Objective To identify the causative variants in 5 Chinese families with tuberous sclerosis complex(TSC)to provide genetic counseling and prenatal diagnosis.Methods Genetic counseling and clinical diagnosis were performed in 8 patients from five unrelated TSC families by teleconsultation.With informed consent obtained from the participants,3 to 5 mL peripheral blood samples were collected from the probands and their family mem-bers for the extraction of genomic DNA.Candidate pathogenic variants were screened by panel sequencing(PS).The candidate pathogenic variants found in TSC1 and TSC2 by PS were validated by PCR-Sanger sequencing and bioinformatics analysis.Results All the pathogenic mutations were identified in the probands and their available family members.Causative variants in TSC1 or TSC2 were detected in all patients,including three reported variants and two novel variants.The two novel variants,TSC2:c.245G＞A and TSC2:c.235delG,which were predicted to cause the nonsense variant p.(Trp82?)and the frameshift variant p.(Val79Lysfs27?)respectively was believed to introduce premature stop codons.The analysis of family co-segregation and bioinformatics were identified as very positive factors for pathogenicity.Conclusions This result provides more evidences for the genetic counseling and prenatal diagnosis in these families and expand the spectrum of TSC2 pathogenic variants.

Objective To analysis the current situation of hospitalized patients seeking medical treatment across different counties and the influencing factors from both the inflow and outflow perspectives.Methods Using the fourth quarter data of 2019 from the medical record index,with Sichuan Province as the research area,it analyzed the spatial flow of patients based on the patient's county of residence,the county where the hospital is located,and the number of mobile patients.By combining information at the individual patient level,healthcare institution level,and county level,it established two-level random intercept logistic regression analysis to explore the influencing factors from the perspectives of inflow and outflow.Results The proportion of patients seeking medical treatment across different counties in Sichuan is 22.90%.The majority of patients,with a population of over one thousand,are concentrated in the eastern region.However,the western region has a higher proportion of patients seeking medical treatment across counties.Chengdu and Mianyang are both the largest sources and recipients of patient flows.Being Han Chinese(49%,P＜0.001),male(2%,P＜0.001),Stable income(6%,P＜0.001)and better medical insurance coverage(16%,P＜0.001)at the patient level,as well as better healthcare resources at the institutional level,and higher economic(20%,P＜0.001)and medical levels(5%,P＜0.001)at the district and county level promote patients seeking medical treatment across counties.Conclusion Hospitalized patients in Sichuan Province tend to seek medical treatment from surrounding counties towards the county centers,as well as flowing to Chengdu from various locations.Promoting hierarchical medical treatment and encouraging patients to seek appropriate medical services can be achieved through strengthening patient health education,improving healthcare service levels,and promoting coordinated development between the economy and medical industry.

Objective:To evaluate the effects of cognitive behavior therapy(CBT)combined with attention training technique(ATT)on auditory hallucinations of schizophrenia.Methods:Sixty schizophrenia patients with au-ditory hallucinations were recruited according to the criteria of International Classification of Diseases,tenth Edition(ICD-10).They were randomly divided into the CBT group(30 cases,26 cases completed)and the CBT+ATT group(30 cases,25 cases completed).The CBT group received only 4 weeks of cognitive behavioral intervention for auditory hallucinations,and the CBT+ATT group received 6 weeks of attention training technology intervention based on cognitive behavioral intervention.At baseline and after 12 weeks,the Psychotic Symptom Rating Scales-Auditory Hallucinations(PSYRATS-AH)and Scale of Social function in Psychosis Inpatients(SSPI)were used to evaluate the auditory hallucinations symptoms and social functioning of the two groups,and the Attentional Control Scale(ACS)was used to evaluate patients'attentional control ability of the CBT+ATT group.Results:After 12 weeks,the differences(post intervention score-baseline score)of PSYRATS-AH total scores[(-6.8±2.2)vs.(-4.2±1.5)],auditory hallucinations'frequency,duration,number of distresses,control of voices were lower in the CBT+ATT group than in the CBT group(Ps＜0.05),and the differences of the SSPI total scores[(13.9± 2.9)vs.(11.6±4.2)]and scores of Factor I and Factor Ⅲ were higher in the CBT+ATT group than in the CBT group(Ps＜0.05).Conclusion:This study shows cognitive behavioral therapy combined with attention training technique could improve auditory hallucinations and social function more effectively in patients with schizophrenia.

