Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

Objective To explore the diagnostic value of MRI quantitative enhancement parameters in breast cancer and their rela-tionships with human epidermal growth factor receptor-2(HER-2)and angiopoietin-2(Ang-2).Methods A total of 80 patients with breast cancer were selected as the study objects.The MRI quantitative enhancement parameters[rate constant(Kep),extravascular extracellular space volume fraction(Ve),volume transfer constant(Ktrans)]of all patients with different clinical staging and lymph node metastasis were compared,respectively.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of MRI quantitative enhancement parameters on the expression of HER-2 and Ang-2.Results Kep and Ktrans in stage Ⅱ group were significantly lower than those in stage Ⅲ and Ⅳ groups(F=6.322,F=6.676;P＜0.05).Kep and Ktrans in lymph node metas-tasis group were significantly higher than those in lymph node non-metastasis group(t=4.265,t=4.557;P＜0.05).Kep and Ktrans in HER-2 positive group were significantly higher than those in HER-2 negative group(t=3.988,t=4.616;P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of the combination of Kep and Ktrans for the diagnosis of HER-2 expression in breast cancer patients was 0.887,with specificity of 0.811 and sensitivity of 0.889,respectively.Kep and Ktrans in Ang-2 positive group were signifi-cantly higher than those in Ang-2 negative group(t=2.534,t=3.189;P＜0.05).ROC curve analysis showed that the AUC of the com-bination of Kep and Ktrans for the diagnosis of Ang-2 expression in breast cancer patients was 0.767,with specificity of 0.867 and sensitivity of 0.569,respectively.Conclusion MRI quantitative enhancement parameters can improve the diagnostic value of breast cancer and the expression of HER-2 and Ang-2,which are beneficial to guide the selections of clinical therapeutic regimens.

Objective To investigate the effect of acacetin on oxidative stress injury in diabetic cataract(DC)rats and its regulation of sirtuin 1(Sirt1)/adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway.Methods Sixty SD rats were randomly divided into the control group,model group,low-dose acacetin group,high-dose acacetin group,and acacetin+Sirt1 inhibitor(EX527)group.DC rat models were constructed except for the control group.Rats in the low-dose and high-dose acacetin groups were injected with 10 mg·kg-1 and 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day,respectively.Rats in the acacetin+EX527 group were injected with 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day;additionally,3.5 mg·kg-1 EX527 was administered subcutaneously through the osmotic micro-pump for 4 weeks.The same amount of nor-mal saline was pumped into rats in the rest groups for 4 weeks.After administration,blood pressure and fasting blood glu-cose(FBG)were measured.The lens opacity was observed under the slit lamp irradiation,and the histopathological chan-ges in the lens were observed after hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was performed to de-termine the serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),in-terleukin(IL)-6,and IL-1 β.Western blot was applied to detect the expression levels of Sirt1,phosphorylated AMPK(p-AMPK),AMPK,and Nrf2 proteins.Results Compared with the control group,the lens epithelial cells(LECs)of rats in the model group showed patchy and striped shapes,and migration and aggregation occurred;the systolic blood pres-sure(SBP),FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Compared with the model group,the migration and aggregation of LECs improved in the low-dose and high-dose acacetin groups,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β decreased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins increased(all P＜0.05).Compared with the high-dose acacetin group,the morphological chan-ges and aggregation of LECs in the acacetin+EX527 group were more significant,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Conclusion Acacetin may protect DC rats from oxidative stress injury by activating the Sirt1/AMPK/Nrf2 pathway.

