BACKGROUND:The granulosa cell state greatly affects the quality of oocytes.As the increased proportion of aged women in assisted reproduction,granulosa cells from patients of different ages are examined at transcript levels in order to better assess oocyte quality. OBJECTIVE:To investigate the expression changes of mRNA and long non-coding RNA in granulosa cells from the young and aged patients. METHODS:Waste cumulus granulosa cells obtained during the assisted reproductive cycle.Young group was in 25-35 years old,and the aged group was in 38-45 years old.Granulosa cells collected from the young and aged females were analyzed using RNA sequencing,three replications for each group. RESULTS AND CONCLUSION:(1)The RNA sequencing analysis results showed that the average sequencing volume of samples was more than 14 G;the data quality Q30 after quality control was more than 93%;the average mapping rate of data was 98.4%,which indicates that the data had good quality.(2)The results of principal component analysis and correlation analysis showed that the samples of the aged group and the young group could be clearly distinguished.(3)The difference analysis results showed that compared with the young group,a total of 410 differentially expressed mRNAs were detected in the aged group(167 up-regulated and 243 down-regulated).GO analysis results showed that the down-regulated genes were mainly enriched in regulatedexocytosis and the emetabolicprocess.GSEA analysis results showed that secretion-related pathways in the aged group were down-regulated.(4)Compared with the young group,662 differentially expressed long non-coding RNAs were detected in the aged group,and 1 772 protein-coding genes were directly regulated by these long non-coding RNAs,among which 59 genes overlaped with differentially expressed genes.The results showed that the expression of secretion-related genes and pathways in granulosa cells of the aged group was down-regulated,thus affecting oocyte quality.At the same time,these down-regulated genes were regulated by long non-coding RNA.Therefore,the expression of long non-coding RNA might be related to age.

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

At present,the quality and safety management of multiple districts of hospital still has problems such as low informatization level,inconsistent quality and safety management mode,and insufficient quality and safety management concept.It takes an orthopedic hospital of Traditional Chinese Medicine as an example to explore the quality and safety management practice of multiple districts of hospital under the homogenization strategy.A three-level quality control management system composed of leadership,executive level and guidance level was constructed,and the general framework of the integrated quality management system and the specific work contents of quality management in each hospital were proposed,in order to provide a standardized and operable management mode for medical institutions to carry out medical quality management.

At present,the quality and safety management of multiple districts of hospital still has problems such as low informatization level,inconsistent quality and safety management mode,and insufficient quality and safety management concept.It takes an orthopedic hospital of Traditional Chinese Medicine as an example to explore the quality and safety management practice of multiple districts of hospital under the homogenization strategy.A three-level quality control management system composed of leadership,executive level and guidance level was constructed,and the general framework of the integrated quality management system and the specific work contents of quality management in each hospital were proposed,in order to provide a standardized and operable management mode for medical institutions to carry out medical quality management.

At present,the quality and safety management of multiple districts of hospital still has problems such as low informatization level,inconsistent quality and safety management mode,and insufficient quality and safety management concept.It takes an orthopedic hospital of Traditional Chinese Medicine as an example to explore the quality and safety management practice of multiple districts of hospital under the homogenization strategy.A three-level quality control management system composed of leadership,executive level and guidance level was constructed,and the general framework of the integrated quality management system and the specific work contents of quality management in each hospital were proposed,in order to provide a standardized and operable management mode for medical institutions to carry out medical quality management.

At present,the quality and safety management of multiple districts of hospital still has problems such as low informatization level,inconsistent quality and safety management mode,and insufficient quality and safety management concept.It takes an orthopedic hospital of Traditional Chinese Medicine as an example to explore the quality and safety management practice of multiple districts of hospital under the homogenization strategy.A three-level quality control management system composed of leadership,executive level and guidance level was constructed,and the general framework of the integrated quality management system and the specific work contents of quality management in each hospital were proposed,in order to provide a standardized and operable management mode for medical institutions to carry out medical quality management.

At present,the quality and safety management of multiple districts of hospital still has problems such as low informatization level,inconsistent quality and safety management mode,and insufficient quality and safety management concept.It takes an orthopedic hospital of Traditional Chinese Medicine as an example to explore the quality and safety management practice of multiple districts of hospital under the homogenization strategy.A three-level quality control management system composed of leadership,executive level and guidance level was constructed,and the general framework of the integrated quality management system and the specific work contents of quality management in each hospital were proposed,in order to provide a standardized and operable management mode for medical institutions to carry out medical quality management.

At present,the quality and safety management of multiple districts of hospital still has problems such as low informatization level,inconsistent quality and safety management mode,and insufficient quality and safety management concept.It takes an orthopedic hospital of Traditional Chinese Medicine as an example to explore the quality and safety management practice of multiple districts of hospital under the homogenization strategy.A three-level quality control management system composed of leadership,executive level and guidance level was constructed,and the general framework of the integrated quality management system and the specific work contents of quality management in each hospital were proposed,in order to provide a standardized and operable management mode for medical institutions to carry out medical quality management.