Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Attention deficit hyperactivity disorder is a common neurodevelopmental disorder characterized by persistent attention deficit, hyperactivity, and impulsive behaviors that are not consistent with developmental age.Academic and vocational difficulties, social exclusion, and delinquent behaviors are manifested in daily life.It is also commonly accompanied by psychiatric problems.At the same time, mental problems are common, and the overall quality of life is greatly affected, placing a heavy burden on society as well as the family.International attention deficit hyperactivity disorder experts have developed a common and comprehensive International Classification of Functioning, Disability and Health core set of classifications for assessing individual functioning in attention deficit hyperactivity disorder.

ObjectiveTo analyze the research hotspots and frontier trends in the field of early screening tools of autism spectrum disorder (ASD) over the past two decades. MethodsThe literature on early screening tools for ASD was searched in Web of Science core collection database from 2002 to 2022. CiteSpace was used for cluster analysis of keywords, to draw knowledge mapping. Research disciplines were analyzed and comprehensively interpreted. ResultsA total of 115 articles were included. The number of researches on early screening tools for ASD had been increasing over the past two decades. The research disciplines with higher publication volume included pediatrics, neurology and neuroscience, and psychology. A total of 191 keywords were identified, and the LLR keyword clustering analysis yielded eleven clusters. ConclusionModified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) and Brief Infant-Toddler Social and Emotional Assessment (BITSEA) have been subjected to large-scale sample screening and follow-up observation for validity, demonstrating good psychometric properties and high clinical diagnostic value. The development of new early screening tools for ASD, validation of the reliability and validity of different language versions of the M-CHAT-R/F, and research on digital and networked M-CHAT-R/F are current research hotspots. Cultural adaptation of early screening tools for ASD and their application within the developmental monitoring framework may represent frontier research trends.

Objective:To explore the long-term effect of endoscopic radiofrequency ablation for the treatment of unresectable ampullary carcinoma.Methods:Clinical data of patients with ampullary carcinoma who received endoscopic radiofrequency ablation in the Third Affiliated Hospital of Naval Medical University from January 2012 to May 2019 were retrospectively collected, including basic information, frequency of radiofrequency ablation, the type of biliary stent, postoperative complications, and follow-up. Kaplan-Meier method was used to analyze the survival of patients after endoscopic radiofrequency ablation. Relationship between frequency of radiofrequency ablation, type of biliary stent and overall survival time was analyzed.Results:A total of 50 patients were enrolled, including 31 males and 19 females, aged 73.0±9.7 years. Twenty-five patients (50.0%) underwent 1 radiofrequency ablation treatment, while 25 patients (50.0%) underwent radiofrequency ablation treatments more than twice. Postoperative complications occurred in 6 patients (12.0%), all of which were mild symptoms. The average follow-up was 22.3 months, with a total of 39 (78.0%) deaths, 5 (10.0%) lost to follow-up, and 6 (12.0%) surviving. The median overall survival time was 16.9 (95% CI: 9.1-24.8) months, with cumulative survival rates of 62.0%, 38.5%, 27.0%, and 12.6% at 1, 2, 3, and 5 years, respectively. The median overall survival time of those treated with radiofrequency ablation ≥2 times showed a trend of prolongation compared to patients treated once, but the difference was not statistically significant [26.7 (95% CI: 9.7-43.7) months VS 12.6 (95% CI: 4.9-20.3) months, χ2=3.049, P=0.081]. Plastic stents were used in 32 patients (64.0%) and metal stents in 18 patients (36.0%). There was no significant difference in median overall survival time between patients using metal and plastic stents [17.1 (95% CI: 6.1-28.0) months VS 15.9 (95% CI: 6.9-24.9) months， χ2=0.029， P=0.865]. Conclusion:Endoscopic radiofrequency ablation is a safe treatment for unresectable ampullary carcinoma, and multiple consecutive treatments may increase the survival benefit.

