Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Objective:To investigate the features and influencing factors of language in children with various types of speech disorders.Methods:A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children′s Healthcare, Children′s Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin‐comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi‐square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors.Results:There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs.96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F=5.46, 4.69, 3.68, all P<0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P<0.01) and the overall language score was lower than that of children with stuttering ( P<0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ2=7.93, 10.28; both P<0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder ( OR=1.87, 2.18, 2.01; 95% CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P<0.01). Negative family history are protective factors for the progress of language ability ( OR=0.37, 95% CI 0.17-0.81, P<0.05). Conclusions:Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.

OBJECTIVE To study effects of Jinshui Liujun decoction(JLD) on pulmonary water metabolism and TNF-α/NF-κB signaling pathway in asthmatic mice. METHODS After 1 week of acclimatization, 10 mice were randomly selected by body weight as a blank control group, and the rest of the mice were sensitized by intraperitoneal and subcutaneous injections of ovalbumin sensitizing solution on the 1st, 8th, and 15th day of the experiment. On the 22nd day, they were randomly divided into model control group, positive control group and JLD low, medium and high dose(4.1, 8.2, 16.4 g·kg−1) group, and replicated the asthma mouse model by inhaling nebulized excitation solution(1% ovalbumin) once every other day for 2 consecutive weeks, and at the same time, were given atomized excitation solution(1% ovalbumin) every other day for two weeks to replicate the asthmatic mouse model, and were given the test drug by gavage daily. The effects of JLD on the behavior, lung wet-dry weight ratio, AQP1, AQP5, TNF-α, NF-κB, and NF-κB mRNA expression in asthmatic mice were observed. RESULTS JLD reduced the number of animals with asthma attacks, alleviated asthma symptoms, decreased the lung index and lung wet-to-dry weight ratio, increased the expression level of AQP1 and AQP5 in lung tissues, reduced the content of TNF-α in bronchoalveolar lavage fluid and lung tissues, and down-regulated the expression level of NF-κB and its genes in lung tissues(P<0.05 or P<0.01). CONCLUSION JLD has an anti-asthma effect and its mechanism of action is partially due to its inhibition of the TNF-α/NF-κB signaling pathway, upregulation of AQP1 and AQP5, and improvement of pulmonary water metabolism.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.