Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To systematically evaluate the psychological characteristics of adolescent inflammatory bowel disease(IBD)patients during the transition period and provide evidence-based guidance for healthcare professionals in developing transition management strategies.Methods A systematic search was conducted across The Cochrane Library,PubMed,Web of Science,CINAHL,Embase,SinoMed,CNKI,Wanfang,and VIP databases for qualitative studies on adolescent IBD patients during transition,from database inception to May 2024.Eligible studies were critically appraised,and themes were synthesized using the meta-aggregation approach of meta-synthesis.Results Twelve studies were included,yielding 13 findings that were synthesized into five categories:self-development challenges,healthcare system transition barriers,family support conflicts,social adaptation difficulties,and lack of societal support systems.Conclusion Adolescents with IBD experience complex psychological challenges during transition,characterized by excessive psychological burdens,inadequate healthcare support,and insufficient societal recognition.Targeted interventions are needed to improve psychological outcomes during this critical phase.

Based on the analysis of relevant policy documents,industry data,and case studies,this paper systematically reviews the current situation,policy environment,and usage of intra-hospital formulations in medical institutions in Guangzhou,and compares them with policies in other countries.It is found that although Guangzhou has achieved certain results in terms of policy support,number of varieties,and usage range of intra-hospital formulations,there are also problems such as limited pro-duction capacity,inadequate quality control,insufficient research and development investment,increasing cost pressure,and in-adequate protection of intellectual property rights.Therefore,this paper suggests the establishment of a regional Chinese medicine formulation industrial park,the development of new dosage forms and technologies,the expansion of medical insurance coverage,the strengthening of research platform construction,and the promotion of multidimensional achievement transformation to promote the high quality development of the intra-hospital formulation industry in Guangzhou.

Based on the analysis of relevant policy documents,industry data,and case studies,this paper systematically reviews the current situation,policy environment,and usage of intra-hospital formulations in medical institutions in Guangzhou,and compares them with policies in other countries.It is found that although Guangzhou has achieved certain results in terms of policy support,number of varieties,and usage range of intra-hospital formulations,there are also problems such as limited pro-duction capacity,inadequate quality control,insufficient research and development investment,increasing cost pressure,and in-adequate protection of intellectual property rights.Therefore,this paper suggests the establishment of a regional Chinese medicine formulation industrial park,the development of new dosage forms and technologies,the expansion of medical insurance coverage,the strengthening of research platform construction,and the promotion of multidimensional achievement transformation to promote the high quality development of the intra-hospital formulation industry in Guangzhou.

Objective To systematically evaluate the psychological characteristics of adolescent inflammatory bowel disease(IBD)patients during the transition period and provide evidence-based guidance for healthcare professionals in developing transition management strategies.Methods A systematic search was conducted across The Cochrane Library,PubMed,Web of Science,CINAHL,Embase,SinoMed,CNKI,Wanfang,and VIP databases for qualitative studies on adolescent IBD patients during transition,from database inception to May 2024.Eligible studies were critically appraised,and themes were synthesized using the meta-aggregation approach of meta-synthesis.Results Twelve studies were included,yielding 13 findings that were synthesized into five categories:self-development challenges,healthcare system transition barriers,family support conflicts,social adaptation difficulties,and lack of societal support systems.Conclusion Adolescents with IBD experience complex psychological challenges during transition,characterized by excessive psychological burdens,inadequate healthcare support,and insufficient societal recognition.Targeted interventions are needed to improve psychological outcomes during this critical phase.

