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1.
Nature ; 628(8009): 818-825, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38658687

ABSTRACT

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2-6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.


Subject(s)
Autistic Disorder , Long QT Syndrome , Oligonucleotides, Antisense , Syndactyly , Animals , Female , Humans , Male , Mice , Alternative Splicing/drug effects , Alternative Splicing/genetics , Autistic Disorder/drug therapy , Autistic Disorder/genetics , Calcium/metabolism , Calcium Channels, L-Type/metabolism , Calcium Channels, L-Type/genetics , Cell Movement/drug effects , Dendrites/metabolism , Exons/genetics , Long QT Syndrome/drug therapy , Long QT Syndrome/genetics , Neurons/metabolism , Neurons/drug effects , Oligonucleotides, Antisense/pharmacology , Oligonucleotides, Antisense/therapeutic use , Organoids/drug effects , Organoids/metabolism , Prosencephalon/metabolism , Prosencephalon/cytology , Syndactyly/drug therapy , Syndactyly/genetics , Interneurons/cytology , Interneurons/drug effects
2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-995927

ABSTRACT

Objective:To investigate the efficacy and safety of fat suction combined with bipolar radiofrequency on face and neck rejuvenation.Methods:A total of 115 patients with face and neck fat deposits and skin laxity underwent fat suction combined with bipolar radiofrequency between December 2021 and October 2022 by the same surgeon in Changsha My Like Medical Cosmetology Hospital. There were 3 men and 112 women in this research. The mean age was 36.1 years (range, 26-55 years) and the mean body mass index was 21.4 (range, 16.8-27.7 kg/cm 2). Postoperative patient satisfaction surveys were conducted and 2 independent doctors evaluated clinical effect with preoperative and postoperative photographs at 3-6 months postoperatively. Results:The mean amount of fat aspirated was 44.5 ml (range, 10-92 ml) and the mean energy delivered was 4.5 kJ (range, 2.1-8.9 ml). 88.7% of patients were satisfied with their postoperative effect (102/115 patients). 92.2% of doctors were satisfied with the postoperative effect (106/115 patients). Four out of 115 patients (3.5%) developed irregularity by fat suction.Conclusions:Fat suction combined with bipolar radiofrequency can effectively reduce the fat accumulation of facial and neck and significantly improve skin relaxation. It is an effective method to rejuvenate facial and neck.

3.
Chinese Journal of Surgery ; (12): 375-380, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970218

ABSTRACT

Objective: To investigate the safety and effect of laparoscopy for the treatment of biliary stricture after the biliary dilatation operation. Methods: The clinical data of 78 patients,including 27 males and 51 females aged (48.6±14.2)years(range:17 to 76 years),who presented biliary stricture after biliary dilatation operation from January 2017 to June 2021 in the Department of Minimally Invasive Hepatobiliary Surgery,Hunan Provincial People's Hospital,were retrospectively collected,with 38 cases in the laparoscopy group and 40 cases in the laparotomy group. Of the 78 patients,there were 67 cases of cholangiojejunostomy stricture and 11 cases of stricture of the high intrahepatic bile duct. Statistical methods such as t-test and χ2 test were carried out to compare perioperative clinical data and follow-up information between the two groups. Results: Less intraoperative blood loss((102.6±76.4)ml vs. (162.5±105.9) ml, t=-2.874,P=0.005),shorter postoperative stay length of stay((10.5±3.7)days vs. (14.5±6.4)days, t=-3.379,P=0.001) and shorter waiting time for postoperative anal exhaust((2.0±0.6)days vs. (2.5±0.9)days, t=-2.827,P=0.006) were found in the laparoscopy group than that in the laparotomy group,with statistically significant differences. While there was no statistically difference in the operative time((252.8±54.7)minutes vs. (257.4±68.6)minutes,t=-0.331,P=0.742). Postoperative review and follow-up did not show statistically significant differences between the two groups in the residual stone rate(5.3%(2/38) vs. 5.0%(2/40)) and the incidence of recurrent biliary stricture(5.3%(2/38) vs. 7.5%(3/40))(both P>0.05). Conclusion: Laparoscopy may be safe and effective in the treatment of biliary stricture after the biliary dilatation operation,with less trauma,faster recovery compared to laparotomy.

