AIM: To explore the clinical application effect of visual training equipment combined with conventional corrective treatment on children with ametropic amblyopia(AMA).METHODS: Prospective randomized control study. A total of 188 children(376 eyes)with AMA treated in our hospital from June 2021 to December 2022 were selected, and they were divided into two groups using a random number table. The conventional correction group(94 cases, 188 eyes)received conventional correction treatment, while the visual training group(94 cases, 188 eyes)received visual training equipment combined with conventional correction treatment, both lasted for 12 mo. The best corrected visual acuity, diopter, eye accommodation function, adverse reactions, amblyopia recurrence rates, and clinical efficacy were compared between the two groups at 6 and 12 mo after treatment.RESULTS:The two groups each had 8 cases(16 eyes)detached, the rate of loss to follow-up was 8.5%, and 86 cases(172 eyes)were included in each group. There were statistically significant differences in the best corrected visual acuity, diopter, amplitude of accommodation, accommodation facility and accommodative lag between the two groups of children before and after treatment(all P<0.05). The total effective rate of the visual training group(98.8%)was higher than that of the conventional correction group(91.9%; P<0.05). There was no statistically significant difference in the total effective rate of clinical efficacy between the two groups in different age groups and different degrees of amblyopia(all P>0.05). There was no statistically significant difference in the incidence of redness and swelling between the two groups(P>0.05). The recurrence rate of amblyopia in the visual training group(1.2%)was lower than that in the conventional correction group(8.1%; P<0.05).CONCLUSION: The combination of visual training equipment and conventional correction therapy has a significant clinical effect on children with AMA, which can effectively correct visual acuity, adjusting diopter and improve eye accommodation function, and recurrence rate of amblyopia is low and safety is high.

ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells（BMSC-exos） modified with Bushen Yisui capsule（BSYS）-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups， including the normal（NC） group， BMSC-exos group， BSYS-BMSC-exos group， BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group， and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay（CCK-8）. Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos， and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR） detection of miR-15b-5p. The expressions of 2′，3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） and myelin proteolipid protein（PLP） in OLN-93 cells were detected by immunocytochemistry（ICC） and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR， and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells， including glycogen synthase kinase（GSK）-3β， β-catenin， and T-cell specific transcription factor 4/transcription factor 7-like 2（TCF4/TCF7L2）， were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L^-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability（P<0.01） and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs， Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs（P<0.01）， and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos（P<0.01）. ICC analysis further revealed an increase in the number of differentiated， mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment（P<0.01）. Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment（P<0.01）. Additionally， BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells， while decreased the mRNA and protein expressions of Wnt3a， as well as the mRNA expressions of β-catenin and TCF4/TCF7L2， and the protein expression level of p-GSK-3β（Ser9） was significantly reduced（P<0.05， P<0.01）. After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos， the above effects were significantly diminished（P<0.05， P<0.01）. ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells， and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells， which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Traditional Chinese medicine (TCM) is an ancient medical system distinctive and effective in treating cancer, depression, coronavirus disease 2019 (COVID-19), and other diseases. However, the relatively abstract diagnostic methods of TCM lack objective measurement, and the complex mechanisms of action are difficult to comprehend, which hinders the application and internationalization of TCM. Recently, while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research, the rise of machine learning (ML) has significantly enhanced their integration with TCM. This article introduces representative methodological cases in quality control, mechanism research, diagnosis, and treatment processes of TCM, revealing the potential applications of ML technology in TCM. Furthermore, the challenges faced by ML in TCM applications are summarized, and future directions are discussed.

Porcine epidemic diarrhea virus (PEDV) is an intestinal coronavirus that can cause porcine epidemic diarrhea, leading to diarrhea, vomiting, weight loss, and even death in piglets. Due to the diversity of PEDV strains, traditional vaccines are difficult to sustainably and effectively prevent and control PEDV. This article reviews the strategies and mechanisms of active substances in regulating intracellular signaling pathways, viral proteins, and microbial metabolites to enhance the host immune function against PEDV. It emphasizes the prevention of PEDV resistance and the potential harm of PEDV breaking through interspecies barriers to the human society, aiming to provide reliable theoretical support for the development of new antiviral drugs or vaccines.
Porcine epidemic diarrhea virus/immunology* ; Animals ; Swine ; Swine Diseases/prevention & control* ; Antiviral Agents/pharmacology* ; Coronavirus Infections/virology* ; Viral Vaccines/immunology* ; Humans ; Signal Transduction

Administrative multi-disciplinary team (MDT) is an efficient management approach that involves multiple administrative departments working together to solve cross functional systemic problems. Grid management improves management efficiency by constructing a three-level management network, efficiently transmitting information and coordinating resources. Starting from 2021, Children′s Hospital, Zhejiang University School of Medicine has adopted a combination of administrative MDT and grid management, with the average length of stay as the starting point to carry out medical efficiency management. Through the three stages of pre-, during-, and post-treatment, the hospital has reconstructed processes from technological innovation, information construction, team collaboration, and other aspects to shorten ineffective length of stay. After 3 years of practice, the average length of stay has been reduced from 6.41 d to 5.54 d, achieving an improvement in service efficiency while ensuring medical quality and safety.

