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 analyze the association between dietary diversity and cognitive function among the elderly using group-based trajectory model, so as to provide the basis for formulating dietary intervention strategies to prevent cognitive impairment. Methods: Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) project, demographic information, lifestyle behaviors, psychological well-being, and activities of daily living of elderly individuals aged ≥65 years from 2008 to 2018 were collected. Dietary diversity was assessed using a food frequency questionnaire, with a score of <7 points defined as low dietary diversity. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). A group-based trajectory model was established based on cognitive function scores from 2008 to 2018 to analyze the trajectories of cognitive function change. The association between dietary diversity and cognitive function was analyzed using a multinomial logistic regression model. Results: A total of 1 613 individuals were collected, with a median age was 72.00 (interquartile range, 10.00) years. There were 810 males (50.22%) and 803 females (49.78%). The group-based trajectory model analysis categorized the participants into three groups: the low-level normal group, the high-level normal group, and the slow-then-rapid decline group, comprising 796 (49.35%), 585 (36.27%), and 232 (14.38%) individuals, respectively. Among these groups, the numbers of individuals with low dietary diversity were 497 (62.44%), 311 (53.16%), and 166 (71.55%), respectively, with a statistically significant difference (P<0.05). Multinomial logistic regression analysis showed that after adjusting for demographic information, lifestyle behaviors, psychological well-being, and activities of daily living, compared with the high-level normal group, low dietary diversity was statistically associated with cognitive function in the slow-then-rapid decline group (OR=1.622, 95%CI: 1.103-2.384). Conclusion Low dietary diversity may increase the risk of cognitive impairment among the elderly.

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 explore the association between blood glucose trajectories within 7 days of intensive care unit (ICU) admission and mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: Based on the MIMIC-IV database, sepsis-associated ARDS patients with daily blood glucose monitoring data within 7 days of ICU admission were selected. Blood glucose trajectories were analyzed using group-based trajectory modeling (GBTM), and the optimal number of groups was determined based on the minimum Akaike information criterion (AIC), Bayesian information criterion (BIC), average posterior probability (AvePP), odds of correct classification (OCC), and proportion of group membership (Prop). Baseline characteristics including demographics, comorbidities, severity scores, vital signs, laboratory indicators within the first 24 hours of ICU admission, and treatments were collected. Kaplan-Meier survival curves were used to compare 28-day and 1-year survival across trajectory groups. Multivariate Logistic regression was performed to evaluate the associations between glucose trajectory groups and in-hospital mortality, ICU mortality. The incidence of hypoglycemia within 7 days in the ICU was analyzed among different groups. RESULTS: A total of 3 869 patients with sepsis-associated ARDS were included, with a median age of 63.52 (52.13, 73.54) years; 59.6% (2 304/3 869) were male. Based on glucose levels within 7 days, patients were categorized into three groups: persistent hyperglycemia group (glucose maintained at 10.6-13.1 mmol/L, n = 894), moderate glucose group (7.8-8.9 mmol/L, n = 1 452), and low-normal glucose group (6.1-7.0 mmol/L, n = 1 523). There were statistically significant differences in 28-day mortality and 1-year mortality among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [28-day mortality: 11.42% (174/1 523), 19.83% (288/1 452), 25.50% (228/894), χ ² = 82.545, P < 0.001; 1-year mortality: 23.31% (355/1 523), 33.75% (490/1 452), 39.49% (353/894), χ ² = 77.376, P < 0.001]. Kaplan-Meier analysis showed that higher glucose trajectories were associated with significantly lower 28-day and 1-year cumulative survival rates (Log-rank test: χ ² were 83.221 and 85.022, both P < 0.001). There were statistically significant differences in in-hospital mortality and ICU mortality among the low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [in-hospital mortality: 9.65% (147/1 523), 19.70% (286/1 452), 24.50% (219/894), χ ² = 102.020, P < 0.001; ICU mortality: 7.22% (110/1 523), 16.05% (233/1 452), 20.13% (180/894), χ ² = 93.050, P < 0.001]. Logistic regression confirmed that, using the persistent hyperglycemia group as the reference, the low-normal glucose group had significantly lower risks of in-hospital mortality and ICU mortality after multiple factor adjustment. Although the moderate glucose group showed a trend toward lower mortality, the differences were not statistically significant. Using the moderate glucose group as a reference, the low-normal glucose group had 43.1% lower in-hospital mortality [odds ratio (OR) = 0.569, 95% confidence interval (95%CI) was 0.445-0.726, P < 0.001] and 42.0% lower ICU mortality (OR = 0.580, 95%CI was 0.439-0.762, P < 0.001). There was no statistically significant difference in the incidence of hypoglycemia within 7 days of ICU admission among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [2.82% (43/1 523), 2.69% (39/1 452), 3.02% (27/894), χ ² = 0.226, P = 0.893]. CONCLUSIONS Blood glucose trajectories during ICU stay are closely associated with prognosis in patients with sepsis-associated ARDS. Persistent hyperglycemia (10.6-13.1 mmol/L) is linked to significantly higher short- and long-term mortality.
Humans ; Respiratory Distress Syndrome/etiology* ; Sepsis/blood* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Blood Glucose/metabolism* ; Hospital Mortality ; Aged