Objective:To document any correlation between eye-tracking test results and cognitive impairment after a stroke.Methods:Forty stroke survivors made up the stroke group, while 20 healthy subjects without a history of stroke formed the normal group. Everyone was given an eye-tracking test, the mini-mental state examination (MMSE), and the Montreal Cognitive Assessment (MoCA). The eye-tracking test results were then tested for any correlation with age, level of education, and the MMSE and MoCA scores.Results:In the static image test and the prosaccade test, the total number of fixations was significantly higher in the stroke group than in the normal group. In the dynamic path test, the ocular motor test and the anti-saccade test, significant differences were observed between the two groups in terms of the duration of total fixation, the fixation duration ratio, and the total number of fixations. In the static image test, the total number of fixations was weakly negatively correlated with the MMSE scores. Total fixation duration and fixation duration ratio were weakly positively correlated with the MoCA scores, while total number of fixations, total saccade distance and average saccade velocity were weakly negatively correlated with the MoCA scores. In the dynamic path test, total fixation duration was weakly positively correlated with the MMSE and MoCA scores. Fixation duration ratio was weakly positively correlated with the MMSE scores and weakly negatively correlated with the MoCA scores. First fixation duration was weakly positively correlated with the MoCA scores. The total number of fixations was weakly positively correlated with age and weakly negatively correlated with the MoCA scores. Total saccade distance was weakly negatively correlated with age and the MoCA scores, and average saccade velocity was weakly negatively correlated with the MMSE and MoCA scores. In the ocular motor test, total fixation duration and fixation duration ratio were weakly positively correlated with the MoCA scores. Total number of fixations, total saccade distance, and average saccade velocity were weakly negatively correlated with the MoCA scores. In the prosaccade test, total fixation duration and fixation duration ratio were weakly positively correlated with the MoCA scores. Total number of fixations was weakly positively correlated with age and weakly negatively correlated with the MoCA scores. Total saccade distance and average saccade velocity were weakly negatively correlated with both the MMSE and MoCA scores. In the anti-saccade test, total fixation duration was weakly and positively correlated with age and the MoCA scores. Fixation duration ratio was weakly and positively correlated with age and the MoCA scores. The total number of fixations was weakly positively correlated with age and weakly negatively correlated with the MoCA scores, and total saccade distance and average saccade velocity were weakly negatively correlated with the MoCA scores.Conclusions:Eye-tracking test results are significantly correlated with post-stroke cognitive impairment, suggesting that such tests can be used in the assessment of post-stroke cognitive dysfunction.

Objective:Based on the principle that the aggregation-induced emission (AIE) fluorescent probe 6PD-DPAN could bind and aggregate with bacteria, and the fluorescence intensity could reflect the quantity of bacteria, a new method for rapid, convenient, and accurate bacterial drug sensitivity testing was established, which provided a basis for rapid and accurate clinical drug use.Methods:This was a methodological evaluation study. A total of 107 clinical isolates were collected from Houjie Hospital of Dongguan City from January to December 2022, among which 46 isolates were used for the establishment of the new method, and 61 isolates were used for methodological validation. The minimum inhibitory concentration (MIC) determined by broth microdilution method was used as the gold standard, and three antibacterial drugs, gentamicin, levofloxacin, and cefotaxime, were used as experimental drugs. The AIE plate was incubated for 4 hours, and the fluorescence intensity was measured every half an hour to draw a fluorescence change curve. The MIC results were compared with the CLSI breakpoints to determine the bacteria as sensitive, intermediate, or resistant. To simplify the detection process, the ratio of fluorescence intensity at 4 hours(R) was calculated, and the ROC curve was used to analyze the efficacy of R in determining bacterial growth and establish its cutoff value. The new method was used to determine the MIC of 61 clinical isolates, with broth microdilution method as the gold standard. The basic consistency, categorical consistency, very major errors, and major errors of the new method were analyzed, and the consistency between the two methods was determined by the Kappa test.Results:ROC curve analysis of the R after 4 hours of culture: The cut-off value was 3.0, with both sensitivity and specificity for determining bacterial growth being 100%. The median (interquartile) R for bacterial growth inhibition was 11.1 (8.6, 14.4); the median R-value for bacterial growth was 1.1 (1.0, 1.2). Compared to the gold standard, the newly established method showed 100% (61/61) essential agreement in detecting MICs of 61 clinical isolates, with a categorical agreement of 96.7% (59/61). There were no very major or major errors, and the Kappa value was 0.94, indicating good consistency between the newly established method and the microbroth dilution method.Conclusions:This study successfully established a new method for bacterial drug sensitivity testing based on AIE technology, which could obtain satisfactory results within 5 hours, providing a basis for early precision drug treatment in clinical practice.

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P < 0.001). There were significant differences in the number of patients with low or high expression of miR-486-5p between the patients with different TNM stages, presence or absence of lymphatic metastasis, and presence or absence of distant metastasis ( χ 2 =13.765, 5.157, and 6.638, all P < 0.05). Compared with CA19-9 alone, miR-486-5p+CA19-9 had a significantly better value in distinguishing the operable group from the benign pancreatic disease group (area under the ROC curve [AUC]=0.87, 95% confidence interval [ CI ]: 0.760-0.942; with a sensitivity of 81.3% and a specificity of 83.3%), distinguishing the operable group from the healthy control group (AUC=0.92, 95% CI : 0.836-0.970; with a sensitivity of 90.6% and a specificity of 86.4%), and distinguishing the operable group from the non-operable group (AUC=0.94, 95% CI : 0.884-0.998; with a sensitivity of 85.7% and a specificity of 93.7%) ( Z =2.841, 2.510, and 2.387, all P < 0.05), and the optimal cut-off values were 3.12, 3.21, and 6.63, respectively. Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.

