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 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 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 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 investigate the effect of long-term alcohol intake on sensory information synaptic transmission of mossy fiber-granular cells in the cerebellar cortex of mice.Methods:Twenty healthy male ICR mice aged 6 to 8 weeks were divided into normal saline group(control group) and alcohol intake group(alcohol group) according to random number table, with 10 mice in each group. The mice in alcohol group were injected intraperitoneally with 20% alcohol and the mice in control group were injected with the same amount of saline for 28 days.After the injection, the scalp, muscle tissue and skull were removed in turn, and the dura mater was removed to fully expose the crus II area of cerebellum. The mice were stimulated by air blowing at 30 mm of the ipsilateral tentacle pad with a gas jet device.When the the maximal response site was determined, the NMDA receptor antagonist (D-APV), metabolic glutamate receptor 1 antagonist (JNJ16259685) and N-methyl-D-aspartic acid (NMDA) were perfused on the brain surface of mice. Each drug was perfused for 20 minutes and ACSF was used between the two drugs until the waveform was recovered. Patch clamp amplifier was used to record the changes of potential waveform in mouse cerebellar granule layer. The data were analyzed by the softwares of Clampfit 10.3 and SPSS 22.0.Results:After exposure to wind stimulation, the latency of field potential response in granular layer of mice in alcohol group (11.8±0.7)ms was significantly longer than that in the control group (10.1±0.2)ms ( t=-8.041, P<0.05), and the amplitude of N1 (1.2±0.1) MV was significantly lower than that in the control group (0.6±0.1) MV ( t=-12.728, P<0.05). Compared with the control group, the rise time of P1 waveform((4.4±0.2)ms, (3.2±0.2)ms), duration ((12.1±0.5)ms, (10.3±0.2)ms), extinction time((7.8±0.2)ms, (6.9± 0.2)ms), volume under waveform ((7.3±0.2)ms, (4.3±0.2)ms) were significantly increased in the alcohol group ( t=16.100, - 11.840, -11.673, -35.576, all P<0.05). There were no significant differences in the amplitude, half width, rise time and decay time of Roff wave between the two groups ( t=-1.909, -0.910, -0.789, 1.462, all P>0.05). When JNJ16259685 was perfused on the brain surface of mice in alcohol group, the amplitude of field potential evoked by five blowing stimuli had no significant difference compared with that before administration (all P>0.05). When D-APV was perfused into the brain surface of mice in the alcohol group, the amplitude of P1 ((42.3±1.5) Mv)was significantly lower than that before administration ((101.1±0.9)mV) and after elution ((100.1±2.2) mV) ( t=106.762, - 69.605, both P<0.05), and the area under waveform of P1 ((42.6±1.3)%) was also significantly lower than that before administration ((100.6±1.6)%) and after elution ((97.6±2.2)%) ( t=88.862, -67.791, both P<0.05).The ratio of N2 / N1 (0.3±0.1) was significantly lower than that before administration (0.4±0.1) and after elution (0.3±0.1) ( t=2.242, 2.121, both P<0.05). When NMDA was perfused on the brain surface of mice in the control group, compared with before administration and after elution, the amplitude of P1 ((110.7±3.2) mV, (100.1±0.9) mV, (102.0±1.7) mV, t=-10.173, 7.669, both P<0.05), the area under the waveform of P1 ((127.9±3.5)%, (100.0±3.1)%, (115.0±5.3)%, t=-18.698, 6.447, both P<0.05), the ratio of N2 / N1 ((0.5±0.1), (0.3±0.1), (0.3±0.1), t=-5.669, 5.669, both P<0.05) were all significantly increased. When D-APV was perfused on the brain surface of mice in control group, the field potential evoked by blowing stimuli had no significant difference compared with that before administration and after elution (all P>0.05). Conclusion:Long-term alcohol intake significantly suppresses the synaptic transmission of excitatory glutamate in MF-GC, and enhances the inhibitory response mediated by GABAA receptor in cerebellar cortex. The inhibitory component is enhanced by NMDA receptor, but not by type 1 metabolic glutamate receptor.

Objective: To investigate the use of conventional MR imaging to guide treatment in patients with cholecystolithiasis and diffuse inflammatory thickening of gallbladder wall. Methods: The clinical data of patients who were treated in the Ningbo Huamei Hospital, University of the Chinese Academy of Sciences between January 2017 and January 2018 were analyzed. These patients were divided into two groups: patients with acute cholecystitis (n=139) and patients with viral hepatitis combined with cholecystolithiasis (n=67). Differences in the imaging signs in standardized upper abdominal contrast enhanced MRI examinations were retrospectively analyzed. Results: The imaging signs, including stone location, continuity of gallbladder mucosa, exudation in peri-gallbladder space, edema of intrahepatic portal area showed significant differences between the two groups (all P<0.05). On stratification analysis, the type of thickened gallbladder wall, background of liver parenchyma and extent of edema in intrahepatic catchment area also showed significant differences (all P<0.05). The imaging signs, including non-gallbladder neck ductal stones, concentric thickening of gallbladder wall, continuous mucous membrane in gallbladder and no peri-gallbladder space exudation but diffuse edema of intrahepatic catchment area supported the diagnosis of viral hepatitis combined with gallstones. The imaging signs, including discontinuity of gallbladder mucosa, exudation of peri-gallbladder space, diffuse edema of gallbladder wall without a cirrhotic background and edema in intrahepatic portal area supported the diagnosis of acute calculous cholecystitis of gallbladder. Conclusions Routine upper abdominal contrast enhanced MRI plays an important role in demonstrating the underlying cause of gallbladder wall diffuse edema thickening in patients with gallstones. It provides an important reference for the choice of clinical treatment pathway.

