Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Patients with diabetes mellitus are at a significantly elevated risk of developing cognitive impairment,which adversely impacts their quality of life and imposes a substantial burden on the healthcare system.Novel antidiabetic agents,including sodium-glucose cotransporter 2 inhibitors(SGLT-2i),dipeptidyl peptidase-4 inhibitors(DPP-4i),glucagon-like peptide-1 receptor agonists(GLP-1RAs),and dual glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonists(e.g.,Tirzepatide),have been shown to not only effectively regulate glycemic control but also mitigate cognitive decline by inhibiting inflammation,reducing oxidative stress,preventing apoptosis,attenuating amyloid β-protein(Aβ)deposition,and suppressing tau protein phosphorylation.

Objective To analyze the efficacy of autologous tissue repair for rectocele through the perineal approach in treating constipation and fecal incontinence in patients.Methods From January 2021 to November 2022,23 female patients with symptomatic rectal protrusion were treated with perineal autologous tissue repair.Preoperatively and at 12 months postoperatively,the Cleveland Clinic Constipation Score(CCCS),Cleveland Clinic Incontinence Score(CCIS),and Patient Assessment of Constipation Quality of Life(PAC-QOL)questionnaires were used to assess postoperative outcomes and quality of life.Results Among the 23 patients,with a median follow-up time of 12.6 months,CCCS decreased from 17.09±1.68 to 3.96±2.08(P＜0.05);CCIS decreased from 1.52±4.15 to 0.52±1.41(P＞0.05);PAC-QOL:physical discomfort decreased from 13.00±1.51 to 4.74±1.98;psychological discomfort decreased from 20.96±3.27 to 5.74±2.67;concern and anxiety decreased from 26.13±4.37 to 8.78±3.14;satisfaction decreased from 15.39±2.35 to 4.60±1.59(P＜0.05).All patients showed significant improvement in constipation and incontinence symptoms postoperatively,with no serious postoperative complications and a marked improvement in postoperative quality of life.Conclusion Rectocele repair with perineal approach using autologous tissue is an effective and safe method,avoiding potential potential complications associated with grafts.

Patients with diabetes mellitus are at a significantly elevated risk of developing cognitive impairment,which adversely impacts their quality of life and imposes a substantial burden on the healthcare system.Novel antidiabetic agents,including sodium-glucose cotransporter 2 inhibitors(SGLT-2i),dipeptidyl peptidase-4 inhibitors(DPP-4i),glucagon-like peptide-1 receptor agonists(GLP-1RAs),and dual glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonists(e.g.,Tirzepatide),have been shown to not only effectively regulate glycemic control but also mitigate cognitive decline by inhibiting inflammation,reducing oxidative stress,preventing apoptosis,attenuating amyloid β-protein(Aβ)deposition,and suppressing tau protein phosphorylation.

Objective To analyze the efficacy of autologous tissue repair for rectocele through the perineal approach in treating constipation and fecal incontinence in patients.Methods From January 2021 to November 2022,23 female patients with symptomatic rectal protrusion were treated with perineal autologous tissue repair.Preoperatively and at 12 months postoperatively,the Cleveland Clinic Constipation Score(CCCS),Cleveland Clinic Incontinence Score(CCIS),and Patient Assessment of Constipation Quality of Life(PAC-QOL)questionnaires were used to assess postoperative outcomes and quality of life.Results Among the 23 patients,with a median follow-up time of 12.6 months,CCCS decreased from 17.09±1.68 to 3.96±2.08(P＜0.05);CCIS decreased from 1.52±4.15 to 0.52±1.41(P＞0.05);PAC-QOL:physical discomfort decreased from 13.00±1.51 to 4.74±1.98;psychological discomfort decreased from 20.96±3.27 to 5.74±2.67;concern and anxiety decreased from 26.13±4.37 to 8.78±3.14;satisfaction decreased from 15.39±2.35 to 4.60±1.59(P＜0.05).All patients showed significant improvement in constipation and incontinence symptoms postoperatively,with no serious postoperative complications and a marked improvement in postoperative quality of life.Conclusion Rectocele repair with perineal approach using autologous tissue is an effective and safe method,avoiding potential potential complications associated with grafts.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Stroke is a prevalent acute cerebrovascular disease associated with significant morbidity and mortality,which highly demand effective prevention and treatment strategies.Glucagon-like peptide-1 receptor agonists(GLP-1RA)is a novel type of antidiabetic drug that exerts hypoglycemic and weight loss effects on GLP-1 receptors.Additionally,GLP-1RA possess the potential to reduce infarction size and promote nerve recovery by inhibiting inflammation,oxidative stress,apoptosis,and improving blood-brain barrier permeability and other pathologies.This paper provides a comprehensive summary of the role of GLP-1 in stroke occurrence while also explores the underlying mechanisms by which GLP-1RA influences stroke pathogenesis.Furthermore,it briefly reviews the therapeutic efficacy of GLP-RA in managing stroke.

