Objective:To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG).Methods:Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People′s Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes ( MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People′s Hospital Affiliated to Jiangsu University (Ethics No. 20150083). Results:① m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. ② mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. ③ Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. ④ MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P<0.05). ⑤ RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P<0.000 5). Conclusion:These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.

OBJECTIVE: To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG). METHODS: Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People's Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes (MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People's Hospital Affiliated to Jiangsu University (Ethics No. 20150083). RESULTS: m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P < 0.05). RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P < 0.000 5). CONCLUSION These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.
Humans ; RNA, Messenger/metabolism* ; Adenocarcinoma/pathology* ; Esophagogastric Junction/metabolism* ; Esophageal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Middle Aged ; DNA Methylation ; Methyltransferases/metabolism* ; Stomach Neoplasms/genetics*

Objective:To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG).Methods:Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People′s Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes ( MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People′s Hospital Affiliated to Jiangsu University (Ethics No. 20150083). Results:① m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. ② mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. ③ Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. ④ MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P<0.05). ⑤ RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P<0.000 5). Conclusion:These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.

Embryo implantation involves a complex interaction between the embryo and the endometrium of the mother, the study of which faces a variety of problems. The modeling of endometrial epithelial organoids and endometrial assembloids provides a new way to study the process of embryo implantation in vitro. This paper summarized the latest research progress in embryo implantation, the regulation mechanism of endometrial receptivity by estrogen- progesterone coordination and embryo-derived signals, the establishment of endometrial organoids, and the development and application of endometrial assembloids in the research on mother-embryo interaction, providing new strategies for studying the communication between embryo and maternal uterus during implantation.
Endometrium/physiology* ; Organoids/cytology* ; Embryo Implantation/physiology* ; Female ; Animals ; Progesterone/pharmacology* ; Pregnancy ; Estrogens/metabolism* ; Humans

BACKGROUND:In consideration of the food safety and ecological safety of transgenic plants,the retention of marker genes is the primary safety issue affecting transgenic plants. OBJECTIVE:Based on the principle of immune caries prevention,our research team successfully constructed the plant anti-caries vaccine fusion gene expression vector pCAMBIA-E8-APB-DOCK8 for these two caries causing virulence factors surface protein and glucosyltransferase,which provides a basis for the research and development of transgenic plant vaccine. METHODS:In this study,the selective marker genes Km and GUS in the plant caries vaccine fusion gene expression vector pCAMBIA-E8-APB-DOCK8 were removed by DNA recombination technology through a series of steps such as DNA fragment separation,connection,transformation,clone detection,and sequencing. RESULTS AND CONCLUSION:The efficiency of marker gene removal was 99%.This study has laid a good experimental foundation for the safe production of transgenic plant vaccine against dental caries,and also provided ideas for the construction of other plant vaccine vectors.

AIM:To explore the effect of the peripheral defocus spectacle lenses and orthokeratology(OK)on the control of myopia progression and the impact on vision related quality of life in children and adolescents.METHODS:Prospective study. A total of 237 children initially diagnosed with myopia in the ophthalmology department of Huzhou Central Hospital from January 2021 to January 2022 were selected and divided into two groups according to different correction methods: peripheral defocus spectacle lenses group(105 cases, 105 eyes)and OK lens group(132 cases, 132 eyes). The Vision Related Quality of Life Questionnaire for Primary and Secondary School Students was used to follow up the both groups of myopic children, and the best corrected visual acuity(BCVA), spherical equivalent(SE), and axial length(AL)were recorded at the first visit and 1 a of follow-up.RESULTS:After wearing lenses for 1 a, both the peripheral defocus spectacle lenses group and OK lens group showed an increase in SE and AL, but there was no statistical difference between two groups(P>0.05). The changes in SE and AL in the peripheral defocus spectacle lenses group were greater than those in the OK lens group(all P=0.001). After 1 a of follow-up, in the emotional dimension scores, the peripheral defocus spectacle lenses group of children's vision-related quality of life scales scored higher than in the OK lens group(P<0.05). Compared with the baseline value, the change in the emotional dimension scores of the OK lens group was greater than that in the peripheral defocus spectacle lens group(P<0.05).CONCLUSION:OK lenses are superior to peripheral defocus spectacle lenses in controlling the progression of myopia in children and adolescents. Both correction methods can significantly improve myopic children's vision-related quality of life, with OK lenses being better at improving the emotional dimension of vision-related quality of life.