Polycystic ovary syndrome (PCOS) women often deal with the main characteristics of obesity, obesity is caused by the endocrine disorder, the menstrual cycle changes, etc. The main causes of infertility, easy cause anxiety, women have a negative impact on the quality of life through the fueling weight management of patients with PCOS were reviewed, summarized method, explore new train of thought, for fueling beset with PCOS patients provide better health and weight management method.

Objective?To investigate the preventive effect of heating pretreatment before coronary artery CTA examination on the contrast agent exudation. Methods?A total of 269 patients accepted coronary artery CTA examination in our hospital from January 1st, 2016 to June 30th, 2016 were recruited in the study. Patients were randomly divided into the observation group (temperature up to 37℃) and the control group (constant temperature 21-25℃) according to heating or no heating pretreatment, with 135 cases in the observation group and 134 cases in the control group. The 18 G retention needles were reserved before examination, and all patients accepted the coronary artery CTA examination after the injection of contrast agent iohexol. The exudation of contrast agent was observed. Results?There was 1 case of contrast agent exudation in the observation group with an exudation rate of 0.74%, and 10 cases of exudation in the control group with an exudation rate of 7.46%. The exudation rate of the observation group was lower than control group; the difference between two groups was statistically significant (χ2=7.748, P＜ 0.01). Conclusions?Contrast agent heating pretreatment can reduce the incidence of exudation of contrast agent.

OBJECTIVETo investigate the association of parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using reference region model with prognostic factors and molecular subtypes of breast cancer.

METHODSMRI and pathological data of 50 patients with pathologically confirmed invasive ductal carcinoma of the breast were retrospectively analyzed. Reference region model was applied to analyze pharmacokinetic quantitative parameters including volume transfer constant (RR K), rate constant (K) and the ratio of Kto extracellular space volume (K/V). The associations of the above parameters with prognostic factors and molecular subtypes of breast cancer were analyzed.

RESULTSRR Kand Kwere significantly higher in patients of histological grade 3 compared with those of histological grade 1 & 2 (all<0.05); and the patients with estrogen receptor (ER)-negative and/or progesterone receptor (PR)-negative also had higher RR Kand Kthan those with ER-positive or PR-positive (all<0.05). For immunohistochemistry, RR Kand Kwere significantly higher in triple negative breast cancer compared with luminal type breast cancer (all<0.05).

CONCLUSIONSHigh RR Kand Kare associated with poor prognosis of breast cancer, and which can also be used to distinguish molecular subtypes of breast cancer.

Objective To evaluate the diagnostic value of MSCT in the differentiation of thymic epithelial tumours (TET)with the maximum diameter equal or less than 3 cm.Methods A retrospective analysis of pathological and imaging data of 56 patients with pathologically confirmed TET with the maximum diameter equal or less than 3 cm was performed.According to the 2004 WHO classification,56 TETs were classified as low-risk thymomas(types A/AB/B1),high-risk thymomas (types B2/B3)and thymic carcinomas (type C).The CT manifestations of TET in each group,including shape of tumor,tumor edge (smooth or spiculate protuberance), presence of small nodule around tumor,enhancement degree,pleura invasion and fat space around tumor,were analyzed retrospectively.The differences in the CT manifestations among three types were compared using chi-square test.If the sample number was too small, Fisher 's exact test was used.Results Compared with high-risk thymomas (23 cases)and thymic carcinomas (6 cases),regular round shape was more often observed in low-risk thymomas (27 cases)(χ2 =73,P <0.001;χ2 =116,P <0.001)and the mediastinum-lung interface was more likely to bulge (χ2 = 3.41,P =0.046;χ2 =7.39,P =0.01).Blurred edge,spiculate protuberance and pleural invasion and so on were significantly more common in high-risk thymomas and thymic carcinomas (P <0.001)and they were the most common in thymic carcinomas (χ2 =11.5,P =0.009).There was a significant difference between type B2 thymomas and thymic carcinomas (χ2 =31.52, P <0.001),however there was no significant difference between type B3 thymomas and thymic carcinomas (χ2 =6.96,P =0.07). Conclusion MSCT can accurately show the shape of tumor,tumor edge,presence of small nodule around tumor,enhancement degree,pleura invasion,which can predict the histologic type of thymomas and also can provide information for preoperative diagnosis and prognosis evaluation.