4.
Sichuan Mental Health ; (6): 254-258, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-986749

ABSTRACT

BackgroundThe improvement of social function in patients with schizophrenia is an important part of their rehabilitation, and peer support services, as a rehabilitation method, may be of great significance to improve the social function of patients with schizophrenia. ObjectiveTo explore the influence of peer support service on the daily living ability and social function of patients with chronic schizophrenia, and to provide references for promoting the rehabilitation of patients with chronic schizophrenia. MethodsA total of 100 patients with chronic schizophrenia who were hospitalized in The Third People's Hospital of Tianshui from January 1 to December 31, 2020 and met the diagnostic criteria of the International Classification of Diseases, 10th edition (ICD-10) were selected as the study objects, and they were divided into the control group and the study group with 50 cases each by random number table method. Patients in both groups received routine treatment and nursing care, on this basis, the study group received peer support service once or twice a week for 12 weeks, and the control group received the same peer support service at the end of the study. Before and at the 1st, 2nd, 4th, 8th and 12th week of the treatment, Activity of Daily Living Scale (ADL) and Social Disability Screening Schedule (SDSS) were used to evaluate the activities of daily living and social function of the two groups. ResultsThe ADL scores of the study group were lower than those of the control group at the 8th week and 12th week of the treatment ( t=-2.420, -2.814, P<0.05 or 0.01) . The SDSS scores of the study group were lower than those of the control group at the 8th week an 12th week of the treatment (t=-2.057, -2.322, P<0.05) . ConclusionPeer support services may help improve the ability of daily life and social function of patients with chronic schizophrenia. [Funded by Tianshui City Livelihood Science and Technology Plan Project (number, 2020-SHFZKJK-9344)]

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-985659

ABSTRACT

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.


Subject(s)
Female , Humans , Uterine Cervical Neoplasms/pathology , Neoplasm Staging , Lymphatic Metastasis , Lymph Node Excision , Retrospective Studies , Prognosis , Chemoradiotherapy/methods , Carcinoma, Squamous Cell/pathology
6.
Nature ; 610(7931): 319-326, 2022 10.
Article in English | MEDLINE | ID: mdl-36224417

ABSTRACT

Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease1-5. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.


Subject(s)
Neural Pathways , Organoids , Animals , Animals, Newborn , Autistic Disorder , Humans , Long QT Syndrome , Motivation , Neurons/physiology , Optogenetics , Organoids/cytology , Organoids/innervation , Organoids/transplantation , Rats , Reward , Somatosensory Cortex/cytology , Somatosensory Cortex/physiology , Stem Cells/cytology , Syndactyly
7.
Nat Protoc ; 17(1): 15-35, 2022 01.
Article in English | MEDLINE | ID: mdl-34992269

ABSTRACT

The development of neural circuits involves wiring of neurons locally following their generation and migration, as well as establishing long-distance connections between brain regions. Studying these developmental processes in the human nervous system remains difficult because of limited access to tissue that can be maintained as functional over time in vitro. We have previously developed a method to convert human pluripotent stem cells into brain region-specific organoids that can be fused and integrated to form assembloids and study neuronal migration. In contrast to approaches that mix cell lineages in 2D cultures or engineer microchips, assembloids leverage self-organization to enable complex cell-cell interactions, circuit formation and maturation in long-term cultures. In this protocol, we describe approaches to model long-range neuronal connectivity in human brain assembloids. We present how to generate 3D spheroids resembling specific domains of the nervous system and then how to integrate them physically to allow axonal projections and synaptic assembly. In addition, we describe a series of assays including viral labeling and retrograde tracing, 3D live imaging of axon projection and optogenetics combined with calcium imaging and electrophysiological recordings to probe and manipulate the circuits in assembloids. The assays take 3-4 months to complete and require expertise in stem cell culture, imaging and electrophysiology. We anticipate that these approaches will be useful in deciphering human-specific aspects of neural circuit assembly and in modeling neurodevelopmental disorders with patient-derived cells.


