Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Objective To observe the repair effect and mechanism of Danhuang Powder-containing serum on high glucose-induced vascular endothelial cell injury.Methods Danhuang Powder-containing serum was prepared.Human umbilical vein endothelial cells(HUVECs)were cultured to be divided into control group,recombinant human epidermal growth factor(called"growth factor"for short)group,Danhuang Powder group,high glucose group,high glucose+growth factor group,and high glucose+Danhuang Powder group.After corresponding intervention in each group for 48 hours,the cell ultrastructure and autophagy were observed under transmission electron microscope,apoptosis was detected by flow cytometry,and the protein expression levels of vascular endothelial growth factor(VEGF),epidermal growth factor(EGF)and basic fibroblast growth factor(bFGF)in the cells were detected by Western Blot.Results(1)The intra-mitochondrial ridges in the control group were clearly visible,autophagosomes and autolysosomes were fewer;mitochondria in the high glucose group were swollen and irregular,and appeared vacuolated;and the more typical autophagy-like structures were seen in the high glucose+Danhuang Powder group.(2)Compared with the high glucose group and high glucose+growth factor group,the apoptosis rate of cells in the high glucose+Danhuang Powder group was significantly decreased(P<0.05).(3)Compared with the high glucose group and the high glucose+growth factor group,the protein expression levels of VEGF,EGF and bFGF in the cells of the high glucose+Danhuang Powder group were significantly increased(P<0.05).Conclusion Danhuang Powder-containing serum can reduce the high glucose-induced damage in HUVEC cells,and its mechanism may be related to the activation of mitochondrial autophagy,and the inhibition of apoptosis,as well as the up-regulation of the expression of VEGF,EGF and bFGF.

Objective To develop and validate a nomogram risk prediction model for in-stent restenosis(ISR)in patients undergoing carotid artery stenting(CAS).Methods A retrospective analysis was conducted on the clinical data from 267 CAS patients.The dataset was randomly divided into training set(187 cases,for modeling)and test set(80 cases,for validation)in a 7∶3 ratio.Based on whether ISR occurred within one year after CAS,patients were divided into ISR and non-ISR groups.Univariate and multivariate logistic regression analyses were conducted on the training set to identify independent influencing factors and to construct a model.The model was then validated using samples from the test set.The model's discrimination was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC),while the calibration was evaluated using the Hosmer-Lemeshow test and calibration plots.Results ISR occurred in 46 out of 267 CAS patients(17.23％)within one year after surgery.Multivariate logistic regression analysis of the training set identified hypertension[odds ratio(OR)=2.730,95％confidence interval(CI)1.124-6.630],hyperlipidemia(OR=3.135,95％CI 1.293-7.599),preoperative calcified plaque(OR=3.485,95％CI 1.422-8.542),and residual stenosis(OR=5.440,95％CI 1.570-18.854)as significant predictors of ISR in patients with CAS within one year after surgery.The predictive model achieved an AUC of 0.798(9 5％CI 0.715-0.881),with a sensitivity of 73.5％,specificity of 75.8％,and accuracy of 75.4％.The AUC of external validation of the test set was 0.764(95％CI 0.599-0.929).Hosmer-Lemeshow test yielded x2=14.76,P=0.12,while calibration plots indicated high concordance between the predicted and actual outcomes in both the training set and the test set.Conclusion The nomogram risk prediction model for ISR in CAS patients within one year after surgery demonstrates good discrimination and calibration,provi-ding valuable insights for clinical assessment of ISR risk,control of ISR incidence and precision treatment planning.

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 develop and validate a nomogram risk prediction model for in-stent restenosis(ISR)in patients undergoing carotid artery stenting(CAS).Methods A retrospective analysis was conducted on the clinical data from 267 CAS patients.The dataset was randomly divided into training set(187 cases,for modeling)and test set(80 cases,for validation)in a 7∶3 ratio.Based on whether ISR occurred within one year after CAS,patients were divided into ISR and non-ISR groups.Univariate and multivariate logistic regression analyses were conducted on the training set to identify independent influencing factors and to construct a model.The model was then validated using samples from the test set.The model's discrimination was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC),while the calibration was evaluated using the Hosmer-Lemeshow test and calibration plots.Results ISR occurred in 46 out of 267 CAS patients(17.23％)within one year after surgery.Multivariate logistic regression analysis of the training set identified hypertension[odds ratio(OR)=2.730,95％confidence interval(CI)1.124-6.630],hyperlipidemia(OR=3.135,95％CI 1.293-7.599),preoperative calcified plaque(OR=3.485,95％CI 1.422-8.542),and residual stenosis(OR=5.440,95％CI 1.570-18.854)as significant predictors of ISR in patients with CAS within one year after surgery.The predictive model achieved an AUC of 0.798(9 5％CI 0.715-0.881),with a sensitivity of 73.5％,specificity of 75.8％,and accuracy of 75.4％.The AUC of external validation of the test set was 0.764(95％CI 0.599-0.929).Hosmer-Lemeshow test yielded x2=14.76,P=0.12,while calibration plots indicated high concordance between the predicted and actual outcomes in both the training set and the test set.Conclusion The nomogram risk prediction model for ISR in CAS patients within one year after surgery demonstrates good discrimination and calibration,provi-ding valuable insights for clinical assessment of ISR risk,control of ISR incidence and precision treatment planning.

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 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 deeply analyze the problems of public hospitals in medical service satisfaction,construct a more applicable and explanatory service satisfaction evaluation model,and provide reference for the improvement path of patients'medical service satisfaction.Methods Based on the ESCI model,this paper puts forward a research hypothesis,compiles the"Medical Service Satisfaction Evaluation Scale of Public Hospitals in S City",selects S public hospitals as the research object,and evaluates medical service satisfaction from the perspective of patients.Results At present,the main problems affecting the improvement of patients'satisfaction with medical service management in public hospitals in S city are as follows:it is urgent to improve the diagnosis and treatment technology in terms of hardware quality and optimize the environmental hygiene of public hos-pitals,and it is an urgent task to shorten the waiting time for medical treatment in software quality.The score of medical service satisfaction evaluation of S public hospitals was 3.76,and the satisfaction of patients in S public hospitals with their medical serv-ices was at a moderately low level.Conclusion In view of the above problems,it is recommended to strengthen the construction of key specialties,strengthen the construction of talent team,optimize the medical process,open digital linkage services,and strengthen service management,so as to promote the improvement of patients'satisfaction with medical services.

Sphingosine-1-phosphate(S1P)is a highly active membrane phospholipid metabolite with important physiological roles in the cardiovascular system.Sphingosine kinase(SphK)is a lipase that is important for main-taining stable S1P levels in vivo.S1P exerts different physiological effects in cardiovascular diseases by catalytically regulating the binding of S1P to G protein-coupled receptors(S1PR1-5)on the cell surface,thus exerting different physiological effects in cardiovascular diseases.For example,they are involved in regulating the development of dis-eases such as atherosclerosis,myocardial ischemia-reperfusion injury,myocardial infarction,heart failure and other diseases,maintaining the barrier function of vascular endothelial cells,protecting the endothelial glycocalyx layer,leukocyte adhesion,inflammatory reactions and other pathophysiologic processes.