Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

The report of the 20th National Congress of the Communist Party of China has made a major deployment to promote the expansion of high-quality medical resources and balanced regional layout, and the construction of national regional medical centers is an important measure to implement the landing. By analyzing the " three co-construction" mode of the National Children′s Regional Medical Center of Henan Children′s Hospital (Beijing Children′s Hospital Zhengzhou Hospital), this paper systematically introduced the internal and external decision-making, management and operation of the regional medical center from four aspects: management, talent, discipline and system. The practice and effectiveness in talent introduction and training, salary distribution, two-way communication, assessment and incentive, discipline construction, technology application, sharing and evaluation of scientific and technological innovation, institutional linkage and integration, as well as the construction of a hierarchical diagnosis and treatment system, were put forward. Suggestions such as construction according to local conditions, strengthening internal coordination, and optimizing external guarantee were put forward, so as to provide practical reference for the in-depth promotion of other national regional medical center construction projects.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

Hyperlipidemia is a dyslipidemia caused by dyslipidemia of lipid metabolism， which can be divided into primary and secondary types. The current clinical diagnostic criteria are mainly changes in lipid levels， which are the inducers of high-risk cardiovascular diseases such as atherosclerosis， pancreatitis and coronary heart disease. As a key target in lipid metabolism， peroxisome proliferator-activated receptor α （PPARα） is involved in a variety of metabolic activities， including fatty acid degradation， synthesis， transport， storage， lipoprotein metabolism， etc. Activation of PPARα can maintain the balance of lipid metabolism through a variety of ways， which is an important way to treat hyperlipidemia. At present， chemical drugs such as statins and bettes are mainly used in the clinical treatment of hyperlipidemia. Although they can slow down the disease to a certain extent， there are many adverse reactions and drug resistance. By reviewing the literature in recent years， the author found that the activation of PPARα pathway by traditional Chinese medicine in the treatment of hyperlipidemia has significant effect and small adverse reactions. The lipid-lowering active ingredients include flavonoids， alkaloids， phenols， terpenoids and other compounds. These active components mainly affect the expression of downstream effectors through the activation of PPARα pathway， thereby inhibiting the synthesis of total cholesterol and promoting fatty acid oxidation， and play a role in the treatment of hyperlipidemia. In this paper， we systematically reviewed the structure types and mechanism of active components of traditional Chinese medicine that activate PPARα pathway， so as to provide guidance for the rational development and clinical application of lipid-lowering traditional Chinese medicine new drugs.

BACKGROUND: Standard two-dimensional (2D) culture has confirmed the mechanism of mast cells (MCs) in the pathogenesis of inflammatory bowel disease (IBD), but the regulation of signaling responses of MCs may well differ in three-dimensional (3D) microenvironments. The aim of the study was to develop a 3D culture model based on decellularized intestinal scaffolds (DIS) and verify how MCs influenced fibroblasts phenotype in the 3D model. METHODS: DIS were achieved using the detergent technique and extracellular matrix (ECM) components were verified by histologic analysis, quantification and scanning electron microscope. After human colon fibroblasts recellularized into the scaffolds and activated by MCs tryptase and TGFb1, the changes in genes and signaling pathways during fibroblasts activation in 3D were studied and compared with the changes in 2D cell culture on plastic plates. RESULTS: Decellularization process effectively removed native cell debris while retaining natural ECM components and structure. The engrafted fibroblasts could penetrate into the scaffolds and maintain its phenotype. No matter whether fibroblasts were cultured in 2D or 3D, MCs tryptase and transforming growth factor b1 (TGF-b1) could promote the differentiation of fibroblasts into fibrotic-phenotype myofibroblasts through Akt and Smad2/3 signaling pathways. Furthermore, the pro-collagen1a1 and fibronectin synthesis of myofibroblasts in 3D was higher than in 2D culture. CONCLUSION Our results demonstrated that the DIS can be used as a bioactive microenvironment for the study of intestinal fibrosis, providing an innovative platform for future intestinal disease modeling and screening of genes and signaling pathways.

