Objective:To investigate the correlation between preoperative calcitonin levels and upper mediastinal lymph node metastasis in medullary thyroid carcinoma (MTC).Methods:A retrospective analysis was conducted on 249 MTC patients who underwent surgery at the Cancer Hospital, Chinese Academy of Medical Sciences between January 2010 and December 2021. Based on postoperative pathology, patients were categorized into the upper mediastinal lymph node metastasis group ( n=41) and the non-upper mediastinal lymph node metastasis group ( n=208). Clinicopathological features were compared, and survival outcomes were assessed using Kaplan-Meier analysis. Receiver operating characteristic (ROC) curves were employed to determine the predictive efficacy and optimal cutoff value of preoperative calcitonin for the upper mediastinal lymph node metastasis group. Logistic regression identified independent risk factors for the upper mediastinal lymph node metastasis group. Results:Compared to the non-upper mediastinal lymph node metastasis group, the upper mediastinal lymph node metastasis group demonstrated a higher proportion of male patients, elevated levels of carcinoembryonic antigen and calcitonin, increased multifocality, larger primary tumor size, higher rates of extrathyroidal extension, advanced T and N stages, and greater incidences of lymph node metastasis and extracapsular invasion (all P＜0.01). Patients with upper mediastinal lymph node metastasis exhibited significantly lower overall survival than those without upper mediastinal lymph node metastasis ( P＜0.001). ROC curve analysis revealed an area under the curve of 0.783 for preoperative calcitonin in predicting upper mediastinal lymph node metastasis, with an optimal cutoff value of 1 865 pg/ml (sensitivity 71.79%, specificity 75.53%). Multivariate logistic regression analysis identified preoperative calcitonin levels >1 865 pg/ml ( OR=5.31, 95% CI: 1.77-15.94) and >15 metastatic lymph nodes ( OR=4.90, 95% CI: 1.87-12.89) as independent risk factors for the upper mediastinal lymph node metastasis group. Conclusions:Preoperative calcitonin＞1 865 pg/ml suggests a higher likelihood of MTC with upper mediastinal lymph node metastasis. For individuals with suspected upper mediastinal lymph node metastasis on imaging, combining preoperative calcitonin levels can reduce false-positive rates.

Objective:To explore the effects of astragaloside (Ast) on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and excitation-inhibition balance in amygdala of mice with autism spectrum disorder(ASD).Methods:The C57BL/6 pregnant mice in model group were intraperitoneally injected with sodium valproate(500 mg/kg) on days 12-13 of pregnancy, while the C57BL/6 pregnant mice in control group were given an equal volume of 0.9% NaCl solution.The offspring mice were then divided into 5 groups according to the nest matching principle: the control+ normal saline group(Con+ NS group), the control+ Ast group (Con+ Ast group), the model+ normal saline group(Mod+ NS group), the model+ Ast group (Mod+ Ast group) and the Model+ Ast+ PI3K inhibitor LY294002 group (Mod+ Ast+ LY group), with 12 mice in each group. At the age of 14 days, the mice in the Con+ Ast group and the Mod+ Ast group were intraperitoneally injected with Ast (20 mg/kg, once a day for 7 consecutive days), the mice in the Mod+ Ast+ LY group were intraperitoneally injected with Ast (20 mg/kg) and LY294002(30 mg/kg), the mice in Con+ NS group and Mod+ NS group were intraperitoneally injected with the same volume of 0.9% NaCl solution.The depressive-like behavior and social function were evaluated by the marble-burying test (MBT), the three-chamber social interaction test(SIT), and the forced swimming test(FST). The expression levels of proteins related to the PI3K/AKT signaling pathway in the amygdala were detected by Western blot. The immunofluorescence method was employed to determine the levels of the neurotransmitters glutamate (Glu) and γ-aminobutyric acid(GABA)in the amygdala region.Statistical analysis was carried out using GraphPad Prism 9.5.0 software, and one-way ANOVA test was utilized for comparisons among multiple groups.Results:(1)Behavioral results showed that there were statistically significant differences in the number of buried beads of the MBT, the social interaction index and social novelty preference index of the SIT, and the immobility time and first immobile state incubation period of the FST among the five groups( F=28.85, 89.23, 77.62, 91.70, 125.40, all P<0.05). The number of buried beads and immobility time in Mod+ NS group were higher than those in Con+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Con+ NS group (all P<0.05). The number of buried beads and immobility time in Mod+ Ast group were lower than those in Mod+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were higher than those in Mod+ NS group(all P<0.05). The number of buried beads and immobility time in Mod+ Ast+ LY group were higher than those in Mod+ Ast group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Mod+ Ast group (all P<0.05).(2) Western blot results showed that there were statistically significant differences in p-PI3K/PI3K, p-AKT/AKT in amygdala among the five groups ( F=27.14, 25.50, both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ NS group were lower than those of Con+ NS group(both P<0.05).The expressions of p-PI3K/PI3K and p-AKT/AKT in amygdala of Mod+ Ast group((0.67±0.04), (0.52±0.09))were higher than those of Mod+ NS group((0.48±0.06), (0.34±0.06))(both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ Ast+ LY group ((0.52±0.04), (0.36±0.10))were lower than those of Mod+ Ast group(both P<0.05). (3)Immunofluorescence results showed that the number of Glu- and GABA- positive cells in the amygdala region of the five groups were significantly different( F=41.84, 37.70, both P<0.05). The number of Glu-positive cells in the amygdala of Mod+ NS group was higher than that of Con+ NS group, and the number of GABA-positive cells in Mod+ NS group was lower than that of Con+ NS group( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast group((54.00±8.48)cells/mm 2)was lower than that of Mod+ NS group((82.17±7.36)cells/mm 2), and the number of GABA-positive cells in Mod+ Ast group((59.20±11.22)cells/mm 2)was higher than that of Mod+ NS group((41.33±7.11)cells/mm 2) ( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast+ LY group((75.67±9.15)cells/mm 2) was higher than that of Mod+ Ast group, and the number of GABA-positive cells in Mod+ Ast+ LY group((43.33±4.27)cells/mm 2)was lower than that of Mod+ Ast group ( P<0.05). Conclusion:Astragaloside can ameliorate social deficits in ASD mice via modulating the PI3K/AKT signaling pathway and excitation-inhibition balance in the amygdala.

