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

OBJECTIVES: To investigate the ethnic origin of Chuanqing people, one of the largest unidentified ethnic groups in Guizhou, China, and analyze its genetic relationships with surrounding populations. METHODS: Based on a self-developed microhaplotype system, we conducted genotyping and analyzed the genetic distribution of microhaplotype loci and their forensic applicability in Chuanqing population in Guizhou Province. Using the microhaplotype data from different intercontinental populations and previously reported data from Han population living in Guizhou Province, we systematically investigated the genetic background of Chuanqing people through population genetic approaches, including genetic distance estimation, principal component analysis, and phylogenetic tree construction. RESULTS: Among the studied population, the number of haplotype per microhaplotype ranged from 6 to 25. The average expected heterozygosity (He), observed heterozygosity (Ho), power of discrimination (PD), and probability of exclusion (PE) were 0.8291, 0.8301, 0.9387, and 0.6593, respectively. The cumulative power of discrimination (CPD) and cumulative probability of exclusion (CPE) for these 33 loci were 1-2.62×10^-41 and 1-7.64×10^-17, respectively. Population genetic analyses revealed that the Chuanqing population had close genetic relationships with the East Asian populations, especially the local Guizhou Han population, Beijing Han population and the Han populations living in southern China. CONCLUSIONS The 33 microhaplotypes exhibit high levels of genetic diversity in the Guizhou Chuanqing population, highlighting their potentials for both forensic identification and parentage testing. The Han populations might have contributed a significant amount of genetic material to the Chuanqing population during the formation and development of the latter.
Humans ; China/ethnology* ; Ethnicity/genetics* ; Forensic Genetics/methods* ; Genetics, Population ; Genotype ; Haplotypes ; Phylogeny ; East Asian People/genetics*

OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

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 safety and effectiveness of the comprehensive therapy of "Five-in-One" of traditional Chinese medicine combined with low concentration of atropine in the prevention and control of myopia in adolescents. Methods Eighty adolescents diagnosed with mild myopia were included in the study. According to the wishes of the subjects and their guardians, they were divided into control group with 40 cases and traditional Chinese medicine intervention group with 40 cases. The control group received 0.01% atropine sulfate eye drops in both eyes once before bedtime every night, the traditional Chinese medicine intervention group underwent twice-weekly comprehensive therapy of "Five-in-One" of traditional Chinese medicine on the basis of local application of medication in the control group. Both groups received a 12-month intervention course. Follow-up visits were conducted before intervention and at 3, 6, and 12 months after treatment. The international standard visual acuity chart was used to examine the changes in unaided distance visual acuity before and after treatment in both groups. The changes of distant visual acuity of naked eye before and after treatment were measured in two groups. The changes in equivalent spherical lens power before and after treatment in both groups were measured by mydriatic refraction combined with a computer optometer. The changes in axial length before and after treatment were measured using an optical biometer. The adverse reactions after treatment in both groups were compared. Results In the control group, the uncorrected distance visual acuity decreased compared with that before intervention as the treatment time prolonged, while was gradually increased in the traditional Chinese medicine intervention group compared with that before intervention (P < 0.05). At 12 months after treatment, the uncorrected distance visual acuity in the traditional Chinese medicine intervention group was higher than that in the control group (P < 0.05). With the prolongation of treatment time, the equivalent spherical lens power gradually increased in both groups (P < 0.05).At 12 months after treatment, the equivalent spherical lens power in the traditional Chinese medicine intervention group was lower than that in the control group (P < 0.05). The axial length gradually increased with the prolongation of treatment time in both groups (P < 0.05). At 6 and 12 months after treatment, the axial length in the traditional Chinese medicine intervention group was shorter than that in the control group (P < 0.05). After using 0.01% atropine, 8 children in the control group developed outdoor photophobia symptoms; after treatment with the comprehensive therapy of "Five-in-One" of traditional Chinese medicine combined with 0.01% atropine sulfate eye drops in the traditional Chinese medicine intervention group, 4 children developed outdoor photophobia symptoms, but the symptoms disappeared after 2 weeks of medication. Conclusion The comprehensive therapy of "Five-in-One" in traditional Chinese medicine combined with low-concentration atropine is significantly more effective than low-concentration atropine alone in effectively controlling the progression of refractive myopia and reducing its adverse reactions.