Objective To compare the effects of the equivalent analgesic doses of sufentanil, fentanyl and dizosin on index of consciousness (IoC) and their adverse reactions. Methods Eighty patients undergoing painless gastroenteroscopy, aged 18～60 years, ASA grade Ⅰ to Ⅱ, were selected. The patients were randomly divided into control group (group C) , sufentanil group (group S) , fentanyl group (group F) , and dizosin group (group D) , with 20 cases in each group. Sufentanil 0.1～0.2 μg/kg, fentanyl 1～2μg/kg and dizocine 0.1～0.2 mg/kg were intravenously injected in group S, F and D respectively. Group C was given saline of equal volume, and then propofol 2～2.5 mg/kg was intravenously injected until consciousness disappeared.Intravenous infusion of propofol50～100 g/ (kg · min) maintained anesthesia. Heart rate, blood pressure, IoC and perioperative adverse events were recorded. Results There was no significant difference in operative time and recovery time among the 4 groups (P> 0.05). Compared with those in group C, the values of IoC at T2, TS, T4 and T5 in group S and F increased significantly (P < 0.05) , and the correlation coefficient between OAA/S and IoC was 0.872 (P < 0.05). Compared with that in group C, the incidence of nausea and vomiting was higher in group D, and the incidence of injection pain was significantly lower in group S, F and D (P < 0.05). Conclusion Compared with propofol alone, opioids used in painless gastrointestinal endoscopy anesthesia lead to loss of consciousness and increase of IoC value at recovery time, but have no significant effect on recovery time.

Background Conventional studies showed that the primary pathological change of diabetic retinopathy (DR) is retinal microangiopathy.However,recent studies found that the disorder of visual function appears prior to retinal microangiopathy in diabetic patients.Thereby,this findings can not be explained by conventional view.Objective The aim of the study was to find the change of retinal nerve fiber layer (RNFL) by frequency domain optical coherence tomography(OCT) in the diabetic patients without retinal microangiopathy and with non-proliferative DR (NPDR) and investigate the relationship between the change of RNFL thickness and DR.Methods Sixty eyes of 56 patients with 2 type diabetes mellitus were enrolled in Shanxi Eye Hospital from October 2012 to September 2013.The patients were divided into the non-diabetic retinopathy (NDR) group (30 eyes of 26 patients) and NPDR group (30 eyes of 30 patients) depending on the findings of fundus fluorescine angiography (FFA) according to the DR International Clinical Classification System.Thirty normal eyes of 30 age-and gendermatched healthy volunteers were included as controls.RNFL thicknesses around optical disc and macular zone were measured by OCT,including average RNFL thickness in 360°,superior nasal,superior temporal,temporal,inferior temporal,inferior nasal and nasal RNFL thicknesses.The measuring results were compared between the three groups.Results The total average thickness values of RNFL around the optic disc for the NDR group,NPDR group and the control group were (97.46-± 8.65) μm,(100.69 ± 16.35) pm and (109.22 ± 8.69) μm,respectively,and the parameters in the NDR group and NPDR group were significantly lower than those in the normal control group (P=0.001,0.006).The RNFL thicknesses were thinning at the superior temporal,temporal,inferior temporal,inferior nasal quadrants around optical disc in NDR group compared with the normal control group (P=0.001,0.001,0.001,0.010),and RNFL thickness values of all the quadrants were decresed in the NPDR group compared with the normal control group,and significant differences were seen in superior temporal and nasal quadrants (P =0.001,0.046).The total average thickness values of RNFL around macular zone for the NDR group,NPDR group and the normal control group were (33.47±3.39),(36.81±3.21) and (38.18±2.16) μm,and parameters in the NDR group was significantly lower than that in the normal control group (P =0.001).The RNFL thicknesses of all the quadrants around macular zone in the NDR group were thinned in comparison with the normal control group (all at P＜0.01),and the RNFL thicknesses at the superior nasal,superior temporal and temporal quadrants were significantly decreased in comparison with the normal control group (P=0.026,0.015,0.001).Conclusions The thinning of the RNFL thickness occurs prior to retinal microangiopathy in diabetic patients,and it may be an early pathological stage for DR.