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

OBJECTIVE To compare five com monly used judgment criteria for potentially inappropriate medication （PIM）in the elderly ，and to provide reference for clinical selection of appropriate PIM evaluation tools for the elderly. METHODS From the aspects of applicable age ，content and scale characteristics ，five commonly used PIM judgment criteria for the elderly at home and abroad were analyzed and compared ，namely Beer ’s criteria ，STOPP/START v 2 criteria，ACOVE 3 criteria，PIM-Check criteria and“Judgment Criteria for Potentially Inappropriate Medication for Chinese Elderly ”（Chinese criteria ）. RESULTS The five standards both overlapped and focused in terms of scale characteristics. In each study ，the incidence of PIM was different according to different standards. Proton pump inhibitors ，diuretics，non-steroidal anti-inflammatory drugs and anticoagulants were the most frequently occurring PIM drugs for the elderly. CONCLUSIONS Combining with the specific conditions of patients and fully considering the benefits and risks of treatment ，rational selection and combination of five PIM judgment criteria ，and necessary supplements to my country ’s PIM judgment criteria ，will help clinicians and pharmacists to improve the efficacy and safety of the medication in the elderly patients.

OBJECTI VE To introduce the evaluation system for clinical value of antineoplastic agents at home and abroad ，and to provide reference for continuous improvement of clinical value-oriented antineoplastic agents development and research guideline in China. METHODS The suggestions were put forward to improve the evaluation system for clinical value of antineoplastic agents in China by consulting the relevant data of evaluation system for clinical value of antineoplastic agents at home and abroad and domestic antineoplastic agents R&D and management policies ，sort outing and analyzing comparatively their dimensions ， perspectives，target audiences ，application scope ，advantages and disadvantages. RESULTS & CONCLUSIONS Seven foreign value evaluation systems （value assessment framework of American Society of Clinical Oncology ，clinical benefit scale of European Society of Clinical Oncology ，value evaluation framework of American Institute of Clinical and Economic Evaluation ， etc.）had their own characteristics and unique advantages under different settings ；several value evaluation systems differed in the criteria for defining value ，depending on the perspective and population they focus on. The value dimensions were constantly changing dynamically in response to scientific values and social needs ，including not only safety ，efficacy and cost-effectiveness ， but also innovation ，fairness，quality of life attributes. Some evaluation systems adopted value assessment tools that followed the trend of the information age in the presentation form and assessment mode ，which promoted shared decision-making between doctors and patients. Combining the characteristics of foreign value evaluation system and the current situation of development and application of antineoplastic agents in China ，we can have a deeper understanding of drug efficacy ，safety，quality of life ，research and development cost and pricing in the future. Antineoplastic 2021-10-28） agents will have a more reasonable position to solve the unmet needs of patients from the perspectives of drug research and development， clinical application ， drug accessibility and fairness.

Objective:To investigate the expression levels of CD4+ CD25+ FOXP3+ Treg cells and interleukin(IL)-10 in serum of patients with myelodysplastic syndrome (MDS) - refractory anemia (RA) and refractory hematopenia with multilineage dysplasia (RCMD), and to evaluate the effect of cyclosporine on CD4+ CD25+ FOXP3+ Treg cells in MDS patients.Methods:From January 2016 to January 2018, 25 MDS-RA and RCMD patients and 13 healthy controls were selected from people′s Hospital of Xinjiang Uygur Autonomous Region for retrospective analysis.The expression of CD4 + CD25 + Foxp3 + Treg and IL-10 in peripheral blood samples were detected by flow cytometry and enzyme-linked immunosorbent assay.The expression of CD4 + CD25 + Foxp3 + Treg and IL-10 in MDS-RA and RCMD patients before and 6 months after the treatment with CSA based immunosuppressive regimen was detected.Results:Of the 25 patients, 13 (52%) were effective and 12 (48%) were ineffective.The proportion of CD4 + CD25 + Foxp3 + Treg in CD4 + T cells of MDS group was significantly higher than that of healthy control group [(0.37 ± 0.10)% and (0.12 ± 0.06)% respectively, t= 2.02, P< 0.001]. The level of IL 10 in MDS group was significantly higher than that in healthy control group ((7.16±1.27) μg /L and (2.75 ± 1.06) μg /L, t= 2.03, P< 0.001). The ratio of CD4 + CD25 + Foxp3 + Treg cells in MDS group was lower than that in MDS Group ((0.15±0.06)% and (0.26±0.08%), t= 1.71, P< 0.001), and the level of IL 10 in MDS group was lower than that in MDS Group ((3.22±1.01) μg /L and (4.25±1.22) μg /L, t= 2.06, P= 0.030). The proportion of CD4 + CD25 + Foxp3 + Treg in peripheral blood of 25 MDS patients was positively correlated with the level of IL-10 expression ( r= 0.35, P= 0.02). Conclusion:The expression of CD4+ CD25+ FOXP3+ Treg cells and IL-10 increased in MDS patients increased, but decreased after cyclosporine treatment.