Objective:To explore the effects of astragaloside (Ast) on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and excitation-inhibition balance in amygdala of mice with autism spectrum disorder(ASD).Methods:The C57BL/6 pregnant mice in model group were intraperitoneally injected with sodium valproate(500 mg/kg) on days 12-13 of pregnancy, while the C57BL/6 pregnant mice in control group were given an equal volume of 0.9% NaCl solution.The offspring mice were then divided into 5 groups according to the nest matching principle: the control+ normal saline group(Con+ NS group), the control+ Ast group (Con+ Ast group), the model+ normal saline group(Mod+ NS group), the model+ Ast group (Mod+ Ast group) and the Model+ Ast+ PI3K inhibitor LY294002 group (Mod+ Ast+ LY group), with 12 mice in each group. At the age of 14 days, the mice in the Con+ Ast group and the Mod+ Ast group were intraperitoneally injected with Ast (20 mg/kg, once a day for 7 consecutive days), the mice in the Mod+ Ast+ LY group were intraperitoneally injected with Ast (20 mg/kg) and LY294002(30 mg/kg), the mice in Con+ NS group and Mod+ NS group were intraperitoneally injected with the same volume of 0.9% NaCl solution.The depressive-like behavior and social function were evaluated by the marble-burying test (MBT), the three-chamber social interaction test(SIT), and the forced swimming test(FST). The expression levels of proteins related to the PI3K/AKT signaling pathway in the amygdala were detected by Western blot. The immunofluorescence method was employed to determine the levels of the neurotransmitters glutamate (Glu) and γ-aminobutyric acid(GABA)in the amygdala region.Statistical analysis was carried out using GraphPad Prism 9.5.0 software, and one-way ANOVA test was utilized for comparisons among multiple groups.Results:(1)Behavioral results showed that there were statistically significant differences in the number of buried beads of the MBT, the social interaction index and social novelty preference index of the SIT, and the immobility time and first immobile state incubation period of the FST among the five groups( F=28.85, 89.23, 77.62, 91.70, 125.40, all P<0.05). The number of buried beads and immobility time in Mod+ NS group were higher than those in Con+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Con+ NS group (all P<0.05). The number of buried beads and immobility time in Mod+ Ast group were lower than those in Mod+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were higher than those in Mod+ NS group(all P<0.05). The number of buried beads and immobility time in Mod+ Ast+ LY group were higher than those in Mod+ Ast group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Mod+ Ast group (all P<0.05).(2) Western blot results showed that there were statistically significant differences in p-PI3K/PI3K, p-AKT/AKT in amygdala among the five groups ( F=27.14, 25.50, both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ NS group were lower than those of Con+ NS group(both P<0.05).The expressions of p-PI3K/PI3K and p-AKT/AKT in amygdala of Mod+ Ast group((0.67±0.04), (0.52±0.09))were higher than those of Mod+ NS group((0.48±0.06), (0.34±0.06))(both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ Ast+ LY group ((0.52±0.04), (0.36±0.10))were lower than those of Mod+ Ast group(both P<0.05). (3)Immunofluorescence results showed that the number of Glu- and GABA- positive cells in the amygdala region of the five groups were significantly different( F=41.84, 37.70, both P<0.05). The number of Glu-positive cells in the amygdala of Mod+ NS group was higher than that of Con+ NS group, and the number of GABA-positive cells in Mod+ NS group was lower than that of Con+ NS group( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast group((54.00±8.48)cells/mm 2)was lower than that of Mod+ NS group((82.17±7.36)cells/mm 2), and the number of GABA-positive cells in Mod+ Ast group((59.20±11.22)cells/mm 2)was higher than that of Mod+ NS group((41.33±7.11)cells/mm 2) ( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast+ LY group((75.67±9.15)cells/mm 2) was higher than that of Mod+ Ast group, and the number of GABA-positive cells in Mod+ Ast+ LY group((43.33±4.27)cells/mm 2)was lower than that of Mod+ Ast group ( P<0.05). Conclusion:Astragaloside can ameliorate social deficits in ASD mice via modulating the PI3K/AKT signaling pathway and excitation-inhibition balance in the amygdala.