Objective To investigate the effect of total flavone of Cydonia oblonga on oxidative damage of human lens epithelial cells induced by high glucose and its mechanism.Methods A cell injury model was established by inducing human lens epithelial cells with high glucose.Human lens epithelial cells were cultured in the medium containing 30 mmol·L-1 glucose for 24 h,which was recorded as the high glucose group.Cells in the control group were cultured in a medium con-tainning 5.5 mmol·L-1 glucose for 24 h.Human lens epithelial cells were inoculated into 96-well plates with 5 × 103 cells per well,and treated with mediums containing 10 mmol·L-1,20 mmol·L-1,and 40 mmol·L-1 total flavone of Cydonia ob-longa combined with 30 mmol·L-1 glucose for 24 h.They were recorded as high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total flavone of Cydonia oblonga group.Human lens epithelial cells were transfected with anti-miR-NC and anti-miR-370 with Lipo-fectamine2000 transfection reagent,and treated with 30 mmol·L-1 glucose for 24 h,which were recorded as high glucose+anti-miR-NC group and high glucose+anti-miR-370 group.Human lens epithelial cells were transfected with miR-NC and miR-370 mimics,and treated with medium containing 30 mmol·L-1 glucose and 40 mmol·L-1 total flavone of Cydonia oblonga for 24 h,which were labeled as high glucose+total flavone of Cydonia oblonga+miR-NC group and high glucose+total flavone of Cydonia oblonga+miR-370 group.The activities of superoxide dismutase(SOD)and cata-lase(CAT),and the content of malondialdehyde(MDA)were measured by Enzyme-linked immunosorbent assay;flow cy-tometry was applied to detect apoptosis rate;quantitative reverse transcription polymerase chain reaction was applied to detect the expression level of miR-370;Western blot was applied to detect the expression of apoptosis-related proteins.Results Compared with the control group,the activities of SOD and CAT decreased and the content of MDA increased in the human lens epithelial cells of the high glucose group,and the differences were statistically significant(all P＜0.05);compared with the high glucose group,the activities of SOD and CAT significantly increased and the content of MDA signifi-cantly decreased in the high glucose+low total flavone of Cydonia oblonga group,the high glucose+medium total fla-vone of Cydonia oblonga group and the high glucose+high total flavone of Cydonia oblonga group(all P＜0.05).Com-pared with the control group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of human lens epithelial cells in the high glucose group significantly increased(all P＜0.05);compared with the high glucose group,the apoptosis rate,Caspase-3 and Caspase-9 protein expressions of human lens epithelial cells in the high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total fla-vone of Cydonia oblonga group significantly decreased(all P＜0.05).The expression levels of miR-370 in human lens epi-thelial cells were 1.00±0.00,4.04±0.36,3.22±0.24,2.42±0.23 and 1.62±0.14 in the control group,high glucose group,high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblon-ga group,and high glucose+high total flavone of Cydonia oblonga group,respectively.There was a statistically different significance among the five groups(F=256.138,P＜0.05).Compared with the high glucose+anti-miR-NC group,the ex-pression of miR-370 significantly decreased,the activities of SOD and CAT significantly increased,and the content of MDA significantly decreased in human lens epithelial cells of the high glucose+anti-miR-370 group(all P＜0.001).Compared with the high glucose+anti-miR-NC group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of the hu-man lens epithelial cells in the high glucose+anti-miR-370 group significantly decreased(all P＜0.001).Compared with the high glucose+total flavone of Cydonia oblonga+miR-NC group,the activities of SOD and CAT significantly de-creased,and the content of MDA,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 significantly in-creased in the human lens epithelial cells of high glucose+total flavone of Cydonia oblonga+miR-370 group(all P＜0.001).Conclusion The expression of miR-370 increases in high glucose-induced human lens epithelial cells.Total fla-vone of Cydonia oblonga can inhibit the oxidative stress and apoptosis of high glucose-induced human lens epithelial cells,and the mechanism may be related to the decreased expression of miR-370.

AIM:To investigate the protective effect of total flavonoids from Patrina villosa Juss(PJF)on the lung in an experimental rat model of acute lung injury(ALI),and to elucidate the potential mechanism.METHODS:The ALI rat model was established by instilling 5 mg/kg of lipopolysaccharide(LPS)into the airway.Sixty male SD rats were randomly divided into 4 groups:control,LPS,LPS+low-dose PJF(receiving 100 mg/kg PJF one hour before ALI modeling)and LPS+high-dose PJF(receiving 300 mg/kg PJF one hour before ALI modeling).Each group consisted of 15 animals.Lung tissues and bronchoalveolar lavage fluid(BALF)were collected from all groups 24 h after modeling.For as-sessment of lung tissue morphology,HE staining was performed.The wet/dry weight ratio of the lung tissue was deter-mined using the wet/dry weighing method.Evans blue staining was conducted to assess epithelial barrier permeability in lung tissues.ELISA was used to detect the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in the BALF,as well as oxidative stress markers including superoxide dismutase(SOD),myeloperoxi-dase(MPO)and glutathione peroxidase(GSH-Px)activity,and malondialdehyde(MDA)content in the lung tissue.The expression levels of C/EBP homologous protein(CHOP),glucose-regulated protein 78(GRP78)and X-box binding pro-tein 1(XBP1)in the lung tissue were analyzed by Western blotting.RESULTS:Compared with control group,the rats in LPS group exhibited a blurred alveolar structure with a significant infiltration of inflammatory cells.The ALI score and the wet/dry weight ratio of the lung tissue were increased(P<0.05).Concurrently,the levels of IL-6,IL-1β and TNF-α in the BALF,along with MDA content and MPO activity in the lung tissue,were elevated(P<0.05).Additionally,the pro-tein levels of CHOP,GRP78 and XBP1 were up-regulated in the lung tissue(P<0.05),while the SOD and GSH-Px activi-ty was significantly decreased(P<0.05).Compared with LPS group,PJF intervention exerted beneficial effects on the lung tissue morphology with reduced ALI score and lower lung wet/dry weight ratio(P<0.05).Moreover,the levels of IL-6,IL-1β and TNF-α in BALF,as well as MDA content,MPO activity and the protein levels of CHOP,GRP78 and XBP1 in the lung tissue were all significantly decreased(P<0.05),while the SOD and GSH-Px activity was significantly in-creased(P<0.05).The efficacy in high-dose group exceeded that in low-dose group.CONCLUSION:The PJF have pro-tective effect on the lungs of rats with ALI,and its mechanism may be related to the inhibition of inflammation,oxidative stress and endoplasmic reticulum stress.

