An alternating continuous integration system for magnetic measurements for experimental advanced superconducting tokamak.

Integrators are critical instruments used for magnetic measurement systems (MMSs) in tokamaks, and, currently, the Experimental Advanced Superconducting Tokamak (EAST) has over 600 deployed. However, these integrators, designed with real-time drift compensation, will not be able to support longer pulse operations in the near future due to saturation and drift. To address these issues, this paper proposes a new alternating integration system combining analog integration with drift digital rectification. This system utilizes a microcontroller unit (MCU) to control two parallel analog integrators to work alternatively, compensate their drifts based on their respective error characteristics, and assemble the two integration segments together. The designed architecture provides highly flexible capabilities in operation modes and error correction, which make the system operation and maintenance highly automated. Performance tests on the EAST experiment site show that the prototype integrator can meet the requirements of real-time plasma control for a duration of hour-level.

[Progress on health-related quality of life and its influencing factors in patients with tuberculosis sequelae].

With the emergence of new tuberculosis patients, the number of patients with tuberculosis sequelae is increasing, which not only increases the medical burden of tuberculosis sequelae year by year, but also affects the health-related quality of life (HRQOL) of patients. The HRQOL of patients with tuberculosis sequelae has gradually received attention, but there are few relevant studies. Studies have shown that HRQOL is related to various factors such as post-tuberculosis lung disease, adverse reaction to anti-tuberculosis drugs, decreased physical activity, psychological barriers, low economic status and marital status. This article reviewed the current situation of HRQOL in patients with sequelae of tuberculosis and its influencing factors, in order to provide a reference for improving the quality of life of patients with sequelae of tuberculosis.

[Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy].

OBJECTIVE: To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA). METHODS: The transgenic mice with type Ⅰ SMA (Smn-/- SMN20tg/2tg) and littermate control mice (Smn+/- SMN20tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 µL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice. RESULTS: The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial ß oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01). CONCLUSION: Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA.

[Genomic structure of varicella-zoster virus and its vaccine application status].

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.

Inhibitory effect and mechanism of Lactobacillus crispatus on cervical precancerous cells Ect1/E6E7 and screening of early warning factors.

OBJECTIVE: To study the potential mechanism of Lactobacillus crispatus inhibiting cervical squamous intraepithelial lesion (SIL) and screen the early warning factors of SIL. METHODS: The effects of Lactobacillus crispatus on the proliferation, apoptosis, cross pore migration and invasion and cytokines of cervical precancerous cells Ect1/E6E7 were detected respectively. The effect of Lactobacillus crispatus on the expression of differential proteins screened in Ect1/E6E7 cells were detected by Western blot. RESULTS: Lactobacillus crispatus significantly inhibited the proliferation, induced apoptosis and inhibited cell migration of Ect1/E6E7 cells in a time-dependent manner (P < 0.05), but had no significant effect on cell invasion. Lactobacillus crispatus significantly promoted the secretion of Th1 cytokines and inhibited the secretion of Th2 cytokines by Ect1/E6E7 cells (P < 0.05). In addition, compared with SiHa cells in the control group, the expression of differential proteins PCNA, ATM, LIG1 and HMGB1 in Ect1/E6E7cells decreased significantly, while the expression of TDG and OGG1 proteins increased significantly (P < 0.05). ABCG2 protein in Ect1/E6E7 cells was slightly higher than that in SiHa cells, but the difference was not statistically significant. What is interesting is that Lactobacillus crispatus significantly inhibited the expression of ABCG2, PCNA, ATM, LIG1, OGG1 and HMGB1 proteins in Ect1/E6E7 cells, and promoted the expression of TDG protein. CONCLUSIONS: Lactobacillus crispatus may inhibit the function of Ect1/E6E7 cells through multiple pathways and exert the potential to reverse the progression of SIL.

Simulations of neutral beam injection and ion cyclotron resonance heating synergy in high power EAST scenarios.

The EAST plasmas heated with deuterium neutral beam injection and ion cyclotron resonance heating (ICRH) have been simulated by the TRANSP code. The analysis has been conducted using the full wave solver TORIC5, the radio frequency (RF)-kick operator, and NUBEAM to model the RF heating effects on fast ion velocity distribution. In this work, we present several simulated results compared with experiments for high power EAST scenarios, indicating that the interactions between ICRH and fast ions can significantly accelerate fast ions, which are confirmed by the increased neutron yield and broadened neutron emission spectrum measurements.

Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes.

BACKGROUND: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method. METHODS: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion protocol (REP) with anti-CD3. Before and after the REP, expanded TIL were phenotyped and the complementarity-determining region 3 ß variable region of the T-cell receptor (TCR) was sequenced to assess the T-cell repertoire. RESULTS: TIL 3.0 robustly expanded NSCLC TIL while enriching for CD8+ TIL in a shorter manufacturing time when compared with the traditional TIL 1.0 method, achieving a higher success rate and producing 5.3-fold more TIL per successful expansion. The higher proliferative capacity and CD8 content of TIL 3.0 was also observed after the REP. Both steps of expansion did not terminally differentiate/exhaust the TIL but a lesser differentiated population was observed after the first step. TIL initially expanded with the 3.0 method exhibited higher breadth of clonotypes than TIL 1.0 corresponding to a higher repertoire homology with the original tumor, including a higher proportion of the top 10 most prevalent clones from the tumor. TIL 3.0 also retained a higher proportion of putative tumor-specific TCR when compared with TIL 1.0. Numerical expansion of TIL in a REP was found to perturb the clonal hierarchy and lessen the proportion of putative tumor-specific TIL from the TIL 3.0 process. CONCLUSIONS: We report the feasibility of robustly expanding a T-cell repertoire recapitulating the clonal hierarchy of the T cells in the NSCLC tumor, including a large number of putative tumor-specific TIL clones, using the TIL 3.0 methodology. If scaled up and employed as a sole expansion platform, the robustness and speed of TIL 3.0 may facilitate the testing of TIL-ACT approaches in NSCLC.

[Effect and mechanism of siRNA targeting α-enolase gene combined with paclitaxel on proliferation, invasion and apoptosis of hepatocellular carcinoma cell].

Objective: To investigate the effect of siRNA targeting inhibition of α-enolase (ENO1) combined with paclitaxel on the proliferation, invasion and apoptosis of hepatocellular carcinoma SK-HEP-1 cell and its mechanism. Methods: siRNA-ENO1 (siRNA-ENO1 group) and siRNA-negative control (siRNA-NC group) were transfected into SK-HEP-1 cells in vitro, the untransfected SK-HEP-1 cells were used as the control group, and the transfection effect was detected by real-time fluorescent quantitative polymerase chain reaction and western blotting. After SK-HEP-1 cells were treated with 0, 2.5, 5, 10, 20 and 40 µg/L paclitaxel for 48 hours, the cell survival rate was measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) method and the semi inhibitory concentration of paclitaxel was calculated. SK-HEP-1 cells transfected with siRNA-ENO1 or siRNA-NC were treated with 10 µg/L paclitaxel as paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group. The proliferation, clonogenesis, invasion and apoptosis of siRNA-NC group, siRNA-ENO1 group, paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group were detected by MTT, clonogenesis, Transwell chamber and flow cytometry respectively. The expression levels of the phosphorylation of phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (Akt) and proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9) and B lymphocytoma-2 gene (Bcl-2) were detected by western blotting. Results: Compared with the control group (1.00±0.00 and 0.69±0.04, respectively), the expression levels of ENO1 mRNA and protein (0.25±0.03 and 0.23±0.02, respectively) in siRNA-ENO1 group decreased significantly (P<0.05), but there were no significant differences in the expression levels of ENO1 mRNA and protein in siRNA-NC group (P>0.05). Compared without treatment group [(100.00±0.00)%, P<0.05], the survival rates of SK-HEP-1 cells treated with 2.5, 5, 10, 20 and 40 µg/L paclitaxel [(88.65±6.46)%, (72.36±6.08)%, (60.48±4.23)%, (38.52±3.56)% and (20.75±2.32)%, respectively] decreased significantly (P<0.05), and the semi inhibitory concentration of paclitaxel was 13.26 µg/L. The cell survival rate and clone formation rate of siRNA-ENO1 group [(68.86±5.12)% and (18.12±2.25)%, respectively] were lower than those of siRNA-NC group [(100.00±0.00)% and (29.65±3.06)%, respectively, P<0.05]. The cell survival rate and clone formation rate of the paclitaxel+ siRNA-ENO1 group [(43.28±2.64)% and (8.72±0.52)%, respectively] were significantly different from those of the paclitaxel+ siRNA-NC group [(61.75±5.06)% and (13.48±2.16)%, respectively, P<0.05] and siRNA-ENO1 groups [(68.86±5.12)% and (18.12±2.25)%, respectively, P<0.05]. Cell invasion number in paclitaxel+ siRNA-ENO1 group (23.64±2.12) was lower than that in siRNA-ENO1 group and paclitaxel+ siRNA-NC group (42.16±2.75 and 37.35±2.42, respectively, P<0.05). The apoptosis rates of paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively] were higher than that of siRNA-NC group [(7.21±0.70)%, P<0.05]. The apoptosis rate in the paclitaxel+ siRNA-ENO1 group [(24.59±2.40)%] was higher than those in the paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively, P<0.05]. The expression levels of ENO1, PI3K/Akt signaling pathway related proteins including p-PI3K and p-Akt and the expression levels of PCNA, MMP-9 and Bcl-2 in siRNA-ENO1 group and paclitaxel+ siRNA-NC group were lower than those in siRNA-NC group (P<0.05). The expression levels of ENO1, p-PI3K, p-Akt, PCNA, MMP-9 and Bcl-2 in paclitaxel+ siRNA-ENO1 group were lower than those in siRNA-ENO1 group or paclitaxel+ siRNA-NC group (P<0.05). Conclusion: siRNA targeting inhibition of ENO1 expression can enhance the inhibitory effect of paclitaxel on proliferation, invasion and apoptosis of SK-HEP-1 cells, and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