Objective:To investigate the correlation between preoperative calcitonin levels and upper mediastinal lymph node metastasis in medullary thyroid carcinoma (MTC).Methods:A retrospective analysis was conducted on 249 MTC patients who underwent surgery at the Cancer Hospital, Chinese Academy of Medical Sciences between January 2010 and December 2021. Based on postoperative pathology, patients were categorized into the upper mediastinal lymph node metastasis group ( n=41) and the non-upper mediastinal lymph node metastasis group ( n=208). Clinicopathological features were compared, and survival outcomes were assessed using Kaplan-Meier analysis. Receiver operating characteristic (ROC) curves were employed to determine the predictive efficacy and optimal cutoff value of preoperative calcitonin for the upper mediastinal lymph node metastasis group. Logistic regression identified independent risk factors for the upper mediastinal lymph node metastasis group. Results:Compared to the non-upper mediastinal lymph node metastasis group, the upper mediastinal lymph node metastasis group demonstrated a higher proportion of male patients, elevated levels of carcinoembryonic antigen and calcitonin, increased multifocality, larger primary tumor size, higher rates of extrathyroidal extension, advanced T and N stages, and greater incidences of lymph node metastasis and extracapsular invasion (all P＜0.01). Patients with upper mediastinal lymph node metastasis exhibited significantly lower overall survival than those without upper mediastinal lymph node metastasis ( P＜0.001). ROC curve analysis revealed an area under the curve of 0.783 for preoperative calcitonin in predicting upper mediastinal lymph node metastasis, with an optimal cutoff value of 1 865 pg/ml (sensitivity 71.79%, specificity 75.53%). Multivariate logistic regression analysis identified preoperative calcitonin levels >1 865 pg/ml ( OR=5.31, 95% CI: 1.77-15.94) and >15 metastatic lymph nodes ( OR=4.90, 95% CI: 1.87-12.89) as independent risk factors for the upper mediastinal lymph node metastasis group. Conclusions:Preoperative calcitonin＞1 865 pg/ml suggests a higher likelihood of MTC with upper mediastinal lymph node metastasis. For individuals with suspected upper mediastinal lymph node metastasis on imaging, combining preoperative calcitonin levels can reduce false-positive rates.

Humans ; Esophageal Squamous Cell Carcinoma ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell ; Microbiota

Objective:To explore the effect and value of the active learning mode based on mind mapping in the teaching of medical service support for major disasters.Methods:A total of 90 undergraduate students of 2016 Clinical Medicine of Naval Medical University were randomly selected as research objects, and they were randomly divided into observation group and control group. The 45 students in the control group used the traditional teaching mode, and the 45 students in the observation group used the mind mapping-based active learning mode for major disaster rescue and medical survice. The teaching time of the two groups was 12 h. The theoretical examination of knowledge and practical skills of the two groups of students were compared after teaching, and the students' satisfaction with the application of mind mapping-based teaching model in the teaching of medical service support for major disaster rescue was investigated. EmpowerStats and R softwares were used for t test and Chi-square test. Results:There were 24 males and 21 females in the observation group, with an average age of (21.40±0.69) years old. There were 22 males and 23 females, with an average age of (21.71±0.55) years old. The theoretical performance of the observation group (91.38±4.37) was significantly higher than that of the control group (84.91±3.98) ( P<0.001), and the practical skill performance of the observation group (92.98±3.24) was significantly higher than that of the control group (87.38±3.80) ( P<0.001). At the same time, the students' satisfaction with teaching effect in the observation group was 82.2% (37/45), which was significantly higher than that in the control group (37.8%, 17/45). Conclusion:The active learning mode based on mind mapping focuses on cultivating students' independent learning, interactive exploration and clinical thinking ability, and has a broad application prospect in the teaching of medical service support for major disasters.

