Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Objective To introduce an innovative technique, the "balance-shaped sternal elevation device" and its application in the subxiphoid uniportal video-assisted thoracoscopic surgery (VATS) for anterior mediastinal masses resection. Methods Patients who underwent single-port thoracoscopic assisted anterior mediastinal tumor resection through the xiphoid process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from May to June 2024 were included, and their clinical data were analyzed. Results A total of 7 patients were included, with 3 males and 4 females, aged 28-72 years. The diameter of the tumor was 1.9-17.0 cm. The operation time was 62-308 min, intraoperative blood loss was 5-100 mL, postoperative chest drainage tube retention time was 0-9 days, pain score on the 7th day after surgery was 0-2 points, and postoperative hospital stay was 3-12 days. All patients underwent successful and complete resection of the masses and thymus, with favorable postoperative recovery. Conclusion The "balance-shaped sternal elevation device" effectively expands the retrosternal space, providing surgeons with satisfactory surgical views and operating space. This technique significantly enhances the efficacy and safety of minimally invasive surgery for anterior mediastinal masses, reduces trauma and postoperative pain, and accelerates patient recovery, demonstrating important clinical significance and application value.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Objective:To discuss the expression of tripartite motif-containing protein 24(TRIM24)in the clear cell renal cell carcinoma(ccRCC)tissue,and to clarify its relationships with the clinicopathological features and prognosis of the ccRCC patients.Methods:The cancer and paracancer normal tissues were collected from 90 ccRCC patients who had not undergone preoperative radiotherapy or chemotherapy.Tissue microarray and immunohistochemistry were used to detect the expression levels of TRIM24 protein in ccRCC tissue.The differences in TRIM24 protein expression between ccRCC and paracancer normal tissues were analyzed.The score of TRIM24 protein expression and the average value were calculated,and based on the average value,the patients were classified into TRIM24 protein low-expression and TRIM24 protein high-expression groups.The associations between the TRIM24 protein expression and different clinicopathological features of the patients were analyzed,and the relationship between the TRIM24 protein expression and the prognosis of the patients was analyzed.Results:The immunohistochemistry results showed that the TRIM24 protein was expressed in both the nucleus and cytoplasm of the ccRCC tumor cells,and there were significant differences in the TRIM24 protein expression level in ccRCC tissue when compared with paracancer normal tissue(P＜0.05).The TRIM24 protein expression in the nucleus of ccRCC tissue was associated with the patient's age,gender,and tumor size(P＜0.05).The Kaplan-Meier survival analysis results showed that the overall survivals of the patients with high TRIM24 protein expression in the cytoplasm of ccRCC tissue,older age,and higher pathological grade were shorter than those with low TRIM24 protein expression,younger age,and lower pathological grade(P＜0.05).The multivariate Cox regression analysis results showed that the prognosis of the patients with high TRIM24 protein expression in the cytoplasm and higher pathological grade were poorer compared with the patients with low TRIM24 protein expression and lower pathological grade(P＜0.05).Conclusion:The ccRCC patients with high TRIM24 expression in the cytoplasm of ccRCC tumor tissue and higher pathological grade have the lower postoperative survival rates and poorer prognosis.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

BACKGROUND:There is a significant correlation between sperm DNA fragmentation index and fertilization,embryonic development potential,embryo implantation,miscarriage,and offspring safety.However,its clinical reference value is affected by many factors,resulting in extremely limited clinical significance.This study took live birth as the outcome,corrected other confounding factors through propensity score matching,constructed the best clinical cutoff value of sperm DNA fragmentation index and live birth,and conducted internal and external tests on it,which has good predictive value and clinical application efficiency. OBJECTIVE:To investigate the reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth. METHODS:A total of 1 921 patients who received in vitro fertilization and embryo transfer in Changzhou Maternal and Child Health Area Hospital from May 2019 to May 2021 were selected.On the basis of tendency matching tolerance of 0.02 and propensity score matching of 1:1,540 cases were successfully matched in each live birth group and non-live birth group,and the model group was established.135 patients who received in vitro fertilization and embryo transfer in Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the external validation group.The optimal clinical cutoff value of sperm DNA fragmentation index for live birth was investigated by the receiver operating characteristic curve.The accuracy and clinical application efficacy of the cutoff value were evaluated by restricted cubic spline curve,standard curve,clinical decision curve,clinical impact curve and internal and external validation tests. RESULTS AND CONCLUSION:(1)The DNA fragmentation index of sperm in the non-live birth group was significantly higher than that in the live birth group and had a significant negative correlation with live birth(r=-0.444,P<0.001).(2)Receiver operating characteristic curve results showed that the optimal cut-off value of DNA fragmentation index for live birth was 24.33%;the area under the curve was 0.775(0.746,0.804);the specificity was 72.60%;the sensitivity was 78.90%,and the accuracy was 75.70%.(3)Restricted cubic spline curve fitting the results of Logistic regression showed that when the sperm DNA fragmentation index was greater than 24.57%,the risk of clinical non-live birth increased.(4)The probability of Logistic regression analysis results showed that sperm DNA fragmentation index was a risk factor for live birth[OR(95%CI)=0.916(0.904,0.928),P<0.001],and when sperm DNA fragmentation index was greater than 27.78%,the probability of clinical live birth would be less than 50%.With the increase of sperm DNA fragmentation index by 1 unit,the probability of a live birth fell by 8.4%.(5)Internal and external to the validation of the clinical cutoff value showed that the cutoff point had certain clinical predictive value and accuracy.(6)Clinical decision curve and clinical impact curve results exhibited that the prediction model based on the clinical cut-off value had the maximum clinical net benefit value when the threshold probability was 0.22-0.73,and the ratio of loss to gain within the threshold probability range was always less than 1,which confirmed that the prediction model had good clinical application effectiveness.(7)The results of sperm DNA fragmentation index and offspring short-term security analysis showed that sperm DNA fragmentation index had no significant differences with preterm birth,body weight,deformity and sex.(8)These findings suggest that the optimal clinical cut-off value of sperm DNA fragmentation index for in vitro fertilization-embryo transfer live birth was 24.33%.The established clinical prediction model has good differentiation,accuracy and clinical application effectiveness.Sperm DNA fragmentation index has no significant impact on offspring short-term security,but large samples and long-term follow-up evaluation are still needed.

Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

Objective:To compare the diagnostic value of contrast-enhanced ultrasound(CEUS)combined with conventional ultrasound and magnetic resonance imaging(MRI)in distinguishing benign and malignant non-mass lesions of breast.Methods:A retrospective analysis was conducted on 131 patients with non-mass lesions of breast(76 benign cases,55 malignant cases),who were pathologically confirmed at The 910th Hospital of People's Liberation Army Joint Service Support Force from January 2019 to January 2024.The CEUS and MRI characteristics between benign and malignant non-mass lesions of breast were compared.Using pathological results as the gold standard,the receiver operating characteristic(ROC)curve were employed to compare the area under curve(AUC)value,sensitivity and specificity of CEUS+conventional ultrasound and MRI in diagnosing malignant non-mass lesions of breast.The diagnostic performances of them on non-mass lesions with different sizes(maximum diameter<10 mm,10-20 mm,and>20 mm)were further explored.Results:Conventional ultrasound identified 131 non-mass lesions of breast,whereas MRI identified 79 non-mass lesions(60.31%),40 cases with mass-like lesions(30.53%),and 12 normal breast(9.16%).The overall consistency between conventional ultrasound and MRI was higher(Kappa=0.603).After CEUS combined with conventional ultrasound,38 lesions that were classified as BI-RADS 4 by conventional ultrasound downgraded to BI-RADS 3.In the 131 patients,the specificity(71.1%)of CEUS combined with conventional ultrasound was significantly higher than that(55.3%)of MRI,with a statistically significant difference(x2=5.775,P=0.016).For all patients,the AUC value(0.828)of CEUS combined with conventional ultrasound in diagnosing malignant non-mass lesions of breast was higher than that(0.776)of MRI(Z=3.246,P=0.006).Among of them,the diagnostic AUC value of CEUS combined with ultrasound was 0.842 for the patients whose size of the non-mass lesions of breast was between 10-20 mm,which was significantly larger than that(0.758)of MRI(Z=4.856,P<0.001).Conclusions:The diagnostic specificity of CEUS+conventional ultrasound is higher than that of MRI for malignant non-mass lesions of breast,which has a certain of advantage.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

OBJECTIVES: To observe the evolution of intrahepatic macrophage polarization in mice with liver fibrosis induced by iron overload. METHODS: Thirty-two C57BL/6 mice (6-8 weeks) were randomized into control group (n=8) and liver fibrosis model group (n=24) induced by aidly intraperitoneal injection of iron dextran. At the 3rd, 5th, and 7th weeks of modeling, 8 mice in the model group were sacrificed for observing liver fibrosis using Masson, Sirius Red and immunohistochemical staining and detecting serum levels of ALT, AST and the levels of serum iron, ferritin, liver total Fe and ferrous Fe. iNOS⁺/F4/80⁺ cells and CD206⁺/F4/80⁺ cells were detected by double immunofluorescence assay to observe the proportion and distribution of M1 and M2 macrophages. The hepatic expressions of Arg-1, iNOS, IL-6, IL-10, and TNF‑α proteins were detected using Western blotting or ELISA, and the expression of CD206 mRNA was detected using RT-PCR. RESULTS: The mice in the model group showed gradual increase of fibrous tissue hyperplasia in the portal area over time, structural destruction of the hepatic lobules and formation of pseudolobules. With the passage of time during modeling, the rat models showed significantly increased hepatic expressions of α-SMA and COL-1, elevated serum levels of ALT, AST, Fe, ferritin, and increased liver total Fe and ferrous Fe levels. The expressions of M1 polarization markers IL-6, TNF‑α, and iNOS all increased with time and reached their peak levels at the 3rd week; The expressions of M2 polarization markers (IL-10 and Arg-1 proteins and CD206 mRNA) significantly increased in the 3rd week and but decreased in the 5th and 7th weeks. CONCLUSIONS Iron overload promotes M1 polarization of macrophages in mice. Liver fibrosis in the early stage promotes M2 polarization of macrophages but negatively regulate M2 polarization at later stages.
Animals ; Mice ; Mice, Inbred C57BL ; Iron Overload/pathology* ; Macrophages/metabolism* ; Male ; Liver Cirrhosis/etiology* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Liver/pathology* ; Interleukin-6/metabolism* ; Mannose Receptor ; Tumor Necrosis Factor-alpha/metabolism* ; Mannose-Binding Lectins/metabolism* ; Arginase