with the operation of optical tweezers (OTs) to achieve selective and targeted capture of single particles and cells. Diverse ordered microcages with different shapes and dimensions were self-assembled by micropillars fabricated via TPP. The micropillars with high aspect ratios were processed by single exposure, and the parameters of the micropillar arrays were investigated to optimize the capillary-force-driven self-assembly process of the anisotropic microcages. Finally, single microparticles and cells were selectively transported to the desired microcages by manipulating the flexibly of the OTs in a few minutes. The captured microparticles and cells were kept trapped without additional forces.

An integrated biomimetic array chip for establishment of collagen-based 3D primary human hepatocyte model for prediction of clinical drug-induced liver injury.

Drug-induced liver injury (DILI) is a leading cause of therapy failure in the clinic and also contributes much to acute liver failure cases. Investigations of predictive sensitivity in animal models have limitations due to interspecies differences. Previously reported in vitro models of liver injury based on primary human hepatocytes (PHHs) cannot meet the requirements of high physiological fidelity, low cost, simple operation, and high throughput with improved sensitivity. Herein, we developed an integrated biomimetic array chip (iBAC) for establishing extracellular matrix (ECM)-based models. A collagen-based 3D PHH model was constructed on the iBAC as a case for the prediction of clinical DILI at throughput. The iBAC has a three-layer structure with a core component of 3D implanting holes. At an initial cell seeding numbers of 5000-10,000, the collagen-based 3D PHH model was optimized with improved and stabilized liver functionality, including cell viability, albumin, and urea production. Moreover, basal activities of most metabolic enzymes on the iBAC were maintained for at least 12 days. Next, a small-scale hepatotoxicity screening indicated that the 3D PHH model on the iBAC was more sensitive for predicting hepatotoxicity than the 2D PHH model on the plate. Finally, a large-scale screening of liver toxicity using 122 clinical drugs further demonstrated that the collagen-based 3D PHH model on the iBAC had superior predictive sensitivity compared to all previously reported in vitro models. These results indicated the importance of 3D collagen for liver physiological functionality and hepatotoxicity prediction. We anticipant it being a promising tool for risk assessment of drug-induced hepatotoxicity with a widespread acceptance in drug industry.

Efficacy and safety of endoscopic full-thickness resection in the colon and rectum using an over-the-scope device: a meta-analysis.

OBJECTIVE: Relevant publications were identified by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science before December 1, 2019. Studies in which ≥ 10 cases of colorectal lesions were resected with endoscopic full-thickness resection (EFTR) were included. Rates of efficacy (technical success (en bloc), full-thickness resection and R0 resection), rates of safety (bleeding, perforation and postpolypectomy syndrome) and rates of follow-up (residual/recurrent adenoma, fate of over-the-scope clip and surgery for any reason) were pooled and analyzed. Forest plots were graphed based on random effects models. Subgroup analyses and sensitivity analyses were also performed if significant heterogeneity existed. RESULTS: A total of 469 patients across 9 studies were eligible for analysis. The pooled rates of technical success, full-thickness resection and R0 resection were 94.0% (95% CI 89.8-97.3%), 89.5% (83.9-94.2%) and 84.9% (75.1-92.8%), respectively. The pooled estimates of bleeding, perforation and postpolypectomy syndrome were 2.2% (95% CI 0.4-4.9%), 0.19% (95% CI 0.00-1.25%) and 2.3% (95% CI 0.1-6.3%), respectively. Finally, the pooled rates of residual/recurrent adenoma, fate of OTSC and surgery for any reason were 8.5% (95% CI 4.1-14.0%), 80.3% (95% CI 67.5-90.8%) and 6.3% (2.4-11.7%), respectively. CONCLUSIONS: EFTR for nonlifting, invasive lesions in the colon and rectum appears to be effective and safe. However, future studies are necessary to explore the role of EFTR in large colorectal lesions and specify its indications.

Effect of dynamic position changes during colonoscope withdrawal: a meta-analysis of randomized controlled trials.

BACKGROUND: Colonoscopies are considered to be the primary screening test and gold standard test for colorectal cancer. Position changes during colonoscope withdrawal are believed to be associated with an increased adenoma detection rate (ADR) and polyp detection rate (PDR). However, previous results conflicted, and this study aimed to elucidate the effectiveness of dynamic position changes during colonoscope withdrawal. METHODS: The relevant publications were identified by searching the medical databases. The primary outcomes were the ADR and PDR, which were pooled and analyzed. The secondary outcome was the withdrawal time. The studies that supplied the ADR and PDR for different segments of the colon were separated into subgroup analyses. RESULTS: Five randomized controlled trials were eligible for analysis. The total ADR was higher with dynamic position changes than with a static position (odds ratio, [OR] 1.34; 95% confidence interval [CI] 1.13-1.59; p < 0.001), with low evidence of between-study heterogeneity (I2 = 0%). Although the total PDR was slightly higher with dynamic position changes than with a static position (OR 1.23; 95% CI 0.88-1.73), there difference was not statistically significant (p = 0.22). The withdrawal time was only increased by 0.47 min (95% CI - 0.11 to 1.06) with dynamic position changes, without statistical significance (p = 0.11). The subgroup analysis showed that the ADR and PDR for the transverse colon were higher with dynamic position changes, with pooled estimates of ADR (OR 1.72; 95% CI 1.02-2.88; p = 0.04) and PDR (OR 1.79; 95% CI 1.08-2.96; p = 0.02). CONCLUSION: Dynamic position changes during colonoscope withdrawal increased the total ADR; however, no obvious increase was found in the total PDR. The withdrawal time was not significantly prolonged with dynamic position changes. Subgroup analysis showed that the ADR and PDR in the transverse colon were obviously improved with dynamic position changes.

Underwater endoscopic mucosal resection for colorectal lesions: a meta-analysis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) of colorectal lesions is emerging as an alternative method to conventional endoscopic mucosal resection (CEMR). This study aimed to evaluate the feasibility and safety of UEMR for colorectal lesions. METHODS: The PubMed, Embase, Cochrane and Web of Science databases were searched before May 10, 2020. The primary outcomes were en bloc resection rate (feasibility) and adverse event rate (safety). The secondary outcome was recurrence and residual adenoma rate. If there was a comparison between UEMR and CEMR, data about en bloc resection, delayed bleeding, and recurrence and residual adenoma were extracted and compared. The pooling of the effect size was conducted using random-effects models, and the Q-statistic, τ2, and I2 were used to evaluate heterogeneity. RESULTS: Seventeen studies (759 patients, 893 lesions) were included. The pooled estimate for the en bloc resection rate was 59% (95% CI 43-75%) with significant heterogeneity (I2 = 97%). Due to the heterogeneity, it is not suitable to conduct pooled estimates analysis, so the en bloc resection rate was from 10 to 89%. The pooled estimate for delayed bleeding was 2% (95% CI, 1%-3%) and only two cases had perforation. The pooled rate of recurrence and residual adenoma was 5% (95% CI 2%-8%). Compared with CEMR, UEMR could achieve a higher en bloc resection rate (OR 1.61; 95% CI 1.02-2.53; p = 0.04) with a lower rate of recurrence and residual adenoma (OR 0.18; 95% CI 0.07-0.46; p < 0.01). CONCLUSIONS: UEMR for colorectal lesions was capable of a high en bloc resection rate, low adverse event rate and low recurrence. UEMR may be considered an effective and safe alternative for treating colorectal lesions.