Neutron emission and fast ion simulation for high performance long pulses at EAST.

Neutron emission spectroscopy and neutron yield measurements are important for high neutral beam injection (NBI) power heating at the Experimental Advanced Superconducting Tokamak (EAST). The neutron yields mainly depend on the deposition from NBI to the deuterium plasmas in the EAST. We have recently used TRANSP with time dependent diagnostic results to simulate the transport process of 30 s long pulse deuterium plasma discharges in the EAST, obtaining the time dependent fast ion distribution, neutron emission spectrum, and total neutron emission rate. Combined with the time trace of the result measured by a standard 235U fission chamber, the effects of different configurations of NBI heating in EAST fusion plasmas have been evaluated.

A compact stilbene crystal neutron spectrometer for NBI-heated plasma neutron diagnostics at EAST.

Stilbene crystal detectors are widely used as fast neutron measurement tools based on recoil proton detection, such as liquid scintillators. A compact stilbene crystal neutron spectrometer (CSCNS) has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to obtain information on fuel ions produced in the plasma core because of its merits of good n/γ discrimination capability, high detection efficiency, and fast response. For the first time, CSCNS has been used for neutron emission spectroscopy measurements in EAST plasmas with neutral beam injection (NBI) heating. The CSCNS has the same horizontal line of sight as the time-of-flight enhanced diagnostics neutron spectrometer. Under NBI heating scenarios, the time trace of the neutron yield monitored by the CSCNS is similar to the one monitored by a standard 235U fission chamber. The experimental pulse height spectra are also similar to the simulated ones generated by folding the simulated neutron energy spectrum with the detector response functions. These results demonstrate the capability of the CSCNS for neutron diagnostics and the study of fast-ion physics in EAST.

Ribosomal protein RPS15A augments proliferation of colorectal cancer RKO cells via regulation of BIRC3, p38 MAPK and Chk1.

OBJECTIVE: Ribosomal protein S15A (RPS15A) has been implicated in tumorigenesis, but its role in colorectal cancer (CRC) is not fully studied. The objective of this study was to investigate the role of RPS15A in CRC carcinogenesis. PATIENTS AND METHODS: RBSP15A expression was detected in 120 colorectal adenocarcinoma biopsies by immunohistological staining, and we examined the association of RSP15A expression with clinicopathological outcomes. We generated RPS15A stable knockdown CRC cell lines using shRNAs and assessed cell proliferation by MTT assays, clonogenicity by colony formation assays, and apoptosis and cell cycle arrest by flow cytometric analyses. A mouse tumor xenograft model was used to confirm the influence of RPS15A expression on CRC in vivo. RESULTS: RPS15A expression was predictive for poor disease-free survival. Knockdown of RPS15A expression significantly inhibited cell proliferation and colony formation and augmented apoptosis in both the RKO and SW620 CRC cell lines. Moreover, RPS15A knockdown arrested RKO cells at the G2/M phase and SW620 cells at the G0/G1 phase. KEGG pathway analysis of 785 genes differentially expressed between wild-type and shRPS15A RKO cells showed enrichment for the pathway in cancer and MAPK signaling pathway KEGG terms. RPS15A knockdown induced apoptosis via regulation of BIRC3, p38 MAPK, and Chk1. Consistently, RPS15A knockdown significantly impaired the growth of subcutaneous CRC xenografts in nude mice. CONCLUSIONS: These results indicate that RPS15A is a novel, potentially oncogenic gene involved in colorectal carcinogenesis. RPS15A knockdown may be an attractive strategy for treating CRC with gene therapy.