Objective:To investigate the efficacy of endoscopic stent placement for patients with Bismuth type Ⅳ hilar cholangiocarcinoma.Methods:Data of 229 patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma who successfully underwent endoscopic stent placement at the Department of Endoscopy, the Third Affiliated Hospital of Naval Medical University from January 2002 to January 2019 were retrospectively analyzed. Outcomes included clinical success rate, complication incidence, stent patency period and overall survival time. The patency of stents and overall survival time of patients were estimated by using the Kaplan-Meier method. The independent predictors for stent patency and overall survival of patients were analyzed by a multivariate Cox proportional regression model.Results:The overall clinical success rate was 78.2% (179/229). The incidence of early cholangitis after endoscopic retrograde cholangiopancreatography was 20.5% (47/229). The median stent patency and overall survival time were 5.7 (95% CI: 4.8-6.7) months and 5.1 (95% CI: 4.2-6.0) months, respectively. Further multivariate Cox regression analysis showed that metal stent ( P<0.001, HR=0.452, 95% CI: 0.307-0.666) and bilateral stents with bilateral angiography ( P=0.036, HR=0.644, 95% CI: 0.427-0.971) were independent predictors of stent patency; total bilirubin>200 μmol/L ( P=0.001, HR=1.627, 95% CI: 1.208-2.192), metal stent ( P=0.004, HR=0.636, 95% CI: 0.467-0.866) and antitumor therapy ( P<0.001, HR=0.439, 95% CI:0.308-0.626) were independent predictors of overall survival. Conclusion:There is high incidence of cholangitis in patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma treated with endoscopic stenting. Longer stent patency can be achieved with metal stent placement and bilateral drainage. In addition, metal stent for drainage and antitumor therapy can also help increase the survival benefit.

Self-injury behavior (SIB) is a common problem behavior of children with autism spectrum disorder (ASD), which is characterized by a series of harmful reactions made by themselves causing tissue and physical damages.It seriously affects the physical and mental health in children.An early identification of SIB in children with ASD is helpful to relieve symptoms and improve the prognosis.Aiming to enrich the understanding of SIB in children with ASD and to promote early detection and intervention, this article reviews and summarizes the research on clinical characteristics, influencing factors, evaluation, detection and intervention methods of SIB in children with ASD in recent years.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, restricted and repetitive behaviors, interests and activities, and abnormal perception.Obsessive compulsive disorder (OCD) is one of the common comorbid mental diseases of ASD.Accurate identification of the obsessive-compulsive symptoms and OCD comorbidity of ASD and early intervention are essential for the prognosis of patients.However, there are few domestic studies on comorbid OCD in ASD.Based on previous studies abroad, the progress of research on the epidemiology, etiology and neural mechanism, clinical characteristics, evaluation, diagnosis, intervention and treatment of comorbid OCD in ASD was reviewed in this paper.It aims to identify the manifestations of OCD in ASD patients in the early stage and improve the prognosis of patients.

To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on ventilator-associated pneumonia (VAP) in neurocritical care patients. Methods A retrospective study was performed to analyze the clinical data of 175 neurocritical care adult patients with mechanical ventilation (MV) more than 48 hours, who were enrolled in three randomized controlled trials (RCT) conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 to March 2019. The following patient clinical data were collected when patients were enrolled: gender, age, neurologic diagnosis, comorbidities, medication, endotracheal reintubation, bronchoscope treatment, the distal site of nasoenteric tubes, and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score, Glasgow coma scale (GCS) score, and acute gastrointestinal injury (AGI) grade assessed. Patients were divided into VAP group and non-VAP group according to the occurrence of VAP, and the differences of each index between the two groups were compared. Then the influencing factors of P < 0.1 were included in multivariate Logistic regression analysis to identify the potential risk factors affecting the incidence of VAP. Furthermore, patients were divided into gastric feeding group and post-pyloric feeding group according to the distal site of nasoenteric tubes, and subgroup analysis was performed to evaluate the variety of VAP in patients with different tube sites and status. Results ① Forty-two patients occurred VAP in 175 MV patients, and the incidence of VAP was 24.0%. ② Univariate analysis showed the P value of post-pyloric feeding, APACHE Ⅱscore, GCS score and bronchoscope treatment were less than 0.1, and post-pyloric feeding and GCS score in VAP group were significantly lower than those in non-VAP group [post-pyloric feeding: 19.0% (8/42) vs. 36.8% (49/133), GCS:5 (3, 7) vs. 6 (4, 9), both P < 0.05]. Multivariate Logistic regression analysis indicated that post-pyloric feeding was independent protective factor [odds ratio (OR) = 0.360, 95% confidence internal (95%CI) = 0.151-0.857, P = 0.021] and bronchoscope treatment was the independent risk factor (OR = 2.210, 95%CI = 1.051-4.647, P = 0.036) for VAP. ③ The incidence of VAP was 28.8% (34/118), 0% (0/4), 8.3% (1/12), 26.7% (4/15), 22.2% (2/9) and 5.9% (1/17) respectively when tube tip in stomach, D1, D2, D3, D4 and jejunum confirmed by abdominal radiography. Post-pyloric feeding in each proportion seemed to present lower VAP rate compared with gastric feeding, however, no significant difference was found (all P > 0.05). ④ The incidence of VAP in post-pyloric feeding group was significantly lower than that in gastric feeding group [14.0% (8/57) vs. 28.8% (34/118), OR = 0.403, 95%CI = 0.173-0.941, P = 0.032]. Lower VAP rate appeared on patients with SOFA < 12 (OR = 0.392, 95%CI = 0.154-0.995, P = 0.044) and AGI grade ≥Ⅱ (OR =0.086, 95%CI = 0.011-0.705, P = 0.006) fed by post-pyloric route according to the result of subgroup analysis stratified by age, gender, APACHEⅡ score, SOFA score and AGI grade. Conclusion Post-pyloric feeding would decrease the incidence of VAP in neurocritical care patients on MV.