Subject(s)
Brain/cytology , Nerve Net , Neurophysiology/methods , Organoids , Cell Culture Techniques/methods , Cells, Cultured , Humans , Molecular Imaging , Nerve Net/cytology , Nerve Net/diagnostic imaging , Nerve Net/physiology , Optogenetics , Organ Culture Techniques/methods , Organoids/cytology , Organoids/diagnostic imaging , Organoids/physiology , Pluripotent Stem Cells/cytology
8.
Cell Stem Cell ; 29(2): 248-264.e7, 2022 02 03.
Article in English | MEDLINE | ID: mdl-34990580

ABSTRACT

Defects in interneuron migration can disrupt the assembly of cortical circuits and lead to neuropsychiatric disease. Using forebrain assembloids derived by integration of cortical and ventral forebrain organoids, we have previously discovered a cortical interneuron migration defect in Timothy syndrome (TS), a severe neurodevelopmental disease caused by a mutation in the L-type calcium channel (LTCC) Cav1.2. Here, we find that acute pharmacological modulation of Cav1.2 can regulate the saltation length, but not the frequency, of interneuron migration in TS. Interestingly, the defect in saltation length is related to aberrant actomyosin and myosin light chain (MLC) phosphorylation, while the defect in saltation frequency is driven by enhanced γ-aminobutyric acid (GABA) sensitivity and can be restored by GABA-A receptor antagonism. Finally, we describe hypersynchronous hCS network activity in TS that is exacerbated by interneuron migration. Taken together, these studies reveal a complex role of LTCC function in human cortical interneuron migration and strategies to restore deficits in the context of disease.


Subject(s)
Autistic Disorder , Syndactyly , Cell Movement/physiology , Cerebral Cortex , Humans , Interneurons/physiology , Long QT Syndrome , Prosencephalon , Syndactyly/genetics
9.
Acta Pharmaceutica Sinica ; (12): 1444-1447, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-924749

ABSTRACT

Two compounds were isolated from 95% ethanol extract of the gum resin of Boswellia carterii by silica gel column chromatography (CC) and high-performance liquid chromatography (HPLC). Their structures were identified with IR, UV, NMR and HR-ESI-MS spectroscopic data as 7α-hydroxy-3,11-dioxo- tirucalla-8,24-dien-21-oic acid (1) and 21β-hydroxy-3-acetyl-11-keto-β-boswellic acid (2). In addition, their absolute configurations were also identified by ECD calculations. Among them, compound 1 is a new compound and the absolute configuration of compound 2 is confirmed by ECD calculation for the first time.

10.
Orphanet J Rare Dis ; 16(1): 344, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34344442

ABSTRACT

BACKGROUND: Many genetic syndromes (GSs) have distinct facial dysmorphism, and facial gestalts can be used as a diagnostic tool for recognizing a syndrome. Facial recognition technology has advanced in recent years, and the screening of GSs by facial recognition technology has become feasible. This study constructed an automatic facial recognition model for the identification of children with GSs. RESULTS: A total of 456 frontal facial photos were collected from 228 children with GSs and 228 healthy children in Guangdong Provincial People's Hospital from Jun 2016 to Jan 2021. Only one frontal facial image was selected for each participant. The VGG-16 network (named after its proposal lab, Visual Geometry Group from Oxford University) was pretrained by transfer learning methods, and a facial recognition model based on the VGG-16 architecture was constructed. The performance of the VGG-16 model was evaluated by five-fold cross-validation. Comparison of VGG-16 model to five physicians were also performed. The VGG-16 model achieved the highest accuracy of 0.8860 ± 0.0211, specificity of 0.9124 ± 0.0308, recall of 0.8597 ± 0.0190, F1-score of 0.8829 ± 0.0215 and an area under the receiver operating characteristic curve of 0.9443 ± 0.0276 (95% confidence interval: 0.9210-0.9620) for GS screening, which was significantly higher than that achieved by human experts. CONCLUSIONS: This study highlighted the feasibility of facial recognition technology for GSs identification. The VGG-16 recognition model can play a prominent role in GSs screening in clinical practice.