Objective:To investigate the prevalence of norovirus and the correlation between norovirus infection and stool traits and clinical symptoms in children with acute gastroenteritis during 2021-2022.Method:A total of 2 195 anal swab samples were collected from cases of acute gastroenteritis in Beijing Children 's Hospital Affiliated to Capital Medical University from January 2021 to December 2022. PCR fluorescent probe assay was performed to detect norovirus，the clinical information and test results were performed by statistical analysis. Results:The detection rate of norovirus was 19.09%（419/2 195）in 2 195 children. The detection rates of male and female were 17.80%（244/1 371）and 21.24%（175/824），respectively，with statistically significant differences between genders（ χ2=3.945, P<0.05）. The positivity rate of noroviruses was higher in aged 1 month to 3 years［29.09%（64/220）~40.69%（94/231）］，especially in 1 year［40.69%（94/231）］. The norovirus detection rate ranged from 2.44%（2/82）to 35.84%（62/173）in different months，with a high detection rate between January and March，higher in the winter and spring［28.36%（150/529），21.07%（146/693）］，showing a clear seasonal distribution.Clinical symptoms of both vomiting and diarrhea were significantly more common among norovirus positive than negative children，the difference was statistically significant（ χ2=57.29, P<0.05）. Conclusion:In the high incidence season of winter and spring，for infants and young children aged 1 month to 3 years with diarrhea accompanied by vomiting symptoms，especially those aged 1 year，it is recommended to undergo norovirus related testing in time. Early treatment and isolation measures should be taken for diagnosed children to reduce cross infection and prevent outbreaks.

Objective:To explore the effects of applying peer-assisted learning (PAL) combined with modular teaching in physiology education, and to explore a more suitable mode for physiology teaching and learning.Methods:We selected a total of 89 undergraduate medical students of grade 2022 from a university offering physiology courses from February 28 to June 30, 2022. They were assigned using a random number table into experimental class (44 students) and control class (45 students). The experimental class adopted PAL with modular teaching, while the control class adopted the online and offline hybrid teaching method. The two classes were compared for teaching effects in terms of the completion rate of task points, final assessment scores, and questionnaire results. SPSS 19.0 was used to perform the independent samples t-test and the chi-square test. Results:The final exam scores for the objective questions of the experimental class and the control class were (43.04±3.25) and (40.24±8.64), respectively; the scores for the subjective items were (44.49±2.80) and (39.21±5.71), respectively; and the total scores were (87.53±4.24) and (79.40±12.08), respectively, all with significant differences between the two classes. There were significant differences in students' learning autonomy, micro-video preview rate, problem discussion participation rate, unit self-test participation rate, and after-class homework completion rate. The questionnaire survey showed that students in the experimental class believed that this teaching model was helpful for improving students' comprehensive qualities.Conclusions:PAL combined with modular teaching can effectively improve physiology teaching effects and students' learning autonomy and comprehensive abilities.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Most patients with stroke experience obstructive sleep apnea (OSA), which has a negative impact on functional outcome and cognitive function in patients with stroke and is associated with increased mortality. Continuous positive airway pressure (CPAP) is a gold standard for treating OSA. This article reviews the effect of CPAP on functional outcome and cognitive function in stroke patients with OSA.

Objective　To explore the effect of Mp1p on host macrophages through transcriptomics combined with metabolomics. Methods Firstly, a THP-1 macrophage strain (THP-1-Mp1p+) stably expressing Mp1p was constructed using lentivirus. Secondly, using high-throughput RNA sequencing (RNA Seq) technology, the expression level of intracellular mRNA was detected in transcriptomics analysis to determine differentially expressed genes; In metabolomics analysis, metabolite identification was performed through database comparison, and pathway analysis was performed on differential metabolites to reveal potential mechanisms of action. Finally, the results of metabolomics and transcriptomics were combined for analysis, and differential metabolites and genes were analyzed to further elucidate the mechanism of action of Mp1p on macrophages. Results Transcriptome analysis showed that, compared with the negative control group, the THP-1-Mp1p+ group had a total of 1 180 differentially expressed genes (DEGs), with 345 upregulated genes and 835 downregulated genes. GO enrichment analysis of DEGs showed that there were 135 differentially expressed genes, including 105 in biological processes (BP), 28 in cellular components (CC), and 2 in molecular functions (MF). The KEGG analysis results showed that the effect of Mp1p on THP-1 macrophages was highly correlated with the TNF pathway. The metabolomic analysis found that both the blank control group and the THP-1-Mp1p+ macrophage group achieved good separation between QC samples in both positive and negative ion modes. The threshold for significant differential metabolites was set at: VIP≥1 and T-test P<0.05, resulting in the identification of 488 differential metabolites, with 230 in the positive ion mode and 258 in the negative ion mode. Pathway enrichment analysis of the identified metabolites pointed to significant enrichment in metabolic pathways. The combined analysis confirmed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway were important metabolic pathways involved. Conclusions The virulence factor Mp1p may affect host macrophages by modulating the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway. The findings contribute to a better understanding of the mechanisms of action of Mp1p and may offer potential directions for the selection of relevant diagnostic and therapeutic targets in the future.