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 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 establish a UPLC method for the simultaneous determination of paeoniflorin,naringin,hesperidin,neohesperidin,costunolide and dehydrocostuslactone to improve the quality standard of Shangke Dieda Tablets.Methods:An Agilent Poroshell 120 C18 column(100 mm × 4.6 mm;2.7 μm)was used with a mobile phase of acetonitrile and 0.1％phosphate solution with binary gradient system at a flow rate of 1.0 mL·min-1.The detection wavelength was 230 nm and the column temperature was 30 ℃.Results:Paeoniflorin,naringin,hesperidin,neohesperidin,cosinolide and dehydrocosinolide showed a good linear relationship between injection concentration and peak area(r＞0.999).The linear ranges of six components were 0.854 2-256.272 μg·mL-1(r=0.999 9),1.057 5-317.247 μg·mL-1(r=0.999 9),and 0.989 5-269.850 μg·mL-1(r=0.999 9),1.055 6-316.689 μg·mL-1(r=0.999 9),0.905 1-271.527 μg·mL-1(r=0.999 8),and 1.064 7-319.395 μg·mL-1(r=0.999 9),respectively.The average recoveries of six components were 99.4％(RSD=1.2％),104.0％(RSD=1.2％),101.6％(RSD=1.0％),102.9％(RSD=0.4％),97.0％(RSD=1.9％),and 104.2％(RSD=1.0％),respectively.A total of 74 batches of samples were collected from 10 manufacturers.The contents of paeoniflorin,naringin,hesperidin,neohesperidin,coxinolactone,and dehydro-cosinolactone were 0.250 8-0.653 2,0.042 2-0.930 9,0.590 9-3.978 0,0.021 2-0.592 6,0.002 4-0.156 7,0.009 2-0.231 3 mg per tablet,respectively.Conclusion:The validated results showed that the method can be used to control the quality of Shangke Dieda Tablets.

Objective To investigate the effects of ethanol extract of Akebia trifoliate(Thunb.)Koidz(EEATK)on the proliferation and apoptosis of human hepatocellular carcinoma Hep3B and Huh-7 cells and to explore its underlying mechanism.Methods Human Hep3B cells and Huh-7 cells were cultured in vitro and separated into control group,Sorafenib group(5 μmol/L),and EEATK groups(0.10 mg/mL,0.15 mg/mL,0.20 mg/mL,0.3 mg/mL)and given the corresponding drug interventions.A CCK-8 assay was used to measure the impact of the different interventions on the proliferation of Hep3B cells and Huh-7 cells to screen the optimal action-inducing concentrations for subsequent experiments.EdU staining assay and colony formation assay were used to explore the effect of EEATK on proliferation,and Annexin V-FITC/PI double-staining assay was applied for apoptotic rate analysis.Transcriptome sequencing(RNA-seq)technology was used to analyze differentially expressed genes(DEGs)related to cell proliferation and apoptosis in the control group and EEATK(0.15 mg/mL)groups of Hep3B cells.DEGs were analyzed for function with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The Comparative Toxicogenomics Database(CTD)was used to validate the expression of key proteins related to cell proliferation and apoptosis,and the findings were verified by qRT-PCR.Results Compared with the control group,different concentration of EEATK significantly inhibited the activity of Hep3B and Huh-7 cells(P＜0.01).Hep3B cells were treated with 0.15 mg/mL EEATK,the EdU-positive cell rate and clone formation rate significantly decreased(all P＜0.01).At the same time,the apoptotic rate of the EEATK group significantly increased(P＜0.01).Transcriptome sequencing of Hep3B cells showed that EEATK induced significant changes in the expression of 1577 genes(P＜0.01),of which 942 were up-regulated and 635 were down-regulated compared with the control group.GO functional enrichment analysis revealed that the DEGs were mainly enriched for cholesterol synthesis,inflammation,and extracellular matrix.KEGG pathway analysis showed that EEATK plays an anti-tumor role,mainly through the TFG-β and NF-κB signaling pathways.CTD and qRT-PCR analysis showed that EEATK significantly down-regulated the expression of apoptosis-related genes such as BIRC5 and CDK1(P＜0.01)and significantly upregulated the expression of CDKN1A and EGLN3(P＜0.01).At the same time,EEATK caused the significant downregulation of cell-proliferation-related genes such as FAM83D and MKI-67(P＜0.01),and significantly upregulated the expression of MYC and FOXC1(P＜0.01).Conclusions EEATK can inhibit cell proliferation and induce apoptosis in a manner that may be related to the regulation of TGF-β and NF-κB signal pathway-related gene expression.