Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.

The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.

Objective:To understand the true feelings of nursing undergraduates about their professional cultural confidence, and to provide reference for nursing educators and managers to formulate ideological and political education programs.Methods:Totally 33 undergraduate nursing students admitted into Guangzhou Medical University in 2020 were selected by purposive sampling from November to December 2020. This study adopted the phenomenological method in qualitative research. Semi-structured group focus interviews were conducted with the nursing undergraduates, and Colaizzi's 7-step analysis was used to analyze the data and refine the themes.Results:The nursing undergraduates showed both positive and negative psychological experience towards nursing culture. Positive experience themes included recognition, acceptance and love, while negative experience themes included conflict, resistance and confusion.Conclusions:This study reveals the psychological experience of nursing undergraduates' cultural confidence in this profession. It is recommended that nursing educators and managers pay attention to and strengthen the positive experience of nursing undergraduates, and devote themselves to ameliorating their negative experience. They should provide targeted education for general culture and nursing culture, help nursing undergraduates establish a positive and stable nursing culture perception, and cultivate their confidence in nursing culture.

Objective:To evaluate the effect of penile dorsal extension and bandaging after concealed penis surgery.Methods:In this study, 80 children who underwent concealed penile correction were randomly divided into a dorsal extension bandaging group (experimental group) and a traditional bandaging group (control group) from Xuzhou Children’s Hospital Affiliated to Xuzhou Medical University during September 2016 to September 2019. The control group was applied with traditional sleeve-type bandaging, and the test group was treated with penile dorsal extension bandaging. A total of 75 children was summarized in this study. Among them, there were 38 children in the experimental group, with a mean age of 64 months. Thirty-seven children were in the control group, with a mean age of 70 months. The incidence of complications during hospitalization, the number of calls to medical staff within the first 24 hours after surgery, the pain score of the child during dressing removal, and the time taken for dressing removal were compared and recorded. Measurement data were analyzed by t-tests and enumeration data were analyzed by chi-square tests between groups. All data were analyzed using software SPSS 17.0. Results:The incidence of complications during hospitalization was 5.26%(2/38) and 10.81%(4/37) in the experimental and control groups, respectively. This difference was not statistically significant( χ2=0.784, P>0.05). In the dorsal extension bandaging group and the traditional bandaging group, the average number of calls to medical staff 24 hours after surgery was (0.87 ± 0.91) and (1.54 ± 1.02) times, the difference was statistically significant ( t=2.996, P=0.003); as for the highest pain scores of the children when the dressing was removed were 5.21 ± 1.19 and 7.24 ± 1.20, the difference was statistically significant ( t=5.697, P< 0.001); the time taken to remove the dressing was (3.21 ± 1.24) min, (7.56 ± 1.88) min, and the difference was statistically significant ( t=11.917, P<0.001). Conclusions:The penile dorsal extension bandaging method after concealed penis surgery can reduce the number of calls to medical staff, reduce the time of dressing removal and the degree of pain in children.

Objective:To evaluate the effect of penile dorsal extension and bandaging after concealed penis surgery.Methods:In this study, 80 children who underwent concealed penile correction were randomly divided into a dorsal extension bandaging group (experimental group) and a traditional bandaging group (control group) from Xuzhou Children’s Hospital Affiliated to Xuzhou Medical University during September 2016 to September 2019. The control group was applied with traditional sleeve-type bandaging, and the test group was treated with penile dorsal extension bandaging. A total of 75 children was summarized in this study. Among them, there were 38 children in the experimental group, with a mean age of 64 months. Thirty-seven children were in the control group, with a mean age of 70 months. The incidence of complications during hospitalization, the number of calls to medical staff within the first 24 hours after surgery, the pain score of the child during dressing removal, and the time taken for dressing removal were compared and recorded. Measurement data were analyzed by t-tests and enumeration data were analyzed by chi-square tests between groups. All data were analyzed using software SPSS 17.0. Results:The incidence of complications during hospitalization was 5.26%(2/38) and 10.81%(4/37) in the experimental and control groups, respectively. This difference was not statistically significant( χ2=0.784, P>0.05). In the dorsal extension bandaging group and the traditional bandaging group, the average number of calls to medical staff 24 hours after surgery was (0.87 ± 0.91) and (1.54 ± 1.02) times, the difference was statistically significant ( t=2.996, P=0.003); as for the highest pain scores of the children when the dressing was removed were 5.21 ± 1.19 and 7.24 ± 1.20, the difference was statistically significant ( t=5.697, P< 0.001); the time taken to remove the dressing was (3.21 ± 1.24) min, (7.56 ± 1.88) min, and the difference was statistically significant ( t=11.917, P<0.001). Conclusions:The penile dorsal extension bandaging method after concealed penis surgery can reduce the number of calls to medical staff, reduce the time of dressing removal and the degree of pain in children.