Objective:To investigate the iodine nutritional status of key populations in iodine adequate areas in Henan Province, and provide a basis for timely adoption of targeted prevention and control measures and scientific formulation of iodine supplementation strategies in iodine adequate areas.Methods:From March to September 2022, a cross-sectional survey was conducted in 60 iodine adequate counties (cities, districts) in 13 provincial-level cities in Henan Province. Administrative villages with a median water iodine level of 40 - 100 μg/L within each county (city, district) were stratified by water iodine value (40 - 49, 50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L). One administrative village was selected from each water iodine layer, and 40 non boarding students aged 8 - 10 years old (age balanced, half male and half female) and 20 pregnant women were selected from each administrative village to collect their household edible salt samples and once random urine sample for test salt iodine and urinary iodine contents; and the thyroid volume of children was measured.Results:A total of 12 203 samples of household edible salt were collected from children aged 8 - 10 years old, with a median salt iodine of 24.5 mg/kg, the iodized salt coverage rate was 85.3% (10 414/12 203), and the qualified iodized salt consumption rate was 77.1% (9 406/12 203). A total of 3 999 samples of household edible salt were collected from pregnant women, with a median salt iodine of 24.0 mg/kg, the iodized salt coverage rate was 84.2% (3 366/3 999), and the qualified iodized salt consumption rate was 74.5% (2 981/3 999). A total of 12 241 urine samples from children aged 8 - 10 years old were collected, with a median urinary iodine of 290.4 μg/L. A total of 4 084 urine samples from pregnant women were collectedd, with a median urinary iodine of 233.0 μg/L. The thyroid volume of 11 971 children was examined, and the rate of goiter was 2.1% (257/11 971). Stratified by water iodine content, the median urinary iodine levels of children in 40 - 59, 60 - 79, and 80 - 100 μg/L water iodine groups were 269.7, 298.0 and 308.0 μg/L, respectively, with a statistically significant difference between the groups ( H = 67.32, P < 0.001). The goiter rates of children were 2.2% (100/4 603), 2.1% (80/3 733), 2.1% (77/3 635), respectively, with no statistically significant difference between the groups (χ 2 = 0.03, P = 0.986). The median urinary iodine levels of pregnant women were 225.4, 243.1, 234.4 μg/L, respectively, with a statistically significant difference between the groups ( H = 10.96, P = 0.004). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is at an excessively suitable level, and pregnant women's iodine nutrition is at an appropriate level. It is recommended to strengthen surveillance on the basis of maintaining current prevention and control measures, and adjust prevention and control measures in a timely manner according to changes in iodine nutrition in the population.

Objective:To investigate the related risk factors of surgical appendectomy after endoscopic retrograde appendicitis therapy (ERAT) in children.Methods:From September 2019 to November 2023 at the Children's Hospital Affiliated to Shandong University,the data from all related children with appendectomy after ERAT were analyzed. The general situation and main clinical manifestations of the children were collected. According to the effect of ERAT,the patients were divided into transfer to surgical group and appendicitis recurrence group by the reasons and time of transfer to surgical treatment. The indexes such as ERAT and reoperation process and pathological types of appendix after operation were collected,and the clinical experience was summarized.Results:Among the 242 children who underwent ERAT,32 cases underwent appendectomy again,including 19 males and 13 females,with an average age of（9.16±2.77）years,and the reoperation rate was 13.2%. The clinical manifestation was abdominal pain (32 cases,100.0%),mainly right lower abdominal pain (28 cases,87.5%),and the main duration was less than 3 months (30 cases,93.8%). Abdominal ultrasound or CT before ERAT mainly indicated appendicitis (11 cases,34.4%) and appendicitis complicated with appendiceal calculus (11 cases,34.4%). There were 9 children in transferred to surgical group,of which 5 cases were transferred to surgery because of ERAT intubation failure,and 4 cases were transferred to surgery because of appendix perforation or abscess. Postoperative pathology showed acute suppurative appendicitis in 5 cases and acute gangrenous appendicitis in 4 cases. There were 23 children in appendicitis recurrence group,whose abdominal pain was relieved after ERAT,but their symptoms were repeated after discharge. After clinical evaluation,they were diagnosed as recurrent appendicitis and underwent surgical appendectomy. Most of them were reoperated within 6 months after ERAT (21 cases,91.3%).Postoperative pathology was mainly chronic appendicitis (10 cases,43.5%).Conclusion:Acute suppurative appendicitis and acute gangrenous appendicitis are prone to catheterization or endoscopic failure during ERAT,and there is a high risk of surgical transfer. ERAT may relieve the symptoms of chronic appendicitis in children. If the symptoms are repeated,surgery is still needed to remove the appendix.