OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant

Objective To explore the influencing factors of device-related pressure injuries (DRPI) in critically ill patients, construct a risk prediction model, and validate its effectiveness. Methods A retrospective analysis was conducted on the clinical data of 136 critically ill patients. Based on the occurrence of DRPIs, the patients were divided into occurrence group (32 patients) and non-occurrence group (104 patients). Univariate analysis and binary Logistic regression analysis were used to investigate the influencing factors of DRPIs, and a binary Logistic regression model was constructed. The Hosmer-Lemeshow test was used to assess the goodness of fit of the model, and the area (AUC) under the receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model.Additionally, the Bootstrap method was employed for internal validation of the model. Results Univariate analysis revealed statistically significant differences between the two groups in terms of age, diabetes, ICU stay duration, duration of non-invasive ventilation mask use, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Braden scale score, use of vasoactive drugs, prone position ventilation, hemoglobin levels, and lactate levels (P < 0.05). Binary Logistic regression analysis indicated that age, diabetes, ICU stay duration, APACHE Ⅱ score, duration of non-invasive ventilation mask use, use of vasoactive drugs, prone position ventilation, lactate levels, Braden scale score, and hemoglobin levels were independent influencing factors for DRPIs in critically ill patients (P < 0.05). A binary Logistic regression model for predicting the risk of DRPIs in critically ill patients was constructed based on these independent factors. The overall prediction accuracy of the model was 99.26%. The Hosmer-Lemeshow goodness-of-fit test showed that the model had good fitness (χ² < 0.001, P>0.999). Internal validation using the Bootstrap method and ROC curve analysis showed that the AUC of the model for predicting DRPIs in critically ill patientswas 0.952, with a sensitivity of 87.5% and a specificity of 93.3%. Conclusion The risk prediction model for DRPIs in critically ill patients constructed in this study demonstrates good stability and predictive performance. It can assist clinical healthcare professionals in screening high-risk patients and formulating personalized intervention plans.

Objective:To explore the characteristic of dynamic function network connectivity (dFNC) of resting brain networks in internet gaming disorder (IGD) adolescents.Methods:Forty-four adolescent IGD subjects (IGD group, male/female: 38/6) and fifty healthy controls (HC group, male/female: 40/10) were collected, and the subjects completed demographic questionnaires, Young internet addiction scale(YIAS), Chinese adolescents' maladaptive cognitions scale(CAMAS), and functional magnetic resonance imaging (fMRI) tests. The fMRI data were preprocessed on the Matlab platform, and the preprocessed data was divided into 64 components for group level independent component analysis.The dynamic functional connectivity of obtained 18 effective independent components was analyzed by sliding time window technique, and the difference of dynamic functional connectivity of brain triple network between the IGD group and HC group was compared using SPSS 22.0 software.Results:Four repeated dFNC states were identified through cluster analysis.Each state indicated that different functional networks had different connection strengths.State 3, the most frequent state, had been indicated that the whole brain network of the subject was in a state of weak functional connectivity.The second frequent state was state 1, which indicated enhanced functional connectivity within the subject's central executive network (CEN).State 2 had been indicated enhanced functional connectivity within the subject's salience network (SN).State 4 had been indicated generally enhanced functional connectivity in the subjects' brain networks, and this state was the least frequent.The results of non-parametric permutation test on the time attribute showed that compared with the HC group, the IGD group had a longer time score (IGD group: 0.24±0.19, HC group: 0.13±0.15, t=1.19, P<0.05, non-parametric substitution test) for state 1 with strong connectivity within the CEN, which was positively correlated with the YIAS score and game time ( r=0.418, P=0.003; r=0.515, P=0.004).Compared with HC group, the functional connectivity of ICD group between the internal insula of the SN and the dorsal anterior cingulate cortex was enhanced ( P<0.05, FDR corrected), while the average residence time in weakly connected state 3 was longer ( Z=2.09, P<0.05, nonparametric substitution test). Conclusions:The difference in dynamic functional connectivity of the triple network in the brain of IGD adolescents under resting state is mainly manifested by strong connections in CEN, functional connections between insula and dorsal anterior cingulate cortex in SN is enhanced, and weakening of overall functional connections, which may play an important role in the pathological mechanism of IGD.

