Objective To evaluate the predictive value of a nomogram model developed by integrating clinical and ultrasound multiparameters for HER-2-positive breast cancer.Methods This study retrospectively enrolled 343 patients with pathologically confirmed breast cancer from three medical centers and randomly divided them into training and validation cohorts.Univariate analysis,LASSO regression,and multivariate logistic regres-sion were conducted on the training set to identify independent prognostic factors and construct a nomogram model.Bootstrap resampling with 1000 iterations was performed to evaluate the model's robustness.Model calibration was assessed using calibration curves and the Hosmer-Lemeshow goodness-of-fit test.Receiver operating characteristic(ROC)curves were generated to evaluate model discrimination,and the area under the curve(AUC)along with other performance metrics were calculated.Decision curve analysis was employed to assess the clinical utility of the model,and the validation cohort was used for external validation.Results Univariate,LASSO,and multivariate regression analyses demonstrated that age,TTP(time to peak),and the presence of a filling defect sign were independent predictors of HER-2-positive breast cancer(all P<0.05).Based on these independent predictors,a nomogram model was constructed.Bootstrap validation with 1,000 resamples indicated that the model's predictive performance was stable.The Hosmer-Lemeshow test confirmed satisfactory model calibration,while the calibration curve illustrated accurate prediction probabilities.The area under the curve(AUC)for the training set was 0.863(95%CI:0.806～0.920),and for the validation set,it was 0.846(95%CI:0.764～0.929),indicating strong discriminative and generalization capabilities.Additionally,the clinical decision curve analysis demonstrated favor-able clinical utility.Conclusion A nomogram model integrating clinical and multimodal ultrasound parameters demonstrates potential utility in predicting HER-2-positive breast cancer.

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 evaluate the predictive value of a nomogram model developed by integrating clinical and ultrasound multiparameters for HER-2-positive breast cancer.Methods This study retrospectively enrolled 343 patients with pathologically confirmed breast cancer from three medical centers and randomly divided them into training and validation cohorts.Univariate analysis,LASSO regression,and multivariate logistic regres-sion were conducted on the training set to identify independent prognostic factors and construct a nomogram model.Bootstrap resampling with 1000 iterations was performed to evaluate the model's robustness.Model calibration was assessed using calibration curves and the Hosmer-Lemeshow goodness-of-fit test.Receiver operating characteristic(ROC)curves were generated to evaluate model discrimination,and the area under the curve(AUC)along with other performance metrics were calculated.Decision curve analysis was employed to assess the clinical utility of the model,and the validation cohort was used for external validation.Results Univariate,LASSO,and multivariate regression analyses demonstrated that age,TTP(time to peak),and the presence of a filling defect sign were independent predictors of HER-2-positive breast cancer(all P<0.05).Based on these independent predictors,a nomogram model was constructed.Bootstrap validation with 1,000 resamples indicated that the model's predictive performance was stable.The Hosmer-Lemeshow test confirmed satisfactory model calibration,while the calibration curve illustrated accurate prediction probabilities.The area under the curve(AUC)for the training set was 0.863(95%CI:0.806～0.920),and for the validation set,it was 0.846(95%CI:0.764～0.929),indicating strong discriminative and generalization capabilities.Additionally,the clinical decision curve analysis demonstrated favor-able clinical utility.Conclusion A nomogram model integrating clinical and multimodal ultrasound parameters demonstrates potential utility in predicting HER-2-positive breast cancer.