Objective:To analyze the data of critical care related literatures published in Web of Science core set by knowledge map visualizing technology, and summarize the research status and hotspots of critical care.Methods:The core set database of Web of Science from January 2011 to December 2020 was searched, the extracted information was standardized and analyzed by knowledge map visualizing technology.Results:A total of 783 articles in the field of critical care were included, and the number of literatures increased year by year, among which the number of articles published in the American Journal of Critical Care(305) was the most. The United States (437) was the country with the most published literatures, and Australia was the country with the highest centrality (centrality=0.67). The number and centrality of articles published from China were at the lower middle level. There was cooperation among countries, but not close cooperation. The cooperation among authors was in the state of small aggregation and large dispersion. Cluster analysis and keyword emergence analysis showed that many aspects in the field of intensive care had been the research hotspots, among which "post intensive care syndrome" and "children′s intensive care" were the research hotspots in recent years.Conclusions:The research field of intensive care is still in the rising stage of development, and post intensive care syndrome and children's intensive care are the latest hotspots in intensive care research.

Objective:To explore the effect of case three-dimensional teaching method (CTTM) combined with multimedia teaching on the practice teaching of liver infectious diseases.Methods:Twenty-five interns of liver infectious diseases received by The Second Hospital of Nanjing from May 2019 to January 2020 were taken as the control group, and 25 interns of liver infectious diseases received from February 2020 to October 2020 were taken as the observation group. The control group was given the conventional teaching mode including the conventional case teaching and the conventional multimedia teaching, while the observation group was given CTTM integrated with multimedia teaching method, and both groups were taught for 4 weeks. After teaching, the examination results of liver infectious disease related theory and practice, the changes of core competence before and after teaching, and the recognition of teaching were compared between the two groups. SPSS 25.0 was used for t test and chi-square test. Results:After teaching, the examination results of liver infectious disease related theory [(92.45±7.23) vs. (81.21±7.11)] and practice [(93.27±6.68) vs. (81.23±6.26)] in the observation group were higher than those in the control group. There was no significant difference in the scores of core competence between the two groups before teaching; after teaching, the scores of autonomous learning, problem analysis and solving, doctor-patient communication and teamwork ability of the two groups were higher than those before teaching, and the scores of observation group were significantly higher than those of the control group ( P<0.05). The recognition rates of interns in the observation group were higher than those in the control group in the improvement of learning initiative, the consolidation of theoretical knowledge, the enhancement of practical ability and the improvement of learning efficiency ( P<0.05). Conclusion:In the teaching of liver infectious disease interns, CTTM integrated with multimedia teaching method can not only improve the examination results, and enhance the core competence, but also improve the recognition of interns on the teaching mode.

The transcription factor c-Myc regulates the proliferation, differentiation, metabolism and other key processes of normal cells extensively.The unleashed MYC oncogene frequently produces abundant c-Myc protein, which directly regulates the gene expression of key metabolic enzymes, or tumor-related metabolic pathways by inhibiting microRNA, leading to abnormal metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis, and elevated fatty acid and nucleotide synthesis.This paper briefly summarizes how c-Myc regulated metabolism on glycolysis, glutamine metabolism, tricarboxylic acid cycle, lipid metabolism and nucleotide synthesis in cancer cell,which provides some theoretical reference for the development of antitumor targets and drugs involving c-Myc.