Objective     To explore the relationship between preoperative fasting plasma glucose (FPG) and postoperative pulmonary complications (PPCs) in type 2 diabetic patients undergoing elective thoracoscopic lung resection, and provide a reference for prediction and prevention of PPCs in the clinic. Methods     A retrospective analysis was performed on the type 2 diabetic patients who underwent elective thoracoscopic lung resection for the first time in our hospital from January 2017 to March 2021. According to the level of FPG one day before the operation, the patients were divided into three groups: a hypoglycemia group (<6.1 mmol/L), a medium level blood glucose group (≥6.1 mmol/L and <8.0 mmol/L) and a high blood glucose group (≥8.0 mmol/L). Besides, the patients were divided into a PPCs group and a non-PPCs group according to whether PPCs occurred. The risk factors for PPCs were analyzed by logistic regression analysis, and the predictive value of preoperative FPG level on PPCs was estimated by the area under the receiver operating characteristic curve (AUC). Results     A total of 130 patients were included, including 75 (57.7%) males and 55 (42.3%) females with an average age of 63.5±9.0 years. Logistic regression analysis showed that compared to non-PPCs patients, the level of preoperative FPG (P=0.023) and smoking history ratio (P=0.036) were higher and the operation time was longer (P=0.004) in the PPCs patients. High FPG level on preoperative day 1 and longer operation time were associated with PPCs risk. Besides, the preoperative FPG of 6.79 mmol/L was the threshold value to predict the occurrence of PPCs [AUC=0.653, 95%CI (0.559, 0.747), P=0.003]. Conclusion     There is a certain correlation between preoperative FPG level and postoperative PPCs, which may be used as an index to predict the occurrence of PPCs.

OBJECTIVE To prepare spider fibroin membrane loaded with Periplaneta americana extract， and investigate its characterization， in vitro drug release property and cytotoxicity. METHODS Using natural spider silk collected from Chilobrachys guangxiensis as raw material， P. americana extract as model drug， the drug-loaded spider fibroin membrane （hereinafter referred to as drug-loaded membrane） was prepared by solvent casting method. The material matrix spider fibroin membrane without P. americana extract （hereinafter referred to as blank membrane） was prepared with same method. The membrane structure was characterized by static water contact angle， Fourier infrared chromatography， X-ray diffraction and scanning electron microscopy from different angles； drug release characteristics in artificial saliva were simulated in vitro to evaluate the drug sustained-release performance. MTT assay was adopted to validate the cytotoxicity of drug-loaded membrane. RESULTS The drug-loaded membrane was prepared， and the static water contact angle was less than 90°， which was less than that of blank membrane. The drug-loaded membrane showed the characteristic absorption peak to polypeptide of P. americana extract at 1 500-1 700 cm－1. X-ray diffraction and scanning electron microscopy also proved that the drug was successfully loaded into the pellicle. The release time of the pellicle in artificial saliva was more than 200 min. The MTT test results showed that the cell proliferation rates of blank membrane and drug-loaded membrane were 84.6% and 79.4% （both greater than 70%）， respectively， without significant potential cytotoxicity. CONCLUSIONS Drug-loaded membrane prepared with natural spider silk has a certain sustained-release effect in artificial saliva， which can be further developed as a drug sustained-release carrier with excellent biological characteristics and biocompatibility.

OBJECTIVE To analyze and identify the metabolites of isoimperatorin in normal rats in vivo. METHODS After the rats were intragastrically administered, the plasma, urine and feces samples of rats in normal and dosed groups were collected, and the samples were processed by solid phase extraction. Then, UHPLC-HRMS(Q-Exactive Orbitrap MS) high- resolution mass spectrometry was used to analyze biological samples, and the metabolites were screened and identified. RESULTS In both positive and negative ion modes, a total of 32 metabolites were accurately analyzed and identified based on the precise molecular masses obtained, chromatographic retention behavior, control mass spectral cleavage patterns, characteristic fragment ions, and relevant literature reports. The main metabolic pathways were furan ring opening, lactone hydrolysis, oxidation, methylation, glucuronidation, sulfation and their complex reactions. Among them, the glucuronidation product was discovered for the first time. CONCLUSION This study comprehensively clarifies the transformation pathways of isoimperatorin in rats, which can provide a basis for its pharmacodynamic study and metabolism study analysis of the other furocoumarins.

Objective:To understand the epidemiological characteristics of human brucellosis in Yantai City, Shandong Province, and to provide scientific basis for the formulation and adjustment of brucellosis prevention and control strategy.Methods:The epidemic data, demographic data and case data of human brucellosis in Yantai City in 2019 were collected from the National Health Insurance Disease Control Information System and the epidemiological case survey of brucellosis in Shandong Province. Descriptive epidemiological method was used to analyze the three distribution characteristics, clinical characteristics and infection routes of brucellosis.Results:In 2019, 158 cases of brucellosis were reported in Yantai City, with an incidence rate of 2.22/100 000 and no deaths. The incidence peak was from April to June, accounting for 43.67% (69/158). In addition to Changdao County, 12 other cities and districts had reported brucellosis cases, and Laizhou City had the largest number of reported cases, accounting for 39.87% (63/158). The ratio of men to women was 2.1 ∶ 1.0 (107 ∶ 51). The age of onset was mainly 40 - 69 years (75.95%, 120/158). Farmer was the main occupation, accounting for 83.54% (132/158). The main clinical manifestations were fever (114 cases), muscle and joint pain (107 cases), fatigue (95 cases), hyperhidrosis (85 cases). Patients had a clear history of livestock contact accounted for 58.86% (93/158). The main contact ways were breeding (68 cases) and slaughter (26 cases). Protective measures were taken in 18.28% (17/93) of the patients, and wearing gloves was the most common protective measure, accounting for 76.47% (13/17). The rate of hand washing after contact was 91.40% (85/93), of which 37.65% (32/85) were washed only with water and 62.35% (53/85) were washed with soap. The percentage of changing laundry after contact was 82.80% (77/93).Conclusions:The awareness and ability of personal protection of brucellosis key population in Yantai City are low. Improving the effectiveness of health education and behavior intervention is an important measure for prevention and control of the disease in the future.