Objective To observe clinical efficacy and safety of less invasive surfactant administration(LISA)in treatment of respiratory distress syndrome(RDS)in extremely premature infants.Methods A total of 65 cases premature infants diagnosed with RDS admitted to neonatal intensive care unit of Xiaogan Central Hospital from January 2021 to December 2023,with gestational age of 28+0～31+6 weeks.They were divided into LISA group(n=33)and intubation administration of surfactant extubation(InSurE)group(n=32)using a random number table method.The incidence of adverse events,blood gas analysis before and after administration,pulse oxygen saturation(SpO2),changes in blood pressure,clinical efficacy,complications,and outcomes were compared between two groups.Results There was no statistically significant difference in the incidence of drug reflux,bradycardia,apnea,or SpO2＜80％between two groups of operations(P＞0.05).During the operation,SpO2 of LISA group was lower than that of InSurE group,and blood pressure monitoring at the 2nd and 4th minutes were lower than those of InSurE group at the corresponding time points,with statistically significant differences(P＜0.05).After 1 hour of treatment,arterial partial pressure of oxygen in LISA group was higher than that in InSurE group,and arterial partial pressure of carbon dioxide was lower than that in InSurE group,with statistically significant differences(P＜0.05).The mechanical ventilation ratio and oxygen therapy time within 72 hours in LISA group were lower than those in InSurE group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in reuse rate of pulmonary surfactant(PS),and hospitalization time between two groups(P＞0.05).The incidence of grade 3-4 periventricular intraventricular hemorrhage,P-IVH in LISA group was lower than that in InSurE group,and the difference was statistically significant(P＜0.05).There was no statistically significant difference in the incidence of other complications between two groups(P＞0.05).Conclusion Less invasive PS treatment for extremely premature infants with RDS can reduce the incidence of mechanical ventilation,shorten oxygen therapy time,and reduce the occurrence of severe P-IVH.

Objective To observe clinical efficacy and safety of less invasive surfactant administration(LISA)in treatment of respiratory distress syndrome(RDS)in extremely premature infants.Methods A total of 65 cases premature infants diagnosed with RDS admitted to neonatal intensive care unit of Xiaogan Central Hospital from January 2021 to December 2023,with gestational age of 28+0～31+6 weeks.They were divided into LISA group(n=33)and intubation administration of surfactant extubation(InSurE)group(n=32)using a random number table method.The incidence of adverse events,blood gas analysis before and after administration,pulse oxygen saturation(SpO2),changes in blood pressure,clinical efficacy,complications,and outcomes were compared between two groups.Results There was no statistically significant difference in the incidence of drug reflux,bradycardia,apnea,or SpO2＜80％between two groups of operations(P＞0.05).During the operation,SpO2 of LISA group was lower than that of InSurE group,and blood pressure monitoring at the 2nd and 4th minutes were lower than those of InSurE group at the corresponding time points,with statistically significant differences(P＜0.05).After 1 hour of treatment,arterial partial pressure of oxygen in LISA group was higher than that in InSurE group,and arterial partial pressure of carbon dioxide was lower than that in InSurE group,with statistically significant differences(P＜0.05).The mechanical ventilation ratio and oxygen therapy time within 72 hours in LISA group were lower than those in InSurE group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in reuse rate of pulmonary surfactant(PS),and hospitalization time between two groups(P＞0.05).The incidence of grade 3-4 periventricular intraventricular hemorrhage,P-IVH in LISA group was lower than that in InSurE group,and the difference was statistically significant(P＜0.05).There was no statistically significant difference in the incidence of other complications between two groups(P＞0.05).Conclusion Less invasive PS treatment for extremely premature infants with RDS can reduce the incidence of mechanical ventilation,shorten oxygen therapy time,and reduce the occurrence of severe P-IVH.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.