OBJECTIVE: To carry out prenatal diagnosis for a fetus with normal ultrasonographic finding at 20 weeks' gestation but a copy number variant(CNV) of 13q indicated by non-invasive prenatal test (NIPT). METHODS: Karyotyping analysis and chromosomal CNV assay were carried out on the amniotic fluid sample. Parental peripheral blood sample was collected for chromosomal analysis. Detailed fetal ultrasound scan was carried out to rule out structural abnormalities of the fetus. RESULTS: The fetus was detected with a heterozygous 10.14 Mb deletion at 13q21.1q21.32, which has originated from the phenotypically normal mother. No apparent karyotypic abnormality was detected in the fetus and its parents. No ultrasonic abnormality was found in the fetus. CONCLUSION Both the fetus and its mother have carried a heterozygous 10.14 Mb deletion at 13q21.1q21.32 and presented normal phenotypes.Combined with literature review, the segmental deletion was judged to be a benign variant.
Female ; Genetic Counseling ; Humans ; Karyotyping ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

OBJECTIVE: To explore the genetic etiology in four patients with hyperbilirubinemia, and discuss the correlation between clinical characteristics and molecular basis. METHODS: The data of clinical manifestation and auxiliary examinations were collected. Genomic DNA of the four patients was extracted and analyzed by next-generation sequencing using the panel including genes involved in hereditary metabolic liver diseases. Suspected variants were verified by Sanger sequencing. RESULTS: All of the four patients were males with normal liver enzymes. It was revealed that all the patients had heterozygous variants, among which c.3011C>T, c.2443C>T and c.2556del were the variants which have not been reported previously. CONCLUSION All of the patients were diagnosed as Dubin-Johnson syndrome (DJS) caused by ABCC2 gene variants. The novel variants add to the spectrum of genetic variants of the disease. Because of the favorite prognosis, precise diagnosis can greatly reduce the psychological pressure of patients and avoid excessive treatments. At the same time, it could provide pertinent genetic counseling for the families.
DNA ; Female ; Heterozygote ; Humans ; Jaundice, Chronic Idiopathic/genetics* ; Male ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Phenotype

Objective:To explore the effect of visual processing patterns on emotional face processing in patients with Alzheimer's disease (AD).Methods:From June 2020 to August 2021, twenty-two AD patients (AD group) who met the conditions of this study were selected from the memory impairment clinic of the First Affiliated Hospital of Anhui Medical University, and demographically matched twenty-one elderly healthy people (control group) were selected from the patients' family members and community residents. The two groups of subjects performed emotional face visual scanning and facial recognition experiments after completing the evaluation of the cognitive scale and eye movement data were recorded in the emotional face visual scanning task. Statistical analysis of the obtained results was performed using SPSS 23.0 Windows version software. The data that conformed to the normal distribution were tested by independent samples t-test and variance analysis, and the data that did not conform to the normal distribution were tested by nonparametric test. Results:(1)In the emotional face recognition task, the total accuracy of facial emotion recognition of AD patients(0.52(0.42, 0.59)) was lower than that of the normal control group(0.67(0.64, 0.69)), and the difference was statistically significant( Z=-4.023, P<0.01), which was mainly manifested in recognizing complex facial emotion. (2) In the emotional face visual processing task, the saccade count ((1.96±0.97), (2.50±0.44)), fixation count ((3.93±2.58), (6.37±2.08))and fixation time ((1 205.89±727.32)s, (1 761.38±525.54)s)of AD patients were lower than those of the control group( t=-2.314, -3.402, -2.880, all P<0.05), and the surrounding facial fixation time (384.95 (276.51, 587.78)s, 276.06 (190.03, 384.55)s) was higher than that of the control group( Z=-2.478, P=0.013). Patients with AD had a lower fixation count than that in the control group on the eye area of surprise ((3.76±2.90), (6.25±2.19)), anger ((4.48±2.72), (7.06±2.55)) and disgust ((4.10±2.45), (6.67±2.45)), and the differences were statistically significant ( t=-3.164, -3.207, -3.436, all P<0.05). Patients with AD had a lower fixation time than those of the control group on the eye area of surprise ((1 150.26±753.22)s, (1 779.91±551.66)s), angry ((1 430.85±869.52)s, (1 944.51±612.63)s) and disgust ((1 266.14±765.67)s, (1 898.33±676.02)s), and the differences were statistically significant ( t=-3.115, -2.247, -2.865, all P<0.05). (3) Spearman correlation analysis showed that the accuracy of overall emotional face recognition was positively correlated with the fixation time in the eye area in AD patients ( r=0.429, P<0.05). Conclusion:The impaired visual processing of AD patients causes emotional face recognition disorders. Therefore, AD patients have different visual processing patterns in emotional face processing than age-matched normal controls, mainly manifested as the decreased fixation on the eye area.

The authors took the management practice of " one hospital with multiple districts" in Children′s Hospital Affiliated of Zhengzhou University as the research object, analyzed the main problems and challenges faced by the multi-district hospital management under the new pattern of national regional medical center. Through coordinating the hospital′s strategic planning and the development of discipline layout, building an integrated management system, improving the level of homogeneous service and other key countermeasures, the hospital has significantly improved its management efficiency and operation efficiency, and the medical service capacity of each district has developed in a balanced way. It could give full play to the pilot value for the construction of national regional medical center, hoping to provide reference for hospital administrators.