OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

The aim of this experiment is to investigate the mechanism of liver cell damage induced by nonylphenol(NP).After establishing an in vitro model of NP induced BRL-3A liver cell injury,changes of oxidative damage markers were evaluated,Fe2+content was determined,the ultrastruc-ture of BRL-3A was observed,and the expression level of iron death marker proteins were deter-mined.The results showed that NP could significantly increase ROS and MDA in BRL-3A cells(P＜0.05);the GSH content,GSH Px activity,and SOD activity were significantly reduced(P＜0.05);the Fe2+content significantly increased(P＜0.05)and showed a dose-dependent effect;the mitochondrial volume of BRL-3A cells significantly decreases,the mitochondrial cristae break or e-ven disappear,and some mitochondria show vacuolization;the expression levels of iron homeostasis related proteins TFR1 and FTH1 were significantly reduced(P＜0.05).The results indicate that ferroptosis is involved in the mechanism of NP induced liver cell damage,which bene-fits for further exploration of NP pathogenesis.

Objective:To explore the genetic etiology of a child with Cowden syndrome 1 (CS1).Methods:A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c. 781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The c. 781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

Objective:To evaluate the role of histogram analysis based on amide proton transfer weighted (APTw) and apparent diffusion coefficient (ADC) imaging in predicting alpha-thalassemia/mental retardation syndrome X-linked ( ATRX) mutation in isocitrate dehydrogenase ( IDH)-mutant WHO grading 2/3 gliomas. Methods:Seventy-eight patients with IDH-mutant WHO grading 2/3 gliomas, admitted to and confirmed by surgical pathology in Department of Functional Neurosurgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from June 2017 to October 2023, including 52 with ATRX wild and 26 with ATRX mutant-type, were selected. Preoperative 3D-APTw and ADC imaging data were collected; after post-processing, the lesions were segmented using lesion outlining method based on inclusion of peri-tumor edema and lesion outlining method based on tumor entity, respectively; after that, the histogram features (the 10 th percentile, 90 th percentile, maximum, mean, median, minimum, skewness, kurtosis, entropy, range, uniformity, and variance) were extracted from 3D-APTw and ADC imaging, respectively. Univariate Logistic regression was used to compare the differences in histogram features between patients in the ATRX mutant group and ATRX wild-type group, and multivariate Logistic regression was used to screen the independent predictors for ATRX mutation (a Logistic regression prediction model was constructed). Predictive values of independent predictors and Logistic regression prediction models in ATRX mutation were evaluated by receiver operating characteristic (ROC) curve. Results:(1) With lesion outlining method based on inclusion of peri-tumor edema, univariate analysis indicated significant difference between ATRX mutant group and ATRX wild-type group in 9 histogram features: relative 3D-APTw minimum, 3D-APTw skewness, relative ADC 90 th percentile, relative ADC mean, relative ADC median, ADC kurtosis, ADC skewness, ADC uniformity, and ADC entropy ( P<0.05). With lesion outlining method based on tumor entity, univariate analysis indicated significant difference between ATRX mutant group and ATRX wild-type group in 9 histogram features: relative 3D-APTw 90 th percentile, 3D-APTw skewness, relative ADC 90 th percentile, relative ADC mean, relative ADC median, ADC kurtosis, ADC skewness, ADC uniformity and ADC entropy ( P<0.05). (2) With lesion outlining method based on inclusion of peri-tumor edema, multivariate Logistic regression showed that 3D-APTw skewness and ADC kurtosis were the independent predictor for ATRX mutation in IDH mutant WHO grading 2/3 glioma patients ( OR=0.168, 95% CI: 0.034-0.800, P=0.025; OR=0.508, 95% CI: 0.319-0.807, P=0.004). The constructed Logistic regression prediction model was P(Y=1|X)=1/1+e -(1.827-1.785×3D-APTw skewness-0.678×ADC kurtosis). With lesion outlining method based on tumor entity, multivariate Logistic regression showed that 3D-APTw skewness and ADC kurtosis were independent predictors for ATRX mutation in IDH mutant WHO grading 2/3 glioma patients ( OR=0.164, 95% CI: 0.034-0.791, P=0.024; OR=0.496, 95% CI: 0.312-0.788, P=0.003); the constructed Logistic regression prediction model was P(Y=1|X)=1/1+e -(1.585-1.810×3D-APTw skewness-0.702×ADC kurtosis). (3) ROC curve analysis showed that, with lesion outlining method based on inclusion of peri-tumor edema, area under ROC curve (AUC) of 3D-APTw skewness and ADC kurtosis was 0.725 (95% CI: 0.608-0.842, P=0.001) and 0.794 (95% CI: 0.685-0.904), respectively ( P<0.001); AUC of Logistic regression prediction model was 0.836 (95% CI: 0.729-0.942, P<0.001), and its sensitivity and specificity were 73.10% and 90.40% when the best threshold was 0.505. ROC curve showed that, with lesion outlining method based on tumor entity, AUC of 3D-APTw skewness and ADC kurtosis was 0.705 (95% CI: 0.587-0.823, P=0.003) and 0.808 (95% CI: 0.704-0.913), respectively ( P<0.001); AUC of Logistic regression prediction model was 0.844 (95% CI: 0.739-0.949, P<0.001), and its sensitivity and specificity were 84.60% and 80.80% when the best threshold was 0.399. Conclusion:Histogram analysis based on 3D-APTw and ADC imaging can predict ATRX mutation in IDH mutant WHO grading 2/3 gliomas to a certain extent.

