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

A 58-year-old female patient presented with erythema on the right shoulder and chest for 8 years. The appearance of erythema was concurrent with numbness and weakness in both lower limbs, elevated peripheral blood M protein levels, thyroid dysfunction, and multiple enlarged lymph nodes in the right axilla, leading to a diagnosis of POEMS syndrome. After autologous hematopoietic stem cell transplantation, erythema subsided but recurred 1 year prior to this visit. Physical examination revealed a pigeon egg-sized swollen lymph node on the right side of the neck. Skin examination showed patchy erythema on the right shoulder and chest, with clear boundaries and a hard texture. Serum protein electrophoresis revealed an elevated M protein level, and serum immunofixation electrophoresis showed a restricted IgG λ band. In addition, peripheral blood levels of vascular endothelial growth factor were elevated. Computed tomography scan images showed an irregular flaky bone destruction area at the acromion end of the right scapula, which was consistent with the manifestations of bone plasmacytoma. Histopathological examination of the skin tissue in the right shoulder revealed a large number of dilated and proliferative vessels between dermal collagen fibers, and the patient was diagnosed with AESOP syndrome. Lenalidomide combined with dexamethasone chemotherapy was administered. After three cycles of treatment, M protein turned negative, and erythema became darker in color, and decreased in size compared with the skin lesion before treatment.

ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination.

A 58-year-old female patient presented with erythema on the right shoulder and chest for 8 years. The appearance of erythema was concurrent with numbness and weakness in both lower limbs, elevated peripheral blood M protein levels, thyroid dysfunction, and multiple enlarged lymph nodes in the right axilla, leading to a diagnosis of POEMS syndrome. After autologous hematopoietic stem cell transplantation, erythema subsided but recurred 1 year prior to this visit. Physical examination revealed a pigeon egg-sized swollen lymph node on the right side of the neck. Skin examination showed patchy erythema on the right shoulder and chest, with clear boundaries and a hard texture. Serum protein electrophoresis revealed an elevated M protein level, and serum immunofixation electrophoresis showed a restricted IgG λ band. In addition, peripheral blood levels of vascular endothelial growth factor were elevated. Computed tomography scan images showed an irregular flaky bone destruction area at the acromion end of the right scapula, which was consistent with the manifestations of bone plasmacytoma. Histopathological examination of the skin tissue in the right shoulder revealed a large number of dilated and proliferative vessels between dermal collagen fibers, and the patient was diagnosed with AESOP syndrome. Lenalidomide combined with dexamethasone chemotherapy was administered. After three cycles of treatment, M protein turned negative, and erythema became darker in color, and decreased in size compared with the skin lesion before treatment.

Objective To establish a method for chiral analysis of dextromethorphan and levomethorphan in hair and urine by high performance liquid chromatography-triple quadrupole mass spectrometry.Methods Hair samples were extracted by grinding ultrasound,and urine samples were extracted by acetonitrile.The supernatant were separated using a Astec CHIROBIOTIC? V2 column(25 cm × 4.6 mm,5 μm)with 0.5 ‰ formic acid and 10 mmol/L ammonium acetate-methanol as mobile phases,then analyzed in scheduled-multiple reaction monitoring mode.Results The limits of detection and lower limits of quantitation of dextromethorphan and levomethorphan were 0.001 ng/mg and 0.005 ng/mg in hair samples,while they were 0.050 ng/mL and 0.200 ng/mL in urine samples.In the corresponding concentration range,there were good linearity for chiral isomers with correlation coefficients over 0.999.Besides,the recovery rates,accuracy and precision met analytical requirements,and no significant matrix effect were exhibited.In the actual case samples,dextromethorphan were detected in hair of 12 cases and in the corresponding urine of 3 cases.Conclusion This method is rapid,sensitive and reliable for chiral analysis of dextromethorphan and levomethorphan in hair and urine.

Objective To establish a method for chiral analysis of dextromethorphan and levomethorphan in hair and urine by high performance liquid chromatography-triple quadrupole mass spectrometry.Methods Hair samples were extracted by grinding ultrasound,and urine samples were extracted by acetonitrile.The supernatant were separated using a Astec CHIROBIOTIC? V2 column(25 cm × 4.6 mm,5 μm)with 0.5 ‰ formic acid and 10 mmol/L ammonium acetate-methanol as mobile phases,then analyzed in scheduled-multiple reaction monitoring mode.Results The limits of detection and lower limits of quantitation of dextromethorphan and levomethorphan were 0.001 ng/mg and 0.005 ng/mg in hair samples,while they were 0.050 ng/mL and 0.200 ng/mL in urine samples.In the corresponding concentration range,there were good linearity for chiral isomers with correlation coefficients over 0.999.Besides,the recovery rates,accuracy and precision met analytical requirements,and no significant matrix effect were exhibited.In the actual case samples,dextromethorphan were detected in hair of 12 cases and in the corresponding urine of 3 cases.Conclusion This method is rapid,sensitive and reliable for chiral analysis of dextromethorphan and levomethorphan in hair and urine.

