ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

Objectives:To analyze the disease burden and changing trends of non-rheumatic valvular heart disease(NRVHD)from 1990 to 2019 in China. Methods:Based on the Global Burden of Disease 2019 database,we collected data related to NRVHD in China from 1990 to 2019,analyzed the crude incidence rate,crude prevalence rate,crude disability-adjusted life year(DALY),and age-scaled rate of NRVHD during this period,and analyzed the corresponding trends.The grey prediction model GM(1,1)was used to predict the disease burden of NRVHD in China from 2020 to 2029. Results:The crude incidence,crude prevalence,and crude DALY rates of NRVHD increased in China from 7.87/100 000,123.21/100 000,and 9.83/100 000 in 1990 to 22.85/100 000,374.16/100 000,and 11.95/100 000 in 2019;the age-standardized incidence rate and the age-standardized prevalence rate increased from 9.22/100 000 and 169.04/100 000 in 1990 to 15.30/100000 and 262.85/100 000 in 2019 respectively,with females being higher than males;the age-standardized DALY rate declined from 13.43/100 000 in 1990 to 9.07/100 000 in 2019,with females being higher than males.Joinpoint regression model analysis showed an increasing trend in the age-standardized incidence rate and age-standardized prevalence rate,and a decreasing trend in the age-standardized DALY rate(annual average percentage change[AAPC]values of 1.86%,1.72%and-1.66%,respectively),trend of change was statistically significant(all P<0.05).The burden of disease for all age groups from 1990 to 2019 showed an overall increasing trend,and the crude incidence rate,crude prevalence rate and crude DALY rate all increased with age,and the elderly group over 60 years old was the main group of disease burden.The results of the grey prediction model showed that by 2029,the age-standardized incidence rate and age-standardized prevalence rate would increase to 18.51/100 000 and 303.26/100 000,respectively,and the age-standardized DALY rate would decrease to 7.42/100 000. Conclusions:From 1990 to 2019,the age-standardized incidence rate and age-standardized prevalence rate of NRVHD in China showed an increasing trend,and the age-standardized DALY rate all showed a decreasing trend.The disease burden of NRVHD in China remains high.Women and the senior population are the main target groups needing special attention in China,and more targeted prevention and treatment strategies are needed for high-risk population.

Objective:To express NY-ESO-1 epitopes using circular RNA (circRNA) and construct circRNA cancer vaccines using a novel lipid-like material C1, and to evaluate the transfection efficiency and T cell activation potential at cellular level.Methods:In vitro transcription was used to synthesize mRNA and circRNA expressing EGFP and NY-ESO-1 epitopes. Then, they were transfected into COS7 cells and the expression of target proteins were detected in vitro. Lipid-like material C1 and commercial transfection agent TransIT-mRNA were used as delivery systems for mRNA NY-ESO-1 and circRNA NY-ESO-1, and their delivery efficiency was compared. Results:The expression of EGFP was observed under fluorescence microscopy after transfection of mRNA EGFP and circRNA EGFP into COS7 cells for 24 h. The secretion of IFN-γ by T cell receptor-engineered T (TCR-T) cells targeting NY-ESO-1/HLA-A2 was stimulated by COS7-A*02: 01 cells transfected with mRNA NY-ESO-1 and circRNA NY-ESO-1. Compared with mRNA NY-ESO-1, circRNA NY-ESO-1 was able to express the target antigen and stimulate the target cells to release IFN-γ more persistently. The delivery efficiency of C1 material was better than that of commercial transfection reagents when COS7 cells were transfected in vitro. Conclusions:Compared with the linear mRNA, transfection of COS7-A*02: 01 cells with circRNA can lead to more efficient and durable activation of T cells, suggesting that it could be a more suitable candidate for clinical treatment of tumors in the future. The lipid-like material C1 can effectively deliver linear mRNA and circular RNA molecules. This study provides reference for further research on circRNA tumor vaccines.

Objective:To explore surgical strategies for acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries.Methods:From January 2019 to March 2023, a total of 29 patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries were included in the study. All patients underwent emergency surgery, with simultaneous intraoperative neck incision and replacement of the unilateral or bilateral carotid arteries. Among them, there were 19 males with a mean age of(49.57±2.14)years old. Preoperative brain CT indicated abnormalities in 15 cases, transient neurological dysfunction occurred in 5 cases, and syncope in 1 case.Results:Procedures included ascending aorta replacement in 10 cases, Bentall procedure in 18 cases, and Wheat procedure in 1 case. Arch operations involved partial arch replacement in 3 cases and Sun’s procedure in 26 cases. Simple left carotid artery replacement was performed in 6 cases, simple right carotid artery replacement in 19 cases, and bilateral carotid artery replacement in 4 cases. Cerebral protection measures during circulatory arrest included unilateral cerebral perfusion in 24 cases and bilateral cerebral perfusion in 5 cases. The mean operation time was(7. 6±0. 3) h, with a mean cardiopulmonary bypass time of(196. 3±8. 7) min, aortic cross-clamp time of(113.2±6.4) min, ischemic time 12(5-16.5) min, and lowest temperature of(26.3±0.4)°C. One patient experienced in-hospital mortality. Postoperatively, new neurological dysfunction occurred in 2 cases, including 1 case with coma and permanent neurological deficit.Conclusion:In patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries, simultaneous carotid artery replacement via neck incision during aortic surgery is a safe and reliable surgical approach.