Objective:To investigate and analyze a human brucellosis (hereinafter referred to as brucellosis) in Fushan District, Yantai City of Shandong Province, and to provide scientific basis for study the main risk factors and doing a good job in brucellosis prevention and control.Methods:Collect the epidemic data of one human brucellosis in Fushan District, Yantai City in 2017. The information comes from the infectious disease report information management system, the epidemiological case questionnaire of brucellosis in Shandong Province, and the medical records of medical institutions. The epidemic situation, cases and epidemiological investigation results were analyzed retrospectively.Results:Serological tests were carried out among 48 close contacts of the reported case and workers in the same village. Among the 3 positive cases, 2 cases had symptoms and positive bacterial culture results, which were diagnosed as confirmed cases. One patient was asymptomatic and negative bacterial culture, and was diagnosed as recessive infection. All of the three confirmed cases and one recessive infection involved in the epidemic had a history of close contact with infected animals, and without protective measures. The serological examination of 70 key people in the district was carried out and the results were all negative. A total of 166 sheep blood samples were collected, including 21 positive samples.Conclusions:The infectious source of this outbreak is the non-quarantine infected sheep. The main exposure factor is personal unprotected exposure to infected sheep. The key of prevention and control is to strengthen the monitoring and quarantine management of brucellosis among livestock, to improve the personal protection consciousness and ability of key population, and to improve the diagnosis ability of medical institutions in low epidemic areas.

Objective:To analyze the epidemiological characteristics of human brucellosis (referred to as brucellosis) from 2011 to 2018 in Yantai City, and to provide scientific basis for formulating and adjusting brucellosis prevention and control strategies.Methods:Descriptive epidemiological method was used to analyze the monitoring data and epidemiological survey data (time, area, population distribution and treatment behavior) of brucellosis in Yantai from 2011 to 2018.Results:From 2011 to 2018, 795 cases of brucellosis were reported in Yantai, with an annual incidence of 1.42/100 000 and no deaths. Most of the cases were sporadic, accounting for 92.20% (733/795). The incidence peak was from March to August, accounting for 67.80% (539/795). In addition to Changdao County, cases of brucellosis had been reported in 12 counties (cities, districts). The incidence rate of the top three counties (cities, districts) were 5.20/100 000 (369 cases, accounting for 46.42%) in Laizhou City, 2.13/100 000 (97 cases, accounting for 12.20%) in Zhaoyuan City, and 1.77/100 000 (62 cases, accounting for 7.80%) in Penglai City. The male and female sex ratio was 2.82 to 1.00 (587 to 208). The age of onset was mainly 40 - 69 years old, accounting for 79.62% (633/795). Occupation was mainly farmers, accounting for 83.90% (667/795). Cases were mainly found in local medical institutions, accounting for 89.56% (712/795). The average interval between onset and diagnosis was 17 days, the longest was 40 days in 2012, and the shortest was 12 days in 2018.Conclusions:From 2011 to 2018, except Changdao County, 12 counties (cities and districts) in Yantai City had reported brucellosis cases. The incidence peak was in spring and summer, mainly in middle-aged and elderly people, so we should carry out targeted prevention and control strategies for different areas and key populations.

Objective:To evaluate the role of ErbB2-interacting protein (Erbin) in muramyl dipeptide (MDP)-induced inflammatory responses in the macrophages of mice.Methods:Erbin gene knockout RAW264.7 cell line (Erbin -/ -RAW264.7) was constructed by CRISPR/CAS9 gene-editing technology.RAW264.7 cells were cultured in vitro.Each type of cells was divided into 2 groups ( n=16 each)by a random number table method: RAW264.7 group, RAW264.7 plus MDP group, erbin -/ -RAW264.7 group, and erbin -/ -RAW264.7 plus MDP group.In each MDP group, cells were incubated with 10 μg/ml MDP for 6 h, then immunofluorescence was used to determine the expression of nuclear factor kappa B (NF-κB) p65, and the concentrations of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the culture medium were determined by enzyme-linked immunosorbent assay. Results:Compared with RAW264.7 group, the concentrations of TNF-α and IL-6 in the culture medium were significantly increased( P<0.05), NF-κB p65 moved to the nucleus, and the red fluorescence area was increased in RAW264.7+ MDP group.Compared with RAW264.7+ MDP group and Erbin -/- RAW264.7 group, the concentrations of TNF-α and IL-6 in the culture medium were significantly increased ( P<0.05), NF-κB p65 moved more markedly to the nucleus, and the red fluorescence area was increased in Erbin -/-RAW264.7+ MDP group. Conclusion:Erbin inhibits MDP-induced inflammatory responses in macrophages through inhibiting the activity of NF-κB p65 in mice.