Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective To investigate the temporal predictive value of soluble triggering receptor expressed on myeloid cells-1(sTREM-1),procalcitonin(PCT),and myeloid-related protein 8/14(MRP8/14)for secondary acute respiratory distress syndrome(ARDS)in patients with severe pulmonary tuberculosis.Methods A retro-spective cohort study was conducted among patients with severe pulmonary tuberculosis admitted between January 2021 and December 2024.Patients were randomly assigned in an 8∶2 ratio to a training set(n=148)and a valida-tion set(n=37).Serum sTREM-1,PCT,and MRP8/14 were extracted from the electronic medical record at three time points:on admission(day 0),day 3,and day 7.Multivariable logistic regression was used to identify risk factors,and predictive performance was evaluated using receiver operating characteristic(ROC)curves.Results A total of 185 patients were included.In the training set(n=148),27 developed ARDS and 121 did not;in the validation set(n=37),7 developed ARDS and 30 did not.In the training set,serum sTREM-1,PCT,and MRP8/14 levels showed significant temporal changes(P<0.05).At admission,day 3,and day 7,levels of sTREM-1,PCT,and MRP8/14 were higher in the ARDS group than in the non-ARDS group(all P<0.05).At each time point,sTREM-1,PCT,and MRP8/14 were independently associated with the development of ARDS(P<0.05).In the training set,the combination of sTREM-1,PCT,and MRP8/14 at admission yielded the largest area under the ROC curve[AUC=0.976;95%confidence interval(CI),0.952～1.000],with a sensitivity of 88.9%and a specificity of 98.3%.In the validation set,the same combination achieved an AUC of 0.957(95%CI,0.895～1.000),with a sensitivity of 100.0%and a specificity of 86.7%.Conclusion Dynamic changes in sTREM-1,PCT,and MRP8/14 provide temporal predictive value for ARDS in patients with severe pulmonary tuberculosis,and the combined assessment improves early warning accuracy.

Objective To investigate the temporal predictive value of soluble triggering receptor expressed on myeloid cells-1(sTREM-1),procalcitonin(PCT),and myeloid-related protein 8/14(MRP8/14)for secondary acute respiratory distress syndrome(ARDS)in patients with severe pulmonary tuberculosis.Methods A retro-spective cohort study was conducted among patients with severe pulmonary tuberculosis admitted between January 2021 and December 2024.Patients were randomly assigned in an 8∶2 ratio to a training set(n=148)and a valida-tion set(n=37).Serum sTREM-1,PCT,and MRP8/14 were extracted from the electronic medical record at three time points:on admission(day 0),day 3,and day 7.Multivariable logistic regression was used to identify risk factors,and predictive performance was evaluated using receiver operating characteristic(ROC)curves.Results A total of 185 patients were included.In the training set(n=148),27 developed ARDS and 121 did not;in the validation set(n=37),7 developed ARDS and 30 did not.In the training set,serum sTREM-1,PCT,and MRP8/14 levels showed significant temporal changes(P<0.05).At admission,day 3,and day 7,levels of sTREM-1,PCT,and MRP8/14 were higher in the ARDS group than in the non-ARDS group(all P<0.05).At each time point,sTREM-1,PCT,and MRP8/14 were independently associated with the development of ARDS(P<0.05).In the training set,the combination of sTREM-1,PCT,and MRP8/14 at admission yielded the largest area under the ROC curve[AUC=0.976;95%confidence interval(CI),0.952～1.000],with a sensitivity of 88.9%and a specificity of 98.3%.In the validation set,the same combination achieved an AUC of 0.957(95%CI,0.895～1.000),with a sensitivity of 100.0%and a specificity of 86.7%.Conclusion Dynamic changes in sTREM-1,PCT,and MRP8/14 provide temporal predictive value for ARDS in patients with severe pulmonary tuberculosis,and the combined assessment improves early warning accuracy.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Objective:To assess the efficacy and safety of “one-stop” procedures combining radiofrequency catheter ablation and left atrial appendage closure by guidance of intracardiac echocardiography(ICE) in elderly patients with atrial fibrillation.Methods:A retrospective cohort study was conducted on patients who underwent ICE-guided “one-stop” procedures at the Department of Cardiology, General Hospital of Northern Theater Command between December 2020 and January 2023. Patients were divided into elderly group (age≥60 years old) and non-elderly group (age 18-59 years old). The clinical characteristics, acute success rate, peri-operative complications and follow-up data between two groups were compared. Multivariate logistic regression analysis was used to analyze whether age was the influencing factor for perioperative complications and atrial fibrillation recurrence.Results:A total of 213 atrial fibrillation patients were enrolled, including 158 (74.18%) in the elderly group (age: (68.3±5.0) years; 56.96% male) and 55 (25.82%) in the non-elderly group (age: (53.7±5.2) years; 81.82% male). The elderly group had lower proportions of males, persistent atrial fibrillation, and left atrial spontaneous echocardiographic contrast compared to the non-elderly group ( P<0.05). CHA 2DS 2-VASc and HAS-BLED scores were higher in elderly group ( P<0.05). The acute success rate,“one-stop” procedure time, fluoroscopy time and the rate of peri-operative complications (6 (3.80%) in elderly group vs. 2 (3.64%) in non-elderly group) were similar between two groups (all P>0.05). The average time of clinical and telephone interviews in elderly group and non-elderly group was (16.9±6.1) months and (17.9±5.9) months, respectively. There was no significant difference in the rate of atrial fibrillation recurrence or clinical events between two groups (47 (30.72%) vs. 14 (26.42%), P=0.554; 10 (6.54%) vs. 2(3.77%), P=0.689, respectively). Iatrogenic atrial septal defects in 3-month transesophageal echocardiography follow up were detected in 44 patients (36.97%) in elderly group and 9 patients (19.57%) in non-elderly group ( P=0.032). Multivariate logistic regression analysis results showed that age was not the influencing factor for peri-operative complications and atrial fibrillation recurrence ( P=0.905 and P=0.676, respectively). Conclusion:Intracardiac echocardiography-guided “one-stop” procedures in the treatment of atrial fibrillation in elderly patients are safe and effective.