Objective To investigate the diagnostic value of three-dimensional power Doppler ultrasound(3D-PDUS)in fetal growth restriction(FGR).Methods A total of 120 pregnant women in the third trimester who were given birth in Wenzhou People's Hospital from September 2021 to December 2023 were selected as study objects,50 pregnant women with FGR confirmed by clinical and ultrasound were included in case group,and 70 pregnant women with normal fetal development were included in control group.The renal volume and renal blood flow parameters of the fetuses in two groups were compared.The pregnancy outcomes and perinatal conditions of two groups were compared.Receiver operating characteristic(ROC)curve was plotted to calculate the area under the curve(AUC),and the diagnostic efficacy of various blood flow parameters for FGR was evaluated.Results The renal volume/gestational week,renal vascularization index,vascularization flow index and renal artery peak systolic velocity of the fetuses in case group were significantly lower than those in control group,while renal artery peak systolic velocity/end diastolic velocity,pulsation index and resistance index were significantly higher than those in control group(P＜0.05).There was no significant difference in renal flow index between two groups(P＞0.05).ROC curve results showed that the diagnostic efficacy of renal volume/gestational week and renal artery peak systolic velocity were higher,while the diagnostic efficacy of combined application was the highest,with an AUC of 0.89.The rate of low birth weight infants in case group was significantly higher than that in control group,and neonatal Apgar score was significantly lower than that in control group(P＜0.01).Conclusion 3D-PDUS quantitative analysis parameters evaluated renal volume and blood perfusion could predict FGR,which is conducive to early diagnosis of FGR and guide clinical intervention,and effectively reduce adverse pregnancy outcomes.

Objective To investigate the effects of dimethyl itaconate(DMI)on the secretion of pro-inflammatory factors in dendritic cells(DCs)and on the interphotoreceptor retinoid-binding protein(IRBP)1-20-specific T helper 17(Th17)cells in mice with experimental autoimmune uveitis(EAU).Methods Bilateral femur and tibia of C57BL/6J mice were isolated to obtain bone marrow cells,and these bone marrow cells were directionally induced with granulocyte macrophage-colony-stimulating factor(GM-CSF)and interleukin(IL)-4 to differentiate DCs.After 6 days,DCs were ran-domly divided into the DMI group and the phosphate-buffered saline(PBS)group.Cells in the DMI group were pretreated with 250 μmol·L-1 DMI,and cells in the PBS group were pretreated with the same volume of PBS for 3 hours.After-wards,100 μg·L-1 lipopolysaccharide was added in the every group to stimulate cells for 24 hours.The relative mRNA ex-pression levels of IL-6,IL-1 β,and IL-23 in DCs were measured by quantitative real-time polymerase chain reaction(qRT-PCR).The EAU model was constructed by actively immunizing mice with IRBP1-20,Freund's incomplete adjuvant,and my-cobacterium tuberculosis H37RA.Thirteen days after immunization,T cells in the spleen and lymph node isolated from EAU mice were cocultured with DMI-treatedor PBS-treated DCs in the medium containing IRBP1-20.They polarized toward Th17 cells.The percentage of Th17 cells in the cocultured cells was detected by flow cytometry.The IL-17 level in the coculture supernatant was detected by enzyme-linked immunosorbent assay(ELISA).qRT-PCR was performed to detect the relative mRNA expression levels of retinoid-related orphan receptor gamma t(RORγt),IL-17,IL-23R,and GM-CSF in the cocultured cells.Results qRT-PCR analysis revealed that the relative mRNA expression levels of IL-6,IL-1β,and IL-23 in the DMI group were significantly lower thanthose in the PBS group(all P＜0.05).Flow cytometry analysis showed that the proportion of Th17 cells in the cocultured cells in the DMI group was significantly lower than that in the PBS group(P＜0.05).ELISA analysis exhibited that the IL-17 level in the coculture supernatant in the DMI group was significantly lower than that in the PBS group(P＜0.05).The relative mRNA expression levels of IL-17,ROR-γt,IL-23R and GM-CSF in cocultured cells in the DMI group significantly decreased compared with the PBS group(all P＜0.05).Conclusion DMI can reduce the expression of IL-6,IL-1β and IL-23 in DCs,thus negatively modulating the responses of IRBP1-20-specific Th17 cells.

