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 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 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 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 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.

Emphasizing symptom efficacy is an important manifestation of the personalized diagnosis and treatment of traditional Chinese medicine （TCM）. However， in current clinical practice of TCM， there are challenges such as diverse symptom expressions， difficulty in standardization， inconsistent evaluation standards for symptom efficacy， lack of universal quantitative methods， and complexity in collecting complete and accurate symptom information. These issues hinder the full and effective utilization of symptom information. Addressing the current research status and existing problems of symptom terminology standardization， quantification and grading of symptom efficacy， and collection of symptom information， this paper proposes methodological strategies for effectively recording and utilizing TCM symptom efficacy information in the era of big data. These strategies include collecting TCM symptom information based on patient reporting， standardizing the evaluation of TCM symptom efficacy from measurement scales and evaluation dimensions， integrating TCM symptom efficacy evaluation into clinical diagnosis and treatment processes， and utilizing artificial intelligence technology to acquire and process TCM symptom efficacy information. TCM symptom efficacy evaluation strategies based on patient perspectives and artificial intelligence technology will help fully explore the value of data elements， promote the objective demonstration of the specific efficacy of TCM， and facilitate the discovery of effective patterns.

Objective To observe the clinical effect of Sijunzi decoction and Fangji Huangqi decoction combined with Sacubitril Valsartan Sodium Tablets in treating chronic heart failure patients with reduced ejec-tion fraction and Qi deficiency,blood stasis and phlegm retention.Methods Ninety-four inpatients with chro-nic heart failure treated in this hospital from January 2021 to December 2022 were selected as the study sub-jects and divided into the Sijunzi Decoction and Fangji Huangqi Decoction combined with Sacubitril Valsartan Sodium Tablets group (the Chinese medicine combined group) and Sacubitril Valsartan Sodium Tablets group (the control group) according to the random number table method.Both groups were treated with standard therapy,and the Chinese medicine combined group added Sijunzi Decoction and Fangji Huangqi Decoction on this basis.Both groups were continuously treated for 8 weeks.The mean systolic blood pressure,left ventricu-lar end diastolic diameter (LVEDD),left ventricular ejection fraction (LVEF),TCM syndrome score and 6 min walking test (6-MWT) results at 24 h before treatment and after treatment were compared between the two groups.Results The average 24 h systolic blood pressure,score of each TCM syndrome and LVEDD after treatment in the two groups were decreased compared with those before treatment (P<0.05),while LVEF and 6-MWT in the two groups were increased,and the differences were statistically significant (P<0.05). Compared with the control group,the average 24 h systolic blood pressure in the Chinese medicine combined group was higher,each score of TCM syndrome score and LVEDD were lower,LVEF and 6-MWT were high-er,and the differences were statistically significant (P<0.05).Conclusion Sijunzi Decoction and Fangji Huangqi Decoction combined with Sacubitril Valsartan Sodium Tablets has a good effect on the patients with chronic heart failure with reduced ejection fraction and Qi deficiency,blood stasis and phlegm retention,which could effectively increase the systolic blood pressure,improve the cardiac coronary arterial perfusion and the quality of life of the patients,and alleviate the left ventricular remodeling status.