Objective:To investigate the effect of aucubin on behaviors and excessive activation of astrocytic in attention deficit/hyperactivity disorder (ADHD) model mice.Methods:Twelve wild-type C57BL/6 pregnant mice (female, clean grade) were intraperitoneally administered with esketamine (15 mg/kg) to establish an ADHD model in offspring mice. The offspring mice were divided into control+ saline group, control+ aucubin group, Ketamine+ saline group and Ketamine+ aucubin group according to the nest matching principle with 15 in each group.At 14 days after birth, mice in the control+ aucubin group and Ketamine+ aucubin group were administered with aucubin (5 mg/kg, once a day) by gavage for 5 days. Mice in control+ saline group and Ketamine+ saline group were administered with equal volume of 0.9% sodium chloride solution. The offspring mice were housed with their mothers in the same cage until 21 days after birth. Twenty-one days after birth, the offspring mice were evaluated by open field test and elevated plus maze tests. Immunofluorescence assay was used to detect the expression of glutamate decarboxylase 2 (GAD2), γ- aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) in the amygdala. The morphological changes of astrocytes were quantitatively analyzed by Sholl analysis. GraphPad Prim 9.0.1 software was used for statistical analysis. The comparison of multiple groups was conducted by one-way ANOVA or Kruskal-Wallis test.Results:(1)The results of behavioral experiments showed that the total distance traveled in the open field test and the residence time in open arm of the elevated plus maze were statistically significant ( F=236.90, H=39.92, both P<0.001). The total distance ((7 044±249)mm, (22 891±2 175)mm, P<0.05) and the residence time in open arm(12.69(9.86, 17.24)s, 2.72(0.57, 3.87)s, P<0.05) of mice in Ketamine+ saline group were both higher than those in control+ saline group.The total distance((22 891±2 175)mm, (8 252±839)mm, P<0.05) and the the residence time in open arm(5.45(1.13, 10.99)s, 12.69(9.86, 17.24)s, P<0.05) of Ketamine+ aucubin group were both lower than those of Ketamine+ saline group.(2)The immunofluorescence results showed that the levels of GAD2, GABA and GFAP intensity in amygdala of mice in the four groups were statistically significant ( F=145.50, 50.08, 53.83, all P<0.05). Compared with control+ saline group, the fluorescence intensities of GAD2 ((100.00±9.60)%, (24.86±4.14)%, P<0.05) and GABA ((100.00±16.84))%, (25.48±5.70)%, P<0.05) of Ketamine+ saline group were down-regulated, and the GFAP((100.00±18.02)%, (223.80±25.85)%, P<0.05) was up-regulated. Compared with Ketamine+ saline group, the fluorescence intensities of GAD2 ((24.86±4.14)%, (56.08±6.55)%, P<0.05) and GABA((25.48±5.70)%, (52.59±15.74)%, P<0.05) in Ketamine+ aucubin group were up-regulated, but the fluorescence intensity of GFAP ((223.80±25.85)%, (157.10±22.10)%, P<0.05) was down-regulated.(3)Sholl analysis indicated that the number of the intersections between the astrocyte processes or the branches of astrocyte processes was statistically significant in the 4 groups ( F=12.47, P<0.05). Compared with control+ saline group, the number of the intersections in Ketamine+ saline group((2.07±0.48), (1.67±0.72), P<0.05) increased. While the number of the intersections in Ketamine+ aucubin group was lower than that of Ketamine+ saline group ((1.20±0.78), (2.07±0.48), P<0.05). Conclusion:Aucubin administration can alleviate ADHD-like behaviors in offspring mice, and the mechanism may be associated with the inhibition of excessive astrocytic activation.

The clinical data of a 64-year-old patient with adrenocortical adenoma complicated with inferior vena cava tumor thrombus(IVCTT) were retrospectively analyzed. The patient was admitted becourse of intermittent dizziness for 4 months. CT examination revealed right adrenal tumor, and IVCTT was found in operation. Adrenal cortical adenoma needs to be distinguished from adrenal cortical carcinoma pathologically. Preoperative color Doppler ultrasonography, CT angiography or inferior vena cava angiography can confirm the diagnosis of IVCTT and tumor thrombus grade, and different surgical methods should be selected according to tumor thrombus grade.

Objective:To construct a biospecimen bank of patient derived organoids (PDOs) from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods:Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital, Nanjing University School of Medicine were collected. Pancreatic cancer PDOs were cultured in vitro and histologically identified; PDOs were treated with gemcitabine, Nab-paclitaxel, fluorouracil, Oxaliplatin, and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results:The PDOs can reproduce the pathological features of corresponding tumor tissues; the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different; The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76% (25/33); organoid organ-based susceptibility testing had predictive value for the treatment response of patients (AUC=0.733, 95% CI: 0.546-0.919, P<0.05). Conclusion:A biobank of pancreatic cancer PDOs was successfully constructed, and the drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.