Objective To investigate the clinical effects and safety differences of endoscopic hormone injection by tympanic membrane puncture and eustachian tube in the treatment of patients with chronic secretory otitis media.Methods From January 2015 to September 2016,90 patients with chronic secretory otitis media in Zhoushan Hospital were chosen.They were randomly divided into two groups according to the digital table.The tympanic membrane puncture group (65 patients) was treated with hormone injection by tympanic membrane puncture and the eustachian tube group(65 patients) was treated with endoscopic hormone injection by eustachian tubeThe total clinical effective rate,the bone conduction threshold value in 1 kHz,2kHz,4kHz and 8kHz,the ETDQ-7 score and the levels of laboratory index before and after treatment,the secondary tympanic effusion rate and the recurrence rate with follow-up of both groups were compared.Results The total clinical effective rate of the tympanic membrane puncture group and eustachian tube group were 77.78％ and 93.33％,respectively.The total clinical effective rate of the eustachian tube group were significant higher than that of the tympanic membrane puncture group (x2 =9.84,P ＜ 0.05).The bone conduction threshold value in l kHz,2kHz,4kHz and 8kHz of the tympanic membrane puncture group after treatment were (10.42 ± 1.60) kHz,(12.86 ± 2.50) kHz,(16.09 ± 2.81) kHz,(15.26 ± 2.68) kHz,respectively.The bone conduction threshold value in 1kHz,2kHz,4kHz and 8kHz of the eustachian tube group after treatment were (9.75 ± 1.36) kHz,(11.13 ± 2.02) kHz,(14.82 ± 2.44) kHz,(13.78 ± 2.11) kHz,respectively.The bone conduction threshold value in 1kHz,2kHz,4kHz and 8kHz of the eustachian tube group after treatment were significant lower than those of the tympanic membrane puncture group and those before treatment(t =3.10,3.56,3.29,3.96,2.87,3.15,2.91,3.28,2.67,2.81,2.78,2.50,all P ＜ 0.05).The ETDQ-7 scores of the eustachian tube group after treatment were significant lower than those of the tympanic membrane puncture group and those before treatment(t =3.31,3.87,2.89,all P ＜ 0.05).The levels of laboratory index of the eustachian tube group after treatment were significant higher than those of the tympanic membrane puncture group and those before treatment (t =3.36,3.77,3.71,4.02,2.83,3.06,all P ＜ 0.05).The secondary tympanic effusion rate and the recurrence rate with follow-up of the eustachian tube group were significant lower than those of the tympanic membrane puncture group(x2 =9.87,12.33,10.67,all P ＜ 0.05).Conclusion Compared with endoscopic hormone injection by tympanic membrane puncture,endoscopic hormone injection by eustachian tube in the treatment of patients with chronic secretory otitis media possess the advantages including relieve the clinical symptoms,improve the bone conduction threshold and eustachian tube function,regulate the laboratory indexes and reduce the risk of recurrence and effusion.