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 use fetal heart quantification ( fetal HQ) technology to compare the coarctation of the aorta (CoA) and normal fetal heart structure and systolic function and to assess whether there are abnormalities in the fetal heart structure and systolic function associated with CoA. Methods::This prospective cohort study was conducted from May 2020 to December 2022 and involved 18-40-week-old singleton pregnancies and 30 fetuses diagnosed with CoA using fetal echocardiography at the General Hospital of Ningxia Medical University and Peking University First Hospital Ningxia Women’s and Children’s Hospital, China. The control group contained 60 normal fetuses. The following parameters were recorded and analyzed statistically: four-chamber view (4CV) end-diastolic long diameter, 4CV epicardial-contralateral epicardial transverse maximum diameter, 4CV global sphericity index (GSI), left ventricular (LV) and right ventricular (RV) 24-segment end-diastolic diameter (EDD), 24-segment sphericity index (SI), LV-fractional area change (LV-FAC), LV-longitudinal strain (LV-LS), RV-fractional area change (RV-FAC), RV-longitudinal strain (RV-LS), and LV and RV 24-segment transverse fractional shortening (FS). Measurement data were compared between the two groups using an independent sample t test, with P < 0.05 indicating statistically significant differences. Moreover, the correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS was assessed. Results::Within and between observer comparisons of the parameters associated with major cardiac function revealed an intragroup correlation coefficient of >0.9, indicating high consistency, and a coefficient of variable of <1 %, indicating low variability. Correlation analysis revealed no obvious correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS. A comparison of the four-chamber morphological structural parameters of the hearts in the two groups revealed that when compared with the control group, the 4CV end-diastolic long diameter was shortened in fetuses in the CoA group and the epicardial-contralateral epicardial transverse maximum diameter was wider, while the GSI was lower ( P < 0.05). A comparison of the LV and RV morphological structure parameters between the two groups revealed that when compared with the control group, the LV’s 24-segment EDD was smaller in the CoA group, the RV’s 24-segment EDD was greater in the control group, the SI of the LV’s segments 16-24 was greater than in the control group, and the SI of the RV’s segments 7-24 was less than in the control group (all P < 0.05). When compared with fetuses in the control group, the LV’s segments 16-24 were greater in the CoA group, whereas the RV’s segment 6-24 was smaller ( P < 0.05). When compared with the control group, LV-FAC, RV-FAC, and LS were lower in the CoA group ( P < 0.05). The FS of the LV segments 1-24 and the FS of the RV segments 1-16 were smaller in the CoA group than in the normal group ( P < 0.05). Conclusion::Fetal HQ, a new simple technique that offers rapid analysis and high repeatability, can quantitatively evaluate structural and systolic function changes in fetuses with CoA.

Objective::To use fetal heart quantification ( fetal HQ) technology to compare the coarctation of the aorta (CoA) and normal fetal heart structure and systolic function and to assess whether there are abnormalities in the fetal heart structure and systolic function associated with CoA. Methods::This prospective cohort study was conducted from May 2020 to December 2022 and involved 18-40-week-old singleton pregnancies and 30 fetuses diagnosed with CoA using fetal echocardiography at the General Hospital of Ningxia Medical University and Peking University First Hospital Ningxia Women’s and Children’s Hospital, China. The control group contained 60 normal fetuses. The following parameters were recorded and analyzed statistically: four-chamber view (4CV) end-diastolic long diameter, 4CV epicardial-contralateral epicardial transverse maximum diameter, 4CV global sphericity index (GSI), left ventricular (LV) and right ventricular (RV) 24-segment end-diastolic diameter (EDD), 24-segment sphericity index (SI), LV-fractional area change (LV-FAC), LV-longitudinal strain (LV-LS), RV-fractional area change (RV-FAC), RV-longitudinal strain (RV-LS), and LV and RV 24-segment transverse fractional shortening (FS). Measurement data were compared between the two groups using an independent sample t test, with P < 0.05 indicating statistically significant differences. Moreover, the correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS was assessed. Results::Within and between observer comparisons of the parameters associated with major cardiac function revealed an intragroup correlation coefficient of >0.9, indicating high consistency, and a coefficient of variable of <1 %, indicating low variability. Correlation analysis revealed no obvious correlation between gestational age and GSI, LV-FAC, LV-LS, RV-FAC, and RV-LS. A comparison of the four-chamber morphological structural parameters of the hearts in the two groups revealed that when compared with the control group, the 4CV end-diastolic long diameter was shortened in fetuses in the CoA group and the epicardial-contralateral epicardial transverse maximum diameter was wider, while the GSI was lower ( P < 0.05). A comparison of the LV and RV morphological structure parameters between the two groups revealed that when compared with the control group, the LV’s 24-segment EDD was smaller in the CoA group, the RV’s 24-segment EDD was greater in the control group, the SI of the LV’s segments 16-24 was greater than in the control group, and the SI of the RV’s segments 7-24 was less than in the control group (all P < 0.05). When compared with fetuses in the control group, the LV’s segments 16-24 were greater in the CoA group, whereas the RV’s segment 6-24 was smaller ( P < 0.05). When compared with the control group, LV-FAC, RV-FAC, and LS were lower in the CoA group ( P < 0.05). The FS of the LV segments 1-24 and the FS of the RV segments 1-16 were smaller in the CoA group than in the normal group ( P < 0.05). Conclusion::Fetal HQ, a new simple technique that offers rapid analysis and high repeatability, can quantitatively evaluate structural and systolic function changes in fetuses with CoA.