Subject(s)
Facial Recognition , Child , Face , Humans , Neural Networks, Computer , Syndrome
11.
Front Genet ; 12: 669841, 2021.
Article in English | MEDLINE | ID: mdl-34163525

ABSTRACT

BACKGROUND: Noonan syndrome (NS), a genetically heterogeneous disorder, presents with hypertelorism, ptosis, dysplastic pulmonary valve stenosis, hypertrophic cardiomyopathy, and small stature. Early detection and assessment of NS are crucial to formulating an individualized treatment protocol. However, the diagnostic rate of pediatricians and pediatric cardiologists is limited. To overcome this challenge, we propose an automated facial recognition model to identify NS using a novel deep convolutional neural network (DCNN) with a loss function called additive angular margin loss (ArcFace). METHODS: The proposed automated facial recognition models were trained on dataset that included 127 NS patients, 163 healthy children, and 130 children with several other dysmorphic syndromes. The photo dataset contained only one frontal face image from each participant. A novel DCNN framework with ArcFace loss function (DCNN-Arcface model) was constructed. Two traditional machine learning models and a DCNN model with cross-entropy loss function (DCNN-CE model) were also constructed. Transfer learning and data augmentation were applied in the training process. The identification performance of facial recognition models was assessed by five-fold cross-validation. Comparison of the DCNN-Arcface model to two traditional machine learning models, the DCNN-CE model, and six physicians were performed. RESULTS: At distinguishing NS patients from healthy children, the DCNN-Arcface model achieved an accuracy of 0.9201 ± 0.0138 and an area under the receiver operator characteristic curve (AUC) of 0.9797 ± 0.0055. At distinguishing NS patients from children with several other genetic syndromes, it achieved an accuracy of 0.8171 ± 0.0074 and an AUC of 0.9274 ± 0.0062. In both cases, the DCNN-Arcface model outperformed the two traditional machine learning models, the DCNN-CE model, and six physicians. CONCLUSION: This study shows that the proposed DCNN-Arcface model is a promising way to screen NS patients and can improve the NS diagnosis rate.

12.
Front Pediatr ; 9: 648255, 2021.
Article in English | MEDLINE | ID: mdl-34095025

ABSTRACT

Background: Williams-Beuren syndrome (WBS) is a rare genetic syndrome with a characteristic "elfin" facial gestalt. The "elfin" facial characteristics include a broad forehead, periorbital puffiness, flat nasal bridge, short upturned nose, wide mouth, thick lips, and pointed chin. Recently, deep convolutional neural networks (CNNs) have been successfully applied to facial recognition for diagnosing genetic syndromes. However, there is little research on WBS facial recognition using deep CNNs. Objective: The purpose of this study was to construct an automatic facial recognition model for WBS diagnosis based on deep CNNs. Methods: The study enrolled 104 WBS children, 91 cases with other genetic syndromes, and 145 healthy children. The photo dataset used only one frontal facial photo from each participant. Five face recognition frameworks for WBS were constructed by adopting the VGG-16, VGG-19, ResNet-18, ResNet-34, and MobileNet-V2 architectures, respectively. ImageNet transfer learning was used to avoid over-fitting. The classification performance of the facial recognition models was assessed by five-fold cross validation, and comparison with human experts was performed. Results: The five face recognition frameworks for WBS were constructed. The VGG-19 model achieved the best performance. The accuracy, precision, recall, F1 score, and area under curve (AUC) of the VGG-19 model were 92.7 ± 1.3%, 94.0 ± 5.6%, 81.7 ± 3.6%, 87.2 ± 2.0%, and 89.6 ± 1.3%, respectively. The highest accuracy, precision, recall, F1 score, and AUC of human experts were 82.1, 65.9, 85.6, 74.5, and 83.0%, respectively. The AUCs of each human expert were inferior to the AUCs of the VGG-16 (88.6 ± 3.5%), VGG-19 (89.6 ± 1.3%), ResNet-18 (83.6 ± 8.2%), and ResNet-34 (86.3 ± 4.9%) models. Conclusions: This study highlighted the possibility of using deep CNNs for diagnosing WBS in clinical practice. The facial recognition framework based on VGG-19 could play a prominent role in WBS diagnosis. Transfer learning technology can help to construct facial recognition models of genetic syndromes with small-scale datasets.