Triglyceride regulate ACE2 level through MTHFD1.

Obesity has been followed with interest as a risk factor for COVID-19, with triglycerides as one of four common criteria used to define obesity, which have been used to study the mechanism of obesity. In this study, we showed that angiotensin-converting enzyme-2 (ACE2) is widely expressed in the mouse body, including the kidney, spleen, brain, heart, lung, liver, and testis, and that ACE2 levels increased after a high-fat diet. The ACE2 levels were recorded at 0 days, 3 days, 7 days, and 14 days after a high-fat diet, and they increased at 14 days after high-fat diet initiation. In addition, triglyceride levels were also significantly increased at 14 days after high-fat diet initiation, but body weight was not changed. Furthermore, we examined the ACE2 levels in Calu3 cells (a lung cancer cell line) after triglyceride treatment, and the results indicated that ACE2 levels were increased at 25 µM and reached their peak at 200 µM. Finally, we found that the mRNA level of mthfd1 was significantly increased in the high-fat diet group. Given these findings, we hypothesize that triglycerides can regulate the expression of ACE2 and Mthfd1.

Applications and future directions for optical coherence tomography in dermatology.

Optical coherence tomography (OCT) is a noninvasive optical imaging method that can generate high-resolution en face and cross-sectional images of the skin in vivo to a maximum depth of 2 mm. While OCT holds considerable potential for noninvasive diagnosis and disease monitoring, it is poorly understood by many dermatologists. Here we aim to equip the practising dermatologist with an understanding of the principles of skin OCT and the potential clinical indications. We begin with an introduction to the technology and discuss the different modalities of OCT including angiographic (dynamic) OCT, which can image cutaneous blood vessels at high resolution. Next we review clinical applications. OCT has been most extensively investigated in the diagnosis of keratinocyte carcinomas, particularly basal cell carcinoma. To date, OCT has not proven sufficiently accurate for the robust diagnosis of malignant melanoma; however, the evaluation of abnormal vasculature with angiographic OCT is an area of active investigation. OCT, and in particular angiographic OCT, also shows promise in monitoring the response to therapy of inflammatory dermatoses, such as psoriasis and connective tissues disease. We additionally discuss a potential role for artificial intelligence in improving the accuracy of interpretation of OCT imaging data.

[Association between ocular dominance and refraction in myopic subjects].

Objective: To determine the association between ocular dominance and myopic-astigmatic characteristics in myopic subjects. Methods: Cross-sectional study. A total of 1 503 myopic subjects visiting from the myopiac clinic from December 2011 to December 2012 were included. The spheres and cylinders were recorded. The ocular dominance was determined by the hole-in-the-card test. The average spherical equivalent (SE) and the cylinder between the dominant eyes and the non-dominant eyes were compared with the paired t test. The associations between ocular dominance laterality and refractive characters were analyzed with the crosstab Chi-square test. Results: There were 527 males and 976 females in this study. The median (min, max) of age was 24 (17, 49) years old. Among the subjects, 66.00% (992/1 503) of subjects were right-eye dominant, while 34.00% (511/1 503) of subjects were left-eye dominant. The dominant eyes had significantly lower average sphere powers ï¼»(-5.01±1.91) D vs. (-5.10±1.99) Dï¼½ and lower average cylinder powers ï¼»(-0.70±0.68) D vs. (-0.76±0.73) Dï¼½ than the non-dominant eyes (t=2.976, 4.319; both P<0.01). In the subgroups of |ΔSE|≤0.50 D, 0.50 D<|ΔSE|≤1.00 D, 1.00 D<|ΔSE|≤2.00 D and |ΔSE|>2.00 D, respectively, the dominant eyes were lower myopic in 49.37% (355/719), 51.10% (163/319), 58.48% (100/171) and 65.56% (59/90) of the subjects. The inter-group difference was statistically significant (χ²=11.588, P=0.009). In the subgroups of |ΔCyl|≤0.25 D, 0.25 D<|ΔCyl|≤0.50 D and |ΔCyl|>0.50 D, the dominant eyes had lower astigmatism in 53.94% (89/165), 65.66% (65/99) and 69.70% (46/66) of the subjects, respectively. The inter-group difference was statistically significant (χ²=6.414, P=0.040). Conclusion: The ocular dominance laterality is significantly associated with lower myopia and lower astigmatism in the myopic subjects. (Chin J Ophthalmol, 2020, 56: 693-698).