We constructed the CS1-targeted second- and third-generation CAR-T cells with genetic engineered 4-1BB or/and ICOS as a costimulatory signaling molecule by use of lentiviral platform. The CS1-targeted second-generation CAR-T cells with ICOS or 4-1BB had similar anti-neoplastic activity. When effector/target ratio was 1:1, the CAR-T cells with ICOS showed better killing effect on IM9-lucgfp cells than those with 4-1BB. However, The CS1-targeted third-generation CAR-T cells exihibited lower cytolytic capacity against IM9-lucgfp cells than the CS1-targeted second-generation CAR-T cells when the ratio of effector/target was 1:1, 2:1 or 5:1. When the ratio of effector/target was 10:1, the killing efficacy of both the second- and third-generation CAR-T cells against IM9-lucgfp cells was more than 85%, significantly higher than that of the control T cells. Taken together, both the CS1-targeted second- and third-generation CAR-T cells with ICOS or/and 4-1BB could efficiently kill CS1-positive multiple myeloma cells, but the CS1-targeted second-generation CAR-T cells had more potent killing effect on CS1-positive multiple myeloma cells than the CS1-targeted third-generation CAR-T cells.
4-1BB Ligand/metabolism* ; Cell Line, Tumor ; Genetic Engineering ; Humans ; Inducible T-Cell Co-Stimulator Protein/metabolism* ; Multiple Myeloma/therapy* ; Signal Transduction ; T-Lymphocytes/chemistry* ; Xenograft Model Antitumor Assays

Objective To investigate the effect of different shear stress on the expression of Interleukin-8 (IL-8) and endothelin-1 (ET-1) in vascular endothelial cells.Methods Umbilical vein endothelial cell line (ECV-304) was used as the research cell.The shear stress of 5 dyne/cm2 and 10 dyne/cm2 was regulated by the self-made shearing stress control device.The shear stress in were maintained at 0,5 dyne/cm2 and 10 dyne/cm2 respectively in the control group,the low shear stress group and the high shear stress group.The effects on the levels of IL-8 and ET-1 were analyzed between the three groups at five time points of 30 min,60 min,120 min,300 min,420 min.Pearson correlation analysis was used to analyze the correlation between IL-8 and ET-1.Results The level of IL-8 in the three groups has been on the rise.At the three time points of 30 min,60 min and 120 min,there was no statistically significant difference in IL-8 level between the three groups (P ＞ 0.05).At the two time points of 300 min and 420 min,the difference of the IL-8 level in the three groups was statistically different (P ＜ 0.05),At the two time points of 300 min and 420 min,the IL-8 level in the low shear stress group was higher than that in the control group and the high shear group,the IL-8 level in the high shear group was higher than that in the control group (P ＜ 0.05).The level of ET-1 in the control group and the low shear group showed an upward trend,and the ET-1 level in the high shear group increased continuously in the former 120 min,but began to decrease continuously since then.At the three time points of 30 min,60 min and 120 min,the difference of the ET-1 level in the three groups was statistically different (P ＜ 0.05).The ET-1 level of the high shear group at three time points of 30 min,60 min and 120 min was higher than that of the control group,the level of ET-1 at two time points of 30 min and 60 min was higher than that in low shear stress group (P ＜ 0.05),the ET-1 level of the low shear group at two time points of 60 min and 120 min was higher than that of the control group (P ＜ 0.05).At the two time points of 300 min and 420 min,there was no significant difference in the level of ET1 between the three groups (P ＞ 0.05).Pearson correlation analysis showed that there was a positive correlation between the expression of IL-8 and ET-1 (r =0.384,P =0.031).Conclusions Shear stress can affect the expression of IL-8 and ET-1 in vascular endothelial cells,the shear stress of 5 dyne/em2 can increase the level of IL-8 more efficiently,the shear force of 10 dyne/cm2 can increase the level of ET-1 more obviously,but it may cause damage to the vascular endothelial cells.

Objective To evaluate the efficacy and safety of tigecycline-based treatment approach on severe infection of patients with hematological diseases. Methods The clinical data of 64 patients who were treated with tigecycline-based treatment approach for severe infection were retrospectively reviewed. The curative effect was evaluated, meanwhile the drug side effects were observed. Results A total of 51 strains of bacteria were isolated from 64 patients, including 12 extended-spectrum β-lactamase(ESBL)and 15 multi-drug resistant strains and the total effective rate was 59.4%(38/64). Five patients diagnosed as carbapenem resistant infection and were treated with the addition dose of tigecycline and 3 patients relieved. Main adverse events were nausea, vomiting, diarrhea and hepatic dysfunction, but all events were slight. Conclusions Tigecycline-based treatment approach has a good clinical efficacy in treating severe infection of patients with hematological diseases, and the side effect is few.Tigecycline-based treatment approach could be used as a new choice for patients non-responding favorably to conventional anti-infective treatment or multiple resistant bacteria.