13.
PLoS One ; 16(3): e0247678, 2021.
Article in English | MEDLINE | ID: mdl-33770816

ABSTRACT

Cognitive dysfunction after surgery under general anesthesia is a well-recognized clinical phenomenon in the elderly. Physiological effects of various anesthetic agents have been studied at length. Very little is known about potential effects of anesthesia on brain structure. In this study we used Diffusion Tensor Imaging to compare the white matter microstructure of healthy control subjects under sevoflurane anesthesia with their awake state. Fractional Anisotropy, a white mater integrity index, transiently decreases throughout the brain during sevoflurane anesthesia and then returns back to baseline. Other DTI metrics such as mean diffusivity, axial diffusivity and radial diffusivity were increased under sevoflurane anesthesia. Although DTI metrics are age dependent, the transient changes due to sevoflurane were independent of age and sex. Volumetric analysis shows various white matter volumes decreased whereas some gray matter volumes increased during sevoflurane anesthesia. These results suggest that sevoflurane anesthesia has a significant, but transient, effect on white matter microstructure. In spite of the transient effects of sevoflurane anesthesia there were no measurable effects on brain white matter as determined by the DTI metrics at 2 days and 7 days following anesthesia. The role of white matter in the loss of consciousness under anesthesia will need to be studied and MRI studies with subjects under anesthesia will need to take these results into account.


Subject(s)
Anesthesia, General/adverse effects , Anesthetics, Inhalation/adverse effects , Brain/pathology , Postoperative Cognitive Complications/pathology , Sevoflurane/adverse effects , White Matter/pathology , Adult , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/drug effects , Brain Mapping , Case-Control Studies , Diffusion Tensor Imaging , Female , Gray Matter/diagnostic imaging , Gray Matter/drug effects , Gray Matter/pathology , Humans , Male , Middle Aged , Neuroglia/drug effects , Neuroglia/pathology , Postoperative Cognitive Complications/chemically induced , Postoperative Cognitive Complications/diagnostic imaging , White Matter/diagnostic imaging , White Matter/drug effects
14.
Chinese Journal of School Health ; (12): 257-259, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-873660

ABSTRACT

Objective@#To investigate HPV vaccine hesitation and associated factors among female college students in Weifang, and to provide a suggestions for improving the coverage rate of HPV vaccine among female college students.@*Methods@#The questionnaire of HPV vaccine hesitancy of female college students was designed. By adopting the stratified sampling method, the survey was conducted among female students at one medical university and three nonmedical universities in Weifang. Chi-square test and Logistic regression were used to analyze the influencing factors of vaccine hesitation.@*Results@#Female college students who had high risk perception toward vaccine (OR=4.15, 95%CI=1.55-11.10) and those who were angry about the sideeffects of the vaccine (OR=3.63, 95%CI=1.95-6.75) were hesitate to vaccinate against HPV. Female college students who believed long protection period of HPV vaccine (OR=0.08, 95%CI=0.04-0.17), that women had a high probability of cervical cancer (OR=0.44, 95%CI=0.21-0.90) and that the knowledge of HPV vaccine scored >6 (OR=0.31, 95%CI=0.15-0.67) were more likely to receive HPV vaccine.@*Conclusion@#High risk perception of vaccines and anger at vaccine adverse reactions are important factors affecting HPV vaccines for female college students. Our findings call for strategic role of the state, school-based health education as well as medical professional guidance in lowering HPV vaccination hesitation among fenale college sutdents.

15.
Neuroscience Bulletin ; (6): 1645-1657, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-951931

ABSTRACT

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) – a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-905310

ABSTRACT

Objective:To explore the characteristics of vowel production of dysarthria after stroke, and the relationship between vowel production and speech clarity. Methods:From October, 2019 to January, 2020, 19 patients with post-stroke dysarthria and 18 healthy controls were asked to read a short essay to extract vowels, and measured the jaw distance, tongue distance, F2i/F2u, vowel space area (VSA), vowel articulation index (VAI), F1 and F2 variability, and speech clarity. The correlation between vowel production and speech clarity were analyzed. Results:Tongue distance, F2i/F2u, VSA, VAI, and speech clarity were less in the patients than in the controls (|t| > 2.268, P < 0.05), while F2 variability was more (t = 2.375, P < 0.05). F2i/F2u (r = 0.465), VAI (r = 0.488) and F2 variability (r = -0.504) were correlated to speech clarity (P < 0.05). Conclusion:The vowel production impaired in patients with post-stroke dysarthria, featured as abnormal articulatory movements, concentration of vowels and poor stability of vowels, which impacts the speech clarity.