Objective:To assess the diagnostic performance of serum anti-toxocara immunoglobulin G (anti-T-IgG) in ocular toxocariasis (OT) patients.Methods:A diagnostic tests. A total of 109 patients (109 eyes) with clinically-suspected OT who treated in Department of Ophthalmology of Xuzhou First People’s Hospital from June 2015 to December 2022 were included. Patients were divided into two groups, 76 with OT and 33 with non-OT, according to the clinical manifestations and Goldmann-Witmer coefficient. Paired serum and intraocular fluid samples from each patient were collected and analyzed for specific anti-T-IgG using enzyme linked immunosorbent assay. Mann-Whitney test was performed for comparison between groups. The area under the receiver operating characteristic curve (ROC) was used to assess the diagnostic performance of serum anti-T-IgG. Kappa analysis was performed to examine the consistency of serum or intraocular fluid anti-T-IgG positive rate with OT diagnostic result. Spearman’s rank correlation test was performed to assess the association.Results:Compared with the non-OT group, the proportions of children and history of exposure to cats and dogs ( χ2=9.785, 12.026) were significantly higher in OT group, and the differences were statistically significant ( P<0.01). The positive rate ( χ2=24.551) and U value ( Z=-4.379) of serum anti-T-IgG in OT group were higher than those in non-OT group, and the differences were statistically significant ( P<0.000 1). The recommended serum anti-T-IgG cut-off value of 11 U had 0.72 sensitivity, 0.79 specificity, 0.89 positive predictive value, 0.55 negative predictive value, and 0.77 area under the ROC with 95% confidence interval ( CI) 0.669-0.860. Correlation analysis showed that serum anti-T-IgG was positively correlated with intraocular fluid anti-T-IgG ( r s=0.520, 95% CI 0.363-0.648, P<0.000 1). The Kappa values of serum and intraocular fluid anti-T-IgG positive rate with OT diagnosis were 0.457 (95% CI 0.292-0.622) and 0.711 (95% CI 0.582-0.840), respectively. The Kappa value of serum anti-T-IgG positive rate with OT diagnosis was lower than that of intraocular fluid. Conclusion:The sensitivity and specificity of serum anti-T-IgG and the consistency between serum anti-T-IgG positive rate and OT diagnosis are low, suggesting that serum anti-T-IgG level cannot be used as a basis for OT diagnosis.

Objective To analyze the causal relationship between serum sex steroid hormone levels and myopia with the Mendelian randomization(MR)methods.Methods Sex hormone genetic tools classified by sex were publicly availa-ble summarized statistical data from the Genome-wide association study(GWAS)of the UK Biobank Consortium on sex hormone-binding globulin(SHBG),total testosterone(TT),bioavailable testosterone(BT),and estradiol(E2).The GWAS summarized statistical data for myopia were obtained from publicly available data published by the FinnGen Consorti-um R10.All data were downloaded from April 18 to April 31,2024 from the corresponding databases and analyzed.All re-sults from the MR study were mainly analyzed by inverse-variance weighting(IVW)method.Results The study showed that a higher serum SHBG level in European increased the risk of myopia development in women(IVW,OR=1.152,95％CI:1.014-1.308,P=0.029);low serum TT level(IVW,OR=0.821,95％CI:0.697-0.967,P=0.018)and serum BT lev-el(IVW,OR=0.820,95％CI:0.691-0.972,P=0.022)increased the risk of myopia development in women.There was no causal relationship between serum SHBG,TT,and BT levels and myopia in men.There was no causal effect between E2 level and myopia in women and men.The stability of our findings was supported by sensitivity analysis.Conclusion In-creased serum SHBG level and decreased serum TT and BT levels are associated with an increased risk of myopia in women,whereas no such association is found in men.There is no causal relationship between E2 and myopia.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

ObjectiveTo identify and clarify the key issues faced by tertiary hospitals in responding to public health emergencies. MethodsA literature review index system was constructed， and key issues were identified using hierarchical analysis. ResultsAfter a systematic literature review， 20 types of problems faced by tertiary hospitals in responding to public health emergencies were identified. Three key issues were ultimately identified by prioritizing the issues that needed to be addressed. ConclusionThe key issues of tertiary hospitals in responding to public health emergencies are concentrated in the areas of emergency response capabilities and competencies of medical staff， the number of emergency response personnel， and the standardization and specificity of training and drills. Tertiary hospitals should focus on these issues in developing public health emergency response systems to improve the effectiveness of their emergency response.

ObjectiveTo identify the key issues in emergency response to public health emergencies in the Yangtze River Delta region， and to provide a basis for the formulation of relevant policies. MethodLiterature on emergency response to public health emergencies in the Yangtze River Delta region was systematically reviewed and collected， and 18 main problems were identified after collecting and organizing the problems. A questionnaire survey and cluster analysis were used to identify the key issues. ResultsThe study of 18 major problems revealed that "insufficient reserve of emergency medical supplies"， "insufficient financial investment to meet the needs of emergency response"， "lack of a sound mechanism for the deployment of supplies， resulting in the untimely deployment of materials"， were the key issues of emergency response to public health emergencies in the Yangtze River Delta region. ConclusionFuture development of the emergency response system in the Yangtze River Delta region should focus on accelerating the integration process of the Yangtze River Delta， establishing and improving information systems， optimizing the material storage and deployment network， prioritizing the fund investment and utilization mechanism， and improving the effectiveness of public health emergency response.