Genomic assessment distinguishes intrapulmonary metastases from synchronous primary lung cancers.

BACKGROUND: Multiple synchronous lung tumors (MSLT), particularly within a single lobe, represent a diagnostic and treatment challenge. While histologic assessment was once the only method to possibly distinguish multiple primary lung cancers, there is a growing interest in identifying unique genomic features or mutations to best characterize these processes. METHODS: In order to differentiate multiple primary lung malignancies from intrapulmonary metastases in patients with MSLT, we performed whole exome sequencing (WES) on 10 tumor samples from 4 patients with MSLT. RESULTS: Shared mutations between tumors from the same patient varied from 0-91%. Patient 3 shared no common mutations; however, in Patients 2 and 4, identical mutations were identified among all tumors from each patient, suggesting that the three tumors identified in Patient 3 represent separate primary lung cancers, while those of Patients 1, 2 and 4 signify hematogenous and lymphatic spread. CONCLUSIONS: A high proportion of shared mutations between different lung tumors is likely indicative of intrapulmonary metastatic disease, while tumors with distinct genomic profiles likely represent multiple primary malignancies driven by distinct molecular events. Application of genomic profiling in the clinical setting may prove to be important to precise management of patients with MSLT.

The utility of dried blood spot monitoring of branched-chain amino acids for maple syrup urine disease: A retrospective chart review study.

BACKGROUND: Branched-chain amino acid (BCAA) concentrations must be tracked and maintained within an optimal range to minimize disease phenotypes in patients with maple syrup urine disease (MSUD). In 2014, the Hospital for Sick Children (SickKids) implemented a dried blood spot (DBS) home monitoring system, allowing patients to track BCAA concentrations without the inconvenience of having to travel to the hospital. METHODS: We conducted a retrospective chart review study (n = 15) to assess the impacts of DBS monitoring implementation on biochemical control. Furthermore, we explored relationships among various MSUD patient parameters, including monitoring frequency, age, biochemical control, and hospitalizations. RESULTS: There was a 35% increase in the proportion of LEU concentrations that met recommended targets post-DBS monitoring implementation. Monitoring frequency was positively associated with better biochemical control in the newborn period (r = 0.68, p = 0.046). Frequency of hospital visits decreased steadily throughout life. CONCLUSION: DBS monitoring has resulted in a sharp increase in monitoring frequency, which is further correlated with biochemical control. Younger patients are more likely to visit the hospital and respond better to increased monitoring efforts. We recommend that DBS monitoring be adopted by other centers more broadly to improve metabolic control in MSUD patients.

[Value of ceramide in the diagnosis and risk prediction of coronary artery disease].

Objective: To evaluate the clinical values of 4 types of ceramides (Cer1, Cer2, Cer3, Cer4) in the coronary artery stenosis, clinical diagnosis and risk prediction. Methods: A total of 890 patients with coronary heart disease (CHD) in Beijing Anzhen Hospital between March 2018 and August 2018 were enrolled. The relationships between different degrees of coronary artery stenosis and ceramide levels was investigated. Diagnostic value of ceramides on acute myocardial infarction was analyzed. Meanwhile, Major adverse cardiac and cerebrovascular events (MACCE) in 1 year after discharging were collected to evaluate the predictive value of ceramides on risk of CHD and stroke. Results: This study showed that there were no significant differences of ceramide levels in CHD patients with different degrees of coronary artery stenosis (P>0.05), and the area under receiver operating characteristic (ROC) curve in the diagnosis of acute myocardial infarction patients was 0.725. Conclusions: Ceramide is proved to be helpful in the diagnosis of acute myocardial infarction and MACCE prediction. The relationships between ceramide and degrees of coronary artery stenosis as well as the prognosis of CHD need further elucidation.

Promising High-Confinement Regime for Steady-State Fusion.

A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.