OBJECTIVE: To develop a noninvasive method for prediction of 1p/19q codeletion in diffuse lower-grade glioma (DLGG) based on multimodal magnetic resonance imaging (MRI) radiomics. METHODS: We collected MRI data from 104 patients with pathologically confirmed DLGG between October, 2015 and September, 2022. A total of 535 radiomics features were extracted from T₂WI, T₁WI, FLAIR, CE-T₁WI and DWI, including 70 morphological features, 90 first order features, and 375 texture features. We constructed logistic regression (LR), logistic regression least absolute shrinkage and selection operator (LRlasso), support vector machine (SVM) and Linear Discriminant Analysis (LDA) radiomics models and compared their predictive performance after 10-fold cross validation. The MRI images were reviewed by two radiologists independently for predicting the 1p/19q status. Receiver operating characteristic curves were used to evaluate classification performance of the radiomics models and the radiologists. RESULTS: The 4 radiomics models (LR, LRlasso, SVM and LDA) achieved similar area under the curve (AUC) in the validation dataset (0.833, 0.819, 0.824 and 0.819, respectively; P>0.1), and their predictive performance was all superior to that of resident physicians of radiology (AUC=0.645, P=0.011, 0.022, 0.016, 0.030, respectively) and similar to that of attending physicians of radiology (AUC=0.838, P>0.05). CONCLUSION Multiparametric MRI radiomics models show good performance for noninvasive prediction of 1p/19q codeletion status in patients with in diffuse lower-grade glioma.
Humans ; Magnetic Resonance Imaging ; Chromosome Aberrations ; Area Under Curve ; Glioma/genetics* ; ROC Curve

Objective:To evaluate the upper airway dimension changes in mandibular prognathism accompanied with maxillary retrognathism patients treated with bimaxillary orthognathic surgery by spiral CT.Methods:The data of patients with mandibular prognathism accompanied with maxillary retrognathism who underwent bimaxillary surgery in the Department of Oral and Maxillofacial Surgery of Nanjing Stomatological Hospital, Medical School of Nanjing University from May 2017 to October 2020 were retrospectively analyzed. The surgical method was LeFort Ⅰ osteotomy and bilateral sagittal split mandibular osteotomy. The patients were divided into 2 groups based on the sagittal setback distance of the supramentale(in group A, the setback distance of the supramentale was more than 5 mm; in group B, the setback distance of the supramentale was less than or equal to 5 mm). Spiral CT data were collected 1 week before surgery(T0), 1 month after surgery(T1), and 6-12 months after surgery(T2). Three-dimensional model reconstruction was performed. The airway cross-sectional measurements, length and volumes in T0, T1 and T2 were measured. The effect of bimaxillary orthognathic surgery on upper airway of the patients was evaluated quantitatively. We performed repeated measures analysis of variance to compare the differences of upper airway among T0, T1 and T2 in the same group. The Bonferroni method was used for multiple comparisons if the difference was statistically significant(α=0.017). We used two-factor repeated measures analysis of variance to compare the differences of the upper airway change trend between the two groups.Results:A total of 30 patients were included, including 15 patients in group A, 5 males and 10 females[aged: (21.2±2.3) years]; and 15 patients in group B, 7 males and 8 females[aged: (23.6±2.4) years]. The cross-section area and sagittal diameter of lower velopharyngeal plane(Lvp), the glossopharynx airway volume and total upper airway volume: group A decreased significantly at T1, and did not return to T0 level at T2(all P<0.017); group B decreased significantly at T1(all P<0.017), and returned to T0 level at T2(all P>0.017); the change trend of these indexes between the two groups was statistically significant(all P<0.05). The airway length of the glossopharynx and the total upper airway: group A increased significantly at T1 and T2(both P<0.017); group B had no significant changes at T1 or T2(both P>0.017); the change trend of these two indexes between the two groups was statistically significant(both P<0.05). Conclusions:The glossopharynx airway volume and total upper airway volume decreased in mandibular prognathism accompanied with maxillary retrognathism patients after bimaxillary orthognathic surgery. If the setback distance of the mandible is less than or equal to 5 mm, they can probably return to the preoperative level 6-12 months after surgery. If the setback distance of the mandible is more than 5 mm, they can not return to the preoperative level 6-12 months after surgery.