17.
Neuroscience Bulletin ; (6): 1645-1657, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-922643

ABSTRACT

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3


Subject(s)
Animals , Mice , Hippocampus , Long-Term Potentiation , Neuronal Plasticity , Nuclear Receptor Coactivator 3/genetics , Synapses
18.
Nat Biotechnol ; 38(12): 1421-1430, 2020 12.
Article in English | MEDLINE | ID: mdl-33273741

ABSTRACT

Cortico-striatal projections are critical components of forebrain circuitry that regulate motivated behaviors. To enable the study of the human cortico-striatal pathway and how its dysfunction leads to neuropsychiatric disease, we developed a method to convert human pluripotent stem cells into region-specific brain organoids that resemble the developing human striatum and include electrically active medium spiny neurons. We then assembled these organoids with cerebral cortical organoids in three-dimensional cultures to form cortico-striatal assembloids. Using viral tracing and functional assays in intact or sliced assembloids, we show that cortical neurons send axonal projections into striatal organoids and form synaptic connections. Medium spiny neurons mature electrophysiologically following assembly and display calcium activity after optogenetic stimulation of cortical neurons. Moreover, we derive cortico-striatal assembloids from patients with a neurodevelopmental disorder caused by a deletion on chromosome 22q13.3 and capture disease-associated defects in calcium activity, showing that this approach will allow investigation of the development and functional assembly of cortico-striatal connectivity using patient-derived cells.


Subject(s)
Cerebral Cortex/cytology , Corpus Striatum/cytology , Organoids/cytology , Pluripotent Stem Cells/cytology , Calcium/metabolism , Female , Humans , Models, Biological , Nerve Net/physiology , Optogenetics , Phenotype , Pregnancy
19.
Nat Med ; 26(12): 1888-1898, 2020 12.
Article in English | MEDLINE | ID: mdl-32989314

ABSTRACT

22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids. Transcriptional profiling across 100 days showed high reliability of differentiation and revealed changes in neuronal excitability-related genes. Using electrophysiology and live imaging, we identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons. The calcium deficit was related to resting membrane potential changes that led to abnormal inactivation of voltage-gated calcium channels. Heterozygous loss of DGCR8 recapitulated the excitability and calcium phenotypes and its overexpression rescued these defects. Moreover, the 22q11DS calcium abnormality could also be restored by application of antipsychotics. Taken together, our study illustrates how stem cell derived models can be used to uncover and rescue cellular phenotypes associated with genetic forms of neuropsychiatric disease.


Subject(s)
Calcium Signaling/genetics , Cerebral Cortex/ultrastructure , DiGeorge Syndrome/diagnosis , Neurons/ultrastructure , Adult , Cell Differentiation/genetics , Cerebral Cortex/pathology , DiGeorge Syndrome/pathology , Female , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/ultrastructure , Male , Neurons/pathology , Organoids/pathology , Organoids/ultrastructure , Young Adult
20.
Cell Rep ; 31(7): 107649, 2020 05 19.
Article in English | MEDLINE | ID: mdl-32433958

ABSTRACT

Coordinated intracellular and extracellular signaling is critical to synapse development and functional neural circuit wiring. Here, we report that unesterified docosahexaenoic acid (DHA) regulates functional synapse formation in vivo via retinoid X receptor α (Rxra) signaling. Using Rxra conditional knockout (cKO) mice and virus-mediated transient gene expression, we show that endogenous Rxra plays important roles in regulating spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. We further show that the effects of RXRA are mediated through its DNA-binding domain in a cell-autonomous and reversible manner. Moreover, unesterified DHA increases spine formation and excitatory synaptic transmission in vivo in an Rxra-dependent fashion. Rxra cKO mice generally behave normally but show deficits in behavior tasks associated with social memory. Together, these results demonstrate that unesterified DHA signals through RXRA to regulate spinogenesis and functional synapse formation, providing insight into the mechanism through which DHA promotes brain development and cognitive function.


Subject(s)
Retinoid X Receptor alpha/metabolism , Synapses/metabolism , Animals , Mice , Mice, Knockout
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