Objective:To investigate the effect of long noncoding RNA (lncRNA) 5033413D16Rik (lncRNA 5033413D16Rik) on the activity of interphotoreceptor retinoid-binding protein 1-20 (IRBP) 1-20-specific T helper 17 (Th17) cells in experimental autoimmune uveitis (EAU). Methods:Twelve SPF grade C57BL/6 female mice aged 8 to 10 weeks were selected and divided into EAU group and normal control group using the random number table method, with 6 mice in each group.Mice in the normal control group received no treatment.Mice in the EAU group were immunized with IRBP 1-20 emulsified in complete Freund's adjuvant to induce EAU.On day 13 after immunization, fundus examination and inflammation scoring were performed, and retinal histopathological changes were observed with hematoxylin and eosin staining.T cells were isolated from the spleen and lymph nodes of EAU mice, and the relative expression of lncRNA 5033413D16Rik was detected by real-time fluorescence quantitative PCR (qRT-PCR).In addition, the isolated T cells were divided into short hairpin RNA (shRNA)-5033413D16Rik transfected group and shRNA-negative control (NC) transfected group, and transfected with corresponding shRNAs, respectively.The knockdown efficiency of shRNA-5033413D16Rik was verified by qRT-PCR.T cells in the two groups were co-cultured with bone marrow-derived dendritic cells (BMDCs) under Th17 polarizing conditions.The relative expression of retinoic acid-related orphan receptor (RORγt), interleukin 17 (IL-17), IL-23 receptor (IL-23R), and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA in co-cultured cells were analyzed by qRT-PCR.The IL-17 concentration in co-culture supernatants was assayed by ELISA and percentages of Th17 cells were determined by flow cytometry.The use and care of experimental animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals promulgated by the State Science and Technology Commission.The study protocol was reviewed and approved by the Experimental Animal Ethics Committee of Tianjin Medical University (No.TJYY2019110117). Results:EAU model was established successfully.qRT-PCR analysis showed that the expression of lncRNA 5033413D16Rik was significantly decreased in T cells from EAU mice compared with normal control mice ( t=-13.332, P<0.001).Compared with the shRNA-NC transfected group, the relative expression of lncRNA 5033413D16Rik in T cells of the shRNA-5033413D16Rik transfected group was significantly reduced ( t=-6.338, P<0.01).In co-cultured T cells, the expression levels of RORγt, IL-17, IL-23R, and GM-CSF mRNA in shRNA-5033413D16Rik transfected group were 1.61±0.13, 1.51±0.13, 1.85±0.33 and 1.45±0.11, which were significantly higher than 1.00±0.01, 1.00±0.01, 1.00±0.01 and 1.00±0.01 in shRNA-NC-transfected group ( t=-6.839, -8.221, -4.538, -4.189; all at P<0.05).ELISA analysis revealed that IL-17 concentraion in shRNA-5033413D16Rik transfected group was (2 350.39±367.02)pg/ml, which was significantly higher than (1 513.31±310.37)pg/ml ( t=-3.016, P=0.039).Flow cytometry showed that the percentage of Th17 cells in shRNA-5033413D16Rik transfected group was (17.20±0.44)%, which was higher than (14.10±0.84)% in normal control group ( t=-3.264, P=0.031). Conclusions:LncRNA 5033413D16Rik can inhibit the expression of pathogenicity related genes in antigen-specific Th17 cells and negatively regulates IRBP 1-20-specific Th17 cell responses.

Objective In order to clarify the identification path and the followed principles in this kind of pathological-related medical damage identification,explore the prevention and resolution ideas of pathological medical disputes in the medical and health departments,and build a path for the people's court to hear the cases of pathological medical injury liability disputes.Methods Taking the judgement of medical damage liability disputes that took effect in 2019-2023 and published on the judgement document network as a sample,conduct a retrospective analysis in terms of the site of lesion,medical fault,the consequences of the damage,the causal relationship and the degree of cause(degree of participation),the degree of accident classification and responsibility,the selection of appraisal method,and the acceptancde of appraisal opinions.Results From the analysis of the lesion site,there is a high proportion of misdiagnosis in breast,lung,thyroid,skin and uterus;from the analysis of medical fault,58.4%of delayed treatment and 41.6%of overtreatment due to improper selection of treatment plan;from the analysis of the consequences of damage,the consequences of death only account for about 20%.Most of them are in the category of living appraisal;from the analysis of responsibility division,medical institutions bear secondary reasons,accounting for 30.3%;from the analysis of appraisal and acceptance,medical damage identification methods are mostly used,and the court's acceptance of appraisal opinions reaches 92.1%.Conclusion(1)There are more pathological disputes involving women's bodies,and misdiagnosis is the most in the type of fault;(2)Forensic clinical professional appraisers can also participate in the identification of medical damage involving pathological diagnosis;(3)For cases of medical damage liability disputes involving pathological diagnosis and the consequences of death,the cause of death should be identified;(4)Medical damage identification should be in accordance with the principle of peer review.