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 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 evaluate the role of ErbB2 interacting protein (Erbin) in sepsis-associated encephalopathy (SAE) in mice and the relationship with nod-like receptor thermoprotein domain associated protein 3 (NLRP3) inflammasomes.Methods:Sixty SPF-grade healthy male wild-type C57BL/6 mice and 60 Erbin (-/-)C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=30 each) by a random number table method: wild-type sham operation group (WT+ Sham group), wild-type SAE group (WT+ SAE group), Erbin (-/-) sham operation group (EKO+ Sham group) and Erbin (-/-) plus SAE group (EKO+ SAE group). The model of SAE was established by cecal ligation and perforation in anesthetized mice.Open field test (total distance moved) was performed at 7 days after establishing the model, new object recognition test (recognition index) was performed at 8 days after establishing the model, and Morris water maze test (time of staying at target quadrant) was performed at 10 days after establishing the model.The mice were sacrificed, and hippocampal tissues were removed for microscopic examination of pathologic changes (by HE staining) and for determination of neuron count, expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot), the number of NLRP3 positive cells (by immunohistochemistry), and contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-18 (by enzyme-linked immunosorbent assay). The cell survival rate was calculated. Results:Compared with group WT+ Sham, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group WT+ SAE ( P<0.05). Compared with group EKO+ Sham, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group EKO+ SAE ( P<0.05). Compared with group WT+ SAE, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group EKO+ SAE ( P<0.05). There was no significant difference in total distance moved between the four groups ( P>0.05). Conclusion:Erbin can exert endogenous protection by inhibiting the activation of NLRP3 inflammasomes in mice with SAE.

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.

Objective:To observe the natural course of cerebral contusion and laceration combined with hematoma formation and analyze the risk factors for its progression.Methods:Patients with cerebral contusion and laceration combined with hematoma formation admitted to our hospital from September 2017 to March 2020 were prospectively selected; and they were divided into progressive and non-progressive groups according to progression of cerebral contusion and laceration combined with hematoma formation. The clinical data of the two groups of patients were compared, and multivariate Logistic regression was used to analyze the independent influencing factors for progressive cerebral contusion and laceration combined with hematoma formation.Results:A total of 197 patients with cerebral contusion and laceration combined with hematoma formation were included in this study, of which, 61 were treated with craniotomy and 136 were treated conservatively; 85 patients had progressive cerebral contusion and laceration combined with hematoma formation and 112 patients had non-progressive cerebral contusion and laceration combined with hematoma formation. As compared with those in the non-progressive group, the baseline Glasgow Coma Scale (GCS) scores of the progressive group were lower, hematoma volume by second CT scan was larger, distance from the center of cerebral contusion and laceration or hematoma to the nearest cortex was shorter, platelet count and thrombin time increased, fibrinogen (FIB) content decreased, and proportion of patients with multiple lesions in the first CT scan was higher in the progressive group, with significant differences ( P<0.05). Multivariate Logistic regression analysis showed that the distance from the center of cerebral contusion and laceration or hematoma to the nearest cortex<1 cm, plasma FIB<2 g/L, multiple lesions of cerebral contusion and laceration or hematoma on first CT scan were risk factors for progression in patients with cerebral contusion and laceration combined with hematoma formation ( OR=6.654, 95%CI: 1.391-35.089, P=0.025; OR=5.617, 95%CI: 1.136-28.022, P=0.034; OR=4.629, 95%CI: 1.178-20.071, P=0.031). Conclusion:The patients with short distance from the center of cerebral contusion and laceration or hematoma to the nearest cortex, low plasma FIB, and multiple lesions of cerebral contusion and laceration or hematoma on first CT scan are prone to have progressive cerebral contusion and hematoma formation.