Objective:To investigate the efficacy and safety of ablation index-guided radiofrequency catheter ablation (RFCA) and second-generation cryoballoon ablation (CBA) in elderly patients with atrial fibrillation (AF).Methods:This retrospective cohort study included 1 986 patients undergoing pulmonary vein isolation for AF at General Hospital of Northern Theater Command from August 2016 to May 2020, comprising 760 RFCA cases and 1 226 CBA cases. Elderly patients were defined as those aged 60 years or older, while non-elderly patients were those under 60 years of age. All patients were followed up for 3 years after the procedure to assess AF recurrence rates. Kaplan-Meier survival curves were plotted and compared by log-rank test. Multivariate logistic regression was used to analyze the influencing factors of AF recurrence.Results:Among 1 986 AF patients (aged (58.7±10.2) years; 1 307 males, 65.81%; 987 elderly patients, 49.70%), the overall AF recurrence rate was 24.37% (484/1 986). Kaplan-Meier analysis demonstrated a higher AF recurrence rate in the elderly group compared to the non-elderly group (log-rank P=0.007). In the RFCA group, AF recurrence rate was 22.50% (171/760), with no significant difference between the elderly (24.44%, 88/360) and non-elderly (20.75%, 83/400) subgroups ( P=0.223). In the CBA group, recurrence rates were 25.53% (313/1 226), with significantly higher recurrence in elderly patients (28.55%, 179/627) than non-elderly (22.37%, 134/599) ( P=0.013). Multivariate logistic regression analysis revealed that advanced age was not an independent predictor of AF recurrence ( P=0.447). Longer AF duration and larger left atrial diameter were independent risk factors for recurrence, while male sex was a protective factor (all P<0.05). Conclusion:Pulmonary vein isolation with second-generation CBA and RFCA guided by ablation index are safe and effective in the treatment of AF in elderly patients.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To assess the efficacy and safety of “one-stop” procedures combining radiofrequency catheter ablation and left atrial appendage closure by guidance of intracardiac echocardiography(ICE) in elderly patients with atrial fibrillation.Methods:A retrospective cohort study was conducted on patients who underwent ICE-guided “one-stop” procedures at the Department of Cardiology, General Hospital of Northern Theater Command between December 2020 and January 2023. Patients were divided into elderly group (age≥60 years old) and non-elderly group (age 18-59 years old). The clinical characteristics, acute success rate, peri-operative complications and follow-up data between two groups were compared. Multivariate logistic regression analysis was used to analyze whether age was the influencing factor for perioperative complications and atrial fibrillation recurrence.Results:A total of 213 atrial fibrillation patients were enrolled, including 158 (74.18%) in the elderly group (age: (68.3±5.0) years; 56.96% male) and 55 (25.82%) in the non-elderly group (age: (53.7±5.2) years; 81.82% male). The elderly group had lower proportions of males, persistent atrial fibrillation, and left atrial spontaneous echocardiographic contrast compared to the non-elderly group ( P<0.05). CHA 2DS 2-VASc and HAS-BLED scores were higher in elderly group ( P<0.05). The acute success rate,“one-stop” procedure time, fluoroscopy time and the rate of peri-operative complications (6 (3.80%) in elderly group vs. 2 (3.64%) in non-elderly group) were similar between two groups (all P>0.05). The average time of clinical and telephone interviews in elderly group and non-elderly group was (16.9±6.1) months and (17.9±5.9) months, respectively. There was no significant difference in the rate of atrial fibrillation recurrence or clinical events between two groups (47 (30.72%) vs. 14 (26.42%), P=0.554; 10 (6.54%) vs. 2(3.77%), P=0.689, respectively). Iatrogenic atrial septal defects in 3-month transesophageal echocardiography follow up were detected in 44 patients (36.97%) in elderly group and 9 patients (19.57%) in non-elderly group ( P=0.032). Multivariate logistic regression analysis results showed that age was not the influencing factor for peri-operative complications and atrial fibrillation recurrence ( P=0.905 and P=0.676, respectively). Conclusion:Intracardiac echocardiography-guided “one-stop” procedures in the treatment of atrial fibrillation in elderly patients are safe and effective.