Objective:To evaluate the upper airway dimension changes in mandibular prognathism accompanied with maxillary retrognathism patients treated with bimaxillary orthognathic surgery by spiral CT.Methods:The data of patients with mandibular prognathism accompanied with maxillary retrognathism who underwent bimaxillary surgery in the Department of Oral and Maxillofacial Surgery of Nanjing Stomatological Hospital, Medical School of Nanjing University from May 2017 to October 2020 were retrospectively analyzed. The surgical method was LeFort Ⅰ osteotomy and bilateral sagittal split mandibular osteotomy. The patients were divided into 2 groups based on the sagittal setback distance of the supramentale(in group A, the setback distance of the supramentale was more than 5 mm; in group B, the setback distance of the supramentale was less than or equal to 5 mm). Spiral CT data were collected 1 week before surgery(T0), 1 month after surgery(T1), and 6-12 months after surgery(T2). Three-dimensional model reconstruction was performed. The airway cross-sectional measurements, length and volumes in T0, T1 and T2 were measured. The effect of bimaxillary orthognathic surgery on upper airway of the patients was evaluated quantitatively. We performed repeated measures analysis of variance to compare the differences of upper airway among T0, T1 and T2 in the same group. The Bonferroni method was used for multiple comparisons if the difference was statistically significant(α=0.017). We used two-factor repeated measures analysis of variance to compare the differences of the upper airway change trend between the two groups.Results:A total of 30 patients were included, including 15 patients in group A, 5 males and 10 females[aged: (21.2±2.3) years]; and 15 patients in group B, 7 males and 8 females[aged: (23.6±2.4) years]. The cross-section area and sagittal diameter of lower velopharyngeal plane(Lvp), the glossopharynx airway volume and total upper airway volume: group A decreased significantly at T1, and did not return to T0 level at T2(all P<0.017); group B decreased significantly at T1(all P<0.017), and returned to T0 level at T2(all P>0.017); the change trend of these indexes between the two groups was statistically significant(all P<0.05). The airway length of the glossopharynx and the total upper airway: group A increased significantly at T1 and T2(both P<0.017); group B had no significant changes at T1 or T2(both P>0.017); the change trend of these two indexes between the two groups was statistically significant(both P<0.05). Conclusions:The glossopharynx airway volume and total upper airway volume decreased in mandibular prognathism accompanied with maxillary retrognathism patients after bimaxillary orthognathic surgery. If the setback distance of the mandible is less than or equal to 5 mm, they can probably return to the preoperative level 6-12 months after surgery. If the setback distance of the mandible is more than 5 mm, they can not return to the preoperative level 6-12 months after surgery.

Background::Previous studies have shown that bufalin exerts antitumor effects through various mechanisms. This study aimed to determine the antineoplastic mechanism of bufalin, an extract of traditional Chinese medicine toad venom, in ovarian cancer.Methods::The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2 ′-deoxyuridine (EdU), and colony formation assays were used to investigate the antiproliferative effect of bufalin on the ovarian cancer cell line SK-OV-3. Molecular docking was used to investigate the combination of bufalin and epidermal growth factor receptor (EGFR) protein. Western blotting was performed to detect the expression of EGFR protein and its downstream targets. Results::Bufalin inhibited the proliferation of SK-OV-3 cells in a dose- and time-dependent manner. Bufalin was confirmed to combine with EGFR protein using molecular docking and downregulate expression of EGFR. Bufalin inhibited phosphorylation of EGFR, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK).Conclusion::Bufalin suppresses the proliferation of ovarian cancer cells through the EGFR/AKT/ERK signaling pathway.

Objective:To evaluate the feasibility of three-dimensional measurement in the study of jaw stability in patients with skeletal Class Ⅲ malocclusion after orthognathic surgery, and to analysis the jaw relapse of risk factors.Methods:Patients with skeletal Class Ⅲ malocclusion who underwent bimaxillary surgery in Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, from July 2019 to December 2019 were included. CT data at 1 week preoperative (T0), 3 days after surgery (T1), and 6-12 months after surgery (T2) were collected respectively. The 3D model was constructed by 3D Slicer, and the movement of maxilla and mandible after surgery was measured by Geomagic Qualify. The paired student t-test, Wilcoxon rank sum test and Pearson correlation was performed in this study. P<0.05 was considered statistically significant. Results:A total of 15 patients were included, including 5 males and 10 females. The age is from 18 to 25 year old. The average age is 21.3. In horizontal direction, the RGo coordinate has significant difference between T1[(-50.47±4.44) mm] and T2[(-50.06±4.66) mm] ( t=2.948, P=0.011), while all other landmarks have no significantly statistic difference. In the anteroposterior direction, there were significant differences for all maxillary landmarks between T1 with T2 ( P< 0.05). The relapse rates at point of A, Rp, Lp, RMF and LMF were 37.7 %(1.36/3.61), 35.7%(1.15/3.22), 25.4%(0.84/3.31), 26.9%(0.84/3.12), 14.0%(0.41/2.92), respectively. There were significant differences in all mandibular landmarks between T1 with T2 ( P<0.01). The relapse rates at point of B, Pog, Gn, Me, RGo and LGo were respectively 36.9%(1.75/4.74), 53.9%(2.45/4.55), 55.5%(2.72/4.90), 61.7%(2.90/4.70), 85.3%(2.20/2.58), 93.4%(2.40/2.57). The distance of skeletal relapse movement was significantly correlated with the surgery-induced distance ( r: 0.572-0.736, P<0.05). In the vertical direction, there was no significant difference of maxillary landmarks between T1 with T2 ( P > 0.05). For B, Pog, Gn and Me points, there were statistically significant differences ( P< 0.01). From T1 to T2, the mandible has tendency of counter-clockwise rotation. Conclusions:The three-dimensional measurement can accurately reflect the three-dimensional changes of jaw in patients with skeletal Class Ⅲ malocclusion after bimaxillary surgery. No significantly statistic relapse was in horizontal direction, while obvious relapse was occurred in anteroposterior directions. The counter-clockwise rotation of mandible was shown in vertical direction.

Objective:To evaluate the feasibility of three-dimensional measurement in the study of jaw stability in patients with skeletal Class Ⅲ malocclusion after orthognathic surgery, and to analysis the jaw relapse of risk factors.Methods:Patients with skeletal Class Ⅲ malocclusion who underwent bimaxillary surgery in Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, from July 2019 to December 2019 were included. CT data at 1 week preoperative (T0), 3 days after surgery (T1), and 6-12 months after surgery (T2) were collected respectively. The 3D model was constructed by 3D Slicer, and the movement of maxilla and mandible after surgery was measured by Geomagic Qualify. The paired student t-test, Wilcoxon rank sum test and Pearson correlation was performed in this study. P<0.05 was considered statistically significant. Results:A total of 15 patients were included, including 5 males and 10 females. The age is from 18 to 25 year old. The average age is 21.3. In horizontal direction, the RGo coordinate has significant difference between T1[(-50.47±4.44) mm] and T2[(-50.06±4.66) mm] ( t=2.948, P=0.011), while all other landmarks have no significantly statistic difference. In the anteroposterior direction, there were significant differences for all maxillary landmarks between T1 with T2 ( P< 0.05). The relapse rates at point of A, Rp, Lp, RMF and LMF were 37.7 %(1.36/3.61), 35.7%(1.15/3.22), 25.4%(0.84/3.31), 26.9%(0.84/3.12), 14.0%(0.41/2.92), respectively. There were significant differences in all mandibular landmarks between T1 with T2 ( P<0.01). The relapse rates at point of B, Pog, Gn, Me, RGo and LGo were respectively 36.9%(1.75/4.74), 53.9%(2.45/4.55), 55.5%(2.72/4.90), 61.7%(2.90/4.70), 85.3%(2.20/2.58), 93.4%(2.40/2.57). The distance of skeletal relapse movement was significantly correlated with the surgery-induced distance ( r: 0.572-0.736, P<0.05). In the vertical direction, there was no significant difference of maxillary landmarks between T1 with T2 ( P > 0.05). For B, Pog, Gn and Me points, there were statistically significant differences ( P< 0.01). From T1 to T2, the mandible has tendency of counter-clockwise rotation. Conclusions:The three-dimensional measurement can accurately reflect the three-dimensional changes of jaw in patients with skeletal Class Ⅲ malocclusion after bimaxillary surgery. No significantly statistic relapse was in horizontal direction, while obvious relapse was occurred in anteroposterior directions. The counter-clockwise rotation of mandible was shown in vertical direction.