Objective:To investigate effect of Galangin on inflammatory response in autoimmune thyroiditis(AIT)rats by regulating chemokine ligand 2(CCL2)/chemokine receptor 2(CCR2)pathway.Methods:A total of 84 rats were randomly grouped into control group,model group,Galangin low dose group,Galangin medium dose group,Galangin high dose group,selenium yeast tablet group,Galangin high-dose+rat CCL2 recombinant protein(rCCL2)group,with 12 rats in each group.Except for control group,AIT models were constructed in rats of all other groups.After successful modeling,medication was administered once a day for 8 weeks.ELISA was applied to detect levels of thyroglobulin antibody(TGAb),thyroid peroxidase antibody(TPOAb),free thyroxine(FT4),free triiodothyronine(FT3)in rats serum and TNF-α,IL-6 and IL-1β in thyroid tissue;HE staining for pathological changes in rat thyroid tissue and scoring of inflammation in thyroid tissue;qRT-PCR was applied to detect expressions of CCL2 and CCR2 mRNA in thyroid tissue;Western blot was applied to detect expressions of CCL2 and CCR2 proteins in thyroid tissue.Results:Com-pared with control group,pathological damage to thyroid tissue of rats in model group was severe,inflammation score,levels of TGAb,TPOAb,FT4,FT3,TNF-α,IL-6,IL-1β,expressions of CCL2,CCR2 mRNA and protein were increased(P<0.05);com-pared with model group,pathological damage of thyroid tissue of rats in Galangin low dose group,Galangin medium dose group,Galangin high dose group and selenium yeast tablet group were reduced,inflammation score,levels of TGAb,TPOAb,FT4,FT3,TNF-α,IL-6,IL-1β,expressions of CCL2,CCR2 mRNA and protein were decreased(P<0.05);compared with Galangin high dose group,pathological damage of thyroid tissue in Galangin high dose+rCCL2 group was aggravated,inflammation score,levels of TGAb,TPOAb,FT4,FT3,TNF-α,IL-6,IL-1β,expressions of CCL2,CCR2 mRNA and protein were increased(P<0.05).Conclusion:Galangin may inhibit inflammatory response of AIT rats by inhibiting CCL2/CCR2 signaling pathway.

Objective Based on the limited time theory,taking tonsillectomy day operation as an example,the whole process nursing list of day operation was constructed,and its application effect was evaluated.Methods The nursing service list of tonsillectomy was constructed based on literature research,field observation and expert correspondence.A total of 197 patients who underwent tonsillectomy in the day ward of a tertiary A general hospital in Hangzhou,Zhejiang Province were selected.Among them,98 patients from April to June 2023 were taken as an experimental group and treated with the whole-process nursing list of daytime tonsillectomy constructed in this study,and 99 patients from January to March 2023 were taken as a control group and routine nursing was adopted.The anxiety degree,postoperative pain score,postoperative complication rate and patients'satisfaction with nursing service were compared between the 2 groups.Results Anxiety scores before operation and at discharge,pain scores at 6 h,12 h and 24 h after operation,and incidence of complications such as infection and gastrointestinal reaction within 14 days after operation in the experimental group were lower than those in the control group,with statistical significance(P＜0.05).The satisfaction of nursing service in the experimental group(99.40±0.69)score was significantly higher than that in the control group(90.36±1.04)score,and the difference was statistically significant(P＜0.001).Conclusion The use of tonsillectomy day whole-process nursing list can improve perioperative anxiety,relieve postoperative pain and reduce the incidence of postoperative complications,and improve patient satisfaction.

This paper aimed to identify etomidate and its structural analogues in hair and urine by HPLC-MS/MS.Hair samples were extracted by ultrasonic grinding and urine samples were extracted by methanol.The samples were on ACQUITY UPLC? HSS T3 column with 10 mmol/L ammonium acetate and 0.5 ‰ formic acid-methanol as mobile phases for gradient elution.Multiple reaction monitoring mode was used for analysis.The separation and detection of structural analogues were realized,especially the isomers propoxate and isopropoxate.There was good linear relationship of the etomidate and its structural analogues in hair and urine,with R greater than 0.998.And the recovery,accuracy and precision all met the requirements.When applied to practical cases,etomidate,metomidate,isopropoxate and etomidate acid were detected simultaneously in the hair samples of 3 cases.And correspondingly,in the urine samples,high content of etomidate acid and low content of the precursor substance metomidate were detected in 2 cases,only etomidate acid was detected in 1case.Etomidate structural analogues have higher content of precursor substances and lower content of metabolite in hair samples,while the opposite was true in urine samples.We cannot reverse confirm the structure of the precursor substances through the detection of the common metabolite etomidate acid in the urine samples.Therefore,ingestion of etomidate structural analogues cannot be accurately assessed from urine samples alone.

This paper aimed to identify etomidate and its structural analogues in hair and urine by HPLC-MS/MS.Hair samples were extracted by ultrasonic grinding and urine samples were extracted by methanol.The samples were on ACQUITY UPLC? HSS T3 column with 10 mmol/L ammonium acetate and 0.5 ‰ formic acid-methanol as mobile phases for gradient elution.Multiple reaction monitoring mode was used for analysis.The separation and detection of structural analogues were realized,especially the isomers propoxate and isopropoxate.There was good linear relationship of the etomidate and its structural analogues in hair and urine,with R greater than 0.998.And the recovery,accuracy and precision all met the requirements.When applied to practical cases,etomidate,metomidate,isopropoxate and etomidate acid were detected simultaneously in the hair samples of 3 cases.And correspondingly,in the urine samples,high content of etomidate acid and low content of the precursor substance metomidate were detected in 2 cases,only etomidate acid was detected in 1case.Etomidate structural analogues have higher content of precursor substances and lower content of metabolite in hair samples,while the opposite was true in urine samples.We cannot reverse confirm the structure of the precursor substances through the detection of the common metabolite etomidate acid in the urine samples.Therefore,ingestion of etomidate structural analogues cannot be accurately assessed from urine samples alone.