Objective:To observe the effect of silicon dioxide (SiO 2) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods:In November 2020, C57BL/6 mice were randomly divided into crystalline SiO 2 group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 μl crystalline SiO 2 suspension (20 mg/ml) or 100 μl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-β (TGF-β) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1β, TNF-α, IL-6, IL-10 and TGF-β were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results:After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO 2 group. Compared with NS group, HYP level of lung tissue in crystalline SiO 2 group were increased, the proportion of M2-typed AMs in crystalline SiO 2 group was increased, the proportion of M1-typed AMs in crystalline SiO 2 group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-β in crystalline SiO 2 group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1β, TNF-α, IL-6 in crystalline SiO 2 group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO 2 group, and the the differences were statistically significant ( P<0.05) . Conclusion:Crystalline SiO 2 may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

Objective:To observe the effect of silicon dioxide (SiO 2) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods:In November 2020, C57BL/6 mice were randomly divided into crystalline SiO 2 group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 μl crystalline SiO 2 suspension (20 mg/ml) or 100 μl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-β (TGF-β) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1β, TNF-α, IL-6, IL-10 and TGF-β were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results:After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO 2 group. Compared with NS group, HYP level of lung tissue in crystalline SiO 2 group were increased, the proportion of M2-typed AMs in crystalline SiO 2 group was increased, the proportion of M1-typed AMs in crystalline SiO 2 group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-β in crystalline SiO 2 group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1β, TNF-α, IL-6 in crystalline SiO 2 group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO 2 group, and the the differences were statistically significant ( P<0.05) . Conclusion:Crystalline SiO 2 may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

Objective:To investigate the clinical characteristics, response, and prognosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL) .Methods:Eight cases of SDRPL were diagnosed and treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between May 2017 and April 2022. Data on the clinical features, laboratory results, bone marrow and spleen biopsy results, response, and prognosis were collected and analyzed.Results:The median age at diagnosis was 54 (42-69) years. Splenomegaly and lymphocytosis were present in all cases, and PET/CT revealed normal to slightly elevated splenic FDG uptake. All cases were in stage Ⅳ, with spleen, peripheral blood, and bone marrow but no proximal lymph nodes involved. The cytoplasm of neoplastic villous cells was abundant, and splenic pathology showed that small homogenous lymphocytes permeated the splenic sinus and splenic cord, and the white pulp atrophied. Immunohistochemistry was not typical, and B-cell markers including CD19, CD20 and CD79α were positive. After a median follow up of 35.5 (4-60) months, 7 cases were alive after splenectomy with or without chemoimmunotherapy. The patient with CCND3 P284A and MYC S146L mutation developed to B-cell prolymphocytic leukemia (B-PLL) 1 month after splenectomy and died at 16 months of follow-up.Conclusion:A rare indolent B-cell lymphoma that primarily affects the elderly, SDRPL. Most patients achieved long-term survival, but the prognosis of